In vivo tracking and immunological properties of pulsed porcine monocyte-derived dendritic cells

Cellular therapies using immune cells and in particular dendritic cells (DCs) are being increasingly applied in clinical trials and vaccines. Their success partially depends on accurate delivery of cells to target organs or migration to lymph nodes. Delivery and subsequent migration of cells to regional lymph nodes is essential for effective stimulation of the immune system. Thus, the design of an optimal DC therapy would be improved by optimizing technologies for monitoring DC trafficking. Magnetic resonance imaging (MRI) represents a powerful tool for non-invasive imaging of DC migration in vivo. Domestic pigs share similarities with humans and represent an excellent animal model for immunological studies. The aim of this study was to investigate the possibility using pigs as models for DC tracking in vivo. Porcine monocyte derived DC (MoDC) culture with superparamagnetic iron oxide (SPIO) particles was standardized on the basis of SPIO concentration and culture viability. Phenotype, cytokine production and mixed lymphocyte reaction assay confirmed that porcine SPIO-MoDC culture were similar to mock MoDCs and fully functional in vivo. Alike, similar patterns were obtained in human MoDCs. After subcutaneous inoculation in pigs, porcine SPIO-MoDC migration to regional lymph nodes was detected by MRI and confirmed by Perls staining of draining lymph nodes. Moreover, after one dose of virus-like particles-pulsed MoDCs specific local and systemic responses were confirmed using ELISPOT IFN-γ in pigs. In summary, the results in this work showed that after one single subcutaneous dose of pulsed MoDCs, pigs were able to elicit specific local and systemic immune responses. Additionally, the dynamic imaging of MRI-based DC tracking was shown using SPIO particles. This proof-of-principle study shows the potential of using pigs as a suitable animal model to test DC trafficking with the aim of improving cellular therapies.We want to thank: Ferrán López, Rosa López, Zoraida Cervera, Pamela Martinez-Orellana, Tufaria Mussá, Massimiliano Baratelli, Diego Pérez, Sergio López from CRESA and José Luis Ruiz de la Torre and Javier Aceña (UAB) for farm and technical support; Jaume Martorell (Fundació Hospital Clínic Veterinari, UAB) for MRI support; Javier Domínguez (INIA) for the porcine antibodies; Antonio Lestuzzi, Michele Crisci and Raif Yucel for MR imaging support; Joaquim Segalés for anatomic pathology analysis; Mónica Pérez for immunohistochemical stainings; Aida Neira and Blanca Pérez for Perls staining; Eva Huerta y Marina Sibila for PCV2 PCR; David Andreu and Beatriz García de la Torre (Pompeu Fabra University, Barcelona), and Esther Blanco (CISA-INIA, Madrid), for the FMDV 3A peptide; Alicia Solórzano for critically reviewing the manuscript. This work was funded by the project AGL2010-22200-C02 of Spanish Ministry of Science and Innovation. PhD studies of Raquel Cabezón are funded by a doctoral FI fellowship from the Generalitat de Catalunya

Molecular Characterization of Imported and Autochthonous Dengue in Northeastern Spain

Autochthonous transmission; Dengue; Molecular epidemiologyTransmissió autòctona; Dengue; Epidemiologia molecularTransmisión autóctona; Dengue; Epidemiología molecularDengue is the most significant arbovirus worldwide and a public health threat to non-endemic areas in which Aedes vectors are present. Autochthonous dengue transmission has been reported in several European countries in the last decade. Infected travelers from endemic regions arriving to areas colonized by Aedes albopictus in Europe need to be monitored in surveillance and control programs. We aimed to perform molecular characterization of RT-PCR-positive dengue cases detected in Catalonia, northeastern Spain, from 2013 to 2018. The basic demographic information and the geographical regions of importation were also analyzed. One-hundred four dengue cases were studied (103 imported infections and the first autochthonous case in our region). The dengue virus strains detected were serotyped and genotyped using molecular methods, and phylogenetic analyses were conducted. All four dengue serotypes were detected in travelers, including up to 10 different genotypes, reflecting the global circulation of dengue in endemic areas. The primary travel-related case of the 2018 autochthonous transmission was not identified, but the molecular analysis revealed dengue serotype 1, genotype I of Asian origin. Our results highlight the diversity of imported dengue virus strains and the role of molecular epidemiology in supporting arbovirus surveillance programs

Correlation between Clinical and Immunological Variables and Humoral Response to SARS-CoV-2 Vaccination in Adult Patients with Antibody Deficiency Disorders

Altres ajuts: Generalitat de Catalunya's Department de salut (SLD015); Consorcio Centro de Investigación Biomédica en Red (CB-2021)Background. Prophylactic vaccination has proven to be the most effective strategy to fight the COVID-19 pandemic. Methods. This was a prospective observational cohort study involving 30 predominantly antibody deficiency disorders (ADD)-afflicted adult patients on immunoglobulin replacement therapy vaccinated with three doses of the mRNA-1273 COVID-19 vaccine, and 10 healthy controls. Anti-RBD IgG antibodies were determined in plasma samples collected just before the first dose of mRNA-based COVID-19 vaccine and on weeks 4, 8, 24, and 28 following the first vaccination. Patients were categorized based on the levels of anti-RBD antibodies determined on w8 as non-, low-, and responders. Chi-square and Kruskal-Wallis tests were used to see if any variables correlated with humoral response levels. Any adverse effects of the mRNA-based vaccine were also noted. Results. The COVID-19 vaccine was safe and well-tolerated. The humoral response elicited at w8 after vaccination depended on the type of ADD, the type of immunoglobulin deficiency, the presence of granulomatous lymphocytic interstitial lung disease, recent use of immunosuppressive drugs, and the switched memory B cells counts. The third vaccine dose boosted humoral response in previous responders to second dose but seldom in non-responders. Conclusions: The humoral response of patients with predominant ADD depends mostly on the type of immunodeficiency and on the frequency of B and T cell populations

Análisis bibliométrico de Economía Azul / Bibliometric Analysis of Blue Economy

Poster del congreso VI ENCUENTRO INTERNACIONAL DE ESPECIALIZACIÓN PARA LA INVESTIGACIÓN EN ECONOMÍA Y EMPRESAThis is the first attempt at bibliometric analysis with SciMAT software from indexed article in the database Web of Science. It was conducted with general terms, only using the first original term Blue Economy. SciMat is a mapping analysis tool created to carry out mapping analysis in a longitudinal environment. Among other results, it is shown: Blue Economy is a new topic -first published as articles in 2002-. From each of the periods studied. (1) 2002-2017: the most important topics are two: 'Blue economy' and 'Economics'. (2) Secondly, between 2018-2019, the most representative words are: 'Carbon‑Economies', 'Fishing', and 'Oceans'. (3) Finally, in the last two years, 2020-2021 the most relevant cluster is the 'Blue Economy' itself. As limitations, ‘Blue-green economy' and 'Blue economy' maybe could be merged into one category or cluster, depending on whether considering or not the same definition.Universidad de Málaga. Campus de Excelencia Internacional Andalucía Tech

Atrofia muscular espinhal tipo 1C: relato de caso clínico

A atrofia muscular espinhal tipo 1c (AME) é uma doença genética recessiva neurodegenerativa e grave. A clínica é heterogênea e inclui fraqueza muscular progressiva, arreflexia e hipotonia. O diagnóstico confirmatório é molecular e a constatação precoce é determinante no prognóstico

CONSTRUCCION DEL PERFIL DEL EGRESADO DEL CICLO CLINICO

Esta investigación fue realizada, como parte integrante del Proyecto de Innovación Curricular, con la necesidad de la construcción de un perfil de egresado, en el ciclo o asignaturas clínicas, para posteriormente, realizar el perfil del Egresado de la Facultad de Ciencias Médicas de la Universidad Nacional de Asunción (FCM-UNA).La misma, la fuimos construyendo a partir de artículos, documentos y actores relevantes tanto dentro y como fuera de la Institución, que permitió así contribuir en la construcción de una propuesta que optimice la formación universitaria de los estudiantes de la carrera de medicina.Como docentes de la universidad hemos constatado una serie de problemas que se relacionan tanto con el aislamiento de las disciplinas que se manejan en forma totalmente independientes dificultando un aprendizaje integrado de los estudiantes, como su poca formación en gestión, en investigación y la necesidad un estudio exhaustivo y de mejor relacionamiento interhumano con los pacientes y con los propios colegas. Seria apropiada para intencionar los procesos de enseñanza y aprendizaje y el perfil de un médico acorde a las necesidades político- social, cultural y de desarrollo económico.Nuestro objetivo fue analizar e interpretar documentos y percepción de los actores relevantes en cuanto a la formación de médico, que permita aportar datos para levantar una propuesta de perfil del ciclo clínico, integrado y pertinente a través de un diseño cualitativo con un énfasis comprensivo.Para el levantamiento de información se recurrió a la revisión de artículos, donde buscamos el perfil de otras Universidades de medicinas referentes, tantos de MERCOSUR, como Internacionales. Se realizaron focus group en docentes, pacientes y egresado de la FCM-UNA, también se utilizó entrevistas a empleadores del sector privado, público y seguro social.Posteriormente, se realizó el proceso de análisis de contenidos con interés interpretativo.En cuanto al resultado obtenido podemos decir que el egresado clínico debe reunir cierta competencia clínicas, además de buenos relacionamientos con los pacientes, parientes y sus propios colegas y el personal de apoyo. Cabe además señalar algunos actores coinciden en interacción comunicativas y además en incorporar tecnología de avanzadas, actualización permanente en los saberes disciplinares y en la investigación, una formación contextualizada social y que atienda las necesidades de salud de la población. Una demanda expresada convergentemente es la consideración de la gestión como parte del desempeño del médico, asimismo, en la dimensión de la responsabilidad social, pacientes, egresados y empleadores; relevan la necesidad de formar médicos con sentido humanista, comprometidos con el proyecto de justicia social y que sean éticos, advierten del peligro de la mercantilización del acto médico como regulador de la relación médico-paciente, entre otros. Un importante hallazgo de la investigación, fue la aparición de dos dimensiones demandadas en la formación del médico como es la enseñanza/docenci

Vejez y vulnerabilidad. Retratos de casos y perfiles de estudio en contextos diversos: grandes regiones, localidades rurales y territorios migrantes

México está inmerso en una acelerada transición demográfica, es el séptimo lugar entre los países con envejecimiento acelerado en Latinoamérica, con 9.7% de adultos mayores de 60 años (CONAPO, 2013). La investigación en nuestro país en torno a los sectores envejecidos tiene ya más de un cuarto de siglo, y ha contribuido al desarrollo de los estudios sobre este grupo de la población bajo las tendencias no sólo locales y regionales, sino también internacionales; respondiendo a las necesidades sociales que se modifican a través de la historia.Desde el área de especialización de cada autor, se pone particular atención en las condiciones de la vida cotidiana y las estrategias que se generan para enfrentar y reducir la vulnerabilidad, así como en los retos que se afrontarán por e l tendiente proceso de envejecimiento de la población, principalmente en los ámbitos socioculturales y de salud.Universidad Autónoma del Estado de Méxic

Evaluation of the relationship between effervescent paracetamol and blood pressure: clinical trial

Background: Paracetamol's solubility is achieved by adding to the excipient sodium salts, either as bicarbonate, carbonate or citrate. As the relationship between salt and hypertension is well known, due to the sodium content it has raised a hypothesis that may interfere with the control of that risk factor. Therefore, the objective of this study is to evaluate the effect on blood pressure of effervescent paracetamol compared to non-effervescent, in hypertensive patients. Methods/Design: This is the protocol of a phase IV multicenter clinical trial, randomized, controlled, crossover, open, which will compare the effect of two different formulations of paracetamol (effervescent or non-effervescent) in the blood pressure of hypertensive patients, with a seven weeks follow up. 49 controlled hypertensive patients will be included (clinical BP lower than 150 and 95 mmHg, and lower than 135 mmHg and 85 mmHg in patients with diabetes or a history of cardiovascular event, and daytime ambulatory measurements lower than 140 and 90 mmHg) and mild to moderate pain (Visual Analog Scale between 1 and 4). The study was approved by the ethics committee of the Fundació Jordi Gol i Gurina and following standards of good clinical practice. The primary endpoint will be the variations in systolic BP in 24 h Ambulatory Blood Pressure Monitoring, considering significant differences 2 or more mmHg among those treated with non-effervescent and effervescent formulations. Intention-to-treat and per-protocol analysis will be held. Discussion: Despite the broad recommendation not to use effervescent drugs in patients with hypertension, there are relatively little studies that show exac tly this pressor effect due to sodium in salt that gives the effervescence of the product. This is the first clinical trial designed to study the effect of effervescence compared to the non-effervescent, in well-controlled hypertensive patients with mild to moderate pain, performed in routine clinical practic

The FANCM:p.Arg658* truncating variant is associated with risk of triple-negative breast cancer.

Breast cancer is a common disease partially caused by genetic risk factors. Germline pathogenic variants in DNA repair genes BRCA1, BRCA2, PALB2, ATM, and CHEK2 are associated with breast cancer risk. FANCM, which encodes for a DNA translocase, has been proposed as a breast cancer predisposition gene, with greater effects for the ER-negative and triple-negative breast cancer (TNBC) subtypes. We tested the three recurrent protein-truncating variants FANCM:p.Arg658*, p.Gln1701*, and p.Arg1931* for association with breast cancer risk in 67,112 cases, 53,766 controls, and 26,662 carriers of pathogenic variants of BRCA1 or BRCA2. These three variants were also studied functionally by measuring survival and chromosome fragility in FANCM -/- patient-derived immortalized fibroblasts treated with diepoxybutane or olaparib. We observed that FANCM:p.Arg658* was associated with increased risk of ER-negative disease and TNBC (OR = 2.44, P = 0.034 and OR = 3.79; P = 0.009, respectively). In a country-restricted analysis, we confirmed the associations detected for FANCM:p.Arg658* and found that also FANCM:p.Arg1931* was associated with ER-negative breast cancer risk (OR = 1.96; P = 0.006). The functional results indicated that all three variants were deleterious affecting cell survival and chromosome stability with FANCM:p.Arg658* causing more severe phenotypes. In conclusion, we confirmed that the two rare FANCM deleterious variants p.Arg658* and p.Arg1931* are risk factors for ER-negative and TNBC subtypes. Overall our data suggest that the effect of truncating variants on breast cancer risk may depend on their position in the gene. Cell sensitivity to olaparib exposure, identifies a possible therapeutic option to treat FANCM-associated tumors