Manual de actividades para la clase única en grupo multigrado en Cuba.

The research article focuses on multigrade didactics in rural elementary schools, for solving deficiencies in the learning of students and in the performance of some teachers. The objective of this research is to implement a manual of activities for the treatment of textual comprehension through the integration of content in rural multigrade school. Classroom observation, interviews with students and teachers and the review of documents made it possible to detect students’ difficulties, in terms of lexical deficiencies, poor use of connectors for adequate oral discourse, limited participation in class and, on occasions, difficulties in the integration of content by teachers according to multigrade didactics. These findings allow us to assume theoretical backgrounds on comprehension levels and the integration of content in the classroom. The results obtained with the proposal of the Manual are favorable, since with its use there is an adequate development of the language in the students both orally and in writing and in their knowledge’s.Este artículo de investigación brinda atención a la didáctica multigrado de la escuela primaria rural, en aras de solucionar falencias en el aprendizaje de los escolares y en el desempeño de algunos maestros. El objetivo es implementar un manual de actividades para el tratamiento a la comprensión textual mediante la integración de contenidos en la escuela rural multigrado. La observación a clases, la entrevista a escolares y maestros y la revisión de documentos posibilitaron corroborar dificultades en escolares referidas a pobreza léxica, poco uso de conectores para un adecuado discurso oral, limitada participación en clases y, en ocasiones, dificultades en la integración de contenidos por los maestros según la didáctica multigrado. Estos hallazgos permiten asumir fundamentos teóricos sobre la comprensión como habilidad esencial, los niveles de comprensión y la integración de contenidos en las clases. Los resultados obtenidos con la implementación del manual son favorables, pues con su uso se muestra un adecuado desarrollo de la lengua en los escolares tanto en el plano oral como escrito y en sus conocimientos

High-resolution copy number analysis of paired normal-tumor samples from diffuse large B cell lymphoma

Copy number analysis can be useful for assessing prognosis in diffuse large B cell lymphoma (DLBCL). We analyzed copy number data from tumor samples of 60 patients diagnosed with DLBCL de novo and their matched normal samples. We detected 63 recurrent copy number alterations (CNAs), including 33 gains, 30 losses, and nine recurrent acquired copy number neutral loss of heterozygosity (CNN-LOH). Interestingly, 20 % of cases acquired CNN-LOH of 6p21 locus, which involves the HLA region. In normal cells, there were no CNAs but we observed CNN-LOH involving some key lymphoma regions such as 6p21 and 9p24.1 (5 %) and 17p13.1 (2.5 %) in DLBCL patients. Furthermore, a model with some specific CNA was able to predict the subtype of DLBCL, 1p36.32 and 10q23.31 losses being restricted to germinal center B cell-like (GCB) DLBCL. In contrast, 8p23.3 losses and 11q24.3 gains were strongly associated with the non-GCB subtype. A poor prognosis was associated with biallelic inactivation of TP53 or 18p11.32 losses, while prognosis was better in cases carrying 11q24.3 gains. In summary, CNA abnormalities identify specific DLBCL groups, and we describe CNN-LOH in germline cells from DLBCL patients that are associated with genes that probably play a key role in DLBCL development.This work was supported by research funding from the Health Council of Castilla y León (GRS265/A/08), the Health Research Program (PS09/01382), and the Red Temática de Investigación Cooperativa en Cáncer (RTICC) grant RD12/0036 (groups 0069, 0029, 0036, 0058, and 0060) included in the National Plan I+D+I supported by the Instituto Carlos III and the Fondo Europeo de Desarrollo Regional (FEDER), the Spanish Ministry of Economy and Competitiveness, and the European Regional Development Fund (ERDF) 'Una manera de hacer Europa' (Innocampus; CEI-2010-1-0010). ES was supported by CM10/00078-Río Hortega, an ISCIII contract, FEHH grant 2013–2014 and JR14/00025-Juan Rodés, an ISCIII contract. IS was supported by the Subprograma Juan de la Cierva (JCI-2011-10232) and a Miguel Servet contract (CP13/00159).Peer Reviewe

Eltrombopag increases the hematopoietic supporting ability of mesenchymal stem/stromal cells

[Background]: Eltrombopag (EP) is a small molecule that acts directly on hematopoietic stem cells (HSCs) and megakaryocytes to stimulate the hematopoietic process. Mesenchymal stem/stromal cells (MSCs) are key hematopoietic niche regulators. [Objectives]: We aimed to determine whether EP has any effect on MSC function and properties (especially on their hematopoietic-supporting ability) and if so, what changes (e.g. genome-wide transcriptomic alterations) are induced in MSC after EP treatment. [Design/Methods]: MSCs were isolated from 12 healthy donors and treated with 15 µM and 50 µM of EP for 24 h. The toxicity of the drug on MSCs and their differentiation ability were analyzed, as well as the transcriptomic profile, reactive oxygen species (ROS) and DNA damage and the changes induced in the clonogenic capacity of HSCs.[Results]: The results show that EP also modifies MSC functions, decreasing their adipogenic differentiation, increasing the expression of genes involved in hypoxia and other pathways related to oxygen homeostasis, and enhancing their ability to support hematopoiesis in vitro.[Conclusion]: Our findings support the use of EP in cases where hematopoiesis is defective, despite its well-known direct effects on hematopoietic cells. Our findings suggest that further studies on the effects of EP on MSCs from patients with aplastic anemia are warranted.This study was supported by research funding from Novartis Pharmaceuticals to FS-G. SP is supported by Fundación Española de Hematología y Hemoterapia (FEHH). SM is supported by RETIC and RICORS programs of ISCIII European Regional Development Fund (RD16/0011/0015, RD21/0017/0006), ‘A way to make Europe’ and NextGenerationEU. GJMC and ESL are supported by the Spanish Ministerio de Ciencia e Innovación (FPU18/03533 and PFIS/19/00272 respectively).Peer reviewe

Using quantification of the PML-RARα transcript to stratify the risk of relapse in patients with acute promyelocytic leukemia

Background and Objectives The detection of PML-RARα by real-time polymerase chain reaction (RQ-PCR) is becoming an important tool for monitoring minimal residual disease (MRD) in patients with acute promyelocytic leukemia (APL). However, its clinical value remains to be determined. Our aim was to analyze any associations between the risk of relapse and RQ-PCR results in different phases of treatment, comparing these data with those yielded by conventional qualitative reverse transcriptase-PCR.Design and Methods Follow-up samples from 145 APL patients treated with the PETHEMA protocols were evaluated by the RQ-PCR protocol (Europe Against Cancer program) and by the RT-PCR method (BIOMED-1 Concerted Action). Hematologic and molecular relapses and relapse-free survival were recorded. We then looked for associations between relapse risk and RQ-PCR results.Results After induction therapy, no association was found between positive RQ-PCR results and relapse. The PCR result here did not imply any change in the scheduled therapy. After the third consolidation course, two out of three cases with positive RQ-PCR relapsed in contrast to 16 out of 119 (13%) patients with negative RQ-PCR. During maintenance therapy and out-of treatment, all patients with >10 PML-RARα normalized copy number (NCN) (n=19) relapsed while all patients wit

Prediction of peripheral neuropathy in multiple myeloma patients receiving bortezomib and thalidomide: a genetic study based on a single nucleotide polymorphism array

GEM (Grupo Español de MM)/PETHEMA (Programa para el Estudio de la Terapéutica en Hemopatías Malignas) cooperative study group.Bortezomib- and thalidomide-based therapies have significantly contributed to improved survival of multiple myeloma (MM) patients. However, treatment-induced peripheral neuropathy (TiPN) is a common adverse event associated with them. Risk factors for TiPN in MM patients include advanced age, prior neuropathy, and other drugs, but there are conflicting results about the role of genetics in predicting the risk of TiPN. Thus, we carried out a genome-wide association study based on more than 300 000 exome single nucleotide polymorphisms in 172 MM patients receiving therapy involving bortezomib and thalidomide. We compared patients developing and not developing TiPN under similar treatment conditions (GEM05MAS65, NCT00443235). The highest-ranking single nucleotide polymorphism was rs45443101, located in the PLCG2 gene, but no significant differences were found after multiple comparison correction (adjusted P =.1708). Prediction analyses, cytoband enrichment, and pathway analyses were also performed, but none yielded any significant findings. A copy number approach was also explored, but this gave no significant results either. In summary, our study did not find a consistent genetic component associated with TiPN under bortezomib and thalidomide therapies that could be used for prediction, which makes clinical judgment essential in the practical management of MM treatment.This work has been partially supported by grants of the Instituto de Salud Carlos III (ISCIII) (CP13/00080), ISCIII (PI12/02311), Red Temática de Investigación Cooperativa en Cáncer (RD12/0036/0069) (RD12/0036/0061), Ministerio de Economía y Competitividad/ Fondo Europeo de Desarrollo Regional (FEDER) “Una manera de hacer Europa” (Innocampus; CEI‐2010‐1‐0010), Asociación Española Contra el Cancer (GCB120981SAN), and Joan Rodes (JR 14/00016). M.E.S. is supported by the Miguel Servet program (CP13/00080) of the ISCIII (Ministerio de Economía y Competitividad).Peer Reviewe

Assessment of the clinical utility of four NGS panels in myeloid malignancies. Suggestions for NGS panel choice or design

The diagnosis of myeloid neoplasms (MN) has significantly evolved through the last few decades. Next Generation Sequencing (NGS) is gradually becoming an essential tool to help clinicians with disease management. To this end, most specialized genetic laboratories have implemented NGS panels targeting a number of different genes relevant to MN. The aim of the present study is to evaluate the performance of four different targeted NGS gene panels based on their technical features and clinical utility. A total of 32 patient bone marrow samples were accrued and sequenced with 3 commercially available panels and 1 custom panel. Variants were classified by two geneticists based on their clinical relevance in MN. There was a difference in panel¿s depth of coverage. We found 11 discordant clinically relevant variants between panels, with a trend to miss long insertions. Our data show that there is a high risk of finding different mutations depending on the panel of choice, due both to the panel design and the data analysis method. Of note, CEBPA, CALR and FLT3 genes, remains challenging the use of NGS for diagnosis of MN in compliance with current guidelines. Therefore, conventional molecular testing might need to be kept in place for the correct diagnosis of MN for now

Genetic complexity impacts the clinical outcome of follicular lymphoma patients

© The Author(s) 2021.Follicular lymphoma (FL) is the second most common non-Hodgkin lymphoma (NHL, 20–30%) after diffuse large B-cell lymphoma (DLBCL). Despite the introduction of rituximab and the high response rate to first-line treatment, approximately 20% of the FL patients relapse or progress within 2 years of receiving first-line therapy. Therefore, the major challenge is finding biomarkers that identify high-risk patients at diagnosis.This work was partially supported by the Instituto de Salud Carlos III (ISCIII), Spanish Ministry of Economy and Competitiveness PI15/01393, PI18/00410, CIBERONC-CB16/12/00233, and “Una manera de hacer Europa” (Innocampus; CEI-2010-1-0010)”, the Education Council or Health Council of the Junta de Castilla y León (CAS102P17, GRS 1180/A/15), Spanish Association Against Cancer (AECC; PROYE18020BEA), and Gilead Sciences (GLD17/00334). CJ, MES, and AMe are supported by the ISCII (CD19/00030, CPII18/00028, and FI19/00320). MGA, IPC, and CJ were supported by the Spanish Society of Hematology Foundation (FEHH). All Spanish funding is co-sponsored by the European Union FEDER program

Implementación de la Simulación Clínica como método de aprendizaje, evaluación y análisis de puntos de mejora para alumnos de 4º curso del Grado de Enfermería en el contexto de los seminarios de Enfermería Clínica III

EL proyecto trata de la implementación de la metodología formativa de la "Simulación Clínica" en el contexto de la asignatira "Enfermería Clínica III". Esta metodología permite un aprendizaje no solo teórico, si no desarrollar competencias prácticas en cuanto habilidades técnicas y no técnicas. El resultado del proyecto es positivo, ya que se consigue implementar dicha metodología con unos resultados bastante buenos y una satisfacción general por parte de los alumnos muy elevada

Desarrollo de competencias clínicas mediante Simulación Virtual en alumnos de último curso del Grado de Enfermería en tiempos de COVID-19

Durante la pandemia Covid-19, la comunidad universitaria se ha visto obligada a reconducir toda la docencia. Con la intención de poder evaluar nuevas herramientas de aprendizaje, que mejoren conocimientos y desarrollen competencias relacionados con los cuidados de enfermería, se realizó un amplio rastreo de herramientas que pudieran ser adecuadas para la formación práctica de nuestros estudiantes. En esta búsqueda, se encontraron diferentes opciones, destacando especialmente la plataforma vSim® For Nursing. La relevancia de esta herramienta se basa en su formato online y la posibilidad de adaptación de toda su metodología a distancia, lo que disminuye el riesgo de contagios por Covid-19. Por ello, nos propusimos como objetivo general: Evaluar la adquisición de competencias clínicas mediante una plataforma de simulación virtual en el último curso del Grado de Enfermería. Los resultados de la utilización de la herramienta fueron óptima. Mejoraron los conocimientos, se incrementaron habilidades clínicas y la satisfacción fue elevada por parte de los participantes

Basophil-lineage commitment in acute promyelocytic leukemia predicts for severe bleeding after starting therapy

Severe hemorrhagic events occur in a significant fraction of acute promyelocytic leukemia patients, either at presentation and/or early after starting therapy, leading to treatment failure and early deaths. However, identification of independent predictors for high-risk of severe bleeding at diagnosis, remains a challenge. Here, we investigated the immunophenotype of bone marrow leukemic cells from 109 newly diagnosed acute promyelocytic leukemia patients, particularly focusing on the identification of basophil-related features, and their potential association with severe bleeding episodes and patient overall survival. From all phenotypes investigated on leukemic cells, expression of the CD203c and/or CD22 basophil-associated markers showed the strongest association with the occurrence and severity of bleeding (p ≤ 0.007); moreover, aberrant expression of CD7, coexpression of CD34+/CD7+ and lack of CD71 was also more frequently found among patients with (mild and severe) bleeding at baseline and/or after starting treatment (p ≤ 0.009). Multivariate analysis showed that CD203c expression (hazard ratio: 26.4; p = 0.003) and older age (hazard ratio: 5.4; p = 0.03) were the best independent predictors for cumulative incidence of severe bleeding after starting therapy. In addition, CD203c expression on leukemic cells (hazard ratio: 4.4; p = 0.01), low fibrinogen levels (hazard ratio: 8.8; p = 0.001), older age (hazard ratio: 9.0; p = 0.002), and high leukocyte count (hazard ratio: 5.6; p = 0.02) were the most informative independent predictors for overall survival. In summary, our results show that the presence of basophil-associated phenotypic characteristics on leukemic cells from acute promyelocytic leukemia patients at diagnosis is a powerful independent predictor for severe bleeding and overall survival, which might contribute in the future to (early) risk-adapted therapy decisions.This work was supported by the Fundación Científica de la Asociación Española Contra el Cáncer (AECC, Madrid, Spain) and the Fundación Rafael del Pino (Madrid, Spain) and both CIBERONC (CB16/12/00400, CB16/12/00233, CB16/12/00480) and grant PI16/00787 from Instituto de Salud Carlos III (Ministerio de Economía y Competitividad, Madrid, Spain)