Integrative Analysis Reveals a Molecular Stratification of Systemic Autoimmune Diseases

Objective Clinical heterogeneity, a hallmark of systemic autoimmune diseases, impedes early diagnosis and effective treatment, issues that may be addressed if patients could be classified into groups defined by molecular pattern. This study was undertaken to identify molecular clusters for reclassifying systemic autoimmune diseases independently of clinical diagnosis. Methods Unsupervised clustering of integrated whole blood transcriptome and methylome cross-sectional data on 955 patients with 7 systemic autoimmune diseases and 267 healthy controls was undertaken. In addition, an inception cohort was prospectively followed up for 6 or 14 months to validate the results and analyze whether or not cluster assignment changed over time. Results Four clusters were identified and validated. Three were pathologic, representing “inflammatory,” “lymphoid,” and “interferon” patterns. Each included all diagnoses and was defined by genetic, clinical, serologic, and cellular features. A fourth cluster with no specific molecular pattern was associated with low disease activity and included healthy controls. A longitudinal and independent inception cohort showed a relapse–remission pattern, where patients remained in their pathologic cluster, moving only to the healthy one, thus showing that the molecular clusters remained stable over time and that single pathogenic molecular signatures characterized each individual patient. Conclusion Patients with systemic autoimmune diseases can be jointly stratified into 3 stable disease clusters with specific molecular patterns differentiating different molecular disease mechanisms. These results have important implications for future clinical trials and the study of nonresponse to therapy, marking a paradigm shift in our view of systemic autoimmune diseases

Estudio de los Ecosistemas Marinos Vulnerables en aguas internacionales del Atlántico Sudoccidental

En este libro, basado en la mejor información científica disponible hasta la fecha, se presentan los resultados y conclusiones de una serie de trece campañas de investigación multidisciplinar realizadas entre octubre de 2007 y abril de 2010 por los componentes del Grupo ATLANTIS a bordo del B/O MIGUEL OLIVER, propiedad de la Secretaría General de Pesca (SGP). El estudio surge a raíz de la solicitud por parte de la SGP (anteriormente denominada Secretaría General del Mar) al Instituto Español de Oceanografía (IEO), para la realización de una serie de campañas de investigación multidisciplinar en aguas internacionales del Atlántico Sudoccidental, dirigidas al estudio de los Ecosistemas Marinos Vulnerables (EMVs) y de las posibles interacciones con las actividades pesqueras. El objetivo final de dichas campañas era el estudio y la identificación cuantitativa, cualitativa y geográfica de los EMVs y de los grupos taxonómicos de organismos sensibles que pudieran existir en la zona de estudio, incluyendo la propuesta de posibles zonas marinas a proteger, para una explotación sostenible de los recursos pesqueros en el ámbito del respeto a los EMVs. Los resultados que se presentan en este libro comprenden los obtenidos a través de los trabajos de geología, geomorfología, bentos, pesca, oceanografía física y análisis de contaminantes en la zona de aguas internacionales del Atlántico Sudoccidental comprendida entre los paralelos 42º y 48ºS, y la isobata de los 1500 m de profundidad (Figura 2.2). Entre estos resultados se incluye el cartografiado y una batimetría detallada de la zona, la descripción del substrato geológico y de los aspectos bentónicos, el análisis de la distribución y abundancia de las especies de mayor interés comercial, la huella de la pesquería, la identificación y descripción preliminar de los EMVs, y la propuesta de Zonas de Protección, basada en criterios Geológicos, Geomorfológicos y Biológicos. Toda esta información ha sido incorporada para su tratamiento en una plataforma SIG (Sistema de Información Geográfica) y los resultados obtenidos y presentados en este libro vienen acompañados de abundante información gráfica, como imágenes batimétricas en 3D, fotografías de bentos (infauna y epifauna), imágenes tomadas con un ROV (Remotely Operated Vehicle) y con una cámara digital submarina, así como una serie de mapas de distribución, capturas y densidad de las principales especies de interés pesquero. Se incluye también un mapa con la huella de la pesquería (1989-2010) que permita observar la incidencia de las Zonas de Protección propuestas en el área en la que faena habitualmente la flota española de arrastre de fondo. Como información adicional a la obtenida en las trece campañas de investigación, también se ha utilizado la base de datos creada con la información recogida por el Programa de Observadores del IEO entre los años 1989-2010, referente a datos comerciales, biológicos, oceanográficos y físicos (batimetría, temperatura superficial del mar y temperatura del fondo). Entre octubre de 2007 y abril de 2010 se han realizado un total de trece campañas de investigación multidisciplinar, que se han concretado en los siguientes trabajos: • 347 días efectivos de mar • Prospección de una superficie total de 59.105 km2 • Realización de un total de 91.905 km de perfiles geofísicos • 102 muestreos con draga de roca • 209 muestreos con draga box corer • 519 estaciones de CTD • 413 lances de pesca • 413 muestras de sedimentos con el colector de red • Recogida de varios miles de lotes de muestras de bentos que representan varios centenares de miles de especímenes y/o colonias • Realización de miles de fotografías de especies bentónicas, centenares de imágenes digitales de alta resolución y decenas de horas de vídeo realizadas con el ROV del barco Entre los principales resultados de los trabajos de investigación multidisciplinar presentados en este libro hay que destacar la identificación, descripción y delimitación de los EMVs, siguiendo criterios biológicos, geológicos y mixtos; la identificación de los principales grupos bentónicos indicadores de EMVs; la determinación de los valores que representan una captura significativa de los distintos taxones considerados como vulnerables según criterios de la ONU y OSPAR, y finalmente, la propuesta de áreas marinas que deberían ser consideradas como candidatas a ser protegidas. En total se proponen nueve polígonos de diferente superficie para su valoración como zonas de protección (Figura 7.5) y se hace referencia a la incidencia que el cierre de dichas zonas podría tener sobre la actividad de la flota, es decir, el grado de solapamiento entre las zonas de protección y la huella de la pesquería (Figura 7.6). Todos estos resultados se presentan acompañados de abundantes gráficas, figuras y mapas.Instituto Español de OceanografíaVersión del edito

Fisiología de la nutrición y del estrés en las primeras fases de vida del pulpo común (Octopus vulgaris). Resultados del proyecto OCTOPHYS

El cultivo del pulpo común (Oclopus vulgaris) está severamente limitado por las altas mortalidades que se producen durante su cultivo larvano, aunque en la actualidad, las causas especfficas de tan alta mortalidad siguen siendo desconocidas. Este proyecto pretende adquirir conocimientos básicos sobre la biología y fisiologia de las paralarvas a través de un enfoque multidisciplinarque incluye aspectos innovadores relacionados con la fisiologia de la nutrición y el estrés. Los objetivos propuestos están basados en un fuerte input zootécnico y prevén el uso de herramientas biométricas, bioquímicas, enzimáticas, moleculares y proteómicas, con el fin último de optimizar la condición y supervivencia de las paralarvas. Incluyen asimismo la búsqueda y selección de biomarcadores capaces de detectar y cuantíñcar el estrés nutricional.The culture oflhe common octopus (Octopus vulgaris) is hindered by high mortalities encountered during its paralarval rearing, allhough at present, Ihe specific causes forlhe high mortalities observed remain unidentified. This project aims at galhering a beller understanding of Ihe basic biology and physiology ofthe paralarvae, through a multidisciplinary and integrated approach, which includes Ihe study oflhe physiology 01 nutrition and!he evaluation 01Ihe stress condition. The objectives proposed are basad on a strong zootechnical input and foresee Ihe use of biometric, biochemical, enzymatic, molecular biology and proteomic tools, pointing towards the ultimate optimisation of Ihe paralarval condition and survival. They also include Ihe study ofthe nutritionally-derived stress and Ihe selection ofbiomarkers capable of its detection and quantification

Conocimientos tradicionales relativos a la biodiversidad agrícola

La biodiversidad agrícola, a diferencia de la silvestre, requiere la acción continuada de los agricultores para su conservación, ya que las plantas cultivadas dependen de la intervención humana, con actividades como la selección, la siembra, el abonado, la poda u otras prácticas agrícolas para su supervivencia. Desde la revolución agrícola del Neolítico hasta la actualidad, estas prácticas y conocimientos han ido generando y conservando una gran diversidad, amenazada a partir de la segunda mitad del siglo XX por las causas que se han indicado anteriormente.Peer reviewe

Childhood acute leukemias are frequent in Mexico City: descriptive epidemiology

<p>Abstract</p> <p>Background</p> <p>Worldwide, acute leukemia is the most common type of childhood cancer. It is particularly common in the Hispanic populations residing in the United States, Costa Rica, and Mexico City. The objective of this study was to determine the incidence of acute leukemia in children who were diagnosed and treated in public hospitals in Mexico City.</p> <p>Methods</p> <p>Included in this study were those children, under 15 years of age and residents of Mexico City, who were diagnosed in 2006 and 2007 with leukemia, as determined by using the International Classification of Childhood Cancer. The average annual incidence rates (AAIR), and the standardized average annual incidence rates (SAAIR) per million children were calculated. We calculated crude, age- and sex-specific incidence rates and adjusted for age by the direct method with the world population as standard. We determined if there were a correlation between the incidence of acute leukemias in the various boroughs of Mexico City and either the number of agricultural hectares, the average number of persons per household, or the municipal human development index for Mexico (used as a reference of socio-economic level).</p> <p>Results</p> <p>Although a total of 610 new cases of leukemia were registered during 2006-2007, only 228 fit the criteria for inclusion in this study. The overall SAAIR was 57.6 per million children (95% CI, 46.9-68.3); acute lymphoblastic leukemia (ALL) was the most frequent type of leukemia, constituting 85.1% of the cases (SAAIR: 49.5 per million), followed by acute myeloblastic leukemia at 12.3% (SAAIR: 6.9 per million), and chronic myeloid leukemia at 1.7% (SAAIR: 0.9 per million). The 1-4 years age group had the highest SAAIR for ALL (77.7 per million). For cases of ALL, 73.2% had precursor B-cell immunophenotype (SAAIR: 35.8 per million) and 12.4% had T-cell immunophenotype (SAAIR 6.3 per million). The peak ages for ALL were 2-6 years and 8-10 years. More than half the children (58.8%) were classified as high risk. There was a positive correlation between the average number of persons per household and the incidence of the pre-B immunophenotype (Pearson's r, 0.789; P = 0.02).</p> <p>Conclusions</p> <p>The frequency of ALL in Mexico City is among the highest in the world, similar to those found for Hispanics in the United States and in Costa Rica.</p

Fisiología de la nutrición y del estrés en las primeras fases de vida del pulpo común (Octopus vulgaris). Resultados del proyecto OCTOPHYS

El cultivo del pulpo común (Oclopus vulgaris) está severamente limitado por las altas mortalidades que se producen durante su cultivo larvano, aunque en la actualidad, las causas especfficas de tan alta mortalidad siguen siendo desconocidas. Este proyecto pretende adquirir conocimientos básicos sobre la biología y fisiologia de las paralarvas a través de un enfoque multidisciplinarque incluye aspectos innovadores relacionados con la fisiologia de la nutrición y el estrés. Los objetivos propuestos están basados en un fuerte input zootécnico y prevén el uso de herramientas biométricas, bioquímicas, enzimáticas, moleculares y proteómicas, con el fin último de optimizar la condición y supervivencia de las paralarvas. Incluyen asimismo la búsqueda y selección de biomarcadores capaces de detectar y cuantíñcar el estrés nutricional.The culture oflhe common octopus (Octopus vulgaris) is hindered by high mortalities encountered during its paralarval rearing, allhough at present, Ihe specific causes forlhe high mortalities observed remain unidentified. This project aims at galhering a beller understanding of Ihe basic biology and physiology ofthe paralarvae, through a multidisciplinary and integrated approach, which includes Ihe study oflhe physiology 01 nutrition and!he evaluation 01Ihe stress condition. The objectives proposed are basad on a strong zootechnical input and foresee Ihe use of biometric, biochemical, enzymatic, molecular biology and proteomic tools, pointing towards the ultimate optimisation of Ihe paralarval condition and survival. They also include Ihe study ofthe nutritionally-derived stress and Ihe selection ofbiomarkers capable of its detection and quantification

Correction : Chaparro et al. Incidence, Clinical Characteristics and Management of Inflammatory Bowel Disease in Spain: Large-Scale Epidemiological Study. J. Clin. Med. 2021, 10, 2885

The authors wish to make the following corrections to this paper [...]

Incidence, Clinical Characteristics and Management of Inflammatory Bowel Disease in Spain : Large-Scale Epidemiological Study

(1) Aims: To assess the incidence of inflammatory bowel disease (IBD) in Spain, to describe the main epidemiological and clinical characteristics at diagnosis and the evolution of the disease, and to explore the use of drug treatments. (2) Methods: Prospective, population-based nationwide registry. Adult patients diagnosed with IBD-Crohn's disease (CD), ulcerative colitis (UC) or IBD unclassified (IBD-U)-during 2017 in Spain were included and were followed-up for 1 year. (3) Results: We identified 3611 incident cases of IBD diagnosed during 2017 in 108 hospitals covering over 22 million inhabitants. The overall incidence (cases/100,000 person-years) was 16 for IBD, 7.5 for CD, 8 for UC, and 0.5 for IBD-U; 53% of patients were male and median age was 43 years (interquartile range = 31-56 years). During a median 12-month follow-up, 34% of patients were treated with systemic steroids, 25% with immunomodulators, 15% with biologics and 5.6% underwent surgery. The percentage of patients under these treatments was significantly higher in CD than UC and IBD-U. Use of systemic steroids and biologics was significantly higher in hospitals with high resources. In total, 28% of patients were hospitalized (35% CD and 22% UC patients, p < 0.01). (4) Conclusion: The incidence of IBD in Spain is rather high and similar to that reported in Northern Europe. IBD patients require substantial therapeutic resources, which are greater in CD and in hospitals with high resources, and much higher than previously reported. One third of patients are hospitalized in the first year after diagnosis and a relevant proportion undergo surgery

Risk Factors for COVID-19 in Inflammatory Bowel Disease: A National, ENEIDA-Based Case–Control Study (COVID-19-EII)

(1) Scant information is available concerning the characteristics that may favour the acquisition of COVID-19 in patients with inflammatory bowel disease (IBD). Therefore, the aim of this study was to assess these differences between infected and noninfected patients with IBD. (2) This nationwide case-control study evaluated patients with inflammatory bowel disease with COVID-19 (cases) and without COVID-19 (controls) during the period March-July 2020 included in the ENEIDA of GETECCU. (3) A total of 496 cases and 964 controls from 73 Spanish centres were included. No differences were found in the basal characteristics between cases and controls. Cases had higher comorbidity Charlson scores (24% vs. 19%; p = 0.02) and occupational risk (28% vs. 10.5%; p < 0.0001) more frequently than did controls. Lockdown was the only protective measure against COVID-19 (50% vs. 70%; p < 0.0001). No differences were found in the use of systemic steroids, immunosuppressants or biologics between cases and controls. Cases were more often treated with 5-aminosalicylates (42% vs. 34%; p = 0.003). Having a moderate Charlson score (OR: 2.7; 95%CI: 1.3-5.9), occupational risk (OR: 2.9; 95%CI: 1.8-4.4) and the use of 5-aminosalicylates (OR: 1.7; 95%CI: 1.2-2.5) were factors for COVID-19. The strict lockdown was the only protective factor (OR: 0.1; 95%CI: 0.09-0.2). (4) Comorbidities and occupational exposure are the most relevant factors for COVID-19 in patients with IBD. The risk of COVID-19 seems not to be increased by immunosuppressants or biologics, with a potential effect of 5-aminosalicylates, which should be investigated further and interpreted with caution

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