Positive airway pressure longer than 24 h is associated with histopathological volutrauma in severe COVID-19 pneumonia—an ESGFOR based narrative case-control review

SARS-CoV-2; Post-mortem microbiology; VolutraumaSARS-CoV-2; Microbiología post mortem; VolutraumaSARS-CoV-2; Microbiologia post mortem; VolutraumaBackground and Objective: A thorough understanding of the pathogenic mechanisms elicited by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) still requires further research. Until recently, only a restricted number of autopsies have been performed, therefore limiting the accurate knowledge of the lung injury associated with SARS-CoV-2. A multidisciplinary European Society of Clinical Microbiology and Infectious Diseases (ESCMID) Study Group of Forensic and Post-mortem Microbiology-ESGFOR team conducted a non-systematic narrative literature review among coronavirus 2019 disease (COVID-19) pneumonia cases assessing the histopathological (HP) effects of positive airways pressure. HP lung features were recorded and compared between mechanically ventilated (>24 hours) and control (ventilation <24 hours) patients. A logistic regression analysis was performed to identify associations between mechanical ventilation (MV) and HP findings. Methods: A PubMed and MEDLINE search was conducted in order to identify studies published between March 1st 2020 and June 30th 2021. Key Content and Findings: Seventy patients (median age: 69 years) from 24 studies were analysed, among whom 38 (54.2%) underwent MV longer than 24 hours. Overall, main HP features were: diffuse alveolar damage (DAD) in 53 (75.7%), fibrosis (interstitial/intra-alveolar) in 43 (61.4%), vascular damage—including thrombosis/emboli- in 41 (58.5%), and endotheliitis in only 8 (11.4%) patients. Association of DAD, fibrosis and vascular damage was detected in 30 (42.8%) patients. Multivariate analysis, adjusted by age and gender, identified MV >24 hours as an independent variable associated with DAD (OR =5.40, 95% CI: 1.48–19.62), fibrosis (OR =3.88, 95% CI: 1.25–12.08), vascular damage (OR =5.49, 95% CI: 1.78–16.95) and association of DAD plus fibrosis plus vascular damage (OR =6.99, 95% CI: 2.04–23.97). Conclusions: We identified that patients mechanically ventilated >24 hours had a significantly higher rate of pulmonary injury on histopathology independently of age and gender. Our findings emphasize the importance of maintaining a protective ventilator strategy when subjects with COVID-19 pneumonia undergo intubation

Estabilidad de rendimiento y características fisicoquímicas de grano de híbridos de maíz en Valles Altos de México

Corn grain crops in High Valleys ofMexico generally do not meet quality requirements for use in the tortilla and dough industry. New hybrids have been released by research centers for these agroecological conditions and it is necessary to evaluate the stability of production and grain quality in different production environments to avoid rejection in the market. The objective of this study was to identify stable hybrids in their yield, physical-chemical characteristics of the grains and quality of tortillas. Ten hybrids were evaluated in five different environments with four replications for each treatment. The data were analyzed with SAS, version 9.0, the Anova was developedand the comparison of means was made with the Tukey test at 5%. Significant differences were detected for hybrids, environment and hybrid*environment interaction; for grain yield, physical-chemical variables of the tortillas. The grain yields ranged from 9 to 12.4 t ha-1. The highest stability due to adaptability and yieldby environments was found for hybrids H-70, H-66 and Tsiri Puma. Within the group of hard grains are the Tsiri Puma and the commercial control Albatros. The Atziri Puma hybrids, in Temascalcingo and H-50 in Atlacomulco, presented the largest grains. Correlations were found between proteins vsoil (r= 0.6), oil vsstarch (r= -0.86) and proteins vsstarch (r= -0.82). The highest doughyield was found in the H-51 AE hybrid, followed by H-47 AE, Albatros and Tsiri Puma with 2 kg of doughfor each kg of nixtamalized corn. The yieldand quality of tortillas of the hybrids evaluated comply with the values demanded by the industry. The results of this research allow us to recommend these new hybrids, due to their stability in yield, in the test environments, commercial quality of the grain and quality of their tortillasLas cosechas de grano de maíz en Valles Altos de México en lo general no cumplen con los requisitos de calidad para su uso en la industria de la masa y la tortilla. Nuevos híbridos han sido liberados por centros de investigación para estas condiciones agroecológicas y es necesario evaluar la estabilidad de producción y calidad de grano en diferentes ambientes de producción para evitar rechazos en el mercado. El objetivo de este estudio fue identificar híbridos estables en su rendimiento, características fisicoquímicas de los granos y calidad de tortillas. Se evaluaron diez híbridos en cinco ambientes diferentes con cuatro repeticiones para cada tratamiento. Los datos se analizaron con SAS, versión 9.0, se desarrolló el Anova y la comparación de medias se hizo con la prueba de Tukey al 5%. Se detectaron diferencias significativas para híbridos, ambiente y la interacción híbrido*ambiente; para rendimiento de grano, variables físico-químicas de las tortillas. Los rendimientos de grano oscilaron entre 9 a 12.4 t ha-1. La mayor estabilidad por adaptabilidad y rendimiento por ambientes se encontró para los híbridos H-70, H-66 y Tsiri Puma. Dentro del grupo de los granos duros se encuentran el Tsiri Puma y el testigo comercial Albatros. Los híbridos Atziri Puma, en Temascalcingo y H-50 en Atlacomulco, presentaron los granos más grandes. Se encontraron correlaciones entre proteínas vs aceite (r = 0.6), aceite vs almidón (r= -0.86) y proteínas vs almidón (r= -0.82). El mayor rendimiento en masa fue el híbrido H-51 AE, seguido de H-47 AE, Albatros y Tsiri Puma con 2 kg de masa por kg de maíz nixtamalizado. El rendimiento y calidad de tortillas de los híbridos evaluados cumplen con los valores demandados por la industria. Los resultados de esta investigación permiten recomendar estos nuevos híbridos, por su estabilidad en el rendimiento, en los ambientes de prueba, calidad comercial del grano y calidad de sus tortillas

Identification of IRX1 as a Risk Locus for Rheumatoid Factor Positivity in Rheumatoid Arthritis in a Genome-Wide Association Study.

Rheumatoid factor (RF) is a well-established diagnostic and prognostic biomarker in rheumatoid arthritis (RA). However, ∼20% of RA patients are negative for this anti-IgG antibody. To date, only variation at the HLA-DRB1 gene has been associated with the presence of RF. This study was undertaken to identify additional genetic variants associated with RF positivity. A genome-wide association study (GWAS) for RF positivity was performed using an Illumina Quad610 genotyping platform. A total of 937 RF-positive and 323 RF-negative RA patients were genotyped for >550,000 single-nucleotide polymorphisms (SNPs). Association testing was performed using an allelic chi-square test implemented in Plink software. An independent cohort of 472 RF-positive and 190 RF-negative RA patients was used to validate the most significant findings. In the discovery stage, a SNP in the IRX1 locus on chromosome 5p15.3 (SNP rs1502644) showed a genome-wide significant association with RF positivity (P = 4.13 × 10(-8) , odds ratio [OR] 0.37 [95% confidence interval (95% CI) 0.26-0.53]). In the validation stage, the association of IRX1 with RF was replicated in an independent group of RA patients (P = 0.034, OR 0.58 [95% CI 0.35-0.97] and combined P = 1.14 × 10(-8) , OR 0.43 [95% CI 0.32-0.58]). To our knowledge, this is the first GWAS of RF positivity in RA. Variation at the IRX1 locus on chromosome 5p15.3 is associated with the presence of RF. Our findings indicate that IRX1 and HLA-DRB1 are the strongest genetic factors for RF production in RA

Variation at interleukin-6 receptor gene is associated to joint damage in rheumatoid arthritis.

Journal Article; Multicenter Study; Research Support, Non-U.S. Gov't;INTRODUCTION Interleukin-6 (IL-6) cytokine signaling is key in Rheumatoid Arthritis (RA) pathophysiology. Blocking IL-6 receptor (IL6R) has proven to be a highly effective treatment to prevent joint damage. This study was performed to investigate the association between the genetic variation at IL6R gene and the severity of joint damage in RA. METHODS IL6R gene tagging SNPs (n = 5) were genotyped in a discovery group of 527 RA patients from 5 different university hospitals from Spain. For each marker, a linear regression analysis was performed using an additive model and adjusting for the years of evolution of the disease, autoantibody status, gender and age. Haplotypes combining the SNPs were also estimated and tested for association with the level of joint destruction. Using an independent cohort of 705 RA patients from 6 university hospitals we performed a validation study of the SNPs associated in the discovery phase. RESULTS In the discovery group we found a highly significant association between IL6R SNP rs4845618 and the level of joint destruction in RA (P = 0.0058, P corrected = 0.026), and a moderate association with SNP rs4453032 (P = 0.02, P corrected = 0.05). The resulting haplotype from both SNPs was more significantly associated with joint damage (P = 0.0037, P corrected = 0.011). Using the validation cohort, we replicated the association between the two IL-6R SNPs with the degree of joint destruction in RA (P = 0.007 and P = 0.04, meta-analysis P = 0.00011 and P = 0.0021, respectively), and the haplotype association (P = 0.0058, meta-analysis P = 6.64 e-5). CONCLUSIONS Genetic variation at IL6R gene is associated with joint damage in RA.This study was funded by the Spanish Ministry of Economy and Competitiveness (grant numbers PSE-010000-2006-6 and IPT-010000-2010-36).Ye

Comparison of carotid artery intima-media thickness (cIMT) according to <i>CD154</i> rs3092920 and rs3092952 SNPs.

<p>Comparison of carotid artery intima-media thickness (cIMT) according to <i>CD154</i> rs3092920 and rs3092952 SNPs.</p

Clinical and demographic characteristics of rheumatoid arthritis (RA) patients included in the study, stratified by gender or by Cardiovascular events.

<p>Except where indicated otherwise, values are n (%). IQR: Interquartile Range. Anti-CCP: anti-Cyclic Citrullinated Peptide antibodies.</p>*<p>A patient was considered to have a cerebrovascular accident when he/she had a stroke and/or transient ischemic attacks (TIAs). Strokes were classified according to their clinical features and they were confirmed by computed tomography and/or magnetic resonance imaging. TIAs were diagnosed if the symptoms were self-limited in less than 24 hours, without residual neurological damage <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0049214#pone.0049214-GonzlezGay2" target="_blank">[41]</a>.</p>**<p>Smoking habit encompassed to those patients who smoked at the time of disease diagnosis, during the follow-up or who had smoked within the 10 years before the onset of RA symptoms or the disease diagnosis.</p

Genotype and minor allele frequencies of SNPs located within <i>CD40</i> (20q13) and <i>CD40L</i> (Xq26) genes in RA Spanish patients and healthy controls.

a<p><i>P</i>-value for the allelic model.</p>b<p>Odds Ratio for the minor allele.</p>c<p>with respect to Controls.</p>d<p>comparing RA patients <u>with CV events</u> versus RA patients <u>without CV events</u>. MAF: minor allele frequency.</p

Comparison of cIMT according to <i>CD154</i> rs3092952 and rs3092920 alleles in an adjusted ANCOVA model, stratified by gender.

*<p>Analyses adjusted for age at rheumatoid arthritis diagnosis, follow-up, and classic CV risk factors and anti-CCP status.</p>**<p>Conditional analysis of the rs3092952 and rs3092920 <i>CD154</i> gene variants.</p