277 research outputs found

    Deciphering predictive factors for choice of thrombopoietin receptor agonist, treatment free responses, and thrombotic events in immune thrombocytopenia

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    Malalties hematològiques; Trastorns immunològicsEnfermedades hematológicas; Trastornos inmunológicosHaematological diseases; Immunological disordersVery few data exist on when a particular thrombopoietin-receptor agonist (TPO-RA) is favored in clinical practice for the treatment of patients with immune thrombocytopenia (ITP), about novel risk factors for vascular events (VE) with these drugs, nor about predictive factors for therapy free responses (TFR). We conducted an observational, retrospective, long-term follow-up multicenter study from November 2016 to January 2018 of 121 adult ITP patients initiating TPO-RA between January 2012 to December 2014. Data reflected that a platelet count ≤25 × 109/l at the time when the TPO-RA was initiated was associated with a 2.8 higher probability of receiving romiplostim vs. eltrombopag (P = 0.010). VE on TPO-RA was related to previous neoplasia in patients over 65 years (50% vs. 2.2%, P < 0.001), and to previous splenectomy in younger patients (100% vs. 33%, P = 0.001). Receiving romiplostim as first TPO-RA with no subsequent TPO-RA switching was associated with a 50% likelihood of TFR after 2.9 years of therapy (3.3 years in chronic ITP patients). These real-world data help deciphering some areas of uncertainty, and offer insight into some of the most relevant challenges of ITP which may help clinicians make appropriate treatment decisions in the management of adult ITP patients with TPO-RA

    Epigenetic alterations in hippocampus of SAMP8 senescent mice and modulation by voluntary physical exercise

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    The senescence-accelerated SAMP8 mouse model displays features of cognitive decline and Alzheimer's disease. With the purpose of identifying potential epigenetic markers involved in aging and neurodegeneration, here we analyzed the expression of 84 mature miRNAs, the expression of histone-acetylation regulatory genes and the global histone acetylation in the hippocampus of 8-month-old SAMP8 mice, using SAMR1 mice as control. We also examined the modulation of these parameters by 8 weeks of voluntary exercise. Twenty-one miRNAs were differentially expressed between sedentary SAMP8 and SAMR1 mice and seven miRNAs were responsive to exercise in both strains. SAMP8 mice showed alterations in genes involved in protein acetylation homeostasis such as Sirt1 and Hdac6 and modulation of Hdac3 and Hdac5 gene exprssion by exercise. Global histone H3 acetylation levels were reduced in SAMP8 compared with SAMR1 mice and reached control levels in response to exercise. In sum, data presented here provide new candidate epigenetic markers for aging and neurodegeneration and suggest that exercise training may prevent or delay some epigenetic alterations associated with accelerated aging

    Primera detección de Lonsdalea quercina subsp. populi en chopo en España

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    Lonsdalea quercina (ex Brenneria quercina) subsp. populi es una bacteria recientemente identificada en Hungría y China como una nueva subespecie causante del chancro de la corteza del chopo. Los árboles afectados presentan chancros longitudinales en el tronco, de los que fluyen abundantes exudados espumosos de color blanco y exudados acuosos oscuros que tiñen la corteza. Los chopos afectados muestran un debilitamiento generalizado. En España se han localizado choperas con síntomas similares y se ha identificado L. quercina subsp. populi como el agente causal de los mismos. En este trabajo se presenta la primera detección de esta bacteria en España y se describen los métodos de diagnóstico e identificación utilizados. Esta nueva bacteriosis podría tener un impacto económico importante, siendo necesario evaluar las pérdidas causadas y realizar nuevas prospecciones para determinar su distribución en el país

    Deficient neutralizing antibody response and specific lack of RBD-responsive B cells in elderly long-term convalescent patients from severe COVID-19

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    Resumen del póster presentado a las III Jornadas Científicas PTI+ Salud Global, celebradas en el Centro de Ciencias Humanas y Sociales (CCHS), CSIC (Madrid) del 20 al 22 de noviembre de 2023.[Background] Severe COVID-19 is defined by admission to intensive care units with respiratory support. This condition increases with age. To investigate in the possible mechanisms by which severe COVID-19 occurs, we compared the response of specific antibodies against the viral antigens RBD, Spike (S), nuclear (N), and membrane (Mpro) and the neutralizing titers in plasma of elderly patients convalescent from severe COVID-19 with convalescent patients from mild disease.[Methods] Plasma was collected from cohort 1: 20 healthy donors (vaccinated and unvaccinated), cohort 2: 40 elderly long-term convalescent patients from severe COVID-19 (mean: 73 years old, 60/40 ratio men/women, and 10 months after infection), and cohort 3: 60 convalescent from mild COVID-19 patients, who were vaccinated (mean: 42 years old, 30/70 ration men/women, 8 months after mild infection, and 5.7 months after last vaccination shoot). To compare reactivity against native S protein, we used a sensitive method to measure specific IgG1 and IgA in plasma by flow cytometry. We assessed the neutralization titers in plasma by infection assays in HEK-293T cells or Vero cells expression ACE-2, using S- and GFP-expressing pseudotyped viruses, and quantified IgG, IgA, and IgM antibodies against RBD, S, N, and mPro antigens using the Multiplex Serological SARS-CoV-2 assay (Immunostep). To evaluate the presence of specific T and B cells specific for S and RBD antigens, we used kits from Miltenyi Biotech and analyzed the expression of activation antigens after cell stimulation with these antigens by flow cytometry.[Results] Significant levels of IgG and IgA against S protein were found in the plasma of convalescent patients from cohorts 2 and 3, with no differences in total anti-S antibody response between the two cohorts. Interestingly, anti-RBD IgG levels were found to be extremely low in plasma samples from cohort 2, but not in plasma samples from cohort 3. In accordance with these results, the neutralizing titers (IC50) found were very low in the plasma samples from cohort 2, compared to those from cohort 3. Analysis of the presence of RBD- and S-specific B cells present in peripheral blood mononuclear cells (PBMCs) of these cohorts revealed significantly lower levels of RBD-specific B cells, but of not S-specific B lymphocytes, in the PBMCs from cohort 2 cells but not in those from cohort 3. Furthermore, lower B cell activation, as demonstrated by CD25 expression, was observed in PBMCs from cohort 2 compared to those from cohort 3 after their stimulation with RBD, but not with S, N or Mpro proteins. These results together indicate the specific lack of RBD-specific B cells in cohort 2 patients.[Conclusions] The low neutralizing capacity observed in the plasma of elderly long-term convalescent patients, who recovered from severe COVID-19 (cohort 2) correlates with low specific levels of anti-RBD antibodies and reduced levels of RBD-responsive B cells. These results could help explain the severity of COVID-19 in patients from cohort 2 compared to those from cohort 3, who had a mild disease. Future experiments will evaluate the presence of neutralizing antibodies in cohort 2 patients after vaccination.Peer reviewe
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