Immune Mechanism of Epileptogenesis and Related Therapeutic Strategies

Immunologic and neuroinflammatory pathways have been found to play a major role in the pathogenesis of many neurological disorders such as epilepsy, proposing the use of novel therapeutic strategies. In the era of personalized medicine and in the face of the exhaustion of anti-seizure therapeutic resources, it is worth looking at the current or future possibilities that neuroimmunomodulator or anti-inflammatory therapy can offer us in the management of patients with epilepsy. For this reason, we performed a narrative review on the recent advances on the basic epileptogenic mechanisms related to the activation of immunity or neuroinflammation with special attention to current and future opportunities for novel treatments in epilepsy. Neuroinflammation can be considered a universal phenomenon and occurs in structural, infectious, post-traumatic, autoimmune, or even genetically based epilepsies. The emerging research developed in recent years has allowed us to identify the main molecular pathways involved in these processes. These molecular pathways could constitute future therapeutic targets for epilepsy. Different drugs current or in development have demonstrated their capacity to inhibit or modulate molecular pathways involved in the immunologic or neuroinflammatory mechanisms described in epilepsy. Some of them should be tested in the future as possible antiepileptic drugThis research was funded by Andalusian Network of Clinical and Translational Research in Neurology (Neuro-RECA) of the Consejería de Salud y Familias de la Junta de Andalucía (Code: RIC-0111-2019). Partial funding for open access charge: Universidad de Málag

Evolution of Quality of Life and Treatment Adherence after One Year of Intermittent Bladder Catheterisation in Functional Urology Unit Patients

Objective: To determine patient difficulties and concerns when performing IBC (Intermittent Bladder Catheterisation), as well as the evolution of adherence, quality of life, and emotional state of patients one year after starting IBC. Method: A prospective, observational, multicentre study conducted in 20 Spanish hospitals with a one-year follow-up. Data sources were patient records and the King's Health Questionnaire on quality of life, the Mini-Mental State Examination (MMSE), and the Hospital Anxiety and Depression Scale (HADS). Perceived adherence was measured using the ICAS (Intermittent Catheterization Adherence Scale) and perceived difficulties with IBC were assessed using the ICDQ (Intermittent Catheterization Difficulty Questionnaire). For data analysis, descriptive and bivariate statistics were performed for paired data at three points in time (T1: one month, T2: three months, T3: one year). Results: A total of 134 subjects initially participated in the study (T0), becoming 104 subjects at T1, 91 at T2, and 88 at T3, with a mean age of 39 years (standard deviation = 22.16 years). Actual IBC adherence ranged from 84.8% at T1 to 84.1% at T3. After one year of follow-up, a statistically significant improvement in quality of life (p <= 0.05) was observed in all dimensions with the exception of personal relationships. However, there were no changes in the levels of anxiety (p = 0.190) or depression (p = 0.682) at T3 compared to T0. Conclusions: Patients requiring IBC exhibit good treatment adherence, with a significant proportion of them performing self-catheterisation. After one year of IBC, a significant improvement in quality of life was noted, albeit with a significant impact on their daily lives and their personal and social relationships. Patient support programmes could be implemented to improve their ability to cope with difficulties and thus enhance both their quality of life and the maintenance of their adherence

Anti-Spike antibodies 3 months after SARS-CoV-2 mRNA vaccine booster dose in patients on hemodialysis: the prospective SENCOVAC study

Background: Patients on hemodialysis are at high-risk for complications derived from coronavirus disease 2019 (COVID-19). The present analysis evaluated the impact of a booster vaccine dose and breakthrough severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections on humoral immunity 3 months after the booster dose. Methods: This is a multicentric and prospective study assessing immunoglobulin G anti-Spike antibodies 6 and 9 months after initial SARS-CoV-2 vaccination in patients on hemodialysis that had also received a booster dose before the 6-month assessment (early booster) or between the 6- and 9-month assessments (late booster). The impact of breakthrough infections, type of vaccine, time from the booster and clinical variables were assessed. Results: A total of 711 patients [67% male, median age (range) 67 (20-89) years] were included. Of these, 545 (77%) received an early booster and the rest a late booster. At 6 months, 64 (9%) patients had negative anti-Spike antibody titers (3% of early booster and 29% of late booster patients, P =. 001). At 9 months, 91% of patients with 6-month negative response had seroconverted and there were no differences in residual prevalence of negative humoral response between early and late booster patients (0.9% vs 0.6%, P =. 693). During follow-up, 35 patients (5%) developed breakthrough SARS-CoV-2 infection. Antibody titers at 9 months were independently associated with mRNA-1273 booster (P =. 001), lower time from booster (P =. 043) and past breakthrough SARS-CoV-2 infection (P <. 001). Conclusions: In hemodialysis patients, higher titers of anti-Spike antibodies at 9 months were associated with mRNA-1273 booster, lower time from booster and past breakthrough SARS-CoV-2 infectionThe present project has been supported by Fresenius Medical Care, Diaverum, Vifor Pharma, Vircell, Fundación Renal Iñigo Álvarez de Toledo and ISCIII FEDER funds RICORS2040 (RD21/0005

Interculturality, extension practices and sign language: story of a shared experience among pre-Columbian musical instruments, quipus and dinosaurs

La Facultad de Ciencias Naturales y Museo, perteneciente a la Universidad Nacional de La Plata, ocupa un lugar destacado para llevar a cabo acciones de vinculación en extensión universitaria. En este ámbito hemos realizado talleres con el propósito de promover la participación de las infancias en el conocimiento científico. La implementación de los talleres se ha centrado en la inclusión y puesta en diálogo, en especial con jóvenes con discapacidad auditiva, siguiendo los principios de accesibilidad cultural. Para lograrlo hemos adoptado la práctica de difundir información de manera bilingüe e intercultural mediante materiales en Lengua de Señas Argentina (LSA). Estos talleres incentivaron la exploración y comprensión del mundo incaico, focalizándose en los quipus como sistema contable y en las sonoridades precolombinas del Noroeste argentino abordadas a través de un análisis detallado de sus instrumentos musicales. De la misma forma, fueron llevadas a cabo actividades sobre los animales actuales y pasados que habitaron el territorio mediante la visita a salas y espacios interactivos del Museo de La Plata. Esta propuesta integral de trabajo continúa con las actividades de comunicación en ciencia, un compromiso en brindar propuestas para la diversidad de públicos, promoviendo la inclusión y la divulgación del conocimiento científico.The Facultad de Ciencias Naturales y Museo, belonging to the Universidad Nacional de La Plata, occupies a prominent place to carry out linkage actions in university extension. In this area we have carried out workshops with the purpose of promoting the participation of children in scientific knowledge. The implementation of the workshops has focused on inclusion and dialogue, especially for young people with hearing disabilities, following the principles of cultural accessibility. To achieve this, we have adopted the practice of disseminating information in a bilingual and intercultural manner using Argentine Sign Language (LSA). These workshops encouraged the exploration and understanding of the Inca world, focusing on the quipus as an accounting system and on the pre-Columbian sonorities of northwestern Argentina, approached through a detailed analysis of their musical instruments. In the same way, activities were carried out on present and past animals that inhabited the territory, through visits to rooms and interactive spaces of the Museum of La Plata. This comprehensive work proposal continues with the activities of communication in Science, a commitment to provide proposals for the diversity of audiences, promoting the inclusion and dissemination of scientific knowledge.Facultad de Ciencias Naturales y Muse

Asymmetric cellulose triacetate is a safe and effective alternative for online haemodiafiltration

Background: In post-dilution haemodiafiltration only synthetic membranes have been used to date. Asymmetric cellulose triacetate (ATA™) is now available, whose characteristics are suitable for this technique. Objectives: To describe the in vivo performance and behaviour of this membrane, to identify its depurative effectiveness, use in clinical practice and its biocompatibility, both acute and after one month of treatment. Methods: Observational prospective study of 23 patients who were dialysed for 4 weeks using an ATA™ membrane and who maintained their prior regimen. Results: A total of 287 sessions were performed and 264 complete sessions were collected. With an effective time of 243.7 (17.6) min and a mean blood flow of 371.7 (23) ml/min, an average Kt of 56.3 (5.3) l was observed, as well as a convection volume of 27.1 (4.2) l, a filtration fraction of 29.9 (3.7) %, a urea reduction ratio (RR) of 81 (5.2) %, a creatinine RR of 74.7 (4.6) %, a β2-microglobulin RR of 76.5 (4.8) % and a retinol binding protein RR of 18.6 (7.6) %. There were no technical problems or alarms. Changing the heparin dosage was not necessary. No increases in C3a or C5a concentrations or leukopenia were observed in the first 30 min of the session. Neither the monocyte subpopulations nor IL-β1 or IL-6 were significantly altered after one month of treatment. Conclusions: The new ATA™ membrane achieves adequate Kt and convection volume, without technical problems and with good biocompatibility and inflammatory profiles. It is therefore a valid option for post-dilution haemodiafiltration, particularly in patients allergic to synthetic membranes. Resumen: Antecedentes: En la hemodiafiltración posdilucional se han usado solo membranas sintéticas. Ahora contamos con un triacetato de celulosa asimétrico (ATA®) cuyas características lo hacen apto para esta técnica. Objetivos: Describir las prestaciones y el comportamiento in vivo de esta membrana estudiando la eficacia depurativa y el uso clínico, además de su biocompatibilidad aguda tras un mes de tratamiento. Métodos: Estudio prospectivo observacional en el que se incluyeron 23 pacientes que se dializaron durante 4 semanas con ATA® manteniendo su pauta previa. Resultados: Se realizaron 287 sesiones y se recogieron 264 sesiones completas. Con un tiempo efectivo de 243,7 (17,6) min y un flujo medio de sangre de 371,7 (23) ml/min, se obtuvo un Kt medio de 56,3 (5,3) l, un volumen convectivo de 27,1 (4,2) l, con una fracción de filtración del 29,9 (3,7) %, un porcentaje de reducción (RR) de urea de 81 (5,2) %, un RR de creatinina de 74,7 (4,6) %, un RR de β2-microglobulina de 76,5 (4,8) % y un RR de proteína transportadora de retinol de 18,6 (7,6) %. No se produjeron problemas técnicos ni alarmas. No fue preciso cambiar la dosificación de heparina. A los 30 min de la sesión no se produjo ningún aumento de C3a, C5a ni leucopenia. Tampoco se modificaron de forma significativa las poblaciones monocitarias ni la IL-β1 ni IL-6 tras un mes de tratamiento. Conclusiones: ATA® logra un Kt y un volumen convectivo adecuados, sin problemas técnicos y con buen perfil de biocompatibilidad e inflamatorio, lo que lo convierte en una posibilidad más de tratamiento para hemodiafiltración posdilucional, máxime en pacientes alérgicos a membranas sintéticas. Keywords: Online haemodiafiltration, Cellulose triacetate, Suitability, Biocompatibility, Inflammation, Palabras clave: Hemodiafiltración en línea, Triacetato de celulosa, Adecuación, Biocompatibilidad, Inflamació

El triacetato de celulosa asimétrico es una alternativa segura y eficaz para la hemodiafiltración en línea

Resumen: Antecedentes: En la hemodiafiltración posdilucional se han usado solo membranas sintéticas. Ahora contamos con un triacetato de celulosa asimétrico (ATA®) cuyas características lo hacen apto para esta técnica. Objetivos: Describir las prestaciones y el comportamiento in vivo de esta membrana estudiando la eficacia depurativa y el uso clínico, además de su biocompatibilidad aguda tras un mes de tratamiento. Métodos: Estudio prospectivo observacional en el que se incluyeron 23 pacientes que se dializaron durante 4 semanas con ATA® manteniendo su pauta previa. Resultados: Se realizaron 287 sesiones y se recogieron 264 sesiones completas. Con un tiempo efectivo de 243,7 (17,6) min y un flujo medio de sangre de 371,7 (23) ml/min, se obtuvo un Kt medio de 56,3 (5,3) l, un volumen convectivo de 27,1 (4,2) l, con una fracción de filtración del 29,9 (3,7) %, un porcentaje de reducción (RR) de urea de 81 (5,2) %, un RR de creatinina de 74,7 (4,6) %, un RR de β2-microglobulina de 76,5 (4,8) % y un RR de proteína transportadora de retinol de 18,6 (7,6) %. No se produjeron problemas técnicos ni alarmas. No fue preciso cambiar la dosificación de heparina. A los 30 min de la sesión no se produjo ningún aumento de C3a, C5a ni leucopenia. Tampoco se modificaron de forma significativa las poblaciones monocitarias ni la IL-β1 ni IL-6 tras un mes de tratamiento. Conclusiones: ATA® logra un Kt y un volumen convectivo adecuados, sin problemas técnicos y con buen perfil de biocompatibilidad e inflamatorio, lo que lo convierte en una posibilidad más de tratamiento para hemodiafiltración posdilucional, máxime en pacientes alérgicos a membranas sintéticas. Abstract: Background: In post-dilution haemodiafiltration only synthetic membranes have been used to date. Asymmetric cellulose triacetate (ATA™) is now available, whose characteristics are suitable for this technique. Objectives: To describe the in vivo performance and behaviour of this membrane, to identify its depurative effectiveness, use in clinical practice and its biocompatibility, both acute and after one month of treatment. Methods: Observational prospective study of 23 patients who were dialysed for 4 weeks using an ATA™ membrane and who maintained their prior regimen. Results: A total of 287 sessions were performed and 264 complete sessions were collected. With an effective time of 243.7 (17.6) min and a mean blood flow of 371.7 (23) ml/min, an average Kt of 56.3 (5.3) l was observed, as well as a convection volume of 27.1 (4.2) l, a filtration fraction of 29.9 (3.7) %, a urea reduction ratio (RR) of 81 (5.2) %, a creatinine RR of 74.7 (4.6) %, a β2-microglobulin RR of 76.5 (4.8) % and a retinol binding protein RR of 18.6 (7.6) %. There were no technical problems or alarms. Changing the heparin dosage was not necessary. No increases in C3a or C5a concentrations or leukopenia were observed in the first 30 min of the session. Neither the monocyte subpopulations nor IL-β1 or IL-6 were significantly altered after one month of treatment. Conclusions: The new ATA™ membrane achieves adequate Kt and convection volume, without technical problems and with good biocompatibility and inflammatory profiles. It is therefore a valid option for post-dilution haemodiafiltration, particularly in patients allergic to synthetic membranes. Palabras clave: Hemodiafiltración en línea, Triacetato de celulosa, Adecuación, Biocompatibilidad, Inflamación, Keywords: Online haemodiafiltration, Cellulose triacetate, Suitability, Biocompatibility, Inflammatio

ERC, 10 años de excelencia en la ciencia

Datos técnicos: 8 minutos, color, español. Ficha técnica: Gabinete de Presidencia CSIC y Departamento de ComunicaciónEl Consejo Europeo de Investigación (ERC, por sus siglas en inglés) cumplió 10 años el 24 de marzo de 2017. A lo largo de esta década de vida, se ha financiado a unos 7.000 investigadores, permitiendo la publicación de cerca de 100.000 artículos en revistas científicas internacionales. En España, cerca de 400 investigadores han recibido un total de 650 millones de euros y el Consejo Superior de Investigaciones Científicas (CSIC) destaca por ser la institución española con mayor número de ayudas, por delante de la Universidad Pompeu Fabra, el Instituto de Ciencias Fotónicas, la Universidad de Barcelona y el Centro de Regulación Genómica. Entre los más de 400 proyectos que han obtenido una ayuda del Consejo Europeo de Investigación en España, más de un centenar han recaído en el CSIC.N

Lack of antibody affinity maturation due to poor Toll-like receptor stimulation leads to enhanced respiratory syncytial virus disease

Respiratory syncytial virus (RSV) is a leading cause of hospitalization in infants. A formalin-inactivated RSV vaccine was used to immunize children and elicited nonprotective, pathogenic antibody. Immunized infants experienced increased morbidity after subsequent RSV exposure. No vaccine has been licensed since that time. A widely accepted hypothesis attributed the vaccine failure to formalin disruption of protective antigens. Here we show that the lack of protection was not due to alterations caused by formalin but instead to low antibody avidity for protective epitopes. Lack of antibody affinity maturation followed poor Toll-like receptor (TLR) stimulation. This study explains why the inactivated RSV vaccine did not protect the children and consequently led to severe disease, hampering vaccine development for 42 years. It also suggests that inactivated RSV vaccines may be rendered safe and effective by inclusion of TLR agonists in their formulation, and it identifies affinity maturation as a key factor for the safe immunization of infants.Fil: Delgado, Maria Florencia. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Fundación para la Investigación en Infectología Infantil; ArgentinaFil: Coviello, Silvina Andrea. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Fundación para la Investigación en Infectología Infantil; ArgentinaFil: Monsalvo, Ana Clara. Fundación para la Investigación en Infectología Infantil; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Melendi, Guillermina Amanda. Fundación para la Investigación en Infectología Infantil; Argentina. University Johns Hopkins; Estados UnidosFil: Hernandez, Johanna Zea. Fundación para la Investigación en Infectología Infantil; Argentina. University Johns Hopkins; Estados UnidosFil: Batalle, Juan Pio. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Fundación para la Investigación en Infectología Infantil; ArgentinaFil: Diaz, Leandro. Fundación para la Investigación en Infectología Infantil; ArgentinaFil: Trento, Alfonsina. Universidad Carlos III de Madrid. Instituto de Salud; EspañaFil: Chang, Herng-Yu. University Johns Hopkins; Estados UnidosFil: Mitzner, Wayne. University Johns Hopkins; Estados UnidosFil: Ravetch, Jeffrey. The Rockefeller University; Estados UnidosFil: Melero, José A.. Universidad Carlos III de Madrid. Instituto de Salud; EspañaFil: Irusta, Pablo M.. University Of Georgetown; Estados Unidos. Fundación para la Investigación en Infectología Infantil; ArgentinaFil: Polack, Fernando Pedro. Fundación para la Investigación en Infectología Infantil; Argentina. University Johns Hopkins; Estados Unido