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"

Bibliografía educativa a través de libros y folletos de Bizkaia, 1900-1936

El trabajo que se presenta viene a cubrir un enorme vacío en la investigación bibliográfica referida a asuntos educativos. En un contexto histórico favorable a las reivindicaciones autonomistas se produce un gran avance en el desarrollo de la educación vasca que se refleja en la constante aparición de artículos en la prensa vasca referidos tanto a la escuela pública como a la privada, a la religiosa y a la laica, a las nuevas teorías pedagógicas, al bilingüismo, a la universidad vasca, coeducación, formación de los maestros y labor de los municipios en la educación de los niñosAurkezten den lana bibliografi ikerkuntzan hezgarri arloari dagokionez dagoen hutsunea betetzera dator. Autonomista eskakizunen aldeko textuinguru historiko batean euskal hezkuntzaren bilakaeran aurrerapen handia ematen da eta hori isladatzen da euskal prentsan etengabe agertzen diren artikuluetan bai eskola publikoa bai pribatuari buruz, elebitasunari, euskal unibertsitateari eta hezkidetzari buruz, eta baita ere irakasleen prestakuntza eta udalen lana umeentzako hezkuntzanThis work covers an enormous void in bibliographic investigation with respect to educational maners. In a historical context favourable to autonomous vindications, a great step for ward has been taken in the development of Basque education, which is reflected in the constant appearance of articles in the Basque press referring both to public and private, religions and secular schools, to new pedagogical theorie, bilingualism, to the Basque university, co-education, teacher training and the work of town councils in relation to children's education

Measuring productivity loss in early relapsing-remitting multiple sclerosis

Background Multiple sclerosis is one of the most common causes of neurological disability in young adults with major consequences for their autonomy and capacity to maintain employment. Objective The aim of this study was to assess the impact on work productivity in early-stage relapsing-remitting multiple sclerosis (RRMS). Methods A multicenter, non-interventional study was conducted. Adult patients with a diagnosis of RRMS, a disease duration ≤ 3 years, and an Expanded Disability Status Scale (EDSS) score of 0–5.5 were included. Absenteeism, presenteeism, and unpaid work loss due to RRMS were measured using the Valuation of Lost Productivity (VOLP) questionnaire. The EDSS, SymptoMScreen, 5-item Modified Fatigue Impact Scale, Hospital Anxiety and Depression Scale, Symbol Digit Modalities Test, and Multiple Sclerosis Work Difficulties Questionnaire were used to gather information on disability, patients’ perception of symptom severity, fatigue, mood/anxiety, cognition, and problems in the workplace, respectively. Associations between the VOLP and clinical and work outcomes were analyzed using Spearman's rank correlations. Results A total of 189 patients were included. Mean age (SD) was 36.1 ± 9.4 years and 71.4% were female. Mean disease duration was 1.2 ± 0.8 years. Median EDSS score was 1.0 (IQR 0, 2.0). One hundred thirty patients (68.8%) were working for pay or self-employed. Fifty-three patients (40.8%) reported absence from work in the past 3 months with an average of 14.3 absent workdays. Their health problems resulted in the loss of 3.4% of their actual work time in the past 7 days. Thirty patients got help (11.8 h) with their unpaid work activities in the past 7 days. Absenteeism was significantly correlated with anxiety and depression (rho=0.298 and 0.291, p<0.001), fatigue (rho=0.214, p = 0.014), and symptom severity (rho=0.213, p = 0.015). Presenteeism was significantly correlated with fatigue (rho=0.375, p<0.001), symptom severity (rho=0.373, p<0.001), depression (rho=0.263, p = 0.008), and disability (rho=0.215, p = 0.031). Conclusions Productivity loss even in a RRMS population with short disease duration stresses the need for more efficient treatment control of disease activity from earlier stages

Doñana. Acta vertebrata. vol 17 (1)

Características de los pelajes y las mudas en Arvicola sapidus (Rodentia, Arvicolidae)Alimentación de la grajilla Corvus monedula en tres zonas del sur de EspañaAltura de nidificación del carbonero común, Parus major, en el naranjal: preferencias, limitaciones del medio y relaciones interespecíficasImportancia de los neveros como sustrato de alimentación para los paseriformes de alta montañaEstimas y tamaños de biomasas de artrópodos aplicables al estudio de la alimentación de vertebrados insectívorosAspectos de la ecología del zarapito real (Numenius arquata) en el intermareal de la Ria de Arosa.Reparto temporal de actividades del jabalí (Sus scrofa) en Doñana (SO, España)First successful breeding record of the tufted duck (Aythya fuligula) in Spain. REgagrópilas de lechuza común (Tyto alba) conteniendo cáscaras de huevo de la misma especieSegunda puesta de lechuza común (Tyto alba) asociada al aumento de consumo de topillo campesino (Microtus arvalisDepredación por la nutria (Lutra lutra) del sapo de la Sierra de Gredos (Bufo bufo gredosicola)Algunos datos sobre la alimentación de los pollos de la cigüenuela (Himantopus himantopus) en humedales de la provincia de Ciudad RealSome preliminary results on rabbit energy utilization by the spanish lynx.Variabilidad morfológica de la jutia conga Capromys pilorides (Rodentia, Capromyidae) de CubaPeer reviewe

Long-term prognosis communication preferences in early-stage relapsing-remitting multiple sclerosis.

Multiple sclerosis is one of the most common causes of neurological disability in young adults with major consequences for their future lives. Improving communication strategies on prognosis may help patients deal with the disease and adjust their long-term life goals. However, there is limited information on patients' preferences of long-term prognosis (LTP) communication and associated factors. The aim of this study was to describe patients' preferences and assess the factors associated with LTP communication preferences in early-stage relapsing-remitting multiple sclerosis (RRMS) patients. A multicenter, non-interventional study was conducted. Adult patients with a diagnosis of RRMS, a disease duration from first attack ≤ 3 years, and an Expanded Disability Status Scale (EDSS) score of 0-5.5 were included. The Prognosis in MS questionnaire was used to assess how much patients want to know about their LTP. Different patient-reported measures were administered to gather information on symptom severity, pain, fatigue, mood/anxiety, quality of life, stigma, illness perception, feeling of hopelessness, self-efficacy, information avoidance and coping strategies. Cognition was assessed using the Symbol Digit Modalities Test (SDMT). A multivariate logistic regression analysis was performed to assess the association between LTP information preference and demographic and clinical characteristics, as well as patients' perspectives. A total of 189 patients were included (mean age: 36.1  ±  9.4 years, 71.4% female, mean disease duration: 1.2  ±  0.8 years). Median EDSS score was 1.0 (IQR = 0.0-2.0). A proportion of 68.5% (n  =  126) of patients had never discussed LTP with their neurologists, whereas 69.2% (n = 126) reported interest in knowing it (73.5% at diagnosis). Bivariate analyses suggested that patients were significantly more likely to have higher LTP information preferences if they were male and had a lower SDMT score. Male gender and a lower SDMT score were predictors of LTP information preferences. Patients with early-stage RRMS want to discuss their LTP shortly after diagnosis. Understanding the factors involved may be useful to design individualized communication strategies

Detecting disability using self-reported and clinical assessments in early-stage relapsing-remitting multiple sclerosis: Looking for a complementary approach

Disability accrual is mainly driven by progression independent of relapse activity, which is present even in early stages of relapsing-remitting multiple sclerosis (RRMS) and sometimes overlooked. This multicenter, non-interventional study evaluated whether patient-reported outcomes measures (PROMs) could capture disability in 189 early-stage RRMS patients (mean age: 36.1 ± 9.4 years, 71.4% female, mean disease duration: 1.4 ± 0.8 years, median EDSS: 1.0). The 9-Hole Peg Test (9-HPT), NeuroQoL Upper Extremity (NeuroQoL-UE), Timed 25-Foot Walk (T25-FW), Multiple Sclerosis Walking Scale (MSWS-12), Symbol Digit Modalities Test (SDMT), and Perceived Deficits Questionnaire (PDQ-5) were used to assess hand function, gait, and cognition, respectively. These functions were at least mildly affected in this early-stage population, finding significant correlations between PROMs and clinical assessments. PROMs could enable early-stage RRMS patients to communicate their perceived disability in different domains, assisting clinicians in disease monitoring and decision making

Symptom Severity in Early-stage Relapsing Remitting Multiple Sclerosis (P5-3.009)

Objective: The aim of this study was to assess the illness perception and associated factors in early-stage relapsing remitting multiple sclerosis (RRMS) patients. Background: Patients with early-stage RRMS experience uncertainty and intense emotions as diagnosis is disclosed. Illness perception at this point can influence levels of adjustment, coping strategies, and patients’ well-being. Design/Methods: A multicentre, non-interventional study was conducted. Adult patients with RRMS, disease duration ≤3 years, and Expanded Disability Status Scale (EDSS) score between 0–5.5 were included. The Brief-Illness Perception Questionnaire (B-IPQ) was used to assess patients’ cognitive and emotional illness representation. Patient-reported measures were administered to gather information on different outcomes. A multivariate logistic regression analysis was performed to assess the association between B-IPQ and demographic, clinical characteristics, and patients’ perspectives. Results: A total of 189 patients were included (mean age: 36.1±9.4 years, 71.4% female, mean disease duration: 1.4±0.8 years). Median EDSS score was 1.0 (IQR=0.0–2.0). A proportion of 36.5% (n=69/189) patients had a moderate-to-high threatening illness perception, and 45.5% of patients thought that their MS was caused by psychological factors. Bivariate analyses suggested that patients were significantly more likely to have a threatening disease perception if they were unemployed, received symptomatic treatment, had a higher EDSS, worse hand dexterity and gait, higher perception of pain, fatigue, symptom severity, hopelessness, and worse perception of their quality of life. Also patients that reported workplace barriers, cognitive complaints, and probable cases of anxiety, depression, and stigma. Higher EDSS, symptom severity, worse psychological quality of life, perception of stigma, and higher hopelessness-trait were predictors of moderate-to-high threatening illness perception (OR=2.349, 95%CI:1.276–5.130; OR=1.208, 95%CI:1.089–1.364; OR=1.051, 95%CI:1.018–1.089; OR=3.365, 95%CI:1.152–10.796; OR=41.177, 95%CI:6.942–388.825, respectively, all p<0.05). Conclusions: Threatening illness perceptions are common among patients with early RRMS. Identifying these beliefs and its associated factors and establishing individualized interventions may help patients deal with their condition

Delayed cognitive processing and treatment status quo bias in early-stage multiple sclerosis

Background The evolving therapeutic landscape requires more participation of patients with relapsing remitting multiple sclerosis (RRMS) in treatment decisions. The aim of this study was to assess the association between patient's self-perception, cognitive impairment and behavioral factors in treatment choices in a cohort of patients at an early stage of RRMS. Methods We conducted a multicenter, non-interventional study including adult patients with a diagnosis of RRMS, a disease duration ≤18 months and receiving care at one of the 21 participating MS centers from across Spain. We used patient-reported measures to gather information on fatigue, mood, quality of life, and perception of severity of their MS. Functional metrics (Expanded Disability Status Scale [EDSS], cognitive function by the Symbol Digit Modalities Test [SDMT], 25-foot walk test) and clinical and radiological data were provided by the treating neurologist. The primary outcome of the study was status quo (SQ) bias, defined as participant's tendency to continue taking a previously selected but inferior treatment when intensification was warranted. SQ bias was assessed based on participants treatment preference in six simulated RRMS case scenarios with evidence of clinical relapses and radiological disease progression. Results Of 189 participants who met the inclusion criteria, 188 (99.5%) fully completed the study. The mean age was 36.6 ± 9.5 years, 70.7% female, mean disease duration: 1.2 ± 0.8 years, median EDSS score: 1.0 [IQR=0.0–2.0]). Overall, 43.1% patients (n = 81/188) had an abnormal SDMT (≤49 correct answers). SQ bias was observed in at least one case scenario in 72.3% (137/188). Participant's perception of their MS severity was associated with higher SQ bias (β coeff 0.042; 95% CI 0.0074–0.076) among those with delayed cognitive processing. Higher baseline EDSS and number of T2 lesions were predictors of delayed processing speed (OR EDSS=1.57, 95% CI: 1.11–2.21, p = 0.011; OR T2 lesions=1.50, 95% CI: 1.11–2.03, p<0.01). Bayesian multilevel model accounting for clustering showed that delayed cognitive processing (exp coeff 1.06; 95% CI 1.04–1.09) and MS symptoms severity (exp coeff 1.28; 95% CI 1.22–1.33) were associated with SQ bias. Conclusion Over 40% of patients in earlier stages of RRMS experience delays in cognitive processing that might affect their decision-making ability. Our findings suggest that patients' self-perception of disease severity combined with a delay in cognitive processing would affect treatment choices leading to status quo bias early in the course of their disease

Political manipulation in the 1385 change of dynasties in Portugal: an Iberian detail named Blanca

This article focuses on the role of Blanca (1319–79?) – the granddaughter of monarchs Sancho IV of Castile and Jaume II of Aragon —in the context of the legal process supporting the election of João I of Portugal in the 1385 Coimbra parliament. The topic prompts an inquiry into the different viewpoints on a little known character in the Iberian royal families. First, the methodology employed contrasts the information known about Blanca and the description that Portuguese documents dating from 1385 make of her. These are an inquest and the official election act of João, the first king of the second Portuguese dynasty. After this section, the article seeks to shed light on the impact which the events described in the latter document had on Blanca’s historical context between the end of the 1320s and the 1340s. The article ends with a fresh look at chroniclers’ portrait of Blanca. In short, this article assesses and contrasts several portrayals of reality over several periods in time: the short term in the 1385 parliamentary meeting, Blanca’s lifespan, and finally a long period during which she almost vanished from historiography.info:eu-repo/semantics/publishedVersio