Increased α1-3 fucosylation of α-1-acid glycoprotein (AGP) in pancreatic cancer

Pancreatic cancer (PDAC) lacks reliable diagnostic biomarkers and the search for new biomarkers represents an important challenge. Previous results looking at a small cohort of patients showed an increase in α-1-acid glycoprotein (AGP) fucosylation in advanced PDAC using N-glycan sequencing. Here, we have analysed AGP glycoforms in a larger cohort using several analytical techniques including mass spectrometry (MS), capillary zone electrophoresis (CZE) and enzyme-linked lectin assays (ELLAs) for determining AGP glycoforms which could be PDAC associated. AGP from 31 serum samples, including healthy controls (HC), chronic pancreatitis (ChrP) and PDAC patients, was purified by immunoaffinity chromatography. Stable isotope labelling of AGP released N-glycans and their analysis by zwitterionic hydrophilic interaction capillary liquid chromatography electrospray MS (μZIC-HILIC-ESI-MS) showed an increase in AGP fucosylated glycoforms in PDAC compared to ChrP and HC. By CZE-UV analysis, relative concentrations of some of the AGP isoforms were found significantly different compared to those in PDAC and HC. Finally, ELLAs using Aleuria aurantia lectin displayed a significant increase in AGP fucosylation, before and after AGP neuraminidase treatment, in advanced PDAC compared to ChrP and HC, respectively. Altogether, these results indicate that α1-3 fucosylated glycoforms of AGP are increased in PDAC and could be potentially regarded as a PDAC biomarker.M.B. acknowledges the University of Girona for a pre-doctoral fel lowship. This work was supported by the Government of Catalonia (grant 2014 SGR 229), the Spanish Ministry of Science and Innovation (grant BIO 2010-16922, awarded to R. P) and the Spanish Ministry of Economy and Competitiveness (grant CTQ2013-43236, awarded to M.F. and grant CTQ2011-27130, awarded to V. S-N)

Flipped Classroon en prácticas de ciencias de la salud

[ES] La introducción de nuevas metodologías pedagógicas en el ámbito de ciencias de la salud es una herramienta necesaria para los alumnos en formación. Flipped Classroom o aula invertida (FC) es una herramienta que proporciona una mayor autonomía para el alumno, así como una mayor asimilación de conocimientos. El objetivo principal del estudio fue la adquisición de competencias básicas de aplicación de conocimientos, comunicación e interpretación de datos relevantes para emitir juicios en estudiantes de ciencias de la salud. Los participantes en el estudio fueron n=1103 estudiantes de odontología, farmacia y enfermería, los cuales se dividieron en 2 grupos de estudio; Grupo A, aplicación de metodologías de clases magistrales (M) y Grupo B aplicación aula invertida “Flipped Classroom” (FC). Al final de las prácticas se realizó un cuestionario para la evaluación de la adquisición de conocimientos y el grado de satisfacción. Los resultados obtenidos demostraro un aumento significativo en el máximo número de preguntas correctamente contestadas (FC) y un mayor grado de satisfacción de los alumnos que realizaron las prácticas mediante FC. Como conclusión podríamos indicar que la aplicación de FC en ciencias de la salud presenta mejores resultados en la adquisición de conocimientos que las metodologías didácticas magistrales.[EN] New pedagogical methodologies in the health sciences area could be necessary for trainees. Flipped Classroom or inverted classroom (FC) is a tool that offers greater autonomy for the student, as well as better knowledge assimilation. The main objective of this study was the achievement of basic skills for the application of knowledge, communication, and interpretation of relevant data to make judgments for health sciences students. The number of students participating in the study was 1103 (n=1103), all of them from different degrees such as dentistry, pharmacy, and nursing. Students were distributed in 2 study groups: Group A, application of masterclass methodologies (M), and Group B, Flipped Classroom (FC) or inverted classroom method. At the end of the practical sessions, a test was used to evaluate the students' knowledge acquisition and their degree of satisfaction with the teaching methodology. The obtained results showed a significant increase in the maximum number of correctly-answered questions and a greater degree of satisfaction from those students who attended the practical lessons taught using the FC method. As a conclusion, the application of the FC method in health sciences leads to better results in the acquisition of the course competencies than the masterclass methodologies.Torres-Cuevas, I.; García Miralles, E.; Ribelles Llop, M.; Marqués Martínez, L. (2021). Flipped Classroon en prácticas de ciencias de la salud. En IN-RED 2020: VI Congreso de Innovación Educativa y Docencia en Red. Editorial Universitat Politècnica de València. 184-192. https://doi.org/10.4995/INRED2020.2020.11982OCS18419

Multidimensional research on university engagement using a mixed method approach

El compromiso o la implicación académica (engagement en inglés) delos estudiantes universitarios se ha convertido en un elemento fundamental desu bienestar y de su rendimiento académico y, además, está muy relacionadotambién con su futuro profesional y compromiso social. Es por esta razón quela definición de dicho concepto y la disposición de instrumentos de evaluacióny estrategias de análisis son imprescindibles para conocer las experiencias deaprendizaje que conducen a mejorar la implicación académica del estudiante.Para el desarrollo de esta investigación hemos utilizado una metodología mixtacuantitativa y cualitativa: análisis factorial exploratorio y confirmatorio, porun lado, y grupos de discusión mediante la técnica de los grupos nominales,por otro. Los objetivos que nos hemos planteado son tres: primero, ahondaren el modelo multidimensional del constructo engagement; segundo, validar uncuestionario que permita evaluar la percepción que tienen los estudiantes delas metodologías de aprendizaje que se utilizan en el aula, y tercero, comprobarla manejabilidad de los grupos nominales como método cualitativo de análisis.Los resultados demuestran que nuestra nueva propuesta ofrece un instrumentoestadísticamente válido para determinar las percepciones del propio engagementy un método cualitativo de utilización eficaz, eficiente y motivador para losestudiantes. Sin embargo, respecto a la multidimensionalidad del constructo, ycontrariamente al punto de vista teórico más aceptado que considera la existencia de tres dimensiones del engagement (comportamiento, cognición y emoción), nuestros resultados solamente revelan dos dimensiones (cognitivo-emocional y comportamental). En la discusión y comentarios damos posibles explicaciones a dicha contradicción.The commitment or academic implication (engagement) of universitystudents has become a fundamental element for their welfare and academicperformance and, furthermore, it is also related to their professional futureand social commitment. For this reason, the definition of the concept and theprovision of assessment strategies and tools are essential to know the learningexperiences that lead to enhancing the academic involvement of the students.To develop our research, we have used a mixed quantitative and qualitativemethodology: exploratory and confirmatory factor analysis on the one hand,and discussion groups using the nominal groups technique on the other hand.We have set three different objectives: first, to delve into the multidimensionalmodel of the construct; second, to validate a questionnaire that allows forevaluation of the students’ perception of the learning methodologies used inthe classroom; and third, to check the manageability of the nominal groupsas a qualitative method of analysis. The results demonstrate that our newproposal provides a statistically valid instrument aimed at determining theperceptions of own engagement and an effective, efficient and motivatingqualitative method for students. However, regarding the multidimensionalityof the construct, contrary to the more accepted theoretical point of view thatconsiders three dimensions of engagement (behaviour, cognition and emotion),our results only reveal two dimensions (cognitive-emotional and behavioural).In the discussion and comments section we give possible explanations for thiscontradiction

Targeting hypersialylation in pancreatic ductal adenocarcinoma to reverts their malignant phenotype

Trabajo presentado en el 15th Jenner Glycobiology and Medicine Symposium, celebrado en Oporto (Portugal), del 14 al 16 de junio de 202

Exposure to Trihalomethanes through Different Water Uses and Birth Weight, Small for Gestational Age, and Preterm Delivery in Spain

Background: Evidence associating exposure to water disinfection by-products with reduced birth weight and altered duration of gestation remains inconclusive

Urease-powered nanobots for radionuclide bladder cancer therapy

Bladder cancer treatment via intravesical drug administration achieves reasonable survival rates but suffers from low therapeutic efficacy. To address the latter, self-propelled nanoparticles or nanobots have been proposed, taking advantage of their enhanced diffusion and mixing capabilities in urine when compared with conventional drugs or passive nanoparticles. However, the translational capabilities of nanobots in treating bladder cancer are underexplored. Here, we tested radiolabelled mesoporous silica-based urease-powered nanobots in an orthotopic mouse model of bladder cancer. In vivo and ex vivo results demonstrated enhanced nanobot accumulation at the tumour site, with an eightfold increase revealed by positron emission tomography in vivo. Label-free optical contrast based on polarization-dependent scattered light-sheet microscopy of cleared bladders confirmed tumour penetration by nanobots ex vivo. Treating tumour-bearing mice with intravesically administered radio-iodinated nanobots for radionuclide therapy resulted in a tumour size reduction of about 90%, positioning nanobots as efficient delivery nanosystems for bladder cancer therapy.</p

Hypoxia Alters Epigenetic and N-Glycosylation Profiles of Ovarian and Breast Cancer Cell Lines in-vitro

Background: Glycosylation is one of the most fundamental post-translational modifications. Importantly, glycosylation is altered in many cancers. These alterations have been proven to impact on tumor progression and to promote tumor cell survival. From the literature, it is known that there is a clear link between chemoresistance and hypoxia, hypoxia and epigenetics and more recently glycosylation and epigenetics. Methods and Results: Our objective was to investigate these differential parameters, in an in vitro model of ovarian and breast cancer. Ovarian (A2780, A2780cis, PEO1, PEO4) and triple negative breast cancer (TNBC) (MDA-MB-231 and MDA-MB-436) cells were exposed to differential hypoxic conditions (0.5–2% O2) and compared to normoxia (21% O2). Results demonstrated that in hypoxic conditions some significant changes in glycosylation on the secreted N-glycans from the ovarian and breast cancer cell lines were observed. These included, alterations in oligomannosylated, bisected glycans, glycans with polylactosamine extensions, in branching, galactosylation and sialylation in all cell lines except for PEO1. In general, hypoxia exposed ovarian and TNBC cells also displayed increased epithelial to mesenchymal transition (EMT) and migration, with a greater effect seen in the 0.5% hypoxia exposed samples compared to 1 and 2% hypoxia (p ≤ 0.05). SiRNA transient knock down of GATA2/3 transcription factors resulted in a decrease in the expression of glycosyltransferases ST3GAL4 and MGAT5, which are responsible for sialylation and branching, respectively. Conclusions: These glycan changes are known to be integral to cancer cell survival and metastases, suggesting a possible mechanism of action, linking GATA2 and 3, and invasiveness of both ovarian and TNBC cells in vitro

Serotypes and Clonal Composition of Streptococcus pneumoniae Isolates Causing IPD in Children and Adults in Catalonia before 2013 to 2015 and after 2017 to 2019 Systematic Introduction of PCV13

The goal of this study was to investigate the distribution of serotypes and clonal composition of Streptococcus pneumoniae isolates causing invasive pneumococcal disease (IPD) in Catalonia, before and after systematic introduction of PCV13. Pneumococcal strains isolated from normally sterile sites obtained from patients of all ages with IPD received between 2013 and 2019 from 25 health centers of Catalonia were included. Two study periods were defined: presystematic vaccination period (2013 and 2015) and systematic vaccination period (SVP) (2017 to 2019). A total of 2,303 isolates were analyzed. In the SVP, there was a significant decrease in the incidence of IPD cases in children 5 to 17 years old (relative risk [RR] 0.61; 95% confidence interval [CI] 0.38 to 0.99), while there was a significant increase in the incidence of IPD cases in 18- to 64-year-old adults (RR 1.33; 95% CI 1.16 to 1.52) and adults over 65 years old (RR 1.23; 95% CI 1.09 to 1.38). Serotype 8 was the major emerging serotype in all age groups except in 5- to 17-year-old children. In children younger than 5 years old, the main serotypes in SVP were 24F, 15A, and 3, while in adults older than 65 years they were serotypes 3, 8, and 12F. A significant decrease in the proportions of clonal complexes CC156, CC191, and ST306 and an increase in those of CC180, CC53, and CC404 were observed. A steady decrease in the incidence of IPD caused by PCV13 serotypes indicates the importance and impact of systematic vaccination. The increase of non-PCV13 serotypes highlights the need to expand serotype coverage in future vaccines and rethink vaccination programs for older adults. IMPORTANCE We found that with the incorporation of the PCV13 vaccine, the numbers of IPD cases caused by serotypes included in this vaccine decreased in all of the age groups. Still, there was an unforeseen increase of the serotypes not included in this vaccine causing IPD, especially in the >65-year-old group. Moreover, a significant increase of serotype 3 included in the vaccine has been observed; this event has been reported by other researchers. These facts call for the incorporation of more serotypes in future vaccines and a more thorough surveillance of the dynamics of this microorganism

Safety and preliminary efficacy on cognitive performance and adaptive functionality of epigallocatechin gallate (EGCG) in children with Down syndrome. A randomized phase Ib clinical trial (PERSEUS study)

Purpose: Although some caregivers are using epigallocatechin gallate (EGCG) off label in hopes of improving cognition in young adults with Down syndrome (DS), nothing is known about its safety, tolerability, and efficacy in the DS pediatric population. We aimed to evaluate safety and tolerability of a dietary supplement containing EGCG and if EGCG improves cognitive and functional performance. Methods: A total of 73 children with DS (aged 6-12 years) were randomized. Participants received 0.5% EGCG (10 mg/kg daily dose) or placebo for 6 months with 3 months follow up after treatment discontinuation. Results: In total, 72 children were treated and 66 completed the study. A total of 38 participants were included in the EGCG group and 35 in the placebo group. Of 72 treated participants, 62 (86%) had 229 treatment-emergent adverse events (AEs). Of 37 participants in the EGCG group, 13 (35%) had 18 drug-related treatment-emergent AEs and 12 of 35 (34%) from the placebo group had 22 events. In the EGCG group, neither severe AEs nor increase in the incidence of AEs related to safety biomarkers were observed. Cognition and functionality were not improved compared with placebo. Secondary efficacy outcomes in girls point to a need for future work. Conclusion: The use of EGCG is safe and well-tolerated in children with DS, but efficacy results do not support its use in this population. (C) 2022 The Authors. Published by Elsevier Inc. on behalf of American College of Medical Genetics and Genomics

The LifeCycle Project-EU Child Cohort Network : a federated analysis infrastructure and harmonized data of more than 250,000 children and parents

Early life is an important window of opportunity to improve health across the full lifecycle. An accumulating body of evidence suggests that exposure to adverse stressors during early life leads to developmental adaptations, which subsequently affect disease risk in later life. Also, geographical, socio-economic, and ethnic differences are related to health inequalities from early life onwards. To address these important public health challenges, many European pregnancy and childhood cohorts have been established over the last 30 years. The enormous wealth of data of these cohorts has led to important new biological insights and important impact for health from early life onwards. The impact of these cohorts and their data could be further increased by combining data from different cohorts. Combining data will lead to the possibility of identifying smaller effect estimates, and the opportunity to better identify risk groups and risk factors leading to disease across the lifecycle across countries. Also, it enables research on better causal understanding and modelling of life course health trajectories. The EU Child Cohort Network, established by the Horizon2020-funded LifeCycle Project, brings together nineteen pregnancy and childhood cohorts, together including more than 250,000 children and their parents. A large set of variables has been harmonised and standardized across these cohorts. The harmonized data are kept within each institution and can be accessed by external researchers through a shared federated data analysis platform using the R-based platform DataSHIELD, which takes relevant national and international data regulations into account. The EU Child Cohort Network has an open character. All protocols for data harmonization and setting up the data analysis platform are available online. The EU Child Cohort Network creates great opportunities for researchers to use data from different cohorts, during and beyond the LifeCycle Project duration. It also provides a novel model for collaborative research in large research infrastructures with individual-level data. The LifeCycle Project will translate results from research using the EU Child Cohort Network into recommendations for targeted prevention strategies to improve health trajectories for current and future generations by optimizing their earliest phases of life.Peer reviewe