Psychiatric comorbidities in Asperger syndrome are related with polygenic overlap and differ from other Autism subtypes

There is great phenotypic heterogeneity within autism spectrum disorders (ASD), which has led to question their classification into a single diagnostic category. The study of the common genetic variation in ASD has suggested a greater contribution of other psychiatric conditions in Asperger syndrome (AS) than in the rest of the DSM-IV ASD subtypes (Non_AS). Here, using available genetic data from previously performed genome-wide association studies (GWAS), we aimed to study the genetic overlap between five of the most related disorders (schizophrenia (SCZ), major depression disorder (MDD), attention deficit hyperactivity disorder (ADHD), obsessive-compulsive disorders (OCD) and anxiety (ANX)), and AS, comparing it with the overlap in Non_AS subtypes. A Spanish cohort of autism trios (N = 371) was exome sequenced as part of the Autism Sequencing Consortium (ASC) and 241 trios were extensively characterized to be diagnosed with AS following DSM-IV and Gillberg's criteria (N = 39) or not (N = 202). Following exome imputation, polygenic risk scores (PRS) were calculated for ASD, SCZ, ADHD, MDD, ANX, and OCD (from available summary data from Psychiatric Genomic Consortium (PGC) repository) in the Spanish trios' cohort. By using polygenic transmission disequilibrium test (pTDT), we reported that risk for SCZ (Pscz = 0.008, corrected-PSCZ = 0.0409), ADHD (PADHD = 0.021, corrected-PADHD = 0.0301), and MDD (PMDD = 0.039, corrected-PMDD = 0.0501) is over-transmitted to children with AS but not to Non_AS. Indeed, agnostic clustering procedure with deviation values from pTDT tests suggested two differentiated clusters of subjects, one of which is significantly enriched in AS (P = 0.025). Subsequent analysis with S-Predixcan, a recently developed software to predict gene expression from genotype data, revealed a clear pattern of correlation between cortical gene expression in ADHD and AS (P < 0.001) and a similar strong correlation pattern between MDD and AS, but also extendable to another non-brain tissue such as lung (P < 0.001). Altogether, these results support the idea of AS being qualitatively distinct from Non_AS autism and consistently evidence the genetic overlap between AS and ADHD, MDD, or SCZ

Increased Serum Levels of sCD14 and sCD163 Indicate a Preponderant Role for Monocytes in COVID-19 Immunopathology

Background: Emerging evidence indicates a potential role for monocytes in COVID-19 immunopathology. We investigated two soluble markers of monocyte activation, sCD14 and sCD163, in COVID-19 patients, with the aim of characterizing their potential role in monocyte-macrophage disease immunopathology. To the best of our knowledge, this is the first study of its kind. Methods: Fifty-nine SARS-Cov-2 positive hospitalized patients, classified according to ICU or non-ICU admission requirement, were prospectively recruited and analyzed by ELISA for levels of sCD14 and sCD163, along with other laboratory parameters, and compared to a healthy control group. Results: sCD14 and sCD163 levels were significantly higher among COVID-19 patients, independently of ICU admission requirement, compared to the control group. We found a significant correlation between sCD14 levels and other inflammatory markers, particularly Interleukin-6, in the non-ICU patients group. sCD163 showed a moderate positive correlation with the time lapsed from admission to sampling, independently of severity group. Treatment with corticoids showed an interference with sCD14 levels, whereas hydroxychloroquine and tocilizumab did not. Conclusions: Monocyte-macrophage activation markers are increased and correlate with other inflammatory markers in SARS-Cov-2 infection, in association to hospital admission. These data suggest a preponderant role for monocyte-macrophage activation in the development of immunopathology of COVID-19 patients

Plan de negocios para la creaci?n de una aplicaci?n multiplataforma y el uso de pulseras inteligentes para el monitoreo de entrenamientos en el sector gimnasios de Lima Metropolitana

El actual sector de los gimnasios en el Per? ha demostrado un gran crecimiento, logrando convertirse atractivo para los inversionistas. Sin embargo, este crecimiento ha venido acompa?ado de grandes desaf?os, entre los cuales destaca la poca innovaci?n en la experiencia de usuario dentro de los gimnasios, catalog?ndose como ?tradicional?, siendo constante y sin ning?n tipo de cambio a lo largo de los a?os. Asimismo, la tecnolog?a wearable ha cambiado la forma en la que vemos los accesorios de vestir como relojes, pulseras, entre otros, en dispositivos que mediante sensores monitorean actividades cotidianas recogiendo informaci?n de manera continua sobre nuestra salud y h?bitos de comportamiento. Finalmente, trataremos c?mo innovar y mejorar la experiencia de usuario en los gimnasios, y m?s concretamente, sobre la propuesta de negocio basada en el uso de una aplicaci?n movil y plataforma web integrando tecnolog?a wearable con el uso de pulseras inteligentes. As? de esta manera lograremos que los gimansios de Lima se conviertan en organizaciones de servicios que venden experiencias, siendo claros ejemplos de organizaciones que satisfacen el inter?s de una comunidad por realizar actividad f?sica y sociabilizar a trav?s de la participaci?n en actividades deportivas

Plan de negocios para la implementaci?n de una cadena de food trucks de comida fusi?n peruano-venezolana en la ciudad de Lima

En los ?ltimos a?os la migraci?n de venezolanos al pa?s por crisis pol?tica y econ?mica que en la actualidad viven est? ha generado la entrada al pa?snuevos productos gastron?micos como la arepa, esto se observa en reportaje realizado por Per? 21 donde se puede ver a venezolanos vendiendo este producto en el gir?n de la uni?n en el centro de Lima (Per? 21). De all? surge la idea de la crear un producto novedoso e innovador, que consiste en la fusi?n de los m?s tradicionales platos de la cocina peruana con la arepa venezolana, es por esto que se plantearon como objetivo general la viabilidad comercial, operativa, legal y econ?mica para la implementaci?n de una cadena de ?food Truck? de comida fusi?n peruano - venezolana en Lima Metropolitana, apoyado en los siguientes objetivos espec?ficos: - Realizar una investigaci?n de mercado para conocer la demanda de comida venezolana, perfil del consumidor y atributos valorados por los consumidores. - Establecer los factores cr?ticos de ?xito para el desarrollo de una cadena de ?food truck?. - Definir las acciones estrat?gicas para la puesta en marcha y gesti?n del negocio en los puntos de venta elegidos. - Desarrollar el plan comercial y operativo para implementar la idea de negocio. - Evaluar la viabilidad econ?mica del negocio de venta de comida r?pida fusi?n peruano-venezolana en ?food truck?

A prospective study of the clinical outcomes and prognosis associated with comorbid COPD in the atrial fibrillation population

Background: Patients with COPD are at higher risk of presenting with atrial fibrillation (AF). Information about clinical outcomes and optimal medical treatment of AF in the setting of COPD remains missing. We aimed to describe the prevalence of COPD in a sizeable cohort of real-world AF patients belonging to the same healthcare area and to examine the relationship between comorbid COPD and AF prognosis. Methods: Prospective analysis performed in a specific healthcare area. Data were obtained from several sources within the "data warehouse of the Galician Healthcare Service" using multiple analytical tools. Statistical analyses were completed using SPSS 19 and STATA 14.0. Results: A total of 7,990 (2.08%) patients with AF were registered throughout 2013 in our healthcare area (n=348,985). Mean age was 76.83+/-10.51 years and 937 (11.7%) presented with COPD. COPD patients had a higher mean CHA2DS2-VASc (4.21 vs 3.46; P=0.02) and received less beta-blocker and more digoxin therapy than those without COPD. During a mean follow-up of 707+/-103 days, 1,361 patients (17%) died. All-cause mortality was close to two fold higher in the COPD group (28.3% vs 15.5%; P<0.001). Independent predictive factors for all-cause mortality were age, heart failure, diabetes, previous thromboembolic event, dementia, COPD, and oral anticoagulation (OA). There were nonsignificant differences in thromboembolic events (1.7% vs 1.5%; P=0.7), but the rate of hemorrhagic events was significantly higher in the COPD group (3.3% vs 1.9%; P=0.004). Age, valvular AF, OA, and COPD were independent predictive factors for hemorrhagic events. In COPD patients, age, heart failure, vasculopathy, lack of OA, and lack of beta-blocker use were independent predictive factors for all-cause mortality. Conclusion: AF patients with COPD have a higher incidence of adverse events with significantly increased rates of all-cause mortality and hemorrhagic events than AF patients without COPD. However, comorbid COPD was not associated with differences in cardiovascular death or stroke rate. OA and beta-blocker treatment presented a risk reduction in mortality while digoxin use exerted a neutral effect

AGT haplotype in ITGA4 gene is related to antibody-mediated rejection in heart transplant patients

[Abstract] Introduction. One of the main problems involved in heart transplantation (HT) is antibody-mediated rejection (AMR). Many aspects of AMR are still unresolved, including its etiology, diagnosis and treatment. In this project, we hypothesize that variants in genes involved in B-cell biology in HT patients can yield diagnostic and prognostic information about AMR. Methods. Genetic variants in 61 genes related to B-cell biology were analyzed by next generation sequencing in 46 HT patients, 23 with and 23 without AMR. Results. We identified 3 single nucleotide polymorphisms in ITGA4 gene (c.1845G>A, c.2633A>G, and c.2883C>T) that conformed the haplotype AGT-ITGA4. This haplotype is associated with the development of AMR. Moreover, AMR patients with the haplotype AGT-ITGA4 present lower levels of integrin α-4 in serum samples compared to the reference GAC haplotype in control patients. Conclusion. We can conclude that polymorphisms in genes related to the biology of B-cells could have an important role in the development of AMR. In fact, the AGT haplotype in ITGA4 gene could potentially increase the risk of AMR.Instituto de Salud Carlos III; PI13/0217

Association between convalescent plasma treatment and mortality in COVID-19: a collaborative systematic review and meta-analysis of randomized clinical trials.

Funder: laura and john arnold foundationBACKGROUND: Convalescent plasma has been widely used to treat COVID-19 and is under investigation in numerous randomized clinical trials, but results are publicly available only for a small number of trials. The objective of this study was to assess the benefits of convalescent plasma treatment compared to placebo or no treatment and all-cause mortality in patients with COVID-19, using data from all available randomized clinical trials, including unpublished and ongoing trials (Open Science Framework, https://doi.org/10.17605/OSF.IO/GEHFX ). METHODS: In this collaborative systematic review and meta-analysis, clinical trial registries (ClinicalTrials.gov, WHO International Clinical Trials Registry Platform), the Cochrane COVID-19 register, the LOVE database, and PubMed were searched until April 8, 2021. Investigators of trials registered by March 1, 2021, without published results were contacted via email. Eligible were ongoing, discontinued and completed randomized clinical trials that compared convalescent plasma with placebo or no treatment in COVID-19 patients, regardless of setting or treatment schedule. Aggregated mortality data were extracted from publications or provided by investigators of unpublished trials and combined using the Hartung-Knapp-Sidik-Jonkman random effects model. We investigated the contribution of unpublished trials to the overall evidence. RESULTS: A total of 16,477 patients were included in 33 trials (20 unpublished with 3190 patients, 13 published with 13,287 patients). 32 trials enrolled only hospitalized patients (including 3 with only intensive care unit patients). Risk of bias was low for 29/33 trials. Of 8495 patients who received convalescent plasma, 1997 died (23%), and of 7982 control patients, 1952 died (24%). The combined risk ratio for all-cause mortality was 0.97 (95% confidence interval: 0.92; 1.02) with between-study heterogeneity not beyond chance (I2 = 0%). The RECOVERY trial had 69.8% and the unpublished evidence 25.3% of the weight in the meta-analysis. CONCLUSIONS: Convalescent plasma treatment of patients with COVID-19 did not reduce all-cause mortality. These results provide strong evidence that convalescent plasma treatment for patients with COVID-19 should not be used outside of randomized trials. Evidence synthesis from collaborations among trial investigators can inform both evidence generation and evidence application in patient care

Los péptidos de proteína MAEBL Plasmodium falciparum se unen específicamente a los eritrocitos e inhiben la invasión in vitro de merozoitos

MAEBL is an erythrocyte binding protein located in the rhoptries and on the surface of mature merozoites, being expressed at the beginning of schizogony. The structure of MAEBL originally isolated from rodent malaria parasites suggested a molecule likely to be involved in invasion. We thus became interested in identifying possible MAEBL functional regions. Synthetic peptides spanning the MAEBL sequence were tested in erythrocyte binding assays to identify such possible MAEBL functional regions. Nine high activity binding peptides (HABPs) were identified: two were found in the M1 domain, one was found between the M1 and M2 regions, five in the erythrocyte binding domain (M2), and one in the protein’s repeat region. The results showed that peptide binding was saturable; some HABPs inhibited in vitro merozoite invasion and specifically bound to a 33 kDa protein on red blood cell membrane. HABPs’ possible function in merozoite invasion of erythrocytes is also discussed

Capacidad de unión de eritrocitos específica y actividad biológica de péptidos de proteína 1 asociados a rhoptry derivados de Plasmodium falciparum

Rhoptry-associated protein 1 (RAP1) is a merozoite antigen within Plasmodium falciparum rhoptries as yet having no specific function described for it. Synthetic peptides spanning the RAP1 sequence were tested in erythrocyte binding assays to identify possible RAP1 functional regions. Five high activity binding peptides (HABPs) were identified; 26201, 26202, 26203 and 26204 spanned residues –K540 within RAP1 Cys region, whilst 26188 (–Y220) was located in p67 amino terminal. The results showed that peptide binding was saturable, some HABPs inhibited in vitro merozoite invasion and specifically bound to a 72 kDa protein in red blood cell membrane. HABP possible function in merozoite invasion of erythrocytes is also discussed