Systemic Effects Induced by Hyperoxia in a Preclinical Model of Intra-abdominal Sepsis

Supplemental oxygen is a supportive treatment in patients with sepsis to balance tissue oxygen delivery and demand in the tissues. However, hyperoxia may induce some pathological effects. We sought to assess organ damage associated with hyperoxia and its correlation with the production of reactive oxygen species (ROS) in a preclinical model of intra-abdominal sepsis. For this purpose, sepsis was induced in male, Sprague-Dawley rats by cecal ligation and puncture (CLP). We randomly assigned experimental animals to three groups: control (healthy animals), septic (CLP), and sham-septic (surgical intervention without CLP). At 18 h after CLP, septic (n = 39), sham-septic (n = 16), and healthy (n = 24) animals were placed within a sealed Plexiglas cage and randomly distributed into four groups for continuous treatment with 21%, 40%, 60%, or 100% oxygen for 24 h. At the end of the experimental period, we evaluated serum levels of cytokines, organ damage biomarkers, histological examination of brain and lung tissue, and ROS production in each surviving animal. We found that high oxygen concentrations increased IL-6 and biomarkers of organ damage levels in septic animals, although no relevant histopathological lung or brain damage was observed. Healthy rats had an increase in IL-6 and aspartate aminotransferase at high oxygen concentration. IL-6 levels, but not ROS levels, are correlated with markers of organ damage. In our study, the use of high oxygen concentrations in a clinically relevant model of intra-abdominal sepsis was associated with enhanced inflammation and organ damage. These findings were unrelated to ROS release into circulation. Hyperoxia could exacerbate sepsis-induced inflammation, and it could be by itself detrimental. Our study highlights the need of developing safer thresholds for oxygen therapy

PICALM Rescues Endocytic Defects Caused by the Alzheimer's Disease Risk Factor APOE4

APOE4 is the strongest genetic risk factor for late-onset Alzheimer's disease (AD). Narayan and Sienski et al. find that APOE4 disrupts early endocytosis, a process by which cells take up external material. By increasing the levels of another AD risk factor, PICALM, the authors are able to reverse these disruptions

Evaluación del impacto de una intervención para mejorar las coberturas de vacunación frente a neumococo en pacientes con VIH

Fundamentos: Las personas infectadas por el vi-rus de la inmunodeficiencia humana (VIH) presentan riesgo elevado de sufrir la enfermedad neumocócica invasiva, motivo por el que se recomienda su vacuna-ción frente al neumococo. El objetivo de este trabajo fue evaluar el impacto de implementar una consulta hospitalaria de vacunas en las coberturas de vacuna-ción de estos pacientes. Métodos: Se elaboró un estudio cuasiexperimental sin grupo control, de tipo antes/después, en el que se realizó un muestreo de casos consecutivos de pacientes con VIH remitidos a nuestra consulta entre el 1 noviembre de 2014 y el 30 junio de 2018. Las coberturas en el momento de la fecha de la cita para la valoración de su estado vacunal (en nuestra consulta) y después de ser atendido se compararon usando la prueba chi-cuadrado. Como referencia se utilizaron las del momento de la fecha de la primera cita. Resultados: Se analizaron 209 pacientes, en los que se obtuvieron mejoras estadísticamente signifi-cativas en sus coberturas vacunales: 2, 9% en el mo-mento de la fecha de la cita para la valoración en nuestra consulta y 88% después de ser atendidos en nuestra consulta (RR [IC95%]= 30, 7 [13, 92-67, 58]) para la vacuna antineumocócica conjugada 13-valen-te, y 16, 3% en el momento de la primera cita y 83, 7% después de ser atendidos en nuestra consulta (RR [IC95%]=5, 2 [3, 76-7, 04]) para la vacuna antineumo-cócica polisacárida 23-valente. Conclusiones: Implementar una consulta hospitalaria de vacunas representa una intervención efectiva para mejorar las coberturas de vacunación frente al neumococo en pacientes con VIH. Background: People affected by the human immunodeficiency virus (HIV) have a higher risk of invasive pneumococcal disease. Therefore, vaccination against streptococcus pneumoniae is recommended for that group. The objective of this study was to analyze the impact of implementing a hospital appointment to assess vaccination status as part of the vaccination schedule of HIV patients. Methods: We carried out a quasi-experimental uncontrolled before and after study with a sampling of consecutive cases of HIV patients referred to our department from November 1, 2014 to June 30, 2018. The study compared the vaccination coverage on the date of the appointment for an assessment of their vaccination status in our department and after the appointment. The analysis used the chi-squared test and the values on the date of the first appointment were taken as a reference. Results: 209 patients were analyzed, and a statistically significant improvement was observed regarding their vaccination coverage: 2.9% of the patients had been vaccinated on the date in which they made an appointment for assessment by our department, and 88.0% were vaccinated after they left (OR [95%CI]: 30.7 [13.92-67.58]) with the 13-valent pneumococcal conjugate vaccine; and 16.3% had been vaccinated on the date they made the first appointment vs. 83.7% after they came to the appointment (OR [95%CI]: 5.2 [3.76-7.04]) with the 23-valent polysaccharide pneumococcal vaccine. Conclusions: Implementing a hospital appointment for vaccination is an effective intervention to improve vaccination coverage against streptococcus pneumoniae in HIV patients

Cohort study protocol: Bioresource in Adult Infectious Diseases (BioAID)

Introduction: Infectious diseases have a major impact on morbidity and mortality in hospital. Microbial diagnosis remains elusive for most cases of suspected infection which impacts on the use of antibiotics. Rapid advances in genomic technologies combined with high-quality phenotypic data have great potential to improve the diagnosis, management and clinical outcomes of infectious diseases.  The aim of the Bioresource in Adult Infectious Diseases (BioAID) is to provide a platform for biomarker discovery, trials and clinical service developments in the field of infectious diseases, by establishing a registry linking clinical phenotype to microbial and biological samples in adult patients who attend hospital with suspected infection. Methods and analysis: BioAID is a cohort study which employs deferred consent to obtain an additional 2.5mL RNA blood sample from patients who attend the Emergency Department (ED) with suspected infection when they undergo peripheral blood culture sampling.  Clinical data and additional biological samples including DNA, serum and microbial isolates are obtained from BioAID participants during hospital admission.  Participants are also asked to consent to be recalled for future studies. BioAID aims to recruit 10,000 patients from 5-8 sites across England.  Since February 2014 >4000 individuals have been recruited to the study.  The final cohort will be characterised using descriptive statistics including information on the number of cases that can be linked to biological and microbial samples to support future research studies. Ethical approval and section 251 exemption have been obtained for BioAID researchers to seek deferred consent from patients from whom a RNA specimen has been collected. Samples and meta-data obtained through BioAID will be made available to researchers worldwide following submission of an application form and research protocol.   Conclusions: BioAID will support a range of study designs spanning discovery science, biomarker validation, disease pathogenesis and epidemiological analyses of clinical infection syndromes

Lifestyle Evolution And Peroxidase Diversity In Agaricales As Revealed By Comparative Genomics

Descripción de 1 páginas de la comunicación oral presentada en Oxizymes2022 10th edition of the international “Oxizymes” meeting. Siena, Italy, July 5-8, 2022Basidiomycetes of the class Agaricomycetes have developed complex enzymatic machineries that allow them to decompose plant polymers, including lignin. Within this group, saprotrophic Agaricales are characterized by an unparalleled diversity of habitats and lifestyles in comparison with fungi from other orders. With the aim of shedding light on the evolution of lignocellulose-decaying lifestyles in Agaricales we conducted a comparative analysis of 52 Agaricomycetes genomes [1]. This study revealed that Agaricales possess a large diversity of hydrolytic and oxidative enzymes. Surprisingly, computer-assisted gene-family evolution analysis of these enzymes revealed that a few oxidoreductase families showed significantly higher evolutionary rates. Based on these gene families we reconstructed the lifestyles of the ancestors that led to the extant lignocellulose-decomposing Agaricomycetes. According to this, we determined that changes in the oxidative enzymatic toolkit of ancestral Agaricales correlate with the evolution of their ability to grow not only on wood, but also on leaf and grass litter and decayed wood. In this context, the aboye families were analyzed and special attention was paid to peroxidases as a central component of the enzymatic toolkit of saprotrophic Agaricomycetes responsible for lignin degradation. We identified a widespread presence of new ligninolytic peroxidase types in Agaricales, some of them not previously identified in this order, and others also not found in woodrottingPolyporales and other orders of Agaricomycetes. Peroxidase evolution was analyzed in Agaricomycetes by ancestral sequence reconstruction and several major evolutionary pathways were unveiled. The study of the newly identified peroxidases will provide insight into their role in the lignin degradation process. In fact, these studies have already been initiated with the expression and characterization of the first lignin peroxidase identified in Agaricales. [1] Ruiz-Dueñas FJ, Barrasa JM, Sánchez-García M, Camarero S, Miyauchi S, Serrano A, et al., 2021, Mol Biol Evol, 38, 1428-1446.Projects/contracts BI02017-86559-R, BI02015-7369-JIN, AGL2014-55971-R, NSFgrant-1457721 , CEFOX-031 B0831 S, PIE-201620E081 , ANR-11-LABX-0002-01 , US-DOE-DE-AC02-05CH11231N

Sentinel surveillance of HIV infection in HIV test clinics, Spain 1992-2002

HIV infection in Spain was monitored in persons undergoing voluntary HIV testing in ten sentinel clinics between 1992 and 2002. Only patients on their first visit were considered for inclusion, and their numbers rose from 4426 in 1992 to 6649 in 2002. Most of them recognised their risk exposure as heterosexual. The proportion of injecting drug users decreased from 19% to 2% of the study population, and the proportion of female sex workers increased from 6% to 26%. The number of patients diagnosed with HIV infection declined from 604 in 1992 to 153 in 2002, and HIV prevalence fell from 13.6% to 2.3% in the same period. In all risk exposure categories, a decrease in HIV prevalence was observed, more pronounced during the first few years and stabilised in the later years. In 2002, the highest HIV prevalence was found in injecting drug users (IDUs) (14.2%), homo/bisexual men (7.5%) and individuals who had an HIV infected heterosexual partner (10.2%).This work was partly funded by FIPSE (Foundation formed by the Spanish Ministry of Health and Consumer Affairs, Abbott Laboratories, Boehringer Ingelheim, Bristol Myers Squibb, GlaxoSmithKline, Merck Sharp and Dohme, and Roche, exp. 3076/99 and 36303/02) and by the Spanish Red de Investigación en Sida - RIS (Network for Research on AIDS) and the Spanish Red de Centros de Investigación Cooperativa en Epidemiología y Salud Pública - RCESP (Network for cooperative research in Epidemiology and Public Health)

Upregulation of Annexin A1 Expression by Butyrate in Human Colon Adenocarcinoma Cells: Role of p53, NF-Y, and p38 Mitogen-Activated Protein Kinase ▿

Annexin A1 is a member of a phospholipid and calcium binding family of proteins; it is involved in anti-inflammation and in the regulation of differentiation, proliferation, and apoptosis. Here, we show the existence of a functional binding site for the tumor suppressor p53 near the proximal CCAAT box and the fact that the basal expression of annexin A1 in human colon adenocarcinoma cells is driven by p53 at the transcriptional level. Posttranscriptional mechanisms may also play an important role in maintaining constitutive annexin A1 expression. In addition, a p53/NF-Y complex is detected bound to the p53 binding site on its promoter. Butyrate is a natural product of fiber degradation in the colon and a key regulator of colonic epithelium homeostasis. We show that butyrate, a class I and II histone deacetylase inhibitor, induces transcriptional activation of annexin A1 expression correlated with differentiation. The effect of butyrate is mediated through a release of NF-Y from the proximal CCAAT box and an enhancement of p53 binding. The interaction of p53 with the promoter is dependent on p38 MAPK activity either in the absence or in the presence of butyrate. Further, activation of p38 MAPK by this agent is required to increase annexin A1 promoter activity and to increase protein expression

Disruption of an Enterococcus faecium Species-Specific Gene, a Homologue of Acquired Macrolide Resistance Genes of Staphylococci, Is Associated with an Increase in Macrolide Susceptibility

The complete sequence (1,479 nucleotides) of msrC, part of which was recently reported by others using a different strain, was determined. This gene was found in 233 of 233 isolates of Enterococcus faecium but in none of 265 other enterococci. Disruption of msrC was associated with a two- to eightfold decrease in MICs of erythromycin azithromycin, tylosin, and quinupristin, suggesting that it may explain in part the apparent greater intrinsic resistance to macrolides of isolates of E. faecium relative to many streptococci. This endogenous, species-specific gene of E. faecium is 53% identical to msr(A), suggesting that it may be a remote progenitor of the acquired macrolide resistance gene found in some isolates of staphylococci

Complex Optimization of Heavy Duty Asphalt Pavement Types in DURABROADS Project

DURABROADS, an EU FP7 financed project launched in 2013, and led by the University of Cantabria (Spain) aims at providing a sustainable growth through the development of innovative, cost-effective and more durable pavements. The new generation of pavement is based on innovative eco-friendly nanotechnology-enhanced asphalts as well on the optimization of procedures to build and rehabilitate durable, safer and greener road infrastructure more adapted to climate change and freight corridor traffic loads. One of the objectives of this project is to identify and evaluate the existing constraints concerning currently used road materials of heavily trafficked roads (TEN-T routes) to withstand current road challenges. Due to different traffic and climate features, four European regions (Northern, Central, Western and Southern Europe) were differentiated. The climate change elements critical to various road types were identified, reviewing the pavement deterioration forms they accelerate. The traffic loads on freight corridors were evaluated considering their accelerated pavement deterioration forms. The synergistic effect of extreme climatic and mechanical loads to pavement surface was scrutinised. A comprehensive quantification methodology for extreme traffic and climatic load combinations was suggested including technical (functional), economic, environmental and social-human aspects with appropriate weighing. Then the European region-specific ?optimal? asphalt wearing course types and road rehabilitation techniques for TEN-T routes were identified. The region-specific material and procedure optimization utilizes ? in addition to the processing of a comprehensive literature survey ? the answers coming from 81 experts of 52 European institutions to targeted questionnaire. These data were used to develop a decision support model based on AHP and TOPSIS models to facilitate the selection of asphalt pavement types. The results suggested Stone Mastic Asphalt (SMA) as the most suitable alternative in different climate change scenarios evaluated by a sensitivity analysis.This paper was possible thanks to the research project DURABROADS financed by the European Commission through the Seventh Framework Programme for Research (FP7). The authors also wish to express their gratitude to the panel of experts that contributed to enrich the quality of this paper through their valuable contribution