Surveillance of Viral Respiratory Infections in the Neonatal Intensive Care Unit-Evolution in the Last 5 Years

Viral respiratory infections (VRIs) in very low birthweight infants can be associated with high rates of morbidity. The COVID-19 pandemic has exerted a strong impact on viral circulation. The purpose of this study is to report on VRIs during NICU admission in infants below 32 weeks' gestation and compare data collected between the pre-and post-COVID-19 pandemic periods. A prospective surveillance study was conducted at a tertiary NICU between April 2016 and June 2022. The COVID-19 post-pandemic period was established as being from March 2020 onwards. Respiratory virus detection was performed by real-time multiplex PCR assays in nasopharyngeal aspirates (NPAs). A total of 366 infants were enrolled. There were no statistical differences between periods regarding infants' birth weight, gestational age, gender distribution, or rates of bronchopulmonary dysplasia. Among the 1589 NPA collected during the pre-COVID-19 period, 8.9% were positive, and among the 1147 NPA collected during the post-pandemic period, only 3% were positive (p < 0.005). The type of viruses detected did not differ according to the study period (pre-COVID19 vs. post-COVID-19): rhinovirus (49.5% vs. 37.5%), adenovirus (22.6% vs. 25%), and human coronavirus (12.9% vs. 16.7%). SARS-CoV-2 was only detected in one patient. In conclusion, the viral profile causing VRI during the pre-COVID-19 and post-COVID-19 era was similar. However, the total number of VRI dropped significantly, most probably due to the global increase in infection prevention measures.This study has been partially supported by ISCIII-Instituto de Salud Carlos III, FIS (Fondo de Investigación Sanitaria-Spanish Health Research Fund) grants PI21CIII/00019, PI18CIII/00009, FI19/00067, PI18/00167, PI21/00896 and PI21/00377.S

Torque Teno Virus in Nasopharyngeal Aspirate of Children With Viral Respiratory Infections

Background: Torque teno virus (TTV) is a ubiquitous anellovirus responsible for persistent infections and is considered a marker of immune function. The role of TTV as a facilitator of respiratory infections (RIs) is unknown. Objectives: Our aim was to estimate, in a prospective study, the prevalence of TTV in the nasopharyngeal aspirate (NPA) of hospitalized children <5 years old, with RIs and correlate them with outcomes and immune response. Patients and methods: NPA was taken for testing of 16 respiratory viruses by reverse transcription-polymerase chain reaction (PCR), TTV PCR, and immunologic study. Results: Sixty hospitalized children with an RI were included. A total of 51/60 patients had positive common respiratory viral (CRV) identification. A total of 23/60 (38.3%) children were TTV+ in NPA. TTV+ patients had other CRVs in 100% of cases versus 78.3% in TTV- ( P = 0.029). The TTV+ patients tended to be older, have fever, and to need pediatric intensive care unit admission more often than TTV- patients. Abnormal chest radiograph was more frequent in the TTV+ patients, odds ratios 2.6 (95% CI: 1.3-5.2). The genetic expression of filaggrin (involved in epithelial barrier integrity) was lower in TTV+ patients; however, the levels of filaggrin in the NPA were increased. Conclusions: TTV infection is common in children with RI and could be associated with abnormal imaging in radiograph, greater severity and an alteration in filaggrin gene expression and protein release.Funded by projects PI18CIII/0009, PI18/00177, and PI21/00377, funded by Instituto de Salud Carlos III (ISCIII) and co-funded by the European Union. There are no conflicts of interest.S

Filaggrin and cytokines in respiratory samples of preterm infants at risk for respiratory viral infection

Respiratory viral infections (RVIs) are frequent in preterm infants possibly inducing long-term impact on respiratory morbidity. Immune response and respiratory barriers are key defense elements against viral insults in premature infants admitted to Neonatal Intensive Care Units (NICUs). Our main goals were to describe the local immune response in respiratory secretions of preterm infants with RVIs during NICU admission and to evaluate the expression and synthesis of lung barrier regulators, both in respiratory samples and in vitro models. Samples from preterm infants that went on to develop RVIs had lower filaggrin gene and protein levels at a cellular level were compared to never-infected neonates (controls). Filaggrin, MIP-1α/CCL3 and MCP-1 levels were higher in pre-infection supernatants compared to controls. Filaggrin, HIF-1α, VEGF, RANTES/CCL5, IL-17A, IL-1β, MIP-1α and MIP-1β/CCL5 levels were higher during and after infection. ROC curve and logistic regression analysis shows that these molecules could be used as infection risk biomarkers. Small airway epithelial cells stimulated by poly:IC presented reduced filaggrin gene expression and increased levels in supernatant. We conclude that filaggrin gene and protein dysregulation is a risk factor of RVI in newborns admitted at the NICU.This study has been partially supported by ISCIII – Instituto de Salud Carlos III, FIS (Fondo de Investigación Sanitaria—Spanish Health Research Fund) grants FI19/00067, PI18/00167, PI21/00896, PI18CIII/00009 and FEDER funds (Fondo Europeo de Desarrollo Regional); Sociedad Española de Alergología e Inmunología Clínica (SEAIC)Beca19A04_Valverde; Alfonso X El Sabio University Grant: VIII Convocatoria Santander-UAX; CIBER de Enfermedades Respiratorias (CIBERES), a Carlos III Institute of Health Initiative.S

Expression of IL-1α correlates with distant metastasis in patients with head and neck squamous cell carcinoma

Altres ajuts: Fondo Europeo de Desarrollo Regional (FEDER)The presence of IL-1 in human cancers is associated with aggressive tumor biology but its prognostic value is unknown. We studied whether IL-1α expression is a prognostic marker of distant metastasis in patients with head and neck squamous cell carcinoma (HNSCC). IL-1α mRNA and protein levels were determined in tumor samples and cancer cell lines using RT-PCR and ELISA. The effects of constitutive IL-1α expression by tumor lines were characterized. IL-1α mRNA and protein secretion were higher in tumor samples from patients who later developed distant metastasis than in patients who did not. By using distant metastasis as a dependent variable, patients were classified into two categories of IL-1α transcript-levels. The high-IL-1α group had a significantly lower five-year distant metastasis-free survival than the low-IL-1α group [70.0% (CI 95%: 55.9-84.1%) vs 94.7% (CI 95%:90.2-99.2%)]. When IL-1α transcript-levels were combined with clinical factors related to tumor metastasis, the predictive power of the model increased significantly. Additionally, transcript levels of IL-1α correlated significantly with those of the IL-1 family genes and genes related to the metastatic process. IL-1 treatment of microvascular endothelial cells increased adhesion of HNSCC cells but no differences were found based on constitutive IL-1α expression by tumor cells. Nevertheless, IL-1α produced by tumor cells effectively increased their transmigration across the endothelium. We found a significant relationship between IL-1α expression and development of distant metastasis in HNSCC patients. IL-1α expression could help to define a subset of patients at high risk of distant metastasis who could benefit from adjuvant treatment

Genome-wide meta-analysis for Alzheimer's disease cerebrospinal fluid biomarkers

Amyloid-beta 42 (A beta 42) and phosphorylated tau (pTau) levels in cerebrospinal fluid (CSF) reflect core features of the pathogenesis of Alzheimer's disease (AD) more directly than clinical diagnosis. Initiated by the European Alzheimer & Dementia Biobank (EADB), the largest collaborative effort on genetics underlying CSF biomarkers was established, including 31 cohorts with a total of 13,116 individuals (discovery n = 8074; replication n = 5042 individuals). Besides the APOE locus, novel associations with two other well-established AD risk loci were observed; CR1 was shown a locus for A beta 42 and BIN1 for pTau. GMNC and C16orf95 were further identified as loci for pTau, of which the latter is novel. Clustering methods exploring the influence of all known AD risk loci on the CSF protein levels, revealed 4 biological categories suggesting multiple A beta 42 and pTau related biological pathways involved in the etiology of AD. In functional follow-up analyses, GMNC and C16orf95 both associated with lateral ventricular volume, implying an overlap in genetic etiology for tau levels and brain ventricular volume.Peer reviewe

Common variants in Alzheimer’s disease and risk stratification by polygenic risk scores

Funder: Funder: Fundación bancaria ‘La Caixa’ Number: LCF/PR/PR16/51110003 Funder: Grifols SA Number: LCF/PR/PR16/51110003 Funder: European Union/EFPIA Innovative Medicines Initiative Joint Number: 115975 Funder: JPco-fuND FP-829-029 Number: 733051061Genetic discoveries of Alzheimer's disease are the drivers of our understanding, and together with polygenetic risk stratification can contribute towards planning of feasible and efficient preventive and curative clinical trials. We first perform a large genetic association study by merging all available case-control datasets and by-proxy study results (discovery n = 409,435 and validation size n = 58,190). Here, we add six variants associated with Alzheimer's disease risk (near APP, CHRNE, PRKD3/NDUFAF7, PLCG2 and two exonic variants in the SHARPIN gene). Assessment of the polygenic risk score and stratifying by APOE reveal a 4 to 5.5 years difference in median age at onset of Alzheimer's disease patients in APOE ɛ4 carriers. Because of this study, the underlying mechanisms of APP can be studied to refine the amyloid cascade and the polygenic risk score provides a tool to select individuals at high risk of Alzheimer's disease

Clonal chromosomal mosaicism and loss of chromosome Y in elderly men increase vulnerability for SARS-CoV-2

The pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2, COVID-19) had an estimated overall case fatality ratio of 1.38% (pre-vaccination), being 53% higher in males and increasing exponentially with age. Among 9578 individuals diagnosed with COVID-19 in the SCOURGE study, we found 133 cases (1.42%) with detectable clonal mosaicism for chromosome alterations (mCA) and 226 males (5.08%) with acquired loss of chromosome Y (LOY). Individuals with clonal mosaic events (mCA and/or LOY) showed a 54% increase in the risk of COVID-19 lethality. LOY is associated with transcriptomic biomarkers of immune dysfunction, pro-coagulation activity and cardiovascular risk. Interferon-induced genes involved in the initial immune response to SARS-CoV-2 are also down-regulated in LOY. Thus, mCA and LOY underlie at least part of the sex-biased severity and mortality of COVID-19 in aging patients. Given its potential therapeutic and prognostic relevance, evaluation of clonal mosaicism should be implemented as biomarker of COVID-19 severity in elderly people. Among 9578 individuals diagnosed with COVID-19 in the SCOURGE study, individuals with clonal mosaic events (clonal mosaicism for chromosome alterations and/or loss of chromosome Y) showed an increased risk of COVID-19 lethality

New insights into the genetic etiology of Alzheimer's disease and related dementias

Characterization of the genetic landscape of Alzheimer's disease (AD) and related dementias (ADD) provides a unique opportunity for a better understanding of the associated pathophysiological processes. We performed a two-stage genome-wide association study totaling 111,326 clinically diagnosed/'proxy' AD cases and 677,663 controls. We found 75 risk loci, of which 42 were new at the time of analysis. Pathway enrichment analyses confirmed the involvement of amyloid/tau pathways and highlighted microglia implication. Gene prioritization in the new loci identified 31 genes that were suggestive of new genetically associated processes, including the tumor necrosis factor alpha pathway through the linear ubiquitin chain assembly complex. We also built a new genetic risk score associated with the risk of future AD/dementia or progression from mild cognitive impairment to AD/dementia. The improvement in prediction led to a 1.6- to 1.9-fold increase in AD risk from the lowest to the highest decile, in addition to effects of age and the APOE ε4 allele

Evaluating the Effects of SARS-CoV-2 Spike Mutation D614G on Transmissibility and Pathogenicity.

Global dispersal and increasing frequency of the SARS-CoV-2 spike protein variant D614G are suggestive of a selective advantage but may also be due to a random founder effect. We investigate the hypothesis for positive selection of spike D614G in the United Kingdom using more than 25,000 whole genome SARS-CoV-2 sequences. Despite the availability of a large dataset, well represented by both spike 614 variants, not all approaches showed a conclusive signal of positive selection. Population genetic analysis indicates that 614G increases in frequency relative to 614D in a manner consistent with a selective advantage. We do not find any indication that patients infected with the spike 614G variant have higher COVID-19 mortality or clinical severity, but 614G is associated with higher viral load and younger age of patients. Significant differences in growth and size of 614G phylogenetic clusters indicate a need for continued study of this variant

Gamificación en Iberoamérica. Experiencias desde la comunicación y la educación

La presente obra capitular es el resultado de las investigaciones sobre las aplicaciones de la gamificación en contextos múltiples, emergentes provenientes de las comunicaciones presentadas en el Simposio 06 del III Congreso Internacional Comunicación y Pensamiento (Sevilla, España), así como de aquellas presentadas por los miembros del Gamelab UPS, del Proyecto I+D+i Coordinado “Competencias mediáticas de la ciudadanía en medios digitales emergentes (smartphones y tablets): Prácticas innovadoras y estrategias educomunicativas en contextos múltiples” (EDU2015-64015-C3-1-R) (MINECO/FEDER), de la “Red de Educación Mediática” del Programa Estatal de Investigación Científica-Técnica de Excelencia, Subprograma Estatal de Generación de Conocimiento (EDU2016-81772-REDT), financiados por el Fondo Europeo de Desarrollo Regional (FEDER) y Ministerio de Economía y Competitividad de España. En este sentido se busca construir, desde una mirada dual desde Europa y América Latina el primer libro iberoamericano de gamificación, avalado por el Gamelab de la Universidad Politécnica Salesiana (Ecuador), el Proyecto I+D+i EDU2015-64015-C3-1-R, la Red Interuniversitaria Euroamericana de Investigación sobre Competencias Mediáticas para la Ciudadanía (Alfamed), el Laboratorio de Estudios en Comunicación (Ladecom) y el Grupo de Investigación Ágora (PAI-HUM-648) de la Universidad de Huelva (España) y el Grupo de Investigación Estructura, Historia y Contenidos de la Comunicación GREHCCO