RB1 gene mutation up-date, a meta-analysis based on 932 reported mutations available in a searchable database

BACKGROUND: Retinoblastoma, a prototype of hereditary cancer, is the most common intraocular tumour in children and potential cause of blindness from therapeutic eye ablation, second tumours in germ line carrier's survivors, and even death when left untreated. The molecular scanning of RB1 in search of germ line mutations lead to the publication of more than 900 mutations whose knowledge is important for genetic counselling and the characterization of phenotypic-genotypic relationships. RESULTS: A searchable database (RBGMdb) has been constructed with 932 published RB1 mutations. The spectrum of these mutations has been analyzed with the following results: 1) the retinoblastoma protein is frequently inactivated by deletions and nonsense mutations while missense mutations are the main inactivating event in most genetic diseases. 2) Near 40% of RB1 gene mutations are recurrent and gather in sixteen hot points, including twelve nonsense, two missense and three splicing mutations. The remainder mutations are scattered along RB1, being most frequent in exons 9, 10, 14, 17, 18, 20, and 23. 3) The analysis of RB1 mutations by country of origin of the patients identifies two groups in which the incidence of nonsense and splicing mutations show differences extremely significant, and suggest the involvement of predisposing ethnic backgrounds. 4) A significant association between late age at diagnosis and splicing mutations in bilateral retinoblastoma patients suggests the occurrence of a delayed-onset genotype. 5) Most of the reported mutations in low-penetrance families fall in three groups: a) Mutations in regulatory sequences at the promoter resulting in low expression of a normal Rb; b) Missense and in-frame deletions affecting non-essential sequence motifs which result in a partial inactivation of Rb functions; c) Splicing mutations leading to the reduction of normal mRNA splicing or to alternative splicing involving either true oncogenic or defective (weak) alleles. CONCLUSION: The analysis of RB1 gene mutations logged in the RBGMdb has shown relevant phenotype-genotype relationships and provided working hypothesis to ascertain mechanisms linking certain mutations to ethnicity, delayed onset of the disease and low-penetrance. Gene profiling of tumors will help to clarify the genetic background linked to ethnicity and variable expressivity or delayed onset phenotypes

Lo que yo pienso : setenta días en Rusia

Copia digital. Valladolid : Junta de Castilla y León. Consejería de Cultura y Turismo, 2009-201

Efecto de diferentes concentraciones de Silicio, adicionado al suelo en el cultivo de Chile Habanero a cielo abierto

El cultivo de chile habanero representa una alternativa de diversificación a la actividad agrícola del municipio de Tierra Blanca Ver., donde la economía gira alrededor de la producción de caña de azúcar. Por lo que es trascendente el diseño de metodologías que optimicen su producción. En las condiciones en que actualmente se siembran, se obtienen rendimientos que no superan las 5 tn/ha, debido a la variabilidad de las precipitaciones, y el aumento de factores que facilitan la presencia de virus y hongos, que afectan el desarrollo de la planta y como consecuencia los niveles de producción. En este trabajo se introdujo un sistema de fertirriego, y adicional al paquete básico de fertilización se incorporó el componente silicio, evaluado a diferentes concentraciones, adicionadas al suelo en un cultivo de Chile Habanero hibrido Kukulcan, en condiciones de cielo abierto, en el Campo Experimental del Instituto Tecnológico Superior de Tierra Blanca, ubicado a los 18º26´latitud Norte y 96º20´ longitud Oeste. Se estableció una parcela de 2450 m2, con una densidad de 1736 plantas, se aplicaron 3 concentraciones de silicio 200, 400 y 600 g por planta, cada tratamiento consistió de 434 plantas. Se midieron las variables de grosor del tallo y altura de la planta, y el registro de número de flores y frutos por planta. Se encontró que la presencia de silicio favoreció al desarrollo vegetativo, y mejoró los rendimientos de producción, al obtener un mayor número de frutos por planta. No se observaron diferencias significativas entre las concentraciones de silicio utilizadas

Sífilis maligna y diagnóstico oculto de infección por VIH

Malignant syphilis is considered to be an atypical manifestation of secondary syphilis. It is characterised by a predominance of nodular-ulcerative lesions, with a higher incidence in patients with human immunodeficiency virus (HIV) infection. The diagnosis is clinical, based on serological and histopathological results. We present the case of a 51-year-old patient with malignant syphilis skin lesions and unknown HIV infection, with a favorable clinical response after starting parenteral antibiotic treatment and adequate viral load control with antiretrovirals.La sífilis maligna es una manifestación agresiva y atípica de la sífilis secundaria. Se caracteriza por la presencia de lesiones nodulares y ulcerativas, siendo su incidencia más elevada en pacientes con infección por virus de la inmunodeficiencia humana (VIH). El diagnóstico es clínico, apoyándose en resultados serológicos e histopatológicos. Se presenta el caso de un paciente de 51 años con manifestaciones cutáneas de sífilis maligna e infección por VIH no conocida, con respuesta clínica favorable tras iniciar tratamiento antibiótico parenteral y control adecuado de carga viral (CV) con antirretrovirales

The evolution of the ventilatory ratio is a prognostic factor in mechanically ventilated COVID-19 ARDS patients

Background: Mortality due to COVID-19 is high, especially in patients requiring mechanical ventilation. The purpose of the study is to investigate associations between mortality and variables measured during the first three days of mechanical ventilation in patients with COVID-19 intubated at ICU admission. Methods: Multicenter, observational, cohort study includes consecutive patients with COVID-19 admitted to 44 Spanish ICUs between February 25 and July 31, 2020, who required intubation at ICU admission and mechanical ventilation for more than three days. We collected demographic and clinical data prior to admission; information about clinical evolution at days 1 and 3 of mechanical ventilation; and outcomes. Results: Of the 2,095 patients with COVID-19 admitted to the ICU, 1,118 (53.3%) were intubated at day 1 and remained under mechanical ventilation at day three. From days 1 to 3, PaO2/FiO2 increased from 115.6 [80.0-171.2] to 180.0 [135.4-227.9] mmHg and the ventilatory ratio from 1.73 [1.33-2.25] to 1.96 [1.61-2.40]. In-hospital mortality was 38.7%. A higher increase between ICU admission and day 3 in the ventilatory ratio (OR 1.04 [CI 1.01-1.07], p = 0.030) and creatinine levels (OR 1.05 [CI 1.01-1.09], p = 0.005) and a lower increase in platelet counts (OR 0.96 [CI 0.93-1.00], p = 0.037) were independently associated with a higher risk of death. No association between mortality and the PaO2/FiO2 variation was observed (OR 0.99 [CI 0.95 to 1.02], p = 0.47). Conclusions: Higher ventilatory ratio and its increase at day 3 is associated with mortality in patients with COVID-19 receiving mechanical ventilation at ICU admission. No association was found in the PaO2/FiO2 variation

Frequent promoter hypermethylation of RASSF1A and CASP8 in neuroblastoma

Background: Epigenetic alterations and loss of heterozygosity are mechanisms of tumor suppressor gene inactivation. A new carcinogenic pathway, targeting the RAS effectors has recently been documented. RASSF1A, on 3p21.3, and NORE1A, on 1q32.1, are among the most important, representative RAS effectors. Methods: We screened the 3p21 locus for the loss of heterozygosity and the hypermethylation status of RASSF1A, NORE1A and BLU ( the latter located at 3p21.3) in 41 neuroblastic tumors. The statistical relationship of these data was correlated with CASP8 hypermethylation. The expression levels of these genes, in cell lines, were analyzed by RT-PCR. Results: Loss of heterozygosity and microsatellite instability at 3p21 were detected in 14% of the analyzed tumors. Methylation was different for tumors and cell lines (tumors: 83% in RASSF1A, 3% in NORE1A, 8% in BLU and 60% in CASP8; cell lines: 100% in RASSF1A, 50% in NORE1A, 66% in BLU and 92% in CASP8). In cell lines, a correlation with lack of expression was evident for RASSF1A, but less clear for NORE1A, BLU and CASP8. We could only demonstrate a statistically significant association between hypermethylation of RASSF1A and hypermethylation of CASP8, while no association with MYCN amplification, 1p deletion, and/or aggressive histological pattern of the tumor was demonstrated. Conclusion: 1) LOH at 3p21 appears in a small percentage of neuroblastomas, indicating that a candidate tumor suppressor gene of neuroblastic tumors is not located in this region. 2) Promoter hypermethylation of RASSF1A and CASP8 occurs at a high frequency in neuroblastomas.This research was supported in part by grants from the Departamentos de Salud y de Educación del Gobierno de Navarra, Pamplona; Fondo de Investigación Sanitaria (PI031356), and Ministerio de Ciencia y Tecnología y Fondo Europeo de Desarrollo Regional (BFI2003-08775), Madrid

Algo más que monos, mucho menos que humanos

Artículo de opinión en prensa diaria accesible en elpais.com/ArchivosCualquiera que sean nuestros imperativos éticos y opciones morales, está claro que los grandes simios merecen un trato singular, incluyendo leyes que prohíban su caza o uso como animal experimental, o regulando las condiciones de su confinamiento, incluso procurando su libertad en alguno de los santuarios ya existentes o por crear. Mucho de esto ya se está promoviendo por la ONU y ciertas naciones. Sin embargo, la rimbombante declaración de derechos de los grandes simios, encaminada a lograr estos mismos objetivos, adolece de unos fundamentos que no se compadecen con la situación "especial" de los humanos en la naturaleza e historia de nuestro planeta. No inventemos planetas nuevos cuando aún queda tanto por hacer en éste

Spanish performance in life sciences. A comparative appraisal of the scientific production of Spain and five other European countries in 1989

The output in life science disciplines from Spain and five other European countries has been measured in datafile derived from the Current Contents-Life Sciences on diskette (19S9). The results of this flash evaluation were contrasted with data retrieved from survey covering the yearly output during the 1973-83 period and thee 1981-85 aggregated value from Schubert, Glänzel, Braun datafiles. The results of these studies showed an increasing share of Spain in the six countries' output, especially in the subfields of organic chemistry and phytochemistry. However, the quality of the Spanish articles as deduced from the journal impact factors (JRC 1989) is below the six countries average. The usefulness of the Current Contents on diskette for handy and reliable flash evaluations has been ascertained through comparative analysis with more comprehensive surveys.Peer Reviewe