Secondary Impacts of COVID-19 Pandemic in Fatigue, Self-Compassion, Physical and Mental Health of People with Multiple Sclerosis and Caregivers: The Teruel Study

COVID-19; Fatiga; AutocompasiónCOVID-19; Fatigue; Self-compassionCOVID-19; Fatiga; AutocompassióThe secondary impacts of the COVID-19 pandemic are distress triggers and risk factors for mental health. Conversely, self-compassion skills and compassionate thoughts/behaviors towards suffering may contribute to their alleviation. Both psychological constructs are interrelated in life-threatening diseases such as multiple sclerosis (MS). The Teruel Study retrospectively evaluated the impact of strict confinement on the 44 people with MS of this Spanish province and 24 caregivers, specifically assessing (1) fears and perceptions; (2) self-compassion (people with MS) and compassion (caregivers); (3) physical and mental health, and fatigue. Despite better housing conditions, people with MS considered confinement very difficult to handle, more than their caregivers, but they were less afraid of COVID-19 and worsening of MS. Still, they recognized worse health than before confinement. Reclusion and lack of walks were the worst of confinement. Caregivers also referred to lack of leisure and uncertainty–fear. All agreed the best was staying with the family, but some found ‘nothing’ positive. Self-compassion remained moderate–high and strongly correlated with their moderate levels of social function, vitality, physical role, and global health. Physical and cognitive fatigue scores were high, and self-compassion negatively correlated with them, explaining a 19% variance in global health. The high compassion of the caregivers did not correlate with any variable.This work received financial support from Memorial Mercedes Llort Sender 2021/80/24091941 to allow this research to be available in open access

Hierarchical Cluster Analysis Based on Clinical and Neuropsychological Symptoms Reveals Distinct Subgroups in Fibromyalgia: A Population-Based Cohort Study

Cluster analysis; Fibromyalgia; Neuropsychological symptomsAnálisis de clústers; Fibromialgia; Síntomas neuropsicológicosAnàlisi de clústers; Fibromiàlgia; Símptomes neuropsicològicsFibromyalgia (FM) is a condition characterized by musculoskeletal pain and multiple comorbidities. Our study aimed to identify four clusters of FM patients according to their core clinical symptoms and neuropsychological comorbidities to identify possible therapeutic targets in the condition. We performed a population-based cohort study on 251 adult FM patients referred to primary care according to the 2010 ACR case criteria. Patients were aggregated in clusters by a K-medians hierarchical cluster analysis based on physical and emotional symptoms and neuropsychological variables. Four different clusters were identified in the FM population. Global cluster analysis reported a four-cluster profile (cluster 1: pain, fatigue, poorer sleep quality, stiffness, anxiety/depression and disability at work; cluster 2: injustice, catastrophizing, positive affect and negative affect; cluster 3: mindfulness and acceptance; and cluster 4: surrender). The second analysis on clinical symptoms revealed three distinct subgroups (cluster 1: fatigue, poorer sleep quality, stiffness and difficulties at work; cluster 2: pain; and cluster 3: anxiety and depression). The third analysis of neuropsychological variables provided two opposed subgroups (cluster 1: those with high scores in surrender, injustice, catastrophizing and negative affect, and cluster 2: those with high scores in acceptance, positive affect and mindfulness). These empirical results support models that assume an interaction between neurobiological, psychological and social factors beyond the classical biomedical model. A detailed assessment of such risk and protective factors is critical to differentiate FM subtypes, allowing for further identification of their specific needs and designing tailored personalized therapeutic interventions.This work was partially supported by the National Institute of Health “Carlos III” in Madrid, Spain through the grant (reference number: PI09/90301)

Análisis descriptivo y comparativo de diferentes métodos de aprendizaje cooperativo (MAC) en el aula

Este proyecto está relacionado con el estudio sobre los métodos de aprendizaje cooperativo en el aula. Este trabajo de colaboración forma parte de otras metodologías, que además de la tradicional, se pueden aplicar en la organización con los alumnos. En el modelo de la escuela tradicional, todavía imperante en la práctica educativa, el profesor es el transmisor del conocimiento, donde las interacciones que se producen son de profesor-alumno y alumno-profesor. Según el enfoque teórico del constructivismo y el aprendizaje entre iguales, es importante que los alumnos construyan sus propios conocimientos y colaboren entre ellos, creando una interdependencia positiva. Este tipo de aprendizaje obedece a un modelo educativo que tiene como base la interacción social (entre los iguales), con el fin de conseguir el progreso de construcción de su propio aprendizaje. A través de este intercambio social, los alumnos adquieren una serie de valores, tales como la participación, toma de decisiones y el respeto hacia los compañeros; en términos generales, predispone hacia el trabajo en equipo y hacia una convivencia pacífica. Es preciso definir el aprendizaje cooperativo, diferenciándolo de la enseñanza tradicional, haciendo hincapié sobre las líneas históricas más relevantes sobre esta cuestión

Evaluación neuropsicológica del aprendizaje verbal y la memoria en mayores de 65 años y estudio de la relación con afectividad

Este estudio evalúa la memoria, las habilidades de aprendizaje y la afectividad de un grupo de personas mayores de 65 años (n=71) con o sin deterioro cognitivo leve (DCL) pertenecientes a 10 Centros de Día de Zaragoza (España). El objetivo es identificar y valorar las variables cognitivas (memoria y habilidades de aprendizaje), así como analizar sus estados emocionales y observar cuál es la capacidad predictiva de éstos en relación a la memoria y al aprendizaje. La muestra presenta ligeras dificultades en el recuerdo inmediato, así como en el recuerdo a corto y largo plazo, muestra también un sesgo de respuesta hacia el “sí” y una baja discriminabilidad. Los afectos tienen validez predictiva sobre las variables relacionadas con la lista de interferencia

Reduced heart rate variability predicts fatigue severity in individuals with chronic fatigue syndrome/myalgic encephalomyelitis

Heart rate variability (HRV) is an objective, non-invasive tool to assessing autonomic dysfunction in chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME). People with CFS/ME tend to have lower HRV; however, in the literature there are only a few previous studies (most of them inconclusive) on their association with illness-related complaints. To address this issue, we assessed the value of different diurnal HRV parameters as potential biomarker in CFS/ME and also investigated the relationship between these HRV indices and self-reported symptoms in individuals with CFS/ME. In this case-control study, 45 female patients who met the 1994 CDC/Fukuda definition for CFS/ME and 25 age- and gender-matched healthy controls underwent HRV recording-resting state tests. The intervals between consecutive heartbeats (RR) were continuously recorded over three 5-min periods. Time- and frequency-domain analyses were applied to estimate HRV variables. Demographic and clinical features, and self-reported symptom measures were also recorded. CFS/ME patients showed significantly higher scores in all symptom questionnaires (p < 0.001), decreased RR intervals (p < 0.01), and decreased HRV time- and frequency-domain parameters (p < 0.005), except for the LF/HF ratio than in the healthy controls. Overall, the correlation analysis reached significant associations between the questionnaires scores and HRV time- and frequency-domain measurements (p < 0.05). Furthermore, separate linear regression analyses showed significant relationships between self-reported fatigue symptoms and mean RR (p = 0.005), RMSSD (p = 0.0268) and HFnu indices (p = 0.0067) in CFS/ME patients, but not in healthy controls. Our findings suggest that ANS dysfunction presenting as increased sympathetic hyperactivity may contribute to fatigue severity in individuals with ME/CFS. Further studies comparing short- and long-term HRV recording and self-reported outcome measures with previous studies in larger CFS/ME cohorts are urgently warranted

Effect of Melatonin Plus Zinc Supplementation on Fatigue Perception in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: A Randomized, Double-Blind, Placebo-Controlled Trial

Síndrome de fatiga crònica; Melatonina; Encefalomielitis miàlgicaSíndrome de fatiga crónica; Melatonina; Encefalomielitis miálgicaChronic fatigue syndrome; Melatonin; Myalgic encephalomyelitisMyalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a complex, multisystem, and profoundly debilitating condition, probably of multifactorial etiology. No effective approved drugs are currently available for its treatment. Several studies have proposed symptomatic treatment with melatonin and zinc supplementation in chronic illnesses; however, little is known about the synergistic effect of this treatment on fatigue-related symptoms in ME/CFS. The primary endpoint of the study was to assess the effect of oral melatonin plus zinc supplementation on fatigue in ME/CFS. Secondary measures included participants’ sleep disturbances, anxiety/depression and health-related quality of life. A proof-of-concept, 16-week, randomized, placebo-controlled, double-blind trial was conducted in 50 ME/CFS patients assigned to receive either oral melatonin (1 mg) plus zinc (10 mg) supplementation (n = 24) or matching placebo (n = 26) once daily. Endpoint outcomes were evaluated at baseline, and then reassessed at 8 and 16 weeks of treatment and 4 weeks after treatment cessation, using self-reported outcome measures. The most relevant results were the significant reduction in the perception of physical fatigue in the Mel-Zinc group at the final treatment follow-up versus placebo (p < 0.05), and the significant improvement in the physical component summary at all follow-up visits in the experimental group. Urinary 6-sulfatoxymelatonin levels were significantly elevated though the treatment in experimental group vs. placebo (p < 0.0001); however, no significantly differences were observed for zinc concentration among participants. Our findings suggest that oral melatonin plus zinc supplementation for 16 weeks is safe and potentially effective in reducing fatigue and improving the quality of life in ME/CFS. This clinical study was registered on ClinicalTrials.gov (NCT03000777)J.C.-M. received financial support from the Laboratorios Viñas, S.A. (Barcelona, Spain). This study was supported by the Vall d’Hebron University Hospital (Barcelona, Spain). The Laboratorios Viñas, S.A. supplied both treatments (melatonin plus zinc supplement and placebo)

Identification of Sclerostin as a Putative New Myokine Involved in the Muscle-to-Bone Crosstalk

Bone and muscle have been recognized as endocrine organs since they produce and secrete “hormone-like factors” that can mutually influence each other and other tissues, giving rise to a “bone–muscle crosstalk”. In our study, we made use of myogenic (C2C12 cells) and osteogenic (2T3 cells) cell lines to investigate the effects of muscle cell-produced factors on the maturation process of osteoblasts. We found that the myogenic medium has inhibitory effects on bone cell differentiation and we identified sclerostin as one of the myokines produced by muscle cells. Sclerostin is a secreted glycoprotein reportedly expressed by bone/cartilage cells and is considered a negative regulator of bone growth due to its role as an antagonist of the Wnt/β-catenin pathway. Given the inhibitory role of sclerostin in bone, we analyzed its expression by muscle cells and how it affects bone formation and homeostasis. Firstly, we characterized and quantified sclerostin synthesis by a myoblast cell line (C2C12) and by murine primary muscle cells by Western blotting, real-time PCR, immunofluorescence, and ELISA assay. Next, we investigated in vivo production of sclerostin in distinct muscle groups with different metabolic and mechanical loading characteristics. This analysis was done in mice of different ages (6 weeks, 5 and 18 months after birth) and revealed that sclerostin expression is dynamically modulated in a muscle-specific way during the lifespan. Finally, we transiently expressed sclerostin in the hind limb muscles of young mice (2 weeks of age) via in vivo electro-transfer of a plasmid containing the SOST gene in order to investigate the effects of muscle-specific overproduction of the protein. Our data disclosed an inhibitory role of the muscular sclerostin on the bones adjacent to the electroporated muscles. This observation suggests that sclerostin released by skeletal muscle might synergistically interact with osseous sclerostin and potentiate negative regulation of osteogenesis possibly by acting in a paracrine/local fashion. Our data point out a role for muscle as a new source of sclerostin.Bone and muscle have been recognized as endocrine organs since they produce and secrete “hormone-like factors” that can mutually influence each other and other tissues, giving rise to a “bone–muscle crosstalk”. In our study, we made use of myogenic (C2C12 cells) and osteogenic (2T3 cells) cell lines to investigate the effects of muscle cell-produced factors on the maturation process of osteoblasts. We found that the myogenic medium has inhibitory effects on bone cell differentiation and we identified sclerostin as one of the myokines produced by muscle cells. Sclerostin is a secreted glycoprotein reportedly expressed by bone/cartilage cells and is considered a negative regulator of bone growth due to its role as an antagonist of the Wnt/β-catenin pathway. Given the inhibitory role of sclerostin in bone, we analyzed its expression by muscle cells and how it affects bone formation and homeostasis. Firstly, we characterized and quantified sclerostin synthesis by a myoblast cell line (C2C12) and by murine primary muscle cells by Western blotting, real-time PCR, immunofluorescence, and ELISA assay. Next, we investigated in vivo production of sclerostin in distinct muscle groups with different metabolic and mechanical loading characteristics. This analysis was done in mice of different ages (6 weeks, 5 and 18 months after birth) and revealed that sclerostin expression is dynamically modulated in a muscle-specific way during the lifespan. Finally, we transiently expressed sclerostin in the hind limb muscles of young mice (2 weeks of age) via in vivo electro-transfer of a plasmid containing the SOST gene in order to investigate the effects of muscle-specific overproduction of the protein. Our data disclosed an inhibitory role of the muscular sclerostin on the bones adjacent to the electroporated muscles. This observation suggests that sclerostin released by skeletal muscle might synergistically interact with osseous sclerostin and potentiate negative regulation of osteogenesis possibly by acting in a paracrine/local fashion. Our data point out a role for muscle as a new source of sclerostin

Cytology Smears: An enhanced alternative method for colorectal cancer pN Stage-A multicentre study

Stage II colorectal cancer (CRC) recurrence remains a clinical problem. Some of these patients are true stage III CRC with a pN0 pathology stage. This large prospective multicentre cohort study aimed at evaluating the diagnostic ability of lymph node (LN) cytology smears to perform the pN stage and compare it with the conventional haematoxylin and eosin (H&E) pathology pN stage. Additionally, we used the One-Step Nucleic Acid Amplification (OSNA), a high-sensitive molecular method of LN staging. A total of 3936 fresh LNs from 217 CRC surgical specimens were examined by three methods, H&E, LN cytology smears, and OSNA. H&E detected 29% of patients with positive LNs, cytology smears 35%, and OSNA 33.2% (p < 0.0001). H&E and cytology concordantly classified 92.2% of tumours, and 88.5% between OSNA and HΕ Cytology had 96.8% sensitivity and 90.3% specificity to discriminate positive/negative patients compared to H&E (p = 0.004), and 87.3% sensitivity and 89% specificity when compared to OSNA (p = 0.56). Patients with positive LNs detected by any of the three methods had significantly worse disease-free and overall survival. We conclude that pN stage accuracy for detecting positive LNs is superior with LN cytological smears than with conventional H&E, which would enable a better pN stage and management of early-stage CRC patients.This research was funded by Fondo de Investigación Sanitaria grant number PI17/01304, PI20/00863, awarded to MC and JC. We acknowledge the Agència de Gestió d’Ajuts Universitaris i de Recerca (Generalitat de Catalunya, GRC 2017SGR653,). This article is based upon work from COST Action CA17118, supported by COST (European Cooperation in Science and Technology). www.cost.eu. SL holds a PFIS grand from Instituto de Salud Carlos iii and co-funded by the European Regional Development Fund (ERDF) (FI18/00221)