Podoplanin expression in the development and progression of laryngeal squamous cell carcinomas

<p>Abstract</p> <p>Background</p> <p>Podoplanin expression is attracting interest as a marker for cancer diagnosis and prognosis. We therefore investigated the expression pattern and clinical significance of podoplanin during the development and progression of laryngeal carcinomas.</p> <p>Results</p> <p>Podoplanin expression was determined by immunohistochemistry in paraffin-embedded tissue specimens from 84 patients with laryngeal premalignancies and 53 patients with laryngeal squamous cell carcinomas. We found podoplanin expression extending from the basal to the suprabasal layer of the epithelium in 37 (44%) of 84 dysplastic lesions, whereas normal epithelium showed negligible expression. Patients carrying podoplanin-positive lesions had a higher laryngeal cancer incidence than those with negative expression reaching borderline statistical significance (51% <it>versus </it>30%, <it>P </it>= 0.071). Podoplanin expression in laryngeal carcinomas exhibited two distinct patterns. 20 (38%) cases showed diffuse expression in most tumour cells and 33 (62%) focal expression at the proliferating periphery of tumour nests. High podoplanin expression was inversely correlated with T classification (<it>P </it>= 0.033), disease stage (<it>P </it>= 0.006), and pathological grade (<it>P </it>= 0.04). There was a trend, although not significant, towards reduced disease-specific survival for patients with low podoplanin levels (<it>P </it>= 0.31) and diffuse expression pattern (<it>P </it>= 0.08).</p> <p>Conclusions</p> <p>Podoplanin expression increases in the early stages of laryngeal tumourigenesis and it seems to be associated with a higher laryngeal cancer risk. Podoplanin expression in laryngeal squamous cell carcinomas, however, diminishes during tumour progression. Taken together, these data support a role for podoplanin expression in the initiation but not in the progression of laryngeal cancers.</p

Novel genes and sex differences in COVID-19 severity

[EN] Here, we describe the results of a genome-wide study conducted in 11 939 coronavirus disease 2019 (COVID-19) positive cases with an extensive clinical information that were recruited from 34 hospitals across Spain (SCOURGE consortium). In sex-disaggregated genome-wide association studies for COVID-19 hospitalization, genome-wide significance (P < 5 × 10−8) was crossed for variants in 3p21.31 and 21q22.11 loci only among males (P = 1.3 × 10−22 and P = 8.1 × 10−12, respectively), and for variants in 9q21.32 near TLE1 only among females (P = 4.4 × 10−8). In a second phase, results were combined with an independent Spanish cohort (1598 COVID-19 cases and 1068 population controls), revealing in the overall analysis two novel risk loci in 9p13.3 and 19q13.12, with fine-mapping prioritized variants functionally associated with AQP3 (P = 2.7 × 10−8) and ARHGAP33 (P = 1.3 × 10−8), respectively. The meta-analysis of both phases with four European studies stratified by sex from the Host Genetics Initiative (HGI) confirmed the association of the 3p21.31 and 21q22.11 loci predominantly in males and replicated a recently reported variant in 11p13 (ELF5, P = 4.1 × 10−8). Six of the COVID-19 HGI discovered loci were replicated and an HGI-based genetic risk score predicted the severity strata in SCOURGE. We also found more SNP-heritability and larger heritability differences by age (<60 or ≥60 years) among males than among females. Parallel genome-wide screening of inbreeding depression in SCOURGE also showed an effect of homozygosity in COVID-19 hospitalization and severity and this effect was stronger among older males. In summary, new candidate genes for COVID-19 severity and evidence supporting genetic disparities among sexes are provided.S

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

Hyperoxemia and excess oxygen use in early acute respiratory distress syndrome : Insights from the LUNG SAFE study

Publisher Copyright: © 2020 The Author(s). Copyright: Copyright 2020 Elsevier B.V., All rights reserved.Background: Concerns exist regarding the prevalence and impact of unnecessary oxygen use in patients with acute respiratory distress syndrome (ARDS). We examined this issue in patients with ARDS enrolled in the Large observational study to UNderstand the Global impact of Severe Acute respiratory FailurE (LUNG SAFE) study. Methods: In this secondary analysis of the LUNG SAFE study, we wished to determine the prevalence and the outcomes associated with hyperoxemia on day 1, sustained hyperoxemia, and excessive oxygen use in patients with early ARDS. Patients who fulfilled criteria of ARDS on day 1 and day 2 of acute hypoxemic respiratory failure were categorized based on the presence of hyperoxemia (PaO2 > 100 mmHg) on day 1, sustained (i.e., present on day 1 and day 2) hyperoxemia, or excessive oxygen use (FIO2 ≥ 0.60 during hyperoxemia). Results: Of 2005 patients that met the inclusion criteria, 131 (6.5%) were hypoxemic (PaO2 < 55 mmHg), 607 (30%) had hyperoxemia on day 1, and 250 (12%) had sustained hyperoxemia. Excess FIO2 use occurred in 400 (66%) out of 607 patients with hyperoxemia. Excess FIO2 use decreased from day 1 to day 2 of ARDS, with most hyperoxemic patients on day 2 receiving relatively low FIO2. Multivariate analyses found no independent relationship between day 1 hyperoxemia, sustained hyperoxemia, or excess FIO2 use and adverse clinical outcomes. Mortality was 42% in patients with excess FIO2 use, compared to 39% in a propensity-matched sample of normoxemic (PaO2 55-100 mmHg) patients (P = 0.47). Conclusions: Hyperoxemia and excess oxygen use are both prevalent in early ARDS but are most often non-sustained. No relationship was found between hyperoxemia or excessive oxygen use and patient outcome in this cohort. Trial registration: LUNG-SAFE is registered with ClinicalTrials.gov, NCT02010073publishersversionPeer reviewe

Six species of Diaporthe associated with Phomopsis stem canker of sunflower in southern Pampean region of Argentina

A survey of 67 commercial fields in 19 locations was conducted in the southern Pampean region of Argentina for Phomopsis stem canker of sunflower (Helianthus annuus L.) between 2014 and 2019. A total of 210 plants having typical symptoms of Phomopsis stem canker were randomly sampled, and fungal isolation was performed. Of the 187 isolates of Diaporthe that were recovered, 94% of the isolates showed morphological characteristics similar to D. helianthi, 3% to D. gulyae, 1% to D. caulivora, 1% to D. sojae, 0.5% to D. kongii, and 0.5% to D. longicolla. Following morphological characterization, the identity of the six morpho-species was confirmed by phylogenetic analyses of b-tubulin, translation elongation factor 1-a, and internal transcribed spacer gene regions. Koch’s postulates were completed for the six fungi by inoculating one susceptible sunflower hybrid with one isolate each of the six species of Diaporthe using the stem-wound inoculation method. Seven days postinoculation, significant differences in disease severity were observed between the six isolates (P < 0.0001), with D. helianthi and D. gulyae isolates causing significantly greater disease severity. To our knowledge, this is the first report of D. kongii, D. longicolla, D. caulivora, and D. sojae associated with Phomopsis stem canker of sunflower in Argentina.Fil: Zambelli, Andres Daniel. Universidad Nacional de Mar del Plata. Facultad de Ciencias Agrarias; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mar del Plata; ArgentinaFil: Mancebo, María F.. Advanta Semillas S.A.I.C.; ArgentinaFil: Bazzalo, María E.. Advanta Semillas S.A.I.C.; ArgentinaFil: Reid, Roberto J.. Advanta Semillas S.A.I.C.; ArgentinaFil: Sanchez, María C.. Universidad Nacional de Mar del Plata. Facultad de Ciencias Agrarias; ArgentinaFil: Kontz, Brian J.. South Dakota State University; Estados UnidosFil: Mathew, Febina M.. South Dakota State University; Estados Unido

Rationale and Protocol of the Multimodality Evaluation of Antibody-Mediated Injury in Heart Transplantation (LEONE-HT) Observational Cross-Sectional Study

Introduction: Heart transplant (HT) survival has barely improved in the last decades, which is unsatisfactory for many HT recipients. The development of anti-human leukocyte antigen (anti-HLA) antibodies in HT patients is associated with a cardiac allograft dysfunction. The mechanisms leading to this damage are unclear. The Multimodality Evaluation Of Antibody-Mediated Injury In Heart Transplantation (LEONE-HT) study aimed to thoroughly describe the damage inflicted on the myocardium by anti-HLA antibodies. Methods and analysis: The LEONE-HT study is a cohort study with a cross-sectional approach in which HT patients with positive anti-HLA antibodies are compared with coetaneous HT patients with negative anti-HLA antibodies. All patients will undergo a state-of-the-art multimodal assessment, including imaging techniques, coronary anatomy and physiology evaluations and histological and immunological analyses. The individual and combined primary outcomes of structural graft injuries and longitudinal secondary outcomes are to be compared between the exposed and non-exposed groups with univariate and multivariable descriptive analyses. Ethics and dissemination: The LEONE-HT study is carried out in accordance with the principles set out in the Declaration of Helsinki and the International Conference on Harmonization guidelines for good clinical practice and following national laws and regulations. The study design, objectives and participant centers have been communicated to clinicaltrials.gov (NCT05184426). The LEONE-HT study counts on the support of patient associations to disseminate the objectives and results of the research. This study was funded by the Spanish Ministry of Science and Innovation and the Spanish Society of Cardiology

¿Cómo presentar con éxito tu trabajo en público?, experiencias en tutorización en las enseñanzas técnicas

Quizás la pregunta con la que empieza el título de esta memoria podría tener infinidad de posibles respuestas, muchas de ellas tendrían en común un buen número de posibles soluciones: mejorar nuestra seguridad, nuestra autoconfianza, aprender de cómo otros pronuncian sus discursos, controlando la ansiedad, no temer a equivocarse, reconociéndolo como algo intrínseco al ser humano etcétera, pero a pesar de todo esto sigue siendo una tarea pendiente de nuestro sistema educativo, ya que miles de estudiantes llegan al sistema universitario sin aún desarrollar ciertas habilidades que le permitan afrontar estos miedos. Con esta memoria nos proponemos presentar nuestras experiencias en el desarrollo del Plan de Acción Tutorial (PAT) en la EPS destacando su evolución a lo largo del curso y los cambios experimentados. En el marco del PAT de la Escuela Politécnica Superior (EPS) y en colaboración del Instituto de Ciencias de la Educación (ICE) hemos animado a la participación de nuestros estudiantes a diversos talleres organizados por el ICE y por la Universidad de Alicante en general con el objetivo de ayudarles a fortalecer su seguridad ante una exposición pública de un trabajo como pudiera ser, por ejemplo, el Trabajo Final de Grado (TFG)