Early development of anti-natalizumab antibodies in MS patients

The purpose of this study is to monitor the development of anti-natalizumab antibodies to evaluate their first appearance in multiple sclerosis patients, since their presence has been associated with a reduction in the efficacy of the treatment and an increase of adverse events. A total of 134 multiple sclerosis patients were included in the trial. Anti-natalizumab antibodies were monthly detected by ELISA up to the first year of treatment and subsequently, a determination was made at 18 months. 15.7% of the patients were positive, being 7.5% transiently positive and 8.2% persistently positive. The first appearance of anti-natalizumab antibodies occurred after the first month of treatment onset in 72% of positive patients; 18% did so after the second month, and 9.7% after the third month. Antibodies were never detected for the first time after the fourth infusion. The development of anti-natalizumab antibodies occurs very early after treatment onset. This observation should be considered when standardizing the follow up of patients treated with this drug in order to minimize the risks and optimize the treatment

Evaluación del trabajo colaborativo en Iniciación a la Investigación en Biología

Tras el trabajo previo de diseño de la asignatura Iniciación a la Investigación en Biología, el equipo multidisciplinar de profesores y profesoras de la Red Docente INVES ha desarrollado una metodología propia de trabajo en equipo, no sólo entre el diferente profesorado que la compone, sino también con el profesorado de la asignatura Estadística, con la que se comparten objetivos de aprendizaje comunes. Se ha optimizado el sistema de evaluación del trabajo colaborativo del alumnado, mediante el uso de rubricas y auto-evaluación. Dicho trabajo consiste en el diseño y desarrollo de un proyecto de investigación bibliométrico de temática biológica realizado por los estudiantes, propiciando la adquisición de competencias transversales mediante una dinámica de trabajo en grupo que culmina en la edición de unas Jornadas Científicas. Por otra parte, se han consensuado criterios comunes de evaluación continua, mejorando en la eficiencia de la evaluación, y determinado un incremento de la capacidad de aprendizaje del alumnado a lo largo de los cursos 2010-11 al 2013-14. La oferta formativa se completa mediante la formación de un grupo de Alto Rendimiento Académico con docencia en lengua inglesa. Esto permite al alumnado implementar el objetivo general de compresión de lengua extranjera inglés en lo relativo al ámbito científico

Avances en el trabajo colaborativo en Iniciación a la Investigación en Biología

Un equipo multidisciplinar de profesores y profesoras que componen la Red Docente INVES e imparten docencia en la asignatura Iniciación a la Investigación en Biología, ha desarrollado una metodología propia de trabajo en equipo, en coordinación con el profesorado de la asignatura Estadística, con la que se comparten objetivos de aprendizaje comunes. El sistema de evaluación del trabajo colaborativo del alumnado se ha optimizado mediante el uso de rúbricas y auto-evaluación. Se ha propiciado la adquisición de competencias transversales mediante una dinámica de trabajo en grupo. El diseño y desarrollo de un proyecto de investigación bibliométrico, de temática biológica, es realizado por los y las estudiantes, y culmina con la edición de unas Jornadas Científicas. Con el fin de mejorar la eficiencia de la evaluación, se han consensuado criterios comunes de evaluación continua entre el profesorado. Ello ha determinado un incremento de la capacidad de aprendizaje del alumnado a lo largo de los cursos 2010-11 al 2013-14. La lectura y compresión de textos científicos en inglés junto a la formación de un grupo de Alto Rendimiento Académico con docencia en lengua inglesa completa la oferta formativa, permitiendo al alumnado implementar el objetivo general de compresión de lengua extranjera inglés en lo relativo al ámbito científico

Gene expression in IFNß signalling pathway differs between monocytes, CD4 and CD8 T cells from MS patients

IFNß exerts its activity through the interaction with IFNAR, through activation of the JAK/STAT pathway. We analyzed the changes in IFNAR1, IFNAR2, STAT1, STAT2, Tyk2, JAK1, IRF9 and MxA gene expressions after prolonged IFNß treatment, in isolated mononuclear-cell subpopulations from MS patients, by real time PCR. The effect of IFNß on gene expression differed depending on the subpopulation assessed. The data suggest that CD8+ T cells are the most influenced by prolonged IFNß therapy as IFNAR2, Tyk2, IRF9 and Jak1 expressions were decreased, whereas MxA expression was increased in these cells

INVES: Docencia en Iniciación a la Investigación en Biología

Un equipo multidisciplinar de profesores y profesoras que imparten docencia en la asignatura Iniciación a la Investigación en Biología, constituyen la Red Docente INVES con el fin de desarrollar una metodología propia de trabajo en equipo, en coordinación con el profesorado de la asignatura Estadística, con la que se comparten objetivos de aprendizaje comunes. Durante el desarrollo de la asignatura, el alumnado diseña y ejecuta un proyecto de investigación bibliométrico de temática biológica sobre un tema actual y de interés. Con ello se favorece la adquisición de competencias transversales del módulo básico del título de grado. La dinámica de trabajo en grupo culmina en la edición de unas Jornadas Científicas, donde los estudiantes exponen los trabajos realizados. Se han consensuado modificaciones en las metodologías y actividades de aprendizaje, mejorando en la eficiencia de la experiencia de enseñanza-aprendizaje

Melanin-Concentrating Hormone acts through hypothalamic kappa opioid system and p70S6K to stimulate acute food intake.

Melanin-Concentrating Hormone (MCH) is one of the most relevant orexigenic factors specifically located in the lateral hypothalamic area (LHA), with its physiological relevance demonstrated in studies using several genetically manipulated mice models. However, the central mechanisms controlling MCH-induced hyperphagia remain largely uncharacterized. Here, we show that central injection of MCH in mice deficient for kappa opoid receptor (k-OR) failed to stimulate feeding. To determine the hypothalamic area responsible for this MCH/k-OR interaction, we performed virogenetic studies and found that downregulation of k-OR by adeno-associated viruses (shOprk1-AAV) in LHA, but not in other hypothalamic nuclei, was sufficient to block MCH-induced food intake. Next, we sought to investigate the molecular signaling pathway within the LHA that mediates acute central MCH stimulation of food intake. We found that MCH activates k-OR and that increased levels of phosphorylated extracellular signal regulated kinase (ERK) are associated with downregulation of phospho-S6 Ribosomal Protein. This effect was prevented when a pharmacological inhibitor of k-OR was co-administered with MCH. Finally, the specific activation of the direct upstream regulator of S6 (p70S6K) in the LHA attenuated MCH-stimulated food consumption. Our results reveal that lateral hypothalamic k-OR system modulates the orexigenic action of MCH via the p70S6K/S6 pathway

Axicabtagene ciloleucel compared to tisagenlecleucel for the treatment of aggressive B-cell lymphoma

Axicabtagene ciloleucel (axi-cel) and tisagenlecleucel (tisa-cel) are CD19-targeted chimeric antigen receptor (CAR) T cells approved for relapsed/refractory (R/R) large B-cell lymphoma (LBCL). We performed a retrospective study to evaluate safety and efficacy of axi-cel and tisa-cel outside the setting of a clinical trial. Data from consecutive patients with R/R LBCL who underwent apheresis for axi-cel or tisa-cel were retrospectively collected from 12 Spanish centers. A total of 307 patients underwent apheresis for axi-cel (n=152) and tisa-cel (n=155) from November 2018 to August 2021, of which 261 (85%) received a CAR T infusion (88% and 82%, respectively). Median time from apheresis to infusion was 41 days for axi-cel and 52 days for tisa-cel (P=0.006). None of the baseline characteristics were significantly different between both cohorts. Both cytokine release syndrome and neurologic events (NE) were more frequent in the axi-cel group (88% vs. 73%, P=0.003, and 42% vs. 16%, P= 2 and progressive disease before lympho-depletion. Safety and efficacy results in our real-world experience were comparable with those reported in the pivotal trials. Patients treated with axi-cel experienced more toxicity but similar non-relapse mortality compared with those re-ceiving tisa-cel. Efficacy was not significantly different between both products

Axicabtagene ciloleucel compared to tisagenlecleucel for the treatment of aggressive B-cell lymphoma

Axicabtagene ciloleucel (axi-cel) and tisagenlecleucel (tisa-cel) are CD19-targeted chimeric antigen receptor (CAR) T cells approved for relapsed/refractory (R/R) large B-cell lymphoma (LBCL). We performed a retrospective study to evaluate safety and efficacy of axi-cel and tisa-cel outside the setting of a clinical trial. Data from consecutive patients with R/R LBCL who underwent apheresis for axi-cel or tisa-cel were retrospectively collected from 12 Spanish centers. A total of 307 patients underwent apheresis for axi-cel (n=152) and tisa-cel (n=155) from November 2018 to August 2021, of which 261 (85%) received a CAR T infusion (88% and 82%, respectively). Median time from apheresis to infusion was 41 days for axi-cel and 52 days for tisa-cel (P =0.006). None of the baseline characteristics were significantly different between both cohorts. Both cytokine release syndrome and neurologic events (NE) were more frequent in the axi-cel group (88% vs. 73%, P =0.003, and 42% vs. 16%, P <0.001, respectively). Infections in the first 6 months post-infusion were also more common in patients treated with axi-cel (38% vs. 25%, P =0.033). Non-relapse mortality was not significantly different between the axi-cel and tisa-cel groups (7% and 4%, respectively, P =0.298). With a median follow-up of 9.2 months, median PFS and OS were 5.9 and 3 months, and 13.9 and 11.2 months for axi-cel and tisa-cel, respectively. The 12-month PFS and OS for axi-cel and tisa-cel were 41% and 33% (P =0.195), 51% and 47% (P =0.191), respectively. Factors associated with lower OS in the multivariate analysis were increased lactate dehydrogenase, ECOG ≥2 and progressive disease before lympho-depletion. Safety and efficacy results in our real-world experience were comparable with those reported in the pivotal trials. Patients treated with axi-cel experienced more toxicity but similar non-relapse mortality compared with those receiving tisa-cel. Efficacy was not significantly different between both products

Production of He-4 and (4) in Pb-Pb collisions at root(NN)-N-S=2.76 TeV at the LHC

Results on the production of He-4 and (4) nuclei in Pb-Pb collisions at root(NN)-N-S = 2.76 TeV in the rapidity range vertical bar y vertical bar <1, using the ALICE detector, are presented in this paper. The rapidity densities corresponding to 0-10% central events are found to be dN/dy4(He) = (0.8 +/- 0.4 (stat) +/- 0.3 (syst)) x 10(-6) and dN/dy4 = (1.1 +/- 0.4 (stat) +/- 0.2 (syst)) x 10(-6), respectively. This is in agreement with the statistical thermal model expectation assuming the same chemical freeze-out temperature (T-chem = 156 MeV) as for light hadrons. The measured ratio of (4)/He-4 is 1.4 +/- 0.8 (stat) +/- 0.5 (syst). (C) 2018 Published by Elsevier B.V.Peer reviewe

Impact of COVID-19 on cardiovascular testing in the United States versus the rest of the world

Objectives: This study sought to quantify and compare the decline in volumes of cardiovascular procedures between the United States and non-US institutions during the early phase of the coronavirus disease-2019 (COVID-19) pandemic. Background: The COVID-19 pandemic has disrupted the care of many non-COVID-19 illnesses. Reductions in diagnostic cardiovascular testing around the world have led to concerns over the implications of reduced testing for cardiovascular disease (CVD) morbidity and mortality. Methods: Data were submitted to the INCAPS-COVID (International Atomic Energy Agency Non-Invasive Cardiology Protocols Study of COVID-19), a multinational registry comprising 909 institutions in 108 countries (including 155 facilities in 40 U.S. states), assessing the impact of the COVID-19 pandemic on volumes of diagnostic cardiovascular procedures. Data were obtained for April 2020 and compared with volumes of baseline procedures from March 2019. We compared laboratory characteristics, practices, and procedure volumes between U.S. and non-U.S. facilities and between U.S. geographic regions and identified factors associated with volume reduction in the United States. Results: Reductions in the volumes of procedures in the United States were similar to those in non-U.S. facilities (68% vs. 63%, respectively; p = 0.237), although U.S. facilities reported greater reductions in invasive coronary angiography (69% vs. 53%, respectively; p < 0.001). Significantly more U.S. facilities reported increased use of telehealth and patient screening measures than non-U.S. facilities, such as temperature checks, symptom screenings, and COVID-19 testing. Reductions in volumes of procedures differed between U.S. regions, with larger declines observed in the Northeast (76%) and Midwest (74%) than in the South (62%) and West (44%). Prevalence of COVID-19, staff redeployments, outpatient centers, and urban centers were associated with greater reductions in volume in U.S. facilities in a multivariable analysis. Conclusions: We observed marked reductions in U.S. cardiovascular testing in the early phase of the pandemic and significant variability between U.S. regions. The association between reductions of volumes and COVID-19 prevalence in the United States highlighted the need for proactive efforts to maintain access to cardiovascular testing in areas most affected by outbreaks of COVID-19 infection