IgM antibodies against malondialdehyde and phosphorylcholine in different systemic rheumatic diseases

IgM antibodies against phosphorylcholine (anti-PC) and malondialdehyde (anti-MDA) may have protective properties in cardiovascular and rheumatic diseases. We here compare these antibodies in systemic rheumatic conditions and study their properties. Anti-PC and anti-MDA was measured using ELISA in patients with SLE (374), RA (354), Mixed connective tissue disease (MCTD, 77), Systemic sclerosis (SSc, 331), Sj\uf6gren\u2019s syndrome (SjS, 324), primary antiphospholipid syndrome (PAPs, 65), undifferentiated connective tissue disease (UCTD, 118) and 515 matched healthy controls (HC). Cardiovascular score (CV) was broadly defined based on clinical disease symptoms. Anti-PC and anti-MDA peptide/protein characterization were compared using a proteomics de novo sequencing approach. anti-MDA and anti-PC were extracted from total IgM. The proportion of Treg cells was determined by flow cytometry. The maximal difference between cases and controls was shown for MCTD: significantly lower IgM Anti-PC but not anti-MDA among patients (median 49.3RU/ml vs 70.4 in healthy controls, p(t-test) = 0.0037). IgM low levels were more prevalent in MCTD, SLE, SjS, SSc and UCTD. IgM anti-PC variable region profiles were different from and more homologous than anti-MDA. Anti-PC but not anti-MDA were significantly negatively correlated with CV in the whole patient group. In contrast to IgM anti-PC, anti-MDA did not promote polarization of Tregs. Taken together, Anti-PC is decreased in MCTD and also in SLE, SjS and SSc but not in other studied diseases. Anti-PC may thus differentiate between these. In contrast, anti-MDA did not show these differences between diseases studied. Anti-PC level is negatively correlated with CV in the patient group cohort. In contrast to anti-PC, anti-MDA did not promote Treg polarization. These findings could have both diagnostic and therapeutic implications, one possibility being active or passive immunization with PC in some rheumatic conditions

Terapia robótica con el exoesqueleto H2 en la rehabilitación de la marcha en pacientes con lesión medular incompleta. Una experiencia clínica

Background and objective: Robotic exoskeletons have emerged as a promising tool in gait rehabilitation in patients with a spinal cord injury. The aim of this study was to assess the clinical applicability of a new robotic exoskeleton model (Exo H2) in the rehabilitation of people with incomplete spinal cord injury. Material and methods: Exo H2 exoskeleton training was performed for 15 sessions in patients with incomplete subacute spinal cord injury. We analysed the appearance of undesirable events and the patient's perception of pain, fatigue and comfort. In addition, a pilot test was carried out on the possible effectiveness of the device by analysing gait characteristics before and after treatment measured by the 10mWT, the 6mWT, the TUG, the WISCI-II, and the impact on the SCIM III scale.Results: Of a group of 8 patients recruited, we were able to analyse data from 4. No undesirable effects were reported. The VAS value was 2.28 ± 1.55 for pain, 3.75 ± 1.55 for fatigue and 4.17 ± 1.68 for comfort. All values improved on the WISCI-I and the TUG and almost all in the 10MWT and in the 6MWT. Conclusions: The performance of the Exo H2 exoskeleton was robust during a clinical protocol for gait rehabilitation. The treatment was safe, without undesirable effects and with good patient tolerance. These results might justify the performance of clinical trials with an adequate sample size.Antecedentes y objetivo: Los exoesqueletos robotizados han aparecido como una herramienta prometedora en la rehabilitación de la marcha de pacientes con lesión medular. El objetivo es valorar la aplicabilidad en un entorno clínico de un nuevo modelo de exoesqueleto robotizado (Exo H2) en la rehabilitación de la marcha de personas con lesión medular incompleta. Material y métodos: Se realizó el entrenamiento con el exoesqueleto Exo H2 durante 15 sesiones a pacientes con lesión medular incompleta subaguda. Se analizaron la aparición de eventos no deseados, la percepción del paciente en cuanto a dolor, fatiga y comodidad. Además, se realizó una prueba piloto sobre la posible eficacia del dispositivo analizando las características de la marcha antes y después del tratamiento medidas por el 10mWT, el 6mWT, el TUG, el WISCI-II, y la repercusión en la escala SCIM III. Resultados: De los 8 pacientes reclutados, se pudieron analizar los datos de 4. No se reportó ningún efecto no deseado. El valor de EVA sobre el dolor fue de 2,28 ± 1,55; sobre la fatiga fue de 3,75 ± 1,55 y la comodidad fue de 4,17 ± 1,68. Todos mejoraron en el WISCI-II, en el TUG y casi todos en el 10MWT y en el 6MWT. Conclusiones: El funcionamiento del exoesqueleto Exo H2 fue consistente durante un protocolo clínico de rehabilitación de la marcha. Se mostró como una terapia segura, sin efectos no deseados y con buena tolerancia por parte de los pacientes. Estos resultados justifican la realización de ensayos clínicos con un tamaño muestral adecuado

Dcc orchestrates the development of the prefrontal cortex during adolescence and is altered in psychiatric patients

Adolescence is a period of heightened susceptibility to psychiatric disorders of medial prefrontal cortex (mPFC) dysfunction and cognitive impairment. mPFC dopamine (DA) projections reach maturity only in early adulthood, when their control over cognition becomes fully functional. The mechanisms governing this protracted and unique development are unknown. Here we identify dcc as the first DA neuron gene to regulate mPFC connectivity during adolescence and dissect the mechanisms involved. Reduction or loss of dcc from DA neurons by Cre-lox recombination increased mPFC DA innervation. Underlying this was the presence of ectopic DA fibers that normally innervate non-cortical targets. Altered DA input changed the anatomy and electrophysiology of mPFC circuits, leading to enhanced cognitive flexibility. All phenotypes only emerged in adulthood. Using viral Cre, we demonstrated that dcc organizes mPFC wiring specifically during adolescence. Variations in DCC may determine differential predisposition to mPFC disorders in humans. Indeed, DCC expression is elevated in brains of antidepressant-free subjects who committed suicide

COVID-19 Vaccination and New Onset Glomerular Disease: Results from the IRocGN2 International Registry

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Integrative epigenomics in Sjögren's syndrome reveals novel pathways and a strong interaction between the HLA, autoantibodies and the interferon signature

Primary Sjögren's syndrome (SS) is a systemic autoimmune disease characterized by lymphocytic infiltration and damage of exocrine salivary and lacrimal glands. The etiology of SS is complex with environmental triggers and genetic factors involved. By conducting an integrated multi-omics study, we confirmed a vast coordinated hypomethylation and overexpression effects in IFN-related genes, what is known as the IFN signature. Stratified and conditional analyses suggest a strong interaction between SS-associated HLA genetic variation and the presence of Anti-Ro/SSA autoantibodies in driving the IFN epigenetic signature and determining SS. We report a novel epigenetic signature characterized by increased DNA methylation levels in a large number of genes enriched in pathways such as collagen metabolism and extracellular matrix organization. We identified potential new genetic variants associated with SS that might mediate their risk by altering DNA methylation or gene expression patterns, as well as disease-interacting genetic variants that exhibit regulatory function only in the SS population. Our study sheds new light on the interaction between genetics, autoantibody profiles, DNA methylation and gene expression in SS, and contributes to elucidate the genetic architecture of gene regulation in an autoimmune populati

La ciencia de la historia entre el positivismo y el idealismo en la universidad de Valencia (1918-1930)

La ciencia de la historia en España, en el primer tercio del siglo XX