Proyecto: creación del laboratorio de investigación en Artes y Tecnologías Lúdico-Informáticas y Electrónicas (ATeLIEr)

El presente trabajo informa acerca de uno de los actuales proyectos del Capítulo Mendoza de la Asociación de Desarrolladores de Videojuegos Argentina (ADVAM). El mismo tiene como objetivo la creación escalonada de un Laboratorio de investigaciones que ofrezca espacio e infraestructura para un aporte desde distintos campos del saber al desarrollo de la industria de los videojuegos en la Provincia de Mendoza (Argentina) y el país. Se relata en este escrito los antecedentes de ADVAM, el por qué del laboratorio y su denominación (ATeLIEr), los objetivos perseguidos y el plan que se pretende seguir para la implementación del proyecto.Sociedad Argentina de Informática e Investigación Operativa (SADIO

Proyecto: creación del laboratorio de investigación en Artes y Tecnologías Lúdico-Informáticas y Electrónicas (ATeLIEr)

El presente trabajo informa acerca de uno de los actuales proyectos del Capítulo Mendoza de la Asociación de Desarrolladores de Videojuegos Argentina (ADVAM). El mismo tiene como objetivo la creación escalonada de un Laboratorio de investigaciones que ofrezca espacio e infraestructura para un aporte desde distintos campos del saber al desarrollo de la industria de los videojuegos en la Provincia de Mendoza (Argentina) y el país. Se relata en este escrito los antecedentes de ADVAM, el por qué del laboratorio y su denominación (ATeLIEr), los objetivos perseguidos y el plan que se pretende seguir para la implementación del proyecto.Sociedad Argentina de Informática e Investigación Operativa (SADIO

Recensiones [Revista de Historia Económica Año IV Invierno 1986 n. 1 pp. 209-252]

Frencesco de Martino. Historia Económica de la Roma Antigua (Por Luis A. García Moreno).-- Manuel Tuñón de Lara (dir.). Textos y documentos de Historia Antigua, Media y Moderna hasta el siglo XVI (Selección de Mangas, Sayas, García Moreno, Valdeón, Salrach, Mina, Arizcun, Arié y Pérez). (Por Javier Faci).-- Manuel Martín Rodríguez. Pensamiento económico español sobre la población. De Soto a Matanegui (Por Vicente Pérez Moreda).-- P. Bairoch y A. M. Piuz (eds.). Les passages des économies traditionnelles européennes aux sociales industrielles (Por Jaume Torras Elías).-- Annales, Économies, Sociétés, Civilisations, año 39, 1984, núm. 5 (Por Gregorio Núñez Romero-Balmas).-- Josep Oliveras i Samitier. Desenvolupament industrial i evolució urbana a Manresa (1800-1870) (Por Caries Sudrià).-- Juan Antonio Vázquez García. La cuestión hullera en Asturias (1918-1935) (Por Sebastián Coll Martín).-- Ignacio Villota Elejalde. Vizcaya en la política minera española. Las asociaciones patronales, 1886-1914 (Por Mercedes Cabrera).-- José García Lasaosa: Basilio Paraíso. Industrial y político aragonés de la Restauración (Por Guillermo Cortázar).-- Bill Albert y Adrian Graves (eds.). Crisis and Change in the International Sugar Economy 1860-1914 (Por Manuel Martín Rodríguez).-- G. R. Hawke. Economía para historiadores (Por Gabriel Tortella).-- Robert William Fogel y G. R. Elton. Which Road to the Past? Two Views of History (Por Donald R. Abbott)Publicad

Risk Factors that Increase Maternal Morbidity in Pregnant Women Between 30 to 34 Years of Age

Introduction. According to the World Health Organization (WHO), the prevalence of obesity worldwide has nearly tripled since 1975. According to 2016 data, 39% of the global adult population was overweight, and 13% was obese. A recent study, including 20 European countries, concluded that 53% of adults were overweight or obese. Increase in overweight and obesity among women of childbearing age (15 to 44 years). Overweight and obesity during pregnancy are associated with many complications, including increased risk of gestational hypertension, preeclampsia, gestational diabetes mellitus, cesarean delivery, preterm delivery, large-for-gestational-age infants, and stillbirths. Additionally, gestational weight gain is associated with diabetes, pregnancy-induced hypertension, cesarean delivery, postpartum weight retention, macrosomia, and childhood obesity. Materials and Methods. An observational, cross-sectional study in 15 pregnant women in 2022 at the Playa del Carmen General Hospital. Results. Were completed variables of interest in prenatal control. Discussion. The short interval between pregnancies is a public health problem because it leads to adverse perinatal outcomes such as postpartum hemorrhage, anemia, preterm delivery, low birth weight, and perinatal deaths. Ineffective or no contraception after one pregnancy contributes to a subsequent pregnancy. Conclusion. It is essential to detect gestational Diabetes mellitus as well as gestational hypertension, and prenatal control should be improved because although pregnant women report carrying it out, it is not reflected in cases of preeclampsia that remains high in pregnant women.&nbsp

Effects of systemic or local administration of mesenchymal stem cells from patients with osteoporosis or osteoarthritis on femoral fracture healing in a mouse model

The purpose of this study was to analyze the regenerative capacity of mesenchymal stem cells (MSCs) in the treatment of fractures. MSCs extracted from patients with osteoporotic hip fractures or hip osteoarthritis undergoing hip replacement surgeries were cultured and injected into mice with femoral fracture. Two experimental models were established, one for the systemic administration of MSCs (n = 29) and another one for local administration (n = 30). Fracture consolidation was assessed by micro-CT and histology. The degree of radiological consolidation and corticalization was better with MSCs from osteoporosis than from osteoarthritis, being significant after systemic administration (p = 0.0302 consolidation; p = 0.0243 corticalization). The histological degree of consolidation was also better with MSCs from osteoporosis than from osteoarthritis. Differences in histological scores after systemic infusion were as follows: Allen, p = 0.0278; Huo, p = 0.3471; and Bone Bridge, p = 0.0935. After local administration at the fracture site, differences in histological scores were as follows: Allen, p = 0.0764; Huo, p = 0.0256; and Bone Bridge, p = 0.0012. As osteoporosis and control groups were similar, those differences depended on an inhibitory influence by MSCs from patients with osteoarthritis. In conclusion, we found an unexpected impairment of consolidation induced by MSCs from patients with osteoarthritis. However, MSCs from patients with osteoporosis compared favorably with cells from patients with osteoarthritis. In other words, based on this study and previous studies, MSCs from patients with osteoporosis do not appear to have worse bone-regenerating capabilities than MSCs from non-osteoporotic individuals of similar age.Funding: This work was supported by a grant from Instituto de Salud Carlos III [PI16-915], which can be cofounded by EU Feder funds. Acknowledgments: Álvaro del Real received support from the postdoctoral grant “Augusto González de Linares” of the University of Cantabria

Co-occurrence of cohesin complex and Ras signaling mutations during progression from myelodysplastic syndromes to secondary acute myeloid leukemia

Myelodysplastic syndromes (MDS) are hematological disorders at high risk of progression to secondary acute myeloid leukemia (sAML). However, the mutational dynamics and clonal evolution underlying disease progression are poorly understood at present. To elucidate the mutational dynamics of pathways and genes occurring during the evolution to sAML, next generation sequencing was performed on 84 serially paired samples of MDS patients who developed sAML (discovery cohort) and 14 paired samples from MDS patients who did not progress to sAML during follow-up (control cohort). Results were validated in an independent series of 388 MDS patients (validation cohort). We used an integrative analysis to identify how mutations, alone or in combination, contribute to leukemic transformation. The study showed that MDS progression to sAML is characterized by greater genomic instability and the presence of several types of mutational dynamics, highlighting increasing (STAG2) and newly-acquired (NRAS and FLT3) mutations. Moreover, we observed cooperation between genes involved in the cohesin and Ras pathways in 15-20% of MDS patients who evolved to sAML, as well as a high proportion of newly acquired or increasing mutations in the chromatin-modifier genes in MDS patients receiving a disease-modifying therapy before their progression to sAML.This work was supported by grants from the Spanish Fondo de Investigaciones Sanitarias FIS PI18/01500, PI17/01741, Instituto de Salud Carlos III (ISCIII), Fondo de Investigación Sanitaria (Instituto de Salud Carlos III – Contratos Río Hortega (CM17/0017), European Regional Development Fund (ERDF), Una manera de hacer Europa, European Union Seventh Framework Programme [FP7/2007-2013] under Grant Agreement nº306242-NGS-PTL, SYNtherapy: Synthetic Lethality for Personalized Therapy-based Stratification in Acute Leukemia (ERAPERMED2018-275); ISCIII (AC18/00093), Proyectos de Investigación del SACYL, Gerencia Regional de Salud de Castilla y León: GRS1850/A18, GRS1653/A17, and Centro de Investigación Biomédica en Red de Cáncer (CIBERONC CB16/12/00233). MMI is supported by a predoctoral grant from the Junta de Castilla y León, and by the Fondo Social Europeo (JCYL-EDU/556/2019 PhD scholarship) and JMHS is supported by a research grant from Fundación Española de Hematología y Hemoterapia

New criteria to identify risk of progression in monoclonal gammopathy of uncertain significance and smoldering multiple myeloma based on multiparameter flow cytometry analysis of bone marrow plasma cells

[EN] Monoclonal gammopathy of uncertain significance (MGUS) and smoldering multiple myeloma (SMM) are plasma cell disorders with a risk of progression of approximately 1% and 10% per year, respectively. We have previously shown that the proportion of bone marrow (BM) aberrant plasma cells (aPCs) within the BMPC compartment (aPC/BMPC) as assessed by flow cytometry (FC) contributes to differential diagnosis between MGUS and multiple myloma (MM). The goal of the present study was to investigate this parameter as a marker for risk of progression in MGUS (n = 407) and SMM (n = 93). Patients with a marked predominance of aPCs/BMPC (> or = 95%) at diagnosis displayed a significantly higher risk of progression both in MGUS and SMM (P or = 95%) as the most important independent variable, together with DNA aneuploidy and immunoparesis, for MGUS and SMM, respectively. Using these independent variables, we have identified 3 risk categories in MGUS (PFS at 5 years of 2%, 10%, and 46%, respectively; P< .001) and SMM patients (PFS at 5 years of 4%, 46%, and 72%, respectively; P < .001). Our results show that multiparameter FC evaluation of BMPC at diagnosis is a valuable tool that could help to individualize the follow-up strategy for MGUS and SMM patients

Table2_Expanding the phenotype of THRB: a range of macular dystrophies as the major clinical manifestations in patients with a dominant splicing variant.PDF

Supplementary Table 2 Different THRB in vivo and in vitro knock-out and knockdown models and its phenotypic effect.Inherited retinal dystrophies (IRDs) are a clinically and genetically heterogeneous group of disorders that often severely impair vision. Some patients manifest poor central vision as the first symptom due to cone-dysfunction, which is consistent with cone dystrophy (COD), Stargardt disease (STGD), or macular dystrophy (MD) among others. Here, we aimed to identify the genetic cause of autosomal dominant COD in one family. WGS was performed in 3 affected and 1 unaffected individual using the TruSeq Nano DNA library kit and the NovaSeq 6,000 platform (Illumina). Data analysis identified a novel spliceogenic variant (c.283 + 1G>A) in the thyroid hormone receptor beta gene (THRB) as the candidate disease-associated variant. Further genetic analysis revealed the presence of the same heterozygous variant segregating in two additional unrelated dominant pedigrees including 9 affected individuals with a diagnosis of COD (1), STGD (4), MD (3) and unclear phenotype (1). THRB has been previously reported as a causal gene for autosomal dominant and recessive thyroid hormone resistance syndrome beta (RTHβ); however, none of the IRD patients exhibited RTHβ. Genotype-phenotype correlations showed that RTHβ can be caused by both truncating and missense variants, which are mainly located at the 3′ (C-terminal/ligand-binding) region, which is common to both THRB isoforms (TRβ1 and TRβ2). In contrast, the c.283 + 1G>A variant is predicted to disrupt a splice site in the 5′-region of the gene that encodes the N-terminal domain of the TRβ1 isoform protein, leaving the TRβ2 isoform intact, which would explain the phenotypic variability observed between RTHβ and IRD patients. Interestingly, although monochromacy or cone response alterations have already been described in a few RTHβ patients, herein we report the first genetic association between a pathogenic variant in THRB and non-syndromic IRDs. We thereby expand the phenotype of THRB pathogenic variants including COD, STGD, or MD as the main clinical manifestation, which also reflects the extraordinary complexity of retinal functions mediated by the different THRB isoforms.Peer reviewe

Expanding the phenotype of THRB: a range of macular dystrophies as the major clinical manifestations in patients with a dominant splicing variant

© 2023 Fernández-Suárez, González-del Pozo, García-Núñez, Méndez-Vidal, Martín-Sánchez, Mejías-Carrasco, Ramos-Jiménez, Morillo-Sánchez, Rodríguez-de la Rúa, Borrego and Antiñolo. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.Inherited retinal dystrophies (IRDs) are a clinically and genetically heterogeneous group of disorders that often severely impair vision. Some patients manifest poor central vision as the first symptom due to cone-dysfunction, which is consistent with cone dystrophy (COD), Stargardt disease (STGD), or macular dystrophy (MD) among others. Here, we aimed to identify the genetic cause of autosomal dominant COD in one family. WGS was performed in 3 affected and 1 unaffected individual using the TruSeq Nano DNA library kit and the NovaSeq 6,000 platform (Illumina). Data analysis identified a novel spliceogenic variant (c.283 + 1G>A) in the thyroid hormone receptor beta gene (THRB) as the candidate disease-associated variant. Further genetic analysis revealed the presence of the same heterozygous variant segregating in two additional unrelated dominant pedigrees including 9 affected individuals with a diagnosis of COD (1), STGD (4), MD (3) and unclear phenotype (1). THRB has been previously reported as a causal gene for autosomal dominant and recessive thyroid hormone resistance syndrome beta (RTHβ); however, none of the IRD patients exhibited RTHβ. Genotype-phenotype correlations showed that RTHβ can be caused by both truncating and missense variants, which are mainly located at the 3′ (C-terminal/ligand-binding) region, which is common to both THRB isoforms (TRβ1 and TRβ2). In contrast, the c.283 + 1G>A variant is predicted to disrupt a splice site in the 5′-region of the gene that encodes the N-terminal domain of the TRβ1 isoform protein, leaving the TRβ2 isoform intact, which would explain the phenotypic variability observed between RTHβ and IRD patients. Interestingly, although monochromacy or cone response alterations have already been described in a few RTHβ patients, herein we report the first genetic association between a pathogenic variant in THRB and non-syndromic IRDs. We thereby expand the phenotype of THRB pathogenic variants including COD, STGD, or MD as the main clinical manifestation, which also reflects the extraordinary complexity of retinal functions mediated by the different THRB isoforms.This work was supported by the Instituto de Salud Carlos III (ISCIII), Spanish Ministry of Science and Innovation, Spain and co-funded by ERDF (“A way to make Europe”) [PI21-00244]; The strategic plan for the Precision Medicine Infrastructure associated with Science and Technology - IMPaCT [IMP-0009], Regional Ministry of Health and Families of the Autonomous Government of Andalusia [PEER-0501-2019] and the Foundation Isabel Gemio/Foundation Cajasol [FGEMIO-2019-01]. EF-S is supported by fellowship FI19/00091 from ISCIII (ESF, “Investing in your future”). MM-S [RH-0049-2021] are supported by a fellowship funded by the Regional Ministry of Health and Families of the Autonomous Government of Andalusia.Peer reviewe

Image1_Expanding the phenotype of THRB: a range of macular dystrophies as the major clinical manifestations in patients with a dominant splicing variant.PDF

Supplementary figure S1. Schematic representation of the hypothetical consequences of the THRB variant. In silico prediction of the effect of the spliceogenic variant identified in TRβ1 isoform (NM_001354712.2: c.283+1G>A) showed two scenarios. (A), The skipping of exon 5 disrupts the A/B domain, leaving a protein of 374 amino acids with a secondary structure different from the wild-type protein. The DNAbinding domain (DBD), hinge domain and ligand-binding domain (LBD) are not affected. (B), The skipping of exons 5 and 6 results in a premature codon stop that produces only a small peptide. The 3D models of the proteins were generated using the IntFOLD and PEP-FOLD4 online servers.Inherited retinal dystrophies (IRDs) are a clinically and genetically heterogeneous group of disorders that often severely impair vision. Some patients manifest poor central vision as the first symptom due to cone-dysfunction, which is consistent with cone dystrophy (COD), Stargardt disease (STGD), or macular dystrophy (MD) among others. Here, we aimed to identify the genetic cause of autosomal dominant COD in one family. WGS was performed in 3 affected and 1 unaffected individual using the TruSeq Nano DNA library kit and the NovaSeq 6,000 platform (Illumina). Data analysis identified a novel spliceogenic variant (c.283 + 1G>A) in the thyroid hormone receptor beta gene (THRB) as the candidate disease-associated variant. Further genetic analysis revealed the presence of the same heterozygous variant segregating in two additional unrelated dominant pedigrees including 9 affected individuals with a diagnosis of COD (1), STGD (4), MD (3) and unclear phenotype (1). THRB has been previously reported as a causal gene for autosomal dominant and recessive thyroid hormone resistance syndrome beta (RTHβ); however, none of the IRD patients exhibited RTHβ. Genotype-phenotype correlations showed that RTHβ can be caused by both truncating and missense variants, which are mainly located at the 3′ (C-terminal/ligand-binding) region, which is common to both THRB isoforms (TRβ1 and TRβ2). In contrast, the c.283 + 1G>A variant is predicted to disrupt a splice site in the 5′-region of the gene that encodes the N-terminal domain of the TRβ1 isoform protein, leaving the TRβ2 isoform intact, which would explain the phenotypic variability observed between RTHβ and IRD patients. Interestingly, although monochromacy or cone response alterations have already been described in a few RTHβ patients, herein we report the first genetic association between a pathogenic variant in THRB and non-syndromic IRDs. We thereby expand the phenotype of THRB pathogenic variants including COD, STGD, or MD as the main clinical manifestation, which also reflects the extraordinary complexity of retinal functions mediated by the different THRB isoforms.Peer reviewe