Differential leukocyte expression of IFITM1 and IFITM3 in patients with severe pandemic influenza A(H1N1) and COVID-19

Interferon-induced transmembrane (IFITM) proteins mediate protection against enveloped viruses by blocking membrane fusion at endosomes. IFITM1 and IFITM3 are crucial for protection against influenza, and various single nucleotide polymorphisms altering their function have been linked to disease susceptibility. However, bulk IFITM1 and IFITM3 mRNA expression dynamics and their correlation with clinical outcomes have not been extensively addressed in patients with respiratory infections. In this study, we evaluated the expression of IFITM1 and IFITM3 in peripheral leukocytes from healthy controls and individuals with severe pandemic influenza A(H1N1) or coronavirus disease 2019 (COVID-19). Comparisons between participants grouped according to their clinical characteristics, underlying disease, and outcomes showed that the downregulation of IFITM1 was a distinctive characteristic of severe pandemic influenza A(H1N1) that correlated with outcomes, including mortality. Conversely, increased IFITM3 expression was a common feature of severe pandemic influenza A(H1N1) and COVID-19. Using a high-dose murine model of infection, we confirmed not only the downregulation of IFITM1 but also of IFITM3 in the lungs of mice with severe influenza, as opposed to humans. Analyses in the comparative cohort also indicate the possible participation of IFITM3 in COVID-19. Our results add to the evidence supporting a protective function of IFITM proteins against viral respiratory infections in humans.Introduction Methods - Human samples - IFITM expression in humans - Influenza infection in mice - IFITM expression in mice - Cytokine levels in mouse lungs - Study approval - Statistical analysis Results - Participant characteristics - IFITM1 and IFITM3 in patients with severe pandemic influenza A(H1N1) - High-dose influenza A (H1N1) virus infection downregulates IFITM expression in mice - IFITM1 and IFITM3 in severe COVID-19 Discussio

Autoantibody screening in Guillain-Barré syndrome

Background: Guillain?Barré syndrome (GBS) is an acute inflammatory neuropathy with a heterogeneous presentation. Although some evidences support the role of autoantibodies in its pathogenesis, the target antigens remain unknown in a substantial proportion of GBS patients. The objective of this study is to screen for autoantibodies targeting peripheral nerve components in Guillain-Barré syndrome. Methods: Autoantibody screening was performed in serum samples from all GBS patients included in the International GBS Outcome study by 11 different Spanish centres. The screening included testing for anti-ganglioside antibodies, anti-nodo/paranodal antibodies, immunocytochemistry on neuroblastoma-derived human motor neurons and murine dorsal root ganglia (DRG) neurons, and immunohistochemistry on monkey peripheral nerve sections. We analysed the staining patterns of patients and controls. The prognostic value of anti-ganglioside antibodies was also analysed. Results: None of the GBS patients (n = 100) reacted against the nodo/paranodal proteins tested, and 61 (61%) were positive for, at least, one anti-ganglioside antibody. GBS sera reacted strongly against DRG neurons more frequently than controls both with IgG (6% vs 0%; p = 0.03) and IgM (11% vs 2.2%; p = 0.02) immunodetection. No differences were observed in the proportion of patients reacting against neuroblastoma-derived human motor neurons. Reactivity against monkey nerve tissue was frequently detected both in patients and controls, but specific patterns were only detected in GBS patients: IgG from 13 (13%) patients reacted strongly against Schwann cells. Finally, we confirmed that IgG anti-GM1 antibodies are associated with poorer outcomes independently of other known prognostic factor

Autoantibody screening in Guillain-Barré syndrome

Background: Guillain-Barré syndrome (GBS) is an acute inflammatory neuropathy with a heterogeneous presentation. Although some evidences support the role of autoantibodies in its pathogenesis, the target antigens remain unknown in a substantial proportion of GBS patients. The objective of this study is to screen for autoantibodies targeting peripheral nerve components in Guillain-Barré syndrome. Methods: Autoantibody screening was performed in serum samples from all GBS patients included in the International GBS Outcome study by 11 different Spanish centres. The screening included testing for anti-ganglioside antibodies, anti-nodo/paranodal antibodies, immunocytochemistry on neuroblastoma-derived human motor neurons and murine dorsal root ganglia (DRG) neurons, and immunohistochemistry on monkey peripheral nerve sections. We analysed the staining patterns of patients and controls. The prognostic value of anti-ganglioside antibodies was also analysed. Results: None of the GBS patients (n = 100) reacted against the nodo/paranodal proteins tested, and 61 (61%) were positive for, at least, one anti-ganglioside antibody. GBS sera reacted strongly against DRG neurons more frequently than controls both with IgG (6% vs 0%; p = 0.03) and IgM (11% vs 2.2%; p = 0.02) immunodetection. No differences were observed in the proportion of patients reacting against neuroblastoma-derived human motor neurons. Reactivity against monkey nerve tissue was frequently detected both in patients and controls, but specific patterns were only detected in GBS patients: IgG from 13 (13%) patients reacted strongly against Schwann cells. Finally, we confirmed that IgG anti-GM1 antibodies are associated with poorer outcomes independently of other known prognostic factors. Conclusion: Our study confirms that (1) GBS patients display a heterogeneous repertoire of autoantibodies targeting nerve cells and structures; (2) gangliosides are the most frequent antigens in GBS patients and have a prognostic value; (3) further antigen-discovery experiments may elucidate other potential antigens in GBS

The significance of cephalopod beaks as a research tool: An update

The use of cephalopod beaks in ecological and population dynamics studies has allowed major advances of our knowledge on the role of cephalopods in marine ecosystems in the last 60 years. Since the 1960's, with the pioneering research by Malcolm Clarke and colleagues, cephalopod beaks (also named jaws or mandibles) have been described to species level and their measurements have been shown to be related to cephalopod body size and mass, which permitted important information to be obtained on numerous biological and ecological aspects of cephalopods in marine ecosystems. In the last decade, a range of new techniques has been applied to cephalopod beaks, permitting new kinds of insight into cephalopod biology and ecology. The workshop on cephalopod beaks of the Cephalopod International Advisory Council Conference (Sesimbra, Portugal) in 2022 aimed to review the most recent scientific developments in this field and to identify future challenges, particularly in relation to taxonomy, age, growth, chemical composition (i.e., DNA, proteomics, stable isotopes, trace elements) and physical (i.e., structural) analyses. In terms of taxonomy, new techniques (e.g., 3D geometric morphometrics) for identifying cephalopods from their beaks are being developed with promising results, although the need for experts and reference collections of cephalopod beaks will continue. The use of beak microstructure for age and growth studies has been validated. Stable isotope analyses on beaks have proven to be an excellent technique to get valuable information on the ecology of cephalopods (namely habitat and trophic position). Trace element analyses is also possible using beaks, where concentrations are significantly lower than in other tissues (e.g., muscle, digestive gland, gills). Extracting DNA from beaks was only possible in one study so far. Protein analyses can also be made using cephalopod beaks. Future challenges in research using cephalopod beaks are also discussed.info:eu-repo/semantics/publishedVersio

Comparative genetic architectures of schizophrenia in East Asian and European populations

Schizophrenia is a debilitating psychiatric disorder with approximately 1% lifetime risk globally. Large-scale schizophrenia genetic studies have reported primarily on European ancestry samples, potentially missing important biological insights. Here, we report the largest study to date of East Asian participants (22,778 schizophrenia cases and 35,362 controls), identifying 21 genome-wide-significant associations in 19 genetic loci. Common genetic variants that confer risk for schizophrenia have highly similar effects between East Asian and European ancestries (genetic correlation = 0.98 ± 0.03), indicating that the genetic basis of schizophrenia and its biology are broadly shared across populations. A fixed-effect meta-analysis including individuals from East Asian and European ancestries identified 208 significant associations in 176 genetic loci (53 novel). Trans-ancestry fine-mapping reduced the sets of candidate causal variants in 44 loci. Polygenic risk scores had reduced performance when transferred across ancestries, highlighting the importance of including sufficient samples of major ancestral groups to ensure their generalizability across populations

A922 Sequential measurement of 1 hour creatinine clearance (1-CRCL) in critically ill patients at risk of acute kidney injury (AKI)

Meeting abstrac

The significance of cephalopod beaks as a research tool: An update

The use of cephalopod beaks in ecological and population dynamics studies has allowed major advances of our knowledge on the role of cephalopods in marine ecosystems in the last 60 years. Since the 1960’s, with the pioneering research by Malcolm Clarke and colleagues, cephalopod beaks (also named jaws or mandibles) have been described to species level and their measurements have been shown to be related to cephalopod body size and mass, which permitted important information to be obtained on numerous biological and ecological aspects of cephalopods in marine ecosystems. In the last decade, a range of new techniques has been applied to cephalopod beaks, permitting new kinds of insight into cephalopod biology and ecology. The workshop on cephalopod beaks of the Cephalopod International Advisory Council Conference (Sesimbra, Portugal) in 2022 aimed to review the most recent scientific developments in this field and to identify future challenges, particularly in relation to taxonomy, age, growth, chemical composition (i.e., DNA, proteomics, stable isotopes, trace elements) and physical (i.e., structural) analyses. In terms of taxonomy, new techniques (e.g., 3D geometric morphometrics) for identifying cephalopods from their beaks are being developed with promising results, although the need for experts and reference collections of cephalopod beaks will continue. The use of beak microstructure for age and growth studies has been validated. Stable isotope analyses on beaks have proven to be an excellent technique to get valuable information on the ecology of cephalopods (namely habitat and trophic position). Trace element analyses is also possible using beaks, where concentrations are significantly lower than in other tissues (e.g., muscle, digestive gland, gills). Extracting DNA from beaks was only possible in one study so far. Protein analyses can also be made using cephalopod beaks. Future challenges in research using cephalopod beaks are also discussed

Role of age and comorbidities in mortality of patients with infective endocarditis

[Purpose]: The aim of this study was to analyse the characteristics of patients with IE in three groups of age and to assess the ability of age and the Charlson Comorbidity Index (CCI) to predict mortality. [Methods]: Prospective cohort study of all patients with IE included in the GAMES Spanish database between 2008 and 2015.Patients were stratified into three age groups:<65 years,65 to 80 years,and ≥ 80 years.The area under the receiver-operating characteristic (AUROC) curve was calculated to quantify the diagnostic accuracy of the CCI to predict mortality risk. [Results]: A total of 3120 patients with IE (1327 < 65 years;1291 65-80 years;502 ≥ 80 years) were enrolled.Fever and heart failure were the most common presentations of IE, with no differences among age groups.Patients ≥80 years who underwent surgery were significantly lower compared with other age groups (14.3%,65 years; 20.5%,65-79 years; 31.3%,≥80 years). In-hospital mortality was lower in the <65-year group (20.3%,<65 years;30.1%,65-79 years;34.7%,≥80 years;p < 0.001) as well as 1-year mortality (3.2%, <65 years; 5.5%, 65-80 years;7.6%,≥80 years; p = 0.003).Independent predictors of mortality were age ≥ 80 years (hazard ratio [HR]:2.78;95% confidence interval [CI]:2.32–3.34), CCI ≥ 3 (HR:1.62; 95% CI:1.39–1.88),and non-performed surgery (HR:1.64;95% CI:11.16–1.58).When the three age groups were compared,the AUROC curve for CCI was significantly larger for patients aged <65 years(p < 0.001) for both in-hospital and 1-year mortality. [Conclusion]: There were no differences in the clinical presentation of IE between the groups. Age ≥ 80 years, high comorbidity (measured by CCI),and non-performance of surgery were independent predictors of mortality in patients with IE.CCI could help to identify those patients with IE and surgical indication who present a lower risk of in-hospital and 1-year mortality after surgery, especially in the <65-year group