Protective Efficacy of H9N2 Avian Influenza Vaccines Inactivated by Ionizing Radiation Methods Administered by the Parenteral or Mucosal Routes

H9N2 viruses have become, over the last 20 years, one of the most diffused poultry pathogens and have reached a level of endemicity in several countries. Attempts to control the spread and reduce the circulation of H9N2 have relied mainly on vaccination in endemic countries. However, the high level of adaptation to poultry, testified by low minimum infectious doses, replication to high titers, and high transmissibility, has severely hampered the results of vaccination campaigns. Commercially available vaccines have demonstrated high efficacy in protecting against clinical disease, but variable results have also been observed in reducing the level of replication and viral shedding in domestic poultry species. Antigenic drift and increased chances of zoonotic infections are the results of incomplete protection offered by the currently available vaccines, of which the vast majority are based on formalin-inactivated whole virus antigens. In our work, we evaluated experimental vaccines based on an H9N2 virus, inactivated by irradiation treatment, in reducing viral shedding upon different challenge doses and compared their efficacy with formalin-inactivated vaccines. Moreover, we evaluated mucosal delivery of inactivated antigens as an alternative route to subcutaneous and intramuscular vaccination. The results showed complete protection and prevention of replication in subcutaneously vaccinated Specific Pathogen Free White Leghorn chickens at low-to-intermediate challenge doses but a limited reduction of shedding at a high challenge dose. Mucosally vaccinated chickens showed a more variable response to experimental infection at all tested challenge doses and the main effect of vaccination attained the reduction of infected birds in the early phase of infection. Concerning mucosal vaccination, the irradiated vaccine was the only one affording complete protection from infection at the lowest challenge dose. Vaccine formulations based on H9N2 inactivated by irradiation demonstrated a potential for better performances than vaccines based on the formalin-inactivated antigen in terms of reduction of shedding and prevention of infection

Anti-transglutaminase antibody in adults with celiac disease and their relation to the presence and duration of gluten-free diet

Correspondencia: Patricia Elena Langjahr Penayo. Instituto de Investigaciones en Ciencias de la Salud, Universidad Nacional de Asunción. Campus Universitario, Dr. Cecilio Báez c/ Dr. Gaspar Villamayor, San Lorenzo, Paraguay. Código postal 2169. E-mail: [email protected]ón: El anticuerpo IgA anti-transglutaminasa tisular 2 (tTG2) es un marcador relevante de la enfermedad celíaca. La utilidad de la determinación de IgA anti-tTG2 está bien establecida para el diagnóstico de la patología, sin embargo su uso para el seguimiento de pacientes con dieta libre de gluten (DLG) no se encuentra del todo esclarecido. Objetivo: Determinar los niveles de IgA anti-tTG2 en pacientes adultos paraguayos con enfermedad celíaca y su relación con la presencia y duración de la DLG. Materiales y métodos: En este estudio observacional descriptivo con componente analítico, transversal, se incluyeron pacientes celíacos adultos, sin (n=23) o con (n=49) DLG. Se determinaron por ELISA los niveles séricos de IgA anti-tTG2. Resultados: Todos (100%) los pacientes celíacos sin DLG presentaron niveles séricos positivos de IgA anti-tTG2. Se observaron niveles séricos de IgA anti-tTG2 significativamente elevados en pacientes celíacos sin DLG en comparación con los niveles en pacientes con DLG. El 35% de los pacientes en tratamiento con DLG (promedio de duración de la dieta = 5,7 años) presentaron niveles positivos (29%) o indeterminados (6%) de IgA anti-tTG2. En relación con la duración de la DLG se observó que al aumentar el tiempo de DLG disminuyen los niveles del auto-anticuerpo (r=-0,2963; p=0,0387). Conclusiones: Los niveles de IgA anti-tTG2 se correlacionaron inversamente con la duración de la DLG. Sin embargo, niveles positivos del anticuerpo persistieron en algunos pacientes, incluso varios años después del inicio de la DLG.Introduction: IgA anti-transglutaminase 2 (tTG2) antibody is a relevant marker in celiac disease. The utility of IgA anti-tTG2 determination is well established for the diagnosis, however their use in the follow-up of patients with gluten free diet (GFD) it is not fully established. Objective: To determine IgA anti-tTG2 antibody levels in adult Paraguayan celiac disease patients and its relation to the presence and duration of the GFD. Materials and methods: Adult celiac disease patients without (n=23) or with (n=49) GFD were included in this observational, descriptive, cross-sectional study with analytical component. IgA anti-tTG2 antibody serum levels were analyzed by ELISA. Results: All (100%) celiac disease patients without GFD had positive anti-tTG2 IgA. Serum levels of IgA anti-tTG2 were significantly elevated in celiac disease patients without GFD compared to levels in patients with GFD. 35% of patients treated with GFD (diet average duration = 5.7 years) had positive (29%) or indeterminate (6%) levels of IgA anti-tTG2. In terms of GFD duration we observed that while the GFD period increased, antibody levels decreased (r=-0.2963; p=0.0387). Conclusion: IgA anti-tTG2 antibody levels correlated inversely with the GFD duration. However, positive levels of these antibodies persisted in some patients, even several years after the onset of GFD.Consejo Nacional de Ciencía y TecnologíaPrograma Paraguayo para el Desarrollo de la Ciencia y Tecnología. Proyectos de investigación y desarroll

Accurate and timely diagnosis of Eosinophilic Esophagitis improves over time in Europe. An analysis of the EoE CONNECT Registry

BACKGROUND: Poor adherence to clinical practice guidelines for eosinophilic esophagitis (EoE) has been described and the diagnostic delay of the disease continues to be unacceptable in many settings. OBJECTIVE: To analyze the impact of improved knowledge provided by the successive international clinical practice guidelines on reducing diagnostic delay and improving the diagnostic process for European patients with EoE. METHODS: Cross‐sectional analysis of the EoE CONNECT registry based on clinical practice. Time periods defined by the publication dates of four major sets of guidelines over 10 years were considered. Patients were grouped per time period according to date of symptom onset. RESULTS: Data from 1,132 patients was analyzed and median (IQR) diagnostic delay in the whole series was 2.1 (0.7‐6.2) years. This gradually decreased over time with subsequent release of new guidelines (p < 0.001), from 12.7 years up to 2007 to 0.7 years after 2017. The proportion of patients with stricturing of mixed phenotypes at the point of EoE diagnosis also decreased over time (41.3% vs. 16%; p < 0.001), as did EREFS scores. The fibrotic sub‐score decreased from a median (IQR) of 2 (1‐2) to 0 (0‐1) when patients whose symptoms started up to 2007 and after 2017 were compared (p < 0.001). In parallel, symptoms measured with the Dysphagia Symptoms Score reduced significantly when patients with symptoms starting before 2007 and after 2012 were compared. A reduction in the number of endoscopies patients underwent before the one that achieved an EoE diagnosis, and the use of allergy testing as part of the diagnostic workout of EoE, also reduced significantly over time (p = 0.010 and p < 0.001, respectively). CONCLUSION: The diagnostic work‐up of EoE patients improved substantially over time at the European sites contributing to EoE CONNECT, with a dramatic reduction in diagnostic delay

The response of plant community diversity to alien invasion: evidence from a sand dune time series

This study examines the process of invasion of coastal dunes in north-eastern Italy along a 60-year time series considering alien attributes (origin, residence time, invasive status, and growth form strategy) and habitat properties (species richness, diversity and evenness, proportion of aliens, and proportion of focal species). Vegetation changes through time were investigated in four sandy coastal habitats, using a fine-scale diachronic approach that compared vegetation data collected by use of the same procedure, in four time periods, from the 1950s to 2011. Our analysis revealed an overall significant decline of species richness over the last six decades. Further, both the average number of species per plot and the mean focal species proportion were proved to be negatively affected by the increasing proportion of alien species at plot level. The severity of the impact, however, was found to be determined by a combination of species attributes, habitat properties, and human disturbance suggesting that alien species should be referred to as ‘‘passengers’’ and not as ‘‘drivers’’ of ecosystem change. Passenger alien species are those which take advantage of disturbances or other changes to which they are adapted but that lead to a decline in native biodiversity. Their spread is facilitated by widespread anthropogenic environmental alterations, which create new, suitable habitats, and ensure human-assisted dispersal, reducing the distinctiveness of plant communities and inducing a process of biotic homogenization

The ALICE experiment at the CERN LHC

ALICE (A Large Ion Collider Experiment) is a general-purpose, heavy-ion detector at the CERN LHC which focuses on QCD, the strong-interaction sector of the Standard Model. It is designed to address the physics of strongly interacting matter and the quark-gluon plasma at extreme values of energy density and temperature in nucleus-nucleus collisions. Besides running with Pb ions, the physics programme includes collisions with lighter ions, lower energy running and dedicated proton-nucleus runs. ALICE will also take data with proton beams at the top LHC energy to collect reference data for the heavy-ion programme and to address several QCD topics for which ALICE is complementary to the other LHC detectors. The ALICE detector has been built by a collaboration including currently over 1000 physicists and engineers from 105 Institutes in 30 countries. Its overall dimensions are 161626 m3 with a total weight of approximately 10 000 t. The experiment consists of 18 different detector systems each with its own specific technology choice and design constraints, driven both by the physics requirements and the experimental conditions expected at LHC. The most stringent design constraint is to cope with the extreme particle multiplicity anticipated in central Pb-Pb collisions. The different subsystems were optimized to provide high-momentum resolution as well as excellent Particle Identification (PID) over a broad range in momentum, up to the highest multiplicities predicted for LHC. This will allow for comprehensive studies of hadrons, electrons, muons, and photons produced in the collision of heavy nuclei. Most detector systems are scheduled to be installed and ready for data taking by mid-2008 when the LHC is scheduled to start operation, with the exception of parts of the Photon Spectrometer (PHOS), Transition Radiation Detector (TRD) and Electro Magnetic Calorimeter (EMCal). These detectors will be completed for the high-luminosity ion run expected in 2010. This paper describes in detail the detector components as installed for the first data taking in the summer of 2008

Creación de modelos in vitro para estudio de enfermedades inflamatorias

Informe sobre la estadía realizada en el Laboratorio de Inmunidad Innata, del Programa Disciplinario de Inmunología, Instituto de Ciencias Biomédicas, Facultad de Medicina, Universidad de Chile.CONACYT – Consejo Nacional de Ciencia y TecnologíaPROCIENCI

Breaking the unvirtuous cycle : barriers and opportunities for research and development in Paraguay. A case study

The author(s) declare that no financial support was received for the research, authorship, and/or publication of this article.Introduction: Medical research and development (R&D) is an undoubtedly relevant activity to drive innovation, improve healthcare policies and bring patients treatment opportunities for common and rare diseases. Equity and inclusion are matters of concern in research. High-income countries' research teams are more likely to have more impactful publications, grant funding, and clinical trials than middle or low-income countries. Low budget allocations to R&D and existing gaps in regulatory frameworks are some obstacles to growth. This unvirtuous cycle results in scarce advances in common endemic diseases and the underrepresentation of specific populations in innovative therapeutics research. Materials and methods: We conducted a policy review and qualitative research to determine the principal characteristics of basic and clinical medical research in Paraguay, as well as barriers and facilitators to improve innovative R&D strategies in this country. To this aim, we examined published articles from 2005 to 2020, the organizational structure of national research agencies, the current regulation framework, and the composition and experience of local research groups and ethical review boards (ERBs). In addition, we performed semi-structured interviews to evaluate perceptions and expectations from different stakeholders, including investigators, ERBs members, sponsor associates, and Regulatory Agency executive staff. Results: In 2018, Paraguay ranked 10th out of 12 South American countries in total number of publications and cumulative h-index score. Total Gross Domestic Product (GDP) allocation for R&D was 0.15%, ranking eighth out of 12 in the region. In 2021, the number of trials registered on ClinicalTrials.gov was 52, with only 16 ongoing recruiting studies at that time. Some of the main barriers identified included low incentives for academic careers and lack of experience in pharmaceutical research. An emergent necessity to develop a straight- forward normative framework was detected. Main facilitators included the development of two research initiative programs (PRONII and PROCIENCIA) from CONACYT (National Council of Science and Technology) which were associated with higher budget allocation and total number of publications in the 2011 to 2017 period. A total of six stakeholders participated in the semi-structured surveys. Interviewees highlighted the necessity of a centralized policy to promote R&D, which incorporates investigators and ERBs training, the development of standardized procedures, and the dissemination of research activities. Sponsor associates underlined that real-world evidence may represent a distinctive opportunity to enhance local research. Conclusion: Coordinated efforts are needed to break the unvirtuous cycle. There is an increasing interest in enhancing health research in Paraguay, materialized in the creation of specific programs that encourage the collaborative work of healthcare providers, basic scientists, and private investors. Nonetheless, a comprehensive approach is needed also to strengthen regulatory agencies and attract external sponsorship. While modern and currently popular topics, including artificial intelligence, real-world data, and translational research may represent key opportunities to seek investment, special policies should be adopted to prioritize research on the determinants of health in the Paraguayan population

Soluble CD14 (sCD14) and Lipopolysaccharide Binding Protein (LBP) in celiac disease

Celiac Disease (CD) is an autoimmune enteropathy of the small intestine caused by the consumption of gluten in genetically susceptible individuals, in which participation of the adaptive immune response, and also of the innate immune response is observed.CONACYT – Consejo Nacional de Ciencia y Tecnologí