80 research outputs found
Caracterización de las alteraciones genéticas de riesgo alto en los síndromes mielodisplásicos : la transformación leucémica
No full textTesis inédita de la Universidad Complutense de Madrid, Facultad de Medicina, leída el 24-02-2022Los síndromes mielodisplásicos (SMD) constituyen un amplio y heterogéneo grupo de desórdenes hematopoyéticos crónicos que presentan un fenotipo tumoral caracterizado por clonalidad y displasia de los tres linajes mieloide. Esto conlleva a una hematopoyesis ineficaz que causa hipercelularidad de la médula ósea y citopenia en sangre periférica. Alrededor de un 30-40% de los SMD progresan a leucemia mieloide aguda debido a la adquisición de diferentes mutaciones y selección de clones. La IPSS-R clasifica los SMD en cinco grupos de riesgo (muy bajo, bajo, intermedio, alto y muy alto).Aproximadamente el 80% de los pacientes con SMD presentan alteraciones en el ADN. Se han descrito más de 40 genes mutados de forma recurrente en esta patología. Algunas de las mutaciones más frecuentes tienen lugar en genes que codifican a factores de transcripción (TP53, RUNX1, ETV6), reguladores epigenéticos (TET2, DNMT3A, ASXL1, EZH2, IDH1/2), factores de splicing o procesadores de ARNm (SF3B1, SRSF2, U2AF1, ZRSR2) y proteínas de señalización celular (NRAS, CBL, JAK2, SETBP1). Varias alteraciones han sido descritas como marcadores moleculares con valor pronóstico de manera independiente para esta enfermedad. Sin embargo, aún se desconoce el motivo de por qué algunos síndromes mielodisplásicos presentan una mayor tendencia a la transformación leucémica pese a no presentar cariotipo complejo o mutaciones de mal pronóstico...Myelodysplastic syndromes (MDS) constitute a large and heterogeneous group of chronic hematopoietic disorders that present a tumor phenotype characterized by clonality and dysplasia of the myeloid, erythroid and megakaryocytic lineages. This leads to ineffective hematopoiesis causing bone marrow hypercellularity and peripheral blood cytopenia.Around 30-40% of MDS progress to acute myeloid leukemia due to the acquisition of different mutations and selection of clones. The IPSS-R classifies MDS into five risk groups ( very low, low, intermediate, high and very high).Approximately 80% of patients with MDS have DNA alterations. More than 40 recurrently mutated genes have been described in this pathology. Some of the most frequent mutations occur in genes encoding transcription factors (TP53, RUNX1, ETV6), epigenetic regulators (TET2, DNMT3A, ASXL1, EZH2, IDH1 / 2), splicing factors or mRNA processors (SF3B1, SRSF2, U2AF1, ZRSR2) and cell signaling proteins (NRAS, CBL, JAK2, SETBP1). Several alterations have been described as molecular markers with independent prognostic value for this disease. However, the reason why some myelodysplastic syndromes show a greater tendency to leukemic transformation is still unknown despite not presenting complex karyotypes or mutations with a poor prognosis...Fac. de MedicinaTRUEunpu
Sexualidades en fuga: cuerpo e identidad en la literatura y el cine de Martín Rejtman
No full textEste artículo busca realizar un análisis de las sexualidades en laobra literaria y cinematográfica de Martín Rejtman. En algunos textos del autor, como en el cuento "Algunas cosas importantes para mi generación" (1992) o en la película Rapado (1992), pueden verse sexualidades que se encuentran en movimiento, que parecen no obedecer al binarismo heterosexual/homosexual, sino que encuentran un punto de fuga a la racionalidad sexual. Por otro lado, los cuerpos en varios de los films y relatos de Rejtman adquieren una enorme importancia, ya que se entraman con los desplazamientos de las identidades. E0stas se juegan en unos cuerpos tecnológicos, cuerpos protésicos, cuerpos cyborgs, que están atravesados por discursos que los dicen y, al hacerlo, los engendran. Las sexualidades, en este sentido, oscilan entre lo decible y lo indecible.The purpose of this article is to analyze sexualities in Martin Rejtman's literary and film work. Insome texts by this author, such as the short story "Algunas cosas importantes para mi generación" ("Some Things That Are Important for My Generation", 1992) or in the film Rapado (1992), we can see sexualities that are in motion, that seem not to abide by the binary heterosexual/homosexual, but seem to find a vanishing point from sexual rationale. Bodies in several of Rejtman's films and stories, however, acquire much importance, since they are intertwined with identity displacements. These displacements take place in bodies that are technological, prosthetic, cyborgs, which are determined by the discourses that utter them and, by doing so, engender them. Sexualities, in this sense, oscillate between what can and cannot be uttered.Documento incorporado en 2019 en el marco del "Programa de becas de experiencia laboral" de la Biblioteca Profesor Guillermo Obiols para estudiantes de Bibliotecología, a partir de un procedimiento técnico de captura de datos desarrollado por el personal del IdIHCS.Facultad de Humanidades y Ciencias de la Educació
The Mutational Landscape of Acute Myeloid Leukaemia Predicts Responses and Outcomes in Elderly Patients from the PETHEMA-FLUGAZA Phase 3 Clinical Trial
No full textNeoplàsia mieloide; Adults majors; Factors pronòsticsNeoplasia mieloide; Adultos mayores; Factores pronósticosMyeloid neoplasia; Older adults; Prognostic factorsWe sought to predict treatment responses and outcomes in older patients with newly diagnosed acute myeloid leukemia (AML) from our FLUGAZA phase III clinical trial (PETHEMA group) based on mutational status, comparing azacytidine (AZA) with fludarabine plus low-dose cytarabine (FLUGA). Mutational profiling using a custom 43-gene next-generation sequencing panel revealed differences in profiles between older and younger patients, and several prognostic markers that were useful in young patients were ineffective in older patients. We examined the associations between variables and overall responses at the end of the third cycle. Patients with mutated DNMT3A or EZH2 were shown to benefit from azacytidine in the treatment-adjusted subgroup analysis. An analysis of the associations with tumor burden using variant allele frequency (VAF) quantification showed that a higher overall response was associated with an increase in TET2 VAF (odds ratio (OR), 1.014; p = 0.030) and lower TP53 VAF (OR, 0.981; p = 0.003). In the treatment-adjusted multivariate survival analyses, only the NRAS (hazard ratio (HR), 1.9, p = 0.005) and TP53 (HR, 2.6, p = 9.8 × 10−7) variants were associated with shorter overall survival (OS), whereas only mutated BCOR (HR, 3.6, p = 0.0003) was associated with a shorter relapse-free survival (RFS). Subgroup analyses of OS according to biological and genomic characteristics showed that patients with low–intermediate cytogenetic risk (HR, 1.51, p = 0.045) and mutated NRAS (HR, 3.66, p = 0.047) benefited from azacytidine therapy. In the subgroup analyses, patients with mutated TP53 (HR, 4.71, p = 0.009) showed a better RFS in the azacytidine arm. In conclusion, differential mutational profiling might anticipate the outcomes of first-line treatment choices (AZA or FLUGA) in older patients with AML. The study is registered at ClinicalTrials.gov as NCT02319135.This study was supported by the Centro de Investigación Biomédica en Red—Área de Oncología–del Instituto de Salud Carlos III (CIBERONC; CB16/12/00369) and the Subdirección General de Investigación Sanitaria (Instituto de Salud Carlos III, Spain) grants PI16/01530, PI16/01661, PI19/01518, and PI19/00730, the CRIS against Cancer foundation, grant 2018/001, and by the Instituto de Investigación Hospital 12 de Octubre (IMAS12) (co-financed by FEDER funds). The study was supported internationally by Cancer Research UK, FCAECC and AIRC under the Accelerator Award Program
Es mi hijo mal estudiante? : causas médicas del fracaso escolar y tratamientos para superarlo
No full textResumen basado en el de la publicaciónSe parte de la premisa de que, a principios del siglo XXI, el fracaso escolar afecta a un número elevado de niños en España, quienes no cumplen los objetivos pedagógicos de Primaria y Secundaria. Se reflexiona sobre las causas de este fenómeno, los factores que contribuyen a su aparición y persistencia, el papel que corresponde a cada uno de los agentes implicados y las medidas que deberían tomarse desde distintos ámbitos para evitarlo y remediarlo. Se trata sobre las causas médicas del fracaso escolar, haciendo también referencia a aspectos educativos, familiares y sociales que tienen un destacado papel en el aprendizaje y rendimiento académico de los niños. Asimismo, se da respuesta a los padres a sus preguntas sobre el mal rendimiento académico de sus hijos.Biblioteca de Educación del Ministerio de Educación, Cultura y Deporte; Calle San Agustín, 5 - 3 planta; 28014 Madrid; Tel. +34917748000; [email protected]
Impact of IPSS-M implementation in real-life clinical practice
No full textObjectivesThe IPSS-M is a recently published score for risk stratification in myelodysplastic syndromes (MDS), based on clinical and molecular data. We aimed to evaluate its relevance on treatment choice in a real-life setting.MethodsWe retrospectively collected clinical, cytogenetic and molecular data from 166 MDS patients. We calculated IPSS-R and IPSS-M scores and compared Overall Survival (OS) and Leukemia Free Survival (LFS). We also analyzed which patients would have been affected by the re-stratification in terms of clinical management.ResultsWe found that 86.1% of the patients had at least one genetic alteration. The most frequent mutated genes were SF3B1 (25.9%), DNMT3A (16.8%) and ASXL1 (14.4%). IPSS-M re-stratified 48.2% of the patients, of which 16.9% were downgraded and 31.3% were upgraded. IPSS-M improved outcome prediction, with a Harrell’s c-index of 0.680 vs 0.626 for OS and 0.801 vs 0.757 for LFS. In 22.2% of the cohort, the reclassification of the IPSS-M could potentially affect clinical management; 17.4% of the patients would be eligible for treatment intensification and 4.8% for treatment reduction.ConclusionsIPSS-M implementation in clinical practice could imply different treatment approaches in a significant number of patients. Our work validates IPSS-M in an external cohort and confirms its applicability in a real-life setting
Students’ Perceptions of Educational Climate in a Spanish School of Dentistry Using the Dundee Ready Education Environment Measure: A Longitudinal Study
No full textBackground: Educational Climate (EC) may determine teacher and student behaviour. Our aim was to evaluate EC longitudinally in a period of ‘curricular transition’ from traditional (teacher-centred learning) to Bologna curricula (interactive student-centred learning). Methods: The ‘Dundee Ready Education Environment Measure’ (DREEM) questionnaire was completed by 397 students from a Spanish School of Dentistry. Students’ perception was assessed in different courses and academic years. Results: The overall EC scale average was 115.70 ± 20.20 (57.85%) and all domain values showed a percentage >52%, which were interpreted as ‘positive and acceptable’. The EC mean was: 118.02 ± 17.37 (59.01%) for 2010–2011; 116.46 ± 19.79 (58.23%) for 2013–2014; 115.60 ± 21.93 (57.80%) for 2014–2015; 112.02 ± 22.28 (56.01%) for 2015–2016, interpreted as ‘more positive than negative EC’. The worst Learning domain scores corresponded to later academic years and may reflect the Bologna curriculum’s more intensive clinical training involving greater responsibility and self-learning. Conclusions: EC and its domains were perceived more positively than negatively. The Social domain was the most positively evaluated, while the Learning domain was the worstS
The Total Synthesis of Dragmacidins D and F
No full textThe dragmacidins are an emerging class of bis(indole) natural products isolated from deep-water marine organisms. Although there has been a substantial effort to prepare the simple piperazine dragmacidins, little synthetic work has been done in the area of the pyrazinone-containing family members, dragmacidins D, E, and F. These compounds are particularly interesting due to their complex structures and broad range of biological activity.
A highly convergent strategy to access dragmacidin D has been developed. In this approach, sequential halogen-selective Suzuki couplings were used to assemble the carbon scaffold of the natural product. After executing a highly optimized sequence of final events, the first completed total synthesis of dragmacidin D was achieved.
An enantiodivergent strategy for the total chemical synthesis of both (+)- and (-)-dragmacidin F from a single enantiomer of quinic acid has been developed and successfully implemented. Although unique, the synthetic routes to these antipodes share a number of key features, including novel reductive isomerization reactions, Pd(II)-mediated oxidative carbocyclization reactions, halogen-selective Suzuki couplings, and high-yielding late-stage Neber rearrangements.
The formal total syntheses of dragmacidin B, trans-dragmacidin C, and dihydrohamacanthin A are described. In addition, preliminary studies involving a novel approach for the preparation of dragmacidin E are reported.</p
A longitudinal study on the relationship between duration of untreated psychosis and executive function in early-onset first-episode psychosis
No full textBackground: The relationship between duration of untreated psychosis (DUP) and executive function (EF) in patients with first-episode psychosis (FEP) is controversial.We aimto assess the influence of DUP on changes in EF over a 2-year period in subjects with early-onset FEP (first psychotic symptom before age 18) and less than 6 months of positive symptoms.
Methods: A total of 66 subjects were included in the study (19 females [28.8%], mean age 16.2± 1.6 years). The influence of DUP on changes in EF over the 2-year follow-up (expressed as a composite score of 5 cognitive abilities: attention, working memory, cognitive flexibility, response inhibition, and problem solving) was estimated using amultivariate linear regressionmodel after removing the effect of intelligence quotient and controlling for age, gender, diagnosis, premorbid adjustment, severity of positive and negative symptoms at baseline, global functioning at baseline, and mean daily antipsychotic dosage during follow-up.
Results: Mean DUP was 65.0 ± 6.9 days (95% confidence interval [CI], 51.2, 78.8). Median DUP was 47.5 days (range 2–180 days). Negative symptoms at baseline was the only variable significantly associated with EF at baseline (10.9% of explained variance [e.v. 10.9%], p= 0.007). Only shorter DUP (e.v. 8.7%, p= 0.013) and greater severity of baseline negative symptoms (e.v. 10.0%, p= 0.008) were significantly associated with greater improvement in EF.
Conclusions: In early-onset FEP, shorterDUPwas associatedwith greater improvement in EF over a 2-year followup period.Depto. de Psicología Experimental, Procesos Cognitivos y LogopediaDepto. de Medicina Legal, Psiquiatría y PatologíaFac. de PsicologíaTRUEpu
Mutations in the DNA methylation pathway and number of driver mutations predict response to azacitidine in myelodysplastic syndromes
No full textWe evaluated the association of mutations in 34 candidate genes and response to azacitidine in 84 patients with myelodysplastic syndrome (MDS), with 217 somatic mutations identified by next-generation sequencing. Most patients (93%) had ≥1 mutation (mean=2.6/patient). The overall response rate to azacitidine was 42%. No clinical characteristic was associated with response to azacitidine. However, total number of mutations/patient was negatively associated with overall drug response (odds ratio [OR]: 0.56, 95% confidence interval [CI]: 0.33–0.94; p=0.028), and a positive association was found for having ≥1 mutation in a DNA methylation-related gene: TET2, DNMT3A, IDH1 and/or IDH2 (OR: 4.76, 95%CI: 1.31–17.27; p=0.017). Mutations in TP53 (hazard ratio [HR]: 3.88; 95%CI: 1.94–7.75) and EZH2 (HR: 2.50; 95%CI: 1.23–5.09) were associated with shorter overall survival. Meta-analysis of 6 studies plus present data (n=815 patients) allowed assessment of the association of drug response with mutations in 9 candidate genes: ASXL1, CBL, EZH2, SF3B1, SRSF2, TET2, DNMT3A, IDH1/2 and TP53. TET2 mutations predicted a more favorable drug response compared with ‘wild-type’ peers (pooled OR: 1.67, 95%CI: 1.14–2.44; p=0.01). In conclusion, mutations in the DNA methylation pathway, especially TET2 mutations, and low number of total mutations are associated with a better response to azacitidine.Sin financiaciónNo data JCR 20171.942 SJR (2017) Q1, 58/378 OncologyNo data IDR 2017UE
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