Assessing the presence of oligoclonal IgM bands as a prognostic biomarker of cognitive decline in the early stages of multiple sclerosis

Bandes oligoclonals; Esclerosi múltiple; Disfunció cognitivaBandas oligoclonales; Esclerosis múltiple; Disfunción cognitivaOligoclonal bands; Multiple sclerosis; Cognitive dysfunctionBackground: An association has been found between the presence of lipid-specific oligoclonal IgM bands (LS-OCMB) in cerebrospinal fluid and a more severe clinical multiple sclerosis course. Objective: To investigate lipid-specific oligoclonal IgM bands as a prognostic biomarker of cognitive impairment in the early stages of multiple sclerosis. Methods: Forty-four patients underwent neuropsychological assessment at baseline and 4 years. Cognitive performance at follow-up was compared adjusting by age, education, anxiety-depression, and baseline performance. Results: LS-OCMB+ patients only performed worse for Long-Term Storage in the Selective Reminding Test (p = .018). Conclusion: There are no remarkable cognitive differences between LS-OCMB- and LS-OCMB+ patients in the early stages of MS

Respuestas de oyentes y expertos musicales a una encuesta para valorar la percepción musical en salas de conciertos, auditorios y teatros

Para valorar la percepción musical en salas de concierto se diseñó una encuesta de 58 preguntas en la que cada una se valoraba de 0 a 5 puntos. A esta encuesta han respondido 1057 personas entre público en general y expertos musicales, sin formación especializada en acústica, tras la audición de un concierto en alguno de los 14 auditorios, salas de conciertos y teatros ubicados en diferentes comunidades de nuestro país (8 en el sur y 6 en levante). El análisis de las respuestas obtenidas ha mostrado que la fluctuación de la valoración media de cada una de las preguntas de la encuesta en una sala es un patrón que se repite aproximadamente en todas las salas estudiadas, formando una banda de aproximadamente 1 punto de variación en cada respuesta que contiene a todas las salas. Los límites de esta banda indicarían los extremos de respuesta subjetiva asociada a las salas de conciertos.Ponencia presentada en el Encuentro Ibérico de Acústica. EAA Symposium. Gandía(España). 2006.In order to evaluate the quality of the musical perception in concert halls, a survey with 58 items was designed in which each question was valued from 0 to 5 points. This survey has been replied by 1057 people between general public and musical experts without any specialized formation in acoustics, after the audition of a concert in any of the 14 auditoriums, concert hall or theatres, located in different regions of our country (8 in the south and 6 in the east). The analysis has shown that the fluctuation of the mean valuation of each question of the survey in a determined room is a pattern that is repeated approximately in all of the studied spaces, forming a band of approximately 1 variation point in each answer and that contains to all rooms. The limits of this band would indicate the ends of the subjective response associated to concert halls

First bioelectronic immunoplatform for quantitative secretomic analysis of total and metastasis-driven glycosylated haptoglobin

The glycosylation status of proteins is increasingly used as biomarker to improve the reliability in the diagnosis and prognosis of diseases as relevant as cancer. This feeds the need for tools that allow its simple and reliable analysis and are compatible with applicability in the clinic. With this objective in mind, this work reports the first bioelectronic immunoplatforms described to date for the determination of glycosylated haptoglobin (Hp) and the simultaneous determination of total and glycosylated Hp. The bioelectronic immunoplatform is based on the implementation of non-competitive bioassays using two different antibodies or an antibody and a lectin on the surface of commercial magnetic microcarriers. The resulting bioconjugates are labeled with the horseradish peroxidase (HRP) enzyme, and after their magnetic capture on disposable electroplatforms, the amperometric transduction using the H2O2/hydroquinone (HQ) system allows the single or multiple detection. The developed immunoplatform achieves limits of detection (LODs) of 0.07 and 0.46 ng mL-1 for total and glycosylated Hp in buffer solution, respectively. The immunoplatform allows accurate determination using simple and relatively short protocols (approx. 75 min) of total and glycosylated Hp in the secretomes of in vitro-cultured colorectal cancer (CRC) cells with different metastatic potentials, which is not feasible, due to lack of sensitivity, by means of some commercial ELISA kits and Western blot methodology.Funding Open Access funding provided thanks to the CRUE-CSIC agreement with Springer Nature. Spanish Ministerio de Ciencia e Innovación (PID2019-103899RB-I00 and RTI2018-095756-B-I00), AES-ISCIII Program co-founded by FEDER funds (PI17CIII/00045 and PI20CIII/00019 grants), TRANSNANOAVANSENS-CM Program from the Comunidad de Madrid (Grant S2018/NMT-4349).S

Elaboration process of a subjective response test from listeners and Musical experts, as a tool of evaluation of the musical perception in Concerts halls, auditoria and theatres

In order to tackle the study related to the requirements for musical audition in concert halls, some measurements and analyses of objective acoustic parameters have been made. However, the subjective evaluation of the sensation that the values of these acoustic parameters have on the listeners, can only be shown by means of a questionnaire that listeners have to answer. Such questionnaire has been formulated in an understandable way and the questions are directly or indirectly related to the abovementioned parameters. The aim of the present article is to present the elaboration process of a test of subjective response addressed to the general public and to some musical experts who have no special skills on acoustics. This study has been made in 13 auditoria, concert rooms and theatres distributed in different Autonomous Regions of Spain.Para abordar el estudio de las exigencias para la audición musical en salas de conciertos se realiza la medida y análisis de parámetros acústicos objetivos. Sin embargo, la valoración subjetiva de la sensación que unos u otros valores de esos parámetros acústicos producen en la audiencia, sólo puede ponerse de manifiesto a través de las respuestas de los oyentes a una encuesta cuyas preguntas, formuladas de manera comprensible, estén relacionadas, directa o indirectamente, con dichos parámetros acústicos. El objeto de este artículo es presentar el proceso de elaboración de un test de respuesta subjetiva dirigido al público en general y a expertos musicales pero sin formación especializada en acústica. Este estudio se ha realizado en 13 auditorios, salas de conciertos y teatros repartidos en diferentes Comunidades Autónomas de nuestro país. Ponencia presentada al Encuentro Ibérico de Acústica. EAA Symposium. Gandía (España). 200

Electrochemical immunosensing of Growth arrest‐specific 6 in human plasma and tumor cell secretomes

Growth arrest-specific 6 (GAS6) protein plays a key role in processes related toproliferation,inflammation,angiogenesis,andatheroscleroticplaqueformation.In addition, it has been reported that plasma levels of GAS6 are related to cancerprognosis and other relevant pathologies, such as heart failure or sepsis. Wereport here the first electrochemical immunoplatform for the determination ofGAS6, which has demonstrated to be competitive with other available method-ologies in terms of cost, simplicity, and decentralized application. The developedimmunoplatform involves a sandwich immunoassay using magnetic microparti-cles (MBs) and uses amperometric detection at disposable screen-printed carbonelectrodes (SPCEs). The MBs were modified with an antibody specific to GAS6for its selective capture, which is further recognized by a biotinylated secondaryantibody subsequently labeled with a streptavidin-horseradish peroxidase(Strep-HRP) conjugate. The electrochemical detection was carried out using thehydroquinone (HQ)/H2O2system. The developed bioplatform exhibits a greatselectivity and low limit of detection (27 pg/mL) that allowed the determinationof the GAS6 circulating level in plasma samples from patients suffering heartfailure (HF) and diagnosed with pancreatic ductal adenocarcinoma (PDAC),as well as the determination of the target protein in raw secretomes of humancolorectal cancer cell lines.This work is part of the POSITION-II project funded by the ECSEL Joint Undertaking under grant number Ecsel-783132-Position-II-2017-IA; www.position-2.eu, and PCI2018-093067 (Spanish Ministerio de Ciencia e Innovación) to M.P. The financial support of PID2019-103899RB-I00 (Spanish Ministerio de Ciencia e Innovación) Research Project to S.C., PI17CIII/00045 and PI20CIII/00019 grants from the AES-ISCIII program to R.B. and the TRANSNANOAVANSENS-CM Program from the Comunidad de Madrid (Grant S2018/NMT-4349) to S.C., RTI2018-095672-B-I00 (Spanish Ministerio de Ciencia e Innovación) to P.G.F.; Fundació la Marató de TV3 project 081010 to M.B.; research project PI20/00625, from the AES-ISCIII/FEDER program, to P.N, are gratefully acknowledged. A. Montero-Calle acknowledges the support of the FPU predoctoral contracts by the Spanish Ministerio de Educación, Cultura y Deporte. G.S-F. is recipient of a predoctoral contract (grant number 1193818N) supported by The Flanders Research Foundation (FWO). C. Muñoz-San Martín acknowledges a predoctoral contract from Complutense University of Madrid. R.M. Torrente-Rodríguez acknowledges a Talento-Contract from Comunidad de Madrid (2019-T2/IND-15965).S

Revealing prevalent cancers by interrogating glycoproteins with sustainable immunoelectrochemical tools

Trabajo presentado en el 4th European Biosensor Symposium, celebrado en Aquisgrán (Alemania), del 27 al 30 de agosto de 2023Introduction. The worldwide incidence and death toll of colorectal and pancreatic cancers (CRC and PDAC) have increased considerably since 1990. For this reason, both early detection and regular follow-up are considered key factors in improving patient prognosis. In this sense, the determination of the total content of specific proteins and their aberrantly glycosylated fraction in oncologic processes could help to achieve the proposed goals. Results and Discussion. In this work, two simple but highly competitive electrochemical immunoplatforms for the determination of total and glycosylated post-translational modified haptoglobin (Hp) [1], and CA19-9 [2] (candidate biomarkers associated with colorectal and pancreatic cancer, respectively) are presented. As seen in Figure 1, these biotools are uplifted in the use of magnetic immunocaptors and another antibody or a lectin as detector elements lastly labeled with HRP, which enables subsequent amperometric detection. The presented bioplatforms exhibit attractive characteristics in terms of simplicity, affordability, and point-of-care application compared to the conventional available methodologies, highlighting low detection limits (0.07 and 0.46 ng mL¿1 for total and glycosylated Hp, respectively, and 1.5 U mL¿1 for CA19-9), and short assay times (< 2 h). The workability of these quantitative bioplatforms for the analysis of secretomes from cultured CRC cells with the distinct potential to metastasize (Hp) or serum samples from healthy and PDAC-diagnosed subjects (CA19-9) was assessed to definitely confirm full exploitation of all the above exposed enticing attributes. Conclusions. Our findings clearly revealed the unquestionable ability of these modern electrochemical immunoplatforms to discriminate between healthy and cancer-diagnosed subjects, as well as to assess disease progression, positioning these simple but effective methodologies as advanced electroanalytical tools with proven real biomedical applications, and the hope of aiding in the accurate diagnosis of prevalent and high mortality cancers

Identification of the Immunological Changes Appearing in the CSF During the Early Immunosenescence Process Occurring in Multiple Sclerosis

Patients with multiple sclerosis (MS) suffer with age an early immunosenescence process, which influence the treatment response and increase the risk of infections. We explored whether lipid-specific oligoclonal IgM bands (LS-OCMB) associated with highly inflammatory MS modify the immunological profile induced by age in MS. This cross-sectional study included 263 MS patients who were classified according to the presence (M+, n=72) and absence (M-, n=191) of LS-OCMB. CSF cellular subsets and molecules implicated in immunosenescence were explored. In M- patients, aging induced remarkable decreases in absolute CSF counts of CD4+ and CD8+ T lymphocytes, including Th1 and Th17 cells, and of B cells, including those secreting TNF-alpha. It also increased serum anti-CMV IgG antibody titers (indicative of immunosenescence) and CSF CHI3L1 levels (related to astrocyte activation). In contrast, M+ patients showed an age-associated increase of TIM-3 (a biomarker of T cell exhaustion) and increased values of CHI3L1, independently of age. Finally, in both groups, age induced an increase in CSF levels of PD-L1 (an inductor of T cell tolerance) and activin A (part of the senescence-associated secretome and related to inflammaging). These changes were independent of the disease duration. Finally, this resulted in augmented disability. In summary, all MS patients experience with age a modest induction of T-cell tolerance and an activation of the innate immunity, resulting in increased disability. Additionally, M- patients show clear decreases in CSF lymphocyte numbers, which could increase the risk of infections. Thus, age and immunological status are important for tailoring effective therapies in MS.This work was supported by grants FIS-PI15/00513, FIS-PI18/00572 and RD16/0015/0001 from the Instituto de Salud Carlos III. Ministerio de Ciencia e Innovación, Spain and FEDER: "Una manera de hacer Europa"

Modulation of GABAA receptors and of GABAergic synapses by the natural alkaloid gelsemine

The Gelsemium elegans plant preparations have shown beneficial activity against common diseases, including chronic pain and anxiety. Nevertheless, their clinical uses are limited by their toxicity. Gelsemine, one of the most abundant alkaloids in the Gelsemium plants, have replicated these therapeutic and toxic actions in experimental behavioral models. However, the molecular targets underlying these biological effects remain unclear. The behavioral activity profile of gelsemine suggests the involvement of GABAA receptors (GABAARs), which are the main biological targets of benzodiazepines (BDZs), a group of drugs with anxiolytic, hypnotic, and analgesic properties. Here, we aim to define the modulation of GABAARs by gelsemine, with a special focus on the subtypes involved in the BDZ actions. The gelsemine actions were determined by electrophysiological recordings of recombinant GABAARs expressed in HEK293 cells, and of native receptors in cortical neurons. Gelsemine inhibited the agonist-evoked currents of recombinant and native receptors. The functional inhibition was not associated with the BDZ binding site. We determined in addition that gelsemine diminished the frequency of GABAergic synaptic events, likely through a presynaptic modulation. Our findings establish gelsemine as a negative modulator of GABAARs and of GABAergic synaptic function. These pharmacological features discard direct anxiolytic or analgesic actions of gelsemine through GABAARs but support a role of GABAARs on the alkaloid induced toxicity. On the other hand, the presynaptic effects of the alkaloid provide an additional mechanism to explain their beneficial effects. Collectively, our results contribute novel information to improve understanding of gelsemine actions in the mammalian nervous system

Grupo de expertos del PAPPS. Recomendaciones sobre el estilo de vida

Los determinantes de salud primarios y secundarios explican gran parte de la morbimortalidad observada en atención primaria. Se presentan las recomendaciones del Programa de Actividades Preventivas y Promoción de la Salud (PAPPS) de la semFyC, para la promoción de un estilo de vida saludable mediante la metodología de intervención y las actuaciones preventivas en consumo de tabaco, consumo de alcohol, alimentación saludable, actividad física en el tiempo libre, prevención de accidentes de tráfico y sistemas de retención infantil. Se señalan las pautas más comunes de prevención clínica. Se actualizan las recomendaciones, se señalan aspectos novedosos como la definición de consumo de alcohol de bajo riesgo y se pone al día la bibliografía. Para las principales recomendaciones se incluyen tablas específicas que recogen la calidad de la evidencia y la fuerza de la recomendación. Primary and secondary health determinants explain a large part of the morbidity and mortality observed in primary care. The recommendations of the Program of Preventive Activities and Health Promotion (PAPPS) of the semFyC are presented, for the promotion of a healthy lifestyle through intervention methodology and preventive actions in tobacco consumption, alcohol consumption, healthy eating, physical activity in free time and prevention of traffic accidents and child restraint systems. The most common clinical prevention guidelines are outlined. The recommendations are updated, new aspects are pointed out, such as the definition of low-risk alcohol consumption, and the bibliography is updated. For the main recommendations, specific tables are included that show the quality of the evidence and the strength of the recommendation