Programme for Harmonization to the International Scale in Latin America for BCR-ABL1 quantification in CML patients: Findings and recommendations

The quantitation of BCR-ABL1 mRNA is mandatory for chronic myeloid leukemia (CML) patients, and RT-qPCR is the most extensively used method in testing laboratories worldwide. Nevertheless, substantial variation in RT-qPCR results makes inter-laboratory comparability hard. To facilitate inter-laboratory comparative assessment, an international scale (IS) for BCR-ABL1 was proposed.The laboratory-specific conversion factor (CF) to the IS can be derived from the World Health Organization (WHO) genetic reference panel; however, this material is limited to the manufacturers to produce and calibrate secondary reference reagents. Therefore, we developed secondary reference calibrators, as lyophilized cellular material, aligned to the IS. Our purpose was both to re-evaluate the CF in 18 previously harmonized laboratories and to propagate the IS to new laboratories.Results Our field trial including 30 laboratories across Latin America showed that, after correction of raw BCR-ABL1/ABL1 ratios using CF, the relative mean bias was significantly reduced. We also performed a follow-up of participating laboratories by annually revalidating the process; our results support the need for continuous revalidation of CFs. All participating laboratories also received a calibrator to determine the limit of quantification (LOQ); 90% of them could reproducibly detect BCR-ABL1, indicating that these laboratories can report a consistent deep molecular response. In addition, aiming to investigate the variability of BCR-ABL1 measurements across different RNA inputs, we calculated PCR efficiency for each individual assay by using different amounts of RNA.Conclusions In conclusion, for the first time in Latin America, we have successfully organized a harmonization platform for BCR-ABL1 measurement that could be of immediate clinical benefit for monitoring the molecular response of patients in low-resource regions.Fil: Ruiz, María Sol. Fundación Cáncer. Centro de Investigaciones Oncológicas; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Sánchez, María Belén. Fundación Cáncer. Centro de Investigaciones Oncológicas; ArgentinaFil: Vera Contreras, Yuly Masiel. Fundación Cáncer. Centro de Investigaciones Oncológicas; ArgentinaFil: Agrielo, Evangelina. Laboratorio Especialidades Bioquímicas; ArgentinaFil: Alonso, Marta. Hospital Nacional Profesor Alejandro Posadas; ArgentinaFil: Altuna, María Eugenia. Clinica Roberto Raña; ArgentinaFil: Anchordoqui, María Sol. Argenomics; ArgentinaFil: Asinari, Mariana. Hospital Privado Centro Médico de Córdoba; ArgentinaFil: Bonetto, María Elisa. Hospital Rawson San Juan; ArgentinaFil: Camargo, Mauricio. Laboratorio Medellin; ColombiaFil: Giere, Isabel. Fundación Para Combatir la Leucemia; ArgentinaFil: González, Javier. Meyer Lab; ParaguayFil: Granda Alacote, Ana Cecilia. Laboratorios Medicos Lima; PerúFil: Guerra, Javier. Nanopharmacia Diagnóstica Mexico; MéxicoFil: Gutiérrez, Marina. Stamboulian; ArgentinaFil: Maldonado, Cecilia. Manlab; ArgentinaFil: Makiya, Ricard. No especifíca;Fil: Manrique, Gonzalo. Asociacion Española de Montevideo; UruguayFil: Monaco, María Eugenia. Laboratorio Tucuman; ArgentinaFil: Rozo, Juan Carlos. Unidad de Diagnóstico Hemato Oncológico; ColombiaFil: Santamaría Martín, Carlos Jose. Hospital de Niños San Jose de Costa Rica; Costa Rica. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Seravalle, Analía. Civic Rosario; ArgentinaFil: Zea, Olga. Laboratorio Medellin Colombia; ColombiaFil: Zubillaga, María Noel. Asociación Española de Socorros Mutuos; UruguayFil: Mordoh, José. Fundación Cáncer. Centro de Investigaciones Oncológicas; ArgentinaFil: Larripa, Irene Beatriz. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; ArgentinaFil: Bianchini, Michele. Fundación Cáncer. Centro de Investigaciones Oncológicas; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentin

Effectiveness of a cognitive behavioral intervention in patients with medically unexplained symptoms: cluster randomized trial

BACKGROUND: Medically unexplained symptoms are an important mental health problem in primary care and generate a high cost in health services.Cognitive behavioral therapy and psychodynamic therapy have proven effective in these patients. However, there are few studies on the effectiveness of psychosocial interventions by primary health care. The project aims to determine whether a cognitive-behavioral group intervention in patients with medically unexplained symptoms, is more effective than routine clinical practice to improve the quality of life measured by the SF-12 questionary at 12 month. METHODS/DESIGN: This study involves a community based cluster randomized trial in primary healthcare centres in Madrid (Spain). The number of patients required is 242 (121 in each arm), all between 18 and 65 of age with medically unexplained symptoms that had seeked medical attention in primary care at least 10 times during the previous year. The main outcome variable is the quality of life measured by the SF-12 questionnaire on Mental Healthcare. Secondary outcome variables include number of consultations, number of drug (prescriptions) and number of days of sick leave together with other prognosis and descriptive variables. Main effectiveness will be analyzed by comparing the percentage of patients that improve at least 4 points on the SF-12 questionnaire between intervention and control groups at 12 months. All statistical tests will be performed with intention to treat. Logistic regression with random effects will be used to adjust for prognostic factors. Confounding factors or factors that might alter the effect recorded will be taken into account in this analysis. DISCUSSION: This study aims to provide more insight to address medically unexplained symptoms, highly prevalent in primary care, from a quantitative methodology. It involves intervention group conducted by previously trained nursing staff to diminish the progression to the chronicity of the symptoms, improve quality of life, and reduce frequency of medical consultations. TRIAL REGISTRATION: The trial was registered with ClinicalTrials.gov, number NCT01484223 [http://ClinicalTrials.gov].S

Cross-disease Meta-analysis of Genome-wide Association Studies for Systemic Sclerosis and Rheumatoid Arthritis Reveals IRF4 as a New Common Susceptibility Locus

Objectives: Systemic sclerosis (SSc) and rheumatoid arthritis (RA) are autoimmune diseases that share clinical and immunological characteristics. To date, several shared SSc- RA loci have been identified independently. In this study, we aimed to systematically search for new common SSc-RA loci through an inter-disease meta-GWAS strategy. Methods: We performed a meta-analysis combining GWAS datasets of SSc and RA using a strategy that allowed identification of loci with both same-direction and opposingdirection allelic effects. The top single-nucleotide polymorphisms (SNPs) were followed-up in independent SSc and RA case-control cohorts. This allowed us to increase the sample size to a total of 8,830 SSc patients, 16,870 RA patients and 43,393 controls. Results: The cross-disease meta-analysis of the GWAS datasets identified several loci with nominal association signals (P-value < 5 x 10-6), which also showed evidence of association in the disease-specific GWAS scan. These loci included several genomic regions not previously reported as shared loci, besides risk factors associated with both diseases in previous studies. The follow-up of the putatively new SSc-RA loci identified IRF4 as a shared risk factor for these two diseases (Pcombined = 3.29 x 10-12). In addition, the analysis of the biological relevance of the known SSc-RA shared loci pointed to the type I interferon and the interleukin 12 signaling pathways as the main common etiopathogenic factors. Conclusions: Our study has identified a novel shared locus, IRF4, for SSc and RA and highlighted the usefulness of cross-disease GWAS meta-analysis in the identification of common risk loci

Clonal chromosomal mosaicism and loss of chromosome Y in elderly men increase vulnerability for SARS-CoV-2

The pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2, COVID-19) had an estimated overall case fatality ratio of 1.38% (pre-vaccination), being 53% higher in males and increasing exponentially with age. Among 9578 individuals diagnosed with COVID-19 in the SCOURGE study, we found 133 cases (1.42%) with detectable clonal mosaicism for chromosome alterations (mCA) and 226 males (5.08%) with acquired loss of chromosome Y (LOY). Individuals with clonal mosaic events (mCA and/or LOY) showed a 54% increase in the risk of COVID-19 lethality. LOY is associated with transcriptomic biomarkers of immune dysfunction, pro-coagulation activity and cardiovascular risk. Interferon-induced genes involved in the initial immune response to SARS-CoV-2 are also down-regulated in LOY. Thus, mCA and LOY underlie at least part of the sex-biased severity and mortality of COVID-19 in aging patients. Given its potential therapeutic and prognostic relevance, evaluation of clonal mosaicism should be implemented as biomarker of COVID-19 severity in elderly people. Among 9578 individuals diagnosed with COVID-19 in the SCOURGE study, individuals with clonal mosaic events (clonal mosaicism for chromosome alterations and/or loss of chromosome Y) showed an increased risk of COVID-19 lethality

Complement component C4 structural variation and quantitative traits contribute to sex-biased vulnerability in systemic sclerosis

Altres ajuts: Fondo Europeo de Desarrollo Regional (FEDER), "A way of making Europe".Copy number (CN) polymorphisms of complement C4 play distinct roles in many conditions, including immune-mediated diseases. We investigated the association of C4 CN with systemic sclerosis (SSc) risk. Imputed total C4, C4A, C4B, and HERV-K CN were analyzed in 26,633 individuals and validated in an independent cohort. Our results showed that higher C4 CN confers protection to SSc, and deviations from CN parity of C4A and C4B augmented risk. The protection contributed per copy of C4A and C4B differed by sex. Stronger protection was afforded by C4A in men and by C4B in women. C4 CN correlated well with its gene expression and serum protein levels, and less C4 was detected for both in SSc patients. Conditioned analysis suggests that C4 genetics strongly contributes to the SSc association within the major histocompatibility complex locus and highlights classical alleles and amino acid variants of HLA-DRB1 and HLA-DPB1 as C4-independent signals

Base de datos de abejas ibéricas

Las abejas son un grupo extremadamente diverso con más de 1000 especies descritas en la península ibérica. Además, son excelentes polinizadores y aportan numerosos servicios ecosistémicos fundamentales para la mayoría de ecosistemas terrestres. Debido a los diversos cambios ambientales inducidos por el ser humano, existen evidencias del declive de algunas de sus poblaciones para ciertas especies. Sin embargo, conocemos muy poco del estado de conservación de la mayoría de especies y de muchas de ellas ignoramos cuál es su distribución en la península ibérica. En este trabajo presentamos un esfuerzo colaborativo para crear una base de datos de ocurrencias de abejas que abarca la península ibérica e islas Baleares que permitirá resolver cuestiones como la distribución de las diferentes especies, preferencia de hábitat, fenología o tendencias históricas. En su versión actual, esta base de datos contiene un total de 87 684 registros de 923 especies recolectados entre 1830 y 2022, de los cuales un 87% presentan información georreferenciada. Para cada registro se incluye información relativa a la localidad de muestreo (89%), identificador y colector de la especie (64%), fecha de captura (54%) y planta donde se recolectó (20%). Creemos que esta base de datos es el punto de partida para conocer y conservar mejor la biodiversidad de abejas en la península ibérica e Islas Baleares. Se puede acceder a estos datos a través del siguiente enlace permanente: https://doi.org/10.5281/zenodo.6354502ABSTRACT: Bees are a diverse group with more than 1000 species known from the Iberian Peninsula. They have increasingly received special attention due to their important role as pollinators and providers of ecosystem services. In addition, various rapid human-induced environmental changes are leading to the decline of some of its populations. However, we know very little about the conservation status of most species and for many species, we hardly know their true distributions across the Iberian Peninsula. Here, we present a collaborative effort to collate and curate a database of Iberian bee occurrences to answer questions about their distribution, habitat preference, phenology, or historical trends. In total we have accumulated 87 684 records from the Iberian Peninsula and the Balearic Islands of 923 different species with 87% of georeferenced records collected between 1830 and 2022. In addition, each record has associated information such as the sampling location (89%), collector and person who identified the species (64%), date of the capture (54%) and plant species where the bees were captured (20%). We believe that this database is the starting point to better understand and conserve bee biodiversity in the Iberian Peninsula. It can be accessed at: https://doi.org/10.5281/zenodo.6354502Esta base de datos se ha realizado con la ayuda de los proyectos EUCLIPO (Fundação para a Ciência e a Tecnologia, LISBOA-01-0145-FEDER-028360/EUCLIPO) y SAFEGUARD (ref. 101003476 H2020 -SFS-2019-2).info:eu-repo/semantics/publishedVersio

CIBERER : Spanish national network for research on rare diseases: A highly productive collaborative initiative

Altres ajuts: Instituto de Salud Carlos III (ISCIII); Ministerio de Ciencia e Innovación.CIBER (Center for Biomedical Network Research; Centro de Investigación Biomédica En Red) is a public national consortium created in 2006 under the umbrella of the Spanish National Institute of Health Carlos III (ISCIII). This innovative research structure comprises 11 different specific areas dedicated to the main public health priorities in the National Health System. CIBERER, the thematic area of CIBER focused on rare diseases (RDs) currently consists of 75 research groups belonging to universities, research centers, and hospitals of the entire country. CIBERER's mission is to be a center prioritizing and favoring collaboration and cooperation between biomedical and clinical research groups, with special emphasis on the aspects of genetic, molecular, biochemical, and cellular research of RDs. This research is the basis for providing new tools for the diagnosis and therapy of low-prevalence diseases, in line with the International Rare Diseases Research Consortium (IRDiRC) objectives, thus favoring translational research between the scientific environment of the laboratory and the clinical setting of health centers. In this article, we intend to review CIBERER's 15-year journey and summarize the main results obtained in terms of internationalization, scientific production, contributions toward the discovery of new therapies and novel genes associated to diseases, cooperation with patients' associations and many other topics related to RD research

Structure of the gonoduct of the viviparous teleost Cnesterodon decemmaculatus (Jenyns, 1842) (Poeciliidae)

During embryogenesis, teleost females do not develop Müllerian ducts, which form the oviducts in all other vertebrates. Thus, when they reach sexual maturity they do not have oviducts. In viviparous teleosts, the lack of oviducts means that the development of the embryos occurs as an intraovarian gestation, unique among vertebrates. The ovary is an unpaired hollow organ whose cavity is continuous with the caudal portion, the gonoduct, characterized by the absence of germinal cells, which opens to the exterior at the gonopore. The gonoduct attains essential function as a barrier between the germinal region of the ovary and the exterior during all reproductive stages. This study describes the functional morphology of the gonoduct in the viviparous teleost Cnesterodon decemmaculatus during non‐gestation (previtellogenesis and vitellogenesis) and gestation. The ovaries were processed using histological techniques and stained with hematoxylin?eosin, and periodic acid Schiff. The gonoduct has two regions: cephalic and caudal, and is formed by three histological layers, which are, from inside to the periphery: (a) tunica mucosa; (b) tunica muscularis; and (c) tunica serosa. In the cephalic region there are mucosal folds extending into the lumen and forming a structure similar to a cervix. The histology of the gonoduct indicates essential functions, that is, (a) the control of the luminal diameter in the limit to the germinal region of the ovary by the presence of a cervix; (b) during insemination the gonoduct receives the spermatozoa, may store and transport them to the germinal region; (c) the presence of melano‐macrophage centers indicates support of immunological processes, especially during gestation when these centers increase in size; (d) production of exocrine secretions; and (e) it is the birth canal, internally lined by an ciliated epithelium and surrounded by smooth musclesboth tissues supposedly supporting the birth process.Fil: Santamaría Martín, Carlos Jose. Universidad Nacional de La Plata. Facultad de Ciencias Veterinarias; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata; ArgentinaFil: Plaul, Silvia Elena. Universidad Nacional de La Plata. Facultad de Ciencias Veterinarias; ArgentinaFil: Campuzano Caballero, Juan C.. Universidad Nacional Autónoma de México. Instituto de Biología; MéxicoFil: Uribe, Mari C. Universidad Nacional Autónoma de México. Instituto de Biología; MéxicoFil: Barbeito, Claudio Gustavo. Universidad Nacional de La Plata. Facultad de Ciencias Veterinarias; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata; Argentin

Morphological techniques used in ichthyopathological diagnosis

In this review, different diagnostic techniques for identifying etiology of fish disease are described. Among microscopictechniques, we find rapid diagnostic tests to observe parasites, gill diseases and bacteria; routine histopathologicaltechniques are also used. In samples having bone tissue, decalcification methods are employed. In recent years, apart fromusing immunohistochemistry and electron microscopy, morphological techniques allow a deep study of diseasepathogenesis. At present, molecular techniques for pathogen identification and atomic-absorption spectrophotometry tomeasure the concentration and distribution of toxic metals in tissues they also use. In conclusion, different techniques cancontribute to the evaluation of disorders and provide tools for a better understanding in fish medicine.Fil: Plaul, Silvia Elena. Universidad Nacional de La Plata. Facultad de Ciencias Veterinarias. Departamento de Ciencias Básicas. Cátedra de Histología y Embriología; ArgentinaFil: Andrés Laube, Pedro Fernando. Universidad Nacional de La Plata. Facultad de Ciencias Veterinarias. Departamento de Ciencias Básicas. Cátedra de Histología y Embriología; ArgentinaFil: Pacheco Marino, Suani Giovanna. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico CONICET- La Plata. Instituto de Genética Veterinaria "Ing. Fernando Noel Dulout". Universidad Nacional de La Plata. Facultad de Ciencias Veterinarias. Instituto de Genética Veterinaria; ArgentinaFil: Santamaría Martín, Carlos Jose. Universidad Nacional de La Plata. Facultad de Ciencias Veterinarias. Departamento de Ciencias Básicas. Cátedra de Histología y Embriología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata; ArgentinaFil: Moyano, Darío Agustín. Universidad Nacional de La Plata. Facultad de Ciencias Exactas; ArgentinaFil: Barbeito, Claudio Gustavo. Universidad Nacional de La Plata. Facultad de Ciencias Veterinarias. Departamento de Ciencias Básicas. Cátedra de Histología y Embriología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata; Argentin

Ovarian changes and development of the branchial placenta occurring in Jenynsia lineata (Cyprinodontiformes, Anablepidae)

In viviparous teleosts, intraovarian gestation occurs intrafollicularly, as in poeciliids, or intraluminally, as in goodeids and anablepids. Furthermore, there are two different forms of embryonic nutrition: lecithotrophy and matrotrophy; depending on the species, these can be exclusive or coexist during gestation. In matrotrophic species, nutrients are transmitted from the mother to the embryo and are especially important in species with intraluminal gestation. Jenynsia lineata is a South American viviparous teleost with intraluminal gestation, characterized by eggs with scarce yolk, which is resorbed when embryos are 6 mm long, thus developing a branchial placenta. Using histological, histochemical, and immunohistochemical techniques, the present study describes the characteristics and changes of the ovarian mucosa in J. lineata during gestational and nongestational phases, and analyzes the embryonic pharyngeal epithelium in the branchial placenta. The ovaries of 30 adult female specimens were processed using histological techniques and stained with hematoxylin-eosin, Masson's trichrome, and Alcian Blue pH 2.5/periodic acid Schiff reagent. To detect cell proliferation, we used antiproliferating cell nuclear antigen antibody. In nonpregnant females, eosinophilic granular cells (EGCs) and lymphocytes were identified in the lamina propria of the tunica mucosa, and melanomacrophage centers (MMCs) and fibroblasts were identified adjacent to tissue debris in the ovarian folds'. In the cellular debris, an embryo in resorption was observed. In pregnant females, the ovarian mucosa has thin vascularization branches entering the opercular chamber of the embryos, in close contact with the forming gill processes, thereby establishing a branchial placenta. Active cell replacement was observed in these ovarian branches. The identification of fibroblasts, lymphocytes, EGCs, and MMCs adjacent to tissue debris could indicate that these cell types are involved in the embryonic resorption process. Considering the new data obtained in this study on the branchial placenta of J. lineata, we conclude that cell proliferation could be involved in the development of maternal–embryonic interaction.Fil: Di Cesare, Luca Sebastian Guido. Universidad Nacional de la Plata. Facultad de Ciencias Veterinarias. Laboratorio de Histología y Embriología Descriptiva, Experimental y Comparada (LHYEDEC); . Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata; ArgentinaFil: Barbeito, Claudio Gustavo. Universidad Nacional de la Plata. Facultad de Ciencias Veterinarias. Laboratorio de Histología y Embriología Descriptiva, Experimental y Comparada (LHYEDEC); . Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata; ArgentinaFil: Santamaría Martín, Carlos Jose. Universidad Nacional de la Plata. Facultad de Ciencias Veterinarias. Laboratorio de Histología y Embriología Descriptiva, Experimental y Comparada (LHYEDEC); . Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata; ArgentinaFil: Montes, Martin Miguel. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Centro de Estudios Parasitológicos y de Vectores. Universidad Nacional de La Plata. Facultad de Ciencias Naturales y Museo. Centro de Estudios Parasitológicos y de Vectores; ArgentinaFil: Uribe, Mari C.. Universidad Nacional Autónoma de México; MéxicoFil: Plaul, Silvia Elena. Universidad Nacional de la Plata. Facultad de Ciencias Veterinarias. Laboratorio de Histología y Embriología Descriptiva, Experimental y Comparada (LHYEDEC)