Differential interactions of virulent and non-virulent H. parasuis strains with naïve or swine influenza virus pre-infected dendritic cells

Pigs possess a microbiota in the upper respiratory tract that includes Haemophilus parasuis. Pigs are also considered the reservoir of influenza viruses and infection with this virus commonly results in increased impact of bacterial infections, including those by H. parasuis. However, the mechanisms involved in host innate responses towards H. parasuis and their implications in a co-infection with influenza virus are unknown. Therefore, the ability of a non-virulent H. parasuis serovar 3 (SW114) and a virulent serovar 5 (Nagasaki) strains to interact with porcine bone marrow dendritic cells (poBMDC) and their modulation in a co-infection with swine influenza virus (SwIV) H3N2 was examined. At 1 hour post infection (hpi), SW114 interaction with poBMDC was higher than that of Nagasaki, while at 8 hpi both strains showed similar levels of interaction. The co-infection with H3N2 SwIV and either SW114 or Nagasaki induced higher levels of IL-1β, TNF-α, IL-6, IL-12 and IL-10 compared to mock or H3N2 SwIV infection alone. Moreover, IL-12 and IFN-α secretion differentially increased in cells co-infected with H3N2 SwIV and Nagasaki. These results pave the way for understanding the differences in the interaction of non-virulent and virulent strains of H. parasuis with the swine immune system and their modulation in a viral co-infection

Clinical response to pandemic H1N1 influenza virus from a fatal and mild case in ferrets

Methods: Viral strains isolated from a patient showing mild disease-M (A/CastillaLaMancha/RR5661/2009) or from a fatal case-F (A/CastillaLaMancha/RR5911/2009), both without known comorbid conditions, were inoculated in two groups of ferrets and clinical and pathological conditions were analysed. Results: Mild to severe clinical symptoms were observed in animals from both groups. A clinical score distribution was applied in which ferrets with mild clinical signs were distributed on a non-severe group (NS) and ferrets with severe clinical signs on a severe group (S), regardless of the virus used in the infection. Animals on S showed a significant decrease in body weight compared to animals on NS at 4 to 7 days post-infection (dpi). Clinical progress correlated with histopathological findings. Concentrations of haptoglobin (Hp) and serum amyloid A (SAA) increased on both groups after 2 dpi. Clinically severe infected ferrets showed a stronger antibody response and higher viral titres after infection (p = 0.001). Conclusions: The severity in the progress of infection was independent from the virus used for infection suggesting that the host immune response was determinant in the outcome of the infection. The diversity observed in ferrets mimicked the variability found in the human population.The authors kindly thank Dr. Juan Ortín for his scientific contribution. This work was partially supported by Instituto de Salud Carlos III (Programa especial de investigación sobre la gripe pándemica GR09/0023, GR09/0040, GR09/0039), AGL2013-48923-C2-02 and CIBER de Enfermedades Infecciosa

Terapia con pregabalina versus bloqueos intervencionistas en dolor neuropático: Un estudio de cohorte

Objective: tcompare the decrease in pain in patients with pregabalin therapy versus interventional blocks. Materials and methods: retrospective cohort study that included patients older than 18 years diagnosed with neuropathic pain from a reference center in Pereira, Colombia, between the years 2010-2016. The outcome was assessed at three months in each cohort and was defined as the change in pain intensity according to the visual analog pain scale. The comparison between cohorts and the effectiveness of the intervention was evaluated through repeated measures analysis with the generalized estimating equation. Results: a total of 1451 patients with pain were selected, of these, only 94 met the inclusion criteria. Sixty-two (66%) patients received a pharmacological scheme with pregabalin, and 32 patients (34%) underwent blockages. The pain intensity prior to pregabalin treatment was 7.3 ± 1.8 and 8.9 ± 1.2 in the group with blocks, p = 0.005. The intensity of posterior pain in the group with pregabalin was 3.5 ± 2.4, with an average improvement of 53.9%, while in the group with blocks, it was 2.5 ± 2 with an average improvement of 70.7%. Interventional management reduces pain 2.09 times more compared to pregabalin therapy (p <0.001). Conclusions: the use of interventional blocks in the treatment of neuropathic pain should be considered in patients with moderate to severe neuropathic pain.Objetivo: comparar la disminución en el dolor en pacientes con terapia con pregabalina frente a bloqueos intervencionistas. Materiales y métodos: estudio de cohorte retrospectiva, se reclutó pacientes mayores de 18 años diagnosticados con dolor de tipo neuropático de centro de referencia de la ciudad de Pereira, Colombia, entre los años 2010 a 2016. Se evaluó la variación en la intensidad del dolor. La comparación entre cohortes y la efectividad de la intervención se evaluó a través del análisis de medias repetidas con la ecuación de estimación generalizada. Resultados: se incluyeron 94 pacientes con dolor neuropático. A 62 (66%) pacientes se les formuló un esquema farmacológico con pregabalina y a 32 (34%) pacientes se les realizó bloqueos. La intensidad del dolor previa al tratamiento con pregabalina fue de 7,3 ± 1,8 y de 8,9 ± 1,2 en el grupo con bloqueos, p=0,005. La intensidad del dolor posterior en el grupo con pregabalina fue de 3,5 ± 2,4, con una mejoría media de 53,9%, mientras que en el grupo con bloqueos fue del 2,5 ± 2 con una mejoría media de 70,7%. El manejo intervencionista logró una reducción 2,09 veces mayor comparada con la pregabalina (p<0,001). Conclusiones: el empleo de bloqueos intervencionistas en el tratamiento del dolor neuropático debe ser considerado en pacientes con dolor neuropático moderado a severo

Terapia con pregabalina versus bloqueos intervencionistas en dolor neuropático: Un estudio de cohorte

Objetivo: comparar la disminución en el dolor en pacientes con terapia con pregabalina frente a bloqueos intervencionistas. Materiales y métodos: estudio de cohorte retrospectiva, se reclutó pacientes mayores de 18 años diagnosticados con dolor de tipo neuropático de centro de referencia de la ciudad de Pereira, Colombia, entre los años 2010 a 2016. Se evaluó la variación en la intensidad del dolor. La comparación entre cohortes y la efectividad de la intervención se evaluó a través del análisis de medias repetidas con la ecuación de estimación generalizada. Resultados: se incluyeron 94 pacientes con dolor neuropático. A 62 (66%) pacientes se les formuló un esquema farmacológico con pregabalina y a 32 (34%) pacientes se les realizó bloqueos. La intensidad del dolor previa al tratamiento con pregabalina fue de 7,3 ± 1,8 y de 8,9 ± 1,2 en el grupo con bloqueos, p=0,005. La intensidad del dolor posterior en el grupo con pregabalina fue de 3,5 ± 2,4, con una mejoría media de 53,9%, mientras que en el grupo con bloqueos fue del 2,5 ± 2 con una mejoría media de 70,7%. El manejo intervencionista logró una reducción 2,09 veces mayor comparada con la pregabalina (p<0,001). Conclusiones: el empleo de bloqueos intervencionistas en el tratamiento del dolor neuropático debe ser considerado en pacientes con dolor neuropático moderado a severo

Multicentre, randomised, open-label, phase IV-III study to evaluate the efficacy of cloxacillin plus fosfomycin versus cloxacillin alone in adult patients with methicillin-susceptible Staphylococcus aureus bacteraemia: study protocol for the SAFO trial

Introduction: Methicillin-susceptible Staphylococcus aureus (MSSA) bacteraemia is a frequent condition, with high mortality rates. There is a growing interest in identifying new therapeutic regimens able to reduce therapeutic failure and mortality observed with the standard of care of beta-lactam monotherapy. In vitro and small-scale studies have found synergy between cloxacillin and fosfomycin against S. aureus. Our aim is to test the hypothesis that cloxacillin plus fosfomycin achieves higher treatment success than cloxacillin alone in patients with MSSA bacteraemia. Methods: We will perform a superiority, randomised, open-label, phase IV-III, two-armed parallel group (1:1) clinical trial at 20 Spanish tertiary hospitals. Adults (≥18 years) with isolation of MSSA from at least one blood culture ≤72 hours before inclusion with evidence of infection, will be randomly allocated to receive either cloxacillin 2 g/4-hour intravenous plus fosfomycin 3 g/6-hour intravenous or cloxacillin 2 g/4-hour intravenous alone for 7 days. After the first week, sequential treatment and total duration of antibiotic therapy will be determined according to clinical criteria by the attending physician. Primary endpoints: (1) Treatment success at day 7, a composite endpoint comprising all the following criteria: patient alive, stable or with improved quick-Sequential Organ Failure Assessment score, afebrile and with negative blood cultures for MSSA at day 7. (2) Treatment success at test of cure (TOC) visit: patient alive and no isolation of MSSA in blood culture or at another sterile site from day 8 until TOC (12 weeks after randomisation). We assume a rate of treatment success of 74% in the cloxacillin group. Accepting alpha risk of 0.05 and beta risk of 0.2 in a two-sided test, 183 subjects will be required in each of the control and experimental groups to obtain statistically significant difference of 12% (considered clinically significant). Ethics and dissemination: Ethical approval has been obtained from the Ethics Committee of Bellvitge University Hospital (AC069/18) and from the Spanish Medicines and Healthcare Product Regulatory Agency (AEMPS, AC069/18), and is valid for all participating centres under existing Spanish legislation. The results will be presented at international meetings and will be made available to patients and funders

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

CIBERER : Spanish national network for research on rare diseases: A highly productive collaborative initiative

Altres ajuts: Instituto de Salud Carlos III (ISCIII); Ministerio de Ciencia e Innovación.CIBER (Center for Biomedical Network Research; Centro de Investigación Biomédica En Red) is a public national consortium created in 2006 under the umbrella of the Spanish National Institute of Health Carlos III (ISCIII). This innovative research structure comprises 11 different specific areas dedicated to the main public health priorities in the National Health System. CIBERER, the thematic area of CIBER focused on rare diseases (RDs) currently consists of 75 research groups belonging to universities, research centers, and hospitals of the entire country. CIBERER's mission is to be a center prioritizing and favoring collaboration and cooperation between biomedical and clinical research groups, with special emphasis on the aspects of genetic, molecular, biochemical, and cellular research of RDs. This research is the basis for providing new tools for the diagnosis and therapy of low-prevalence diseases, in line with the International Rare Diseases Research Consortium (IRDiRC) objectives, thus favoring translational research between the scientific environment of the laboratory and the clinical setting of health centers. In this article, we intend to review CIBERER's 15-year journey and summarize the main results obtained in terms of internationalization, scientific production, contributions toward the discovery of new therapies and novel genes associated to diseases, cooperation with patients' associations and many other topics related to RD research

Memorias de investigación: Feria de Semilleros y Jornadas de Investigación de uniminuto, Seccional Antioquia - Chocó.

Feria de Semilleros y Jornadas de Investigación de uniminuto, Seccional Antioquia - Chocó.Esta publicación busca divulgar investigaciones y producción académica en diferentes disciplinas, realizadas por estudiantes y docentes de UNIMINUTO Seccional Antioquia – Chocó, así como dar a conocer los semilleros de investigación que participaron en la V Feria de Semilleros, con el fin de visibilizar el trabajo que realiza el Centro de Investigación para el Desarrollo de UNIMINUTO Bello —CIDUB—, con respecto a debates académicos y espacios de interlocución. Igualmente, permite que la comunidad educativa conozca los temas de investigación y las discusiones que se están dando entre los semilleros y grupos de investigación, para así buscar puntos de encuentro y sinergias entre los investigadores. Adicionalmente, el texto se convierte en una invitación para que se vinculen otros investigadores, docentes, estudiantes e incluso otras instituciones a los procesos investigativos coordinados desde el CIDUB

Memorias de investigación: Feria de Semilleros y Jornadas de Investigación de uniminuto, Seccional Antioquia - Chocó.

Feria de Semilleros y Jornadas de Investigación de uniminuto, Seccional Antioquia - Chocó.Esta publicación busca divulgar investigaciones y producción académica en diferentes disciplinas, realizadas por estudiantes y docentes de UNIMINUTO Seccional Antioquia – Chocó, así como dar a conocer los semilleros de investigación que participaron en la V Feria de Semilleros, con el fin de visibilizar el trabajo que realiza el Centro de Investigación para el Desarrollo de UNIMINUTO Bello —CIDUB—, con respecto a debates académicos y espacios de interlocución. Igualmente, permite que la comunidad educativa conozca los temas de investigación y las discusiones que se están dando entre los semilleros y grupos de investigación, para así buscar puntos de encuentro y sinergias entre los investigadores. Adicionalmente, el texto se convierte en una invitación para que se vinculen otros investigadores, docentes, estudiantes e incluso otras instituciones a los procesos investigativos coordinados desde el CIDUB