A rare finding of plasma cell leukaemia with hairy-cell morphology.

The authors state that there are no conflicts of interest to disclose. This publication was funded by the CNIC. The CNIC is supported by the Instituto de Salud Carlos III (ISCIII), the Ministerio de Ciencia e Innovación (MCIN) and the Pro CNIC Foundation, and is a Severo Ochoa Center of Excellence (grant CEX2020- 001041-S funded by MICIN/AEI/10.13039/501100011033).S

Genetic landscape of 6089 inherited retinal dystrophies affected cases in Spain and their therapeutic and extended epidemiological implications

ESRETNET Study Group, The ERDC Study Group, The Associated Clinical Study Group.Inherited retinal diseases (IRDs), defined by dysfunction or progressive loss of photoreceptors, are disorders characterized by elevated heterogeneity, both at the clinical and genetic levels. Our main goal was to address the genetic landscape of IRD in the largest cohort of Spanish patients reported to date. A retrospective hospital-based cross-sectional study was carried out on 6089 IRD affected individuals (from 4403 unrelated families), referred for genetic testing from all the Spanish autonomous communities. Clinical, demographic and familiar data were collected from each patient, including family pedigree, age of appearance of visual symptoms, presence of any systemic findings and geographical origin. Genetic studies were performed to the 3951 families with available DNA using different molecular techniques. Overall, 53.2% (2100/3951) of the studied families were genetically characterized, and 1549 different likely causative variants in 142 genes were identified. The most common phenotype encountered is retinitis pigmentosa (RP) (55.6% of families, 2447/4403). The most recurrently mutated genes were PRPH2, ABCA4 and RS1 in autosomal dominant (AD), autosomal recessive (AR) and X-linked (XL) NON-RP cases, respectively; RHO, USH2A and RPGR in AD, AR and XL for non-syndromic RP; and USH2A and MYO7A in syndromic IRD. Pathogenic variants c.3386G > T (p.Arg1129Leu) in ABCA4 and c.2276G > T (p.Cys759Phe) in USH2A were the most frequent variants identified. Our study provides the general landscape for IRD in Spain, reporting the largest cohort ever presented. Our results have important implications for genetic diagnosis, counselling and new therapeutic strategies to both the Spanish population and other related populations.This work was supported by the Instituto de Salud Carlos III (ISCIII) of the Spanish Ministry of Health (FIS; PI16/00425 and PI19/00321), Centro de Investigación Biomédica en Red Enfermedades Raras (CIBERER, 06/07/0036), IIS-FJD BioBank (PT13/0010/0012), Comunidad de Madrid (CAM, RAREGenomics Project, B2017/BMD-3721), European Regional Development Fund (FEDER), the Organización Nacional de Ciegos Españoles (ONCE), Fundación Ramón Areces, Fundación Conchita Rábago and the University Chair UAM-IIS-FJD of Genomic Medicine. Irene Perea-Romero is supported by a PhD fellowship from the predoctoral Program from ISCIII (FI17/00192). Ionut F. Iancu is supported by a grant from the Comunidad de Madrid (CAM, PEJ-2017-AI/BMD7256). Marta del Pozo-Valero is supported by a PhD grant from the Fundación Conchita Rábago. Berta Almoguera is supported by a Juan Rodes program from ISCIII (JR17/00020). Pablo Minguez is supported by a Miguel Servet program from ISCIII (CP16/00116). Marta Corton is supported by a Miguel Servet program from ISCIII (CPII17/00006)

Allelic overload and its clinical modifier effect in Bardet-Biedl syndrome

Bardet–Biedl syndrome (BBS) is an autosomal recessive ciliopathy characterized by extensive inter- and intra-familial variability, in which oligogenic interactions have been also reported. Our main goal is to elucidate the role of mutational load in the clinical variability of BBS. A cohort of 99 patients from 77 different families with biallelic pathogenic variants in a BBS-associated gene was retrospectively recruited. Human Phenotype Ontology terms were used in the annotation of clinical symptoms. The mutational load in 39 BBS-related genes was studied in index cases using different molecular and next-generation sequencing (NGS) approaches. Candidate allele combinations were analysed using the in silico tools ORVAL and DiGePred. After clinical annotation, 76 out of the 99 cases a priori fulfilled established criteria for diagnosis of BBS or BBS-like. BBS1 alleles, found in 42% of families, were the most represented in our cohort. An increased mutational load was excluded in 41% of the index cases (22/54). Oligogenic inheritance was suspected in 52% of the screened families (23/45), being 40 tested by means of NGS data and 5 only by traditional methods. Together, ORVAL and DiGePred platforms predicted an oligogenic effect in 44% of the triallelic families (10/23). Intrafamilial variable severity could be clinically confirmed in six of the families. Our findings show that the presence of more than two alleles in BBSassociated genes correlated in six families with a more severe phenotype and associated with specific findings, highlighting the role of the mutational load in the management of BBS casesInstituto de Salud Carlos III | Ref. PI15/00049Instituto de Salud Carlos III | Ref. PI16/00425Instituto de Salud Carlos III | Ref. PI19/00321Instituto de Salud Carlos III | Ref. PI19/00332CIBERER | Ref. 07/06/0036IIS-FJD BioBank | Ref. PT13/0010/0012Comunidad de Madrid | Ref. B2017/BMD-3721Xunta de Galicia | Ref. ED431G-2019/06Xunta de Galicia | Ref. ED431C-2018/54ISCIII | Ref. FI17/00192Ministerio de Educación, Cultura y Deporte | Ref. FPU 19/00175ISCIII | Ref. CP16/0011

Many Labs 2: Investigating Variation in Replicability Across Samples and Settings

We conducted preregistered replications of 28 classic and contemporary published findings, with protocols that were peer reviewed in advance, to examine variation in effect magnitudes across samples and settings. Each protocol was administered to approximately half of 125 samples that comprised 15,305 participants from 36 countries and territories. Using the conventional criterion of statistical significance (p < .05), we found that 15 (54%) of the replications provided evidence of a statistically significant effect in the same direction as the original finding. With a strict significance criterion (p < .0001), 14 (50%) of the replications still provided such evidence, a reflection of the extremely highpowered design. Seven (25%) of the replications yielded effect sizes larger than the original ones, and 21 (75%) yielded effect sizes smaller than the original ones. The median comparable Cohen’s ds were 0.60 for the original findings and 0.15 for the replications. The effect sizes were small (< 0.20) in 16 of the replications (57%), and 9 effects (32%) were in the direction opposite the direction of the original effect. Across settings, the Q statistic indicated significant heterogeneity in 11 (39%) of the replication effects, and most of those were among the findings with the largest overall effect sizes; only 1 effect that was near zero in the aggregate showed significant heterogeneity according to this measure. Only 1 effect had a tau value greater than .20, an indication of moderate heterogeneity. Eight others had tau values near or slightly above .10, an indication of slight heterogeneity. Moderation tests indicated that very little heterogeneity was attributable to the order in which the tasks were performed or whether the tasks were administered in lab versus online. Exploratory comparisons revealed little heterogeneity between Western, educated, industrialized, rich, and democratic (WEIRD) cultures and less WEIRD cultures (i.e., cultures with relatively high and low WEIRDness scores, respectively). Cumulatively, variability in the observed effect sizes was attributable more to the effect being studied than to the sample or setting in which it was studied.UCR::Vicerrectoría de Investigación::Unidades de Investigación::Ciencias Sociales::Instituto de Investigaciones Psicológicas (IIP

Studies on mutagenicity of 2 bronchodilators under development in Cuba

2 pyridoquinazolones, 2-amino-11 H-pyrido[2,1- b]quinazolin-11-one (2-APQ) and 11 H-pyrido[2,1- b]quinazolin-11-one (PQ), under development as anti-asthma drugs, were studied for mutagenicity. 2-APQ was found to be a strong mutagen in 5 strains of Salmonella typhimurium and a mild one in the forward-mutation system of the yeast Schizosaccharomyces pombe. Furthermore, 2-APQ had strong clastogenic effects in mouse bone marrow. Because of these results, development of 2-APQ as a bronchodilator was stopped. PQ, on the other hand, did not induce mutation in the 5 Salmonella strains or in S. pombe. S9 mix generally increased the response of 2-APQ in Salmonella dramatically. On the contrary, the mutagenic effectiveness of this compound in S. pombe was only slightly higher in the presence of S9 than without it, suggesting that metabolic activation was not effective in this system

Factores predictivos de mortalidad en pacientes con infarto agudo del miocardio con elevación del ST.

Introducción Objetivo Método Resultados Fueron incluidos 137 pacientes. La edad media fue de 65,8 años ypredominó el sexo masculino (63,5%). Dentro de los factores de  riesgo predominaron la hipertensión arterial (71,01%) seguida por elhábito de fumar (63,04 %), la hipertrigliceridemia (62,77%) y el infartode cara inferior fue el más frecuente. Se presentó una mortalidadde un 12%.Conclusiones La edad de más de 65 años, el tabaquismo, la enfermedad vascularperiférica, la taquicardia, la hipotensión y la clase IV en la escala deKillip-Kimball fueron factores predictivos de mortalidad en pacientescon infarto agudo del miocardio.Se realizó un estudio descriptivo, transversal con los pacientes queingresaron en la unidad de cuidados coronarios intensivos del hospitaluniversitario “Comandante Manuel Fajardo” con diagnóstico confirmadode infarto agudo del miocardio, en el período comprendidode junio del 2009 a julio del 2010. Se utilizaron distribuciones de frecuencia,medidas de tendencia central, cálculos porcentuales y oddsratio, asumiendo p<0,05 como nivel de significación estadística.Por lo cual pretendemos determinar los factores predictivos de mortalidaden los pacientes con infarto agudo del miocardio con elevacióndel segmento ST.La estratificación precoz de pacientes con síndrome coronario agudoes fundamental para su evolución y pronóstico

Factores predictivos de mortalidad en pacientes con infarto agudo del miocardio con elevación del ST.

Introducción Objetivo Método Resultados Fueron incluidos 137 pacientes. La edad media fue de 65,8 años ypredominó el sexo masculino (63,5%). Dentro de los factores de  riesgo predominaron la hipertensión arterial (71,01%) seguida por elhábito de fumar (63,04 %), la hipertrigliceridemia (62,77%) y el infartode cara inferior fue el más frecuente. Se presentó una mortalidadde un 12%.Conclusiones La edad de más de 65 años, el tabaquismo, la enfermedad vascularperiférica, la taquicardia, la hipotensión y la clase IV en la escala deKillip-Kimball fueron factores predictivos de mortalidad en pacientescon infarto agudo del miocardio.Se realizó un estudio descriptivo, transversal con los pacientes queingresaron en la unidad de cuidados coronarios intensivos del hospitaluniversitario “Comandante Manuel Fajardo” con diagnóstico confirmadode infarto agudo del miocardio, en el período comprendidode junio del 2009 a julio del 2010. Se utilizaron distribuciones de frecuencia,medidas de tendencia central, cálculos porcentuales y oddsratio, asumiendo p<0,05 como nivel de significación estadística.Por lo cual pretendemos determinar los factores predictivos de mortalidaden los pacientes con infarto agudo del miocardio con elevacióndel segmento ST.La estratificación precoz de pacientes con síndrome coronario agudoes fundamental para su evolución y pronóstico

Author Correction: Genetic landscape of 6089 inherited retinal dystrophies affected cases in Spain and their therapeutic and extended epidemiological implications

ESRETNET Study Group, The ERDC Study Group, The Associated Clinical Study Group.Inherited retinal diseases (IRDs), defined by dysfunction or progressive loss of photoreceptors, are disorders characterized by elevated heterogeneity, both at the clinical and genetic levels. Our main goal was to address the genetic landscape of IRD in the largest cohort of Spanish patients reported to date. A retrospective hospital-based cross-sectional study was carried out on 6089 IRD affected individuals (from 4403 unrelated families), referred for genetic testing from all the Spanish autonomous communities. Clinical, demographic and familiar data were collected from each patient, including family pedigree, age of appearance of visual symptoms, presence of any systemic findings and geographical origin. Genetic studies were performed to the 3951 families with available DNA using different molecular techniques. Overall, 53.2% (2100/3951) of the studied families were genetically characterized, and 1549 different likely causative variants in 142 genes were identified. The most common phenotype encountered is retinitis pigmentosa (RP) (55.6% of families, 2447/4403). The most recurrently mutated genes were PRPH2, ABCA4 and RS1 in autosomal dominant (AD), autosomal recessive (AR) and X-linked (XL) NON-RP cases, respectively; RHO, USH2A and RPGR in AD, AR and XL for non-syndromic RP; and USH2A and MYO7A in syndromic IRD. Pathogenic variants c.3386G > T (p.Arg1129Leu) in ABCA4 and c.2276G > T (p.Cys759Phe) in USH2A were the most frequent variants identified. Our study provides the general landscape for IRD in Spain, reporting the largest cohort ever presented. Our results have important implications for genetic diagnosis, counselling and new therapeutic strategies to both the Spanish population and other related populations.Peer reviewe

Memorias. Encuentro de Experiencias en Inventarios y Monitoreo Biológico

Las discusiones temáticas alrededor de la consolidación del Inventario Nacional de Biodiversidad para Colombia y la Red de Monitoreo de Biodiversidad como una estrategia de largo plazo, sin duda temas complejos que requerirán de grandes esfuerzos, coordinación y generosidad institucional y personal, los podrá apreciar el lector a lo largo del presente documento, esperando que pueda entender también la importancia que tienen los resultados y la agenda propuesta si en el futuro queremos tomar decisiones con bases científicas