Pathological responses of glial cells in spinal cord injury and rheumatoid arthritis

Scientists have considered glia as mere passive allies of neurons for a long time. As a consequence, their functions have been greatly underestimated. Major discoveries made in the last three decades have changed our view on glial cells and it is now accepted that they play important roles in health and disease. In this thesis, we have investigated the role of 3 glial cell types - astrocytes, microglia and ependymal cells - in spinal cord injury (SCI), rheumatoid arthritis (RA) and in pain-related processes. In Study I, we have delineated the mechanisms that regulate interleukin-6 (IL-6) expression and secretion in adult rat astrocyte cultures. We found that the PI3K-mTORAKT pathway negatively regulates IL-6 expression and that IL-6 secretion is calcium (Ca2+)-dependent. Interestingly, we observed that astrocytes express IL-6 in vivo after SCI, however IL-6 levels decline after 2-3 weeks. Since induction of IL-6 in reactive astrocytes could be beneficial due to the regenerative properties of this cytokine, we treated adult rats 2 weeks after SCI with mTOR inhibitors, torin2 and rapamycin, to boost astrocytic IL-6 secretion by blocking the PI3K-mTOR-AKT pathway and increasing cytosolic Ca2+, respectively. This combinatorial treatment led to a transient improvement in mechanical hypersensitivity during the treatment period. In Study II, we have established an adult ex vivo model of SCI, to facilitate the study of cellular processes that are difficult to address using animal models. In particular, we focused on assessing the ependymal cell response to injury in our model, which is based on adult mouse spinal cord cultured tissue slices. Interestingly, we found that, ependymal cells become activated, proliferate, migrate out of the ependymal layer and differentiate in a manner that fundamentally resembles their response to injury in vivo. Moreover, we show that these cells can respond to external adenosine triphosphate (ATP) stimulation and that some of them have spontaneous Ca2+ activity. We believe that this model is a useful platform to study and modulate ependymal cell responses and could contribute to the development of novel treatment avenues for SCI. In Study III, we have investigated mechanisms that may participate in central sensitization in the context of RA. Here, we report for the first time the presence of disease associated autoantibodies known as ACPA (anti-citrullinated protein antibodies) in the cerebrospinal fluid (CSF) of a subset of RA patients. Moreover, we show that intrathecal injection of such antibodies into the CSF of mice led to pain-like behavior, while injection of other antibodies from RA patients or from healthy individuals did not. Furthermore, we show that co-stimulation of human astrocytes in culture with ACPA and interleukin-1beta (IL-1ß) led to IL-6 secretion in these cells, an effect that was blocked upon addition of an Fc-gamma receptor 1 (FcγRI) inhibitor. These findings support the notion that ACPA may enter the central nervous system (CNS) of RA patients, act on glial cells and activate pathways that could contribute to centrally mediated pain. In Study IV, we have investigated differences between male and female spinal microglia in the context of arthritis-induced persistent pain. We focused on the late phase of the collagen type-II antibody induced arthritis (CAIA) animal model, which occurs after joint inflammation has resolved and it is characterized by persistent mechanical hypersensitivity and spinal glial activation. We found that intrathecal delivery of minocycline, often described as a microglial inhibitor, was able to revert CAIA-induced pain in male, but not female mice. Moreover, using flow cytometry we found that females had lower dorsal horn spinal microglial relative numbers as compared to males. Furthermore, genome-wide RNA sequencing results pointed to several transcriptional differences between male and female microglia, while no convincing differences were identified between control and CAIA groups. Taken together, these results suggest that during the late phase of the CAIA model changes in microglial gene expression might be highly localized or short-lasting, and that the sexually dimorphic response to minocycline might additionally involve other factors such as changes in protein expression or epigenetic modifications. In summary, this thesis expands our understanding of mechanisms that are important in glial cell responses to pathological events and opens new avenues to explore the modulation of glial cells. The ultimate hope is that continued efforts will result in the discovery of suitable targets for therapy in individuals with spinal cord injury, rheumatoid arthritis and chronic pain

Disrupted neuroglial metabolic coupling after peripheral surgery

Immune-related events in the periphery can remotely affect brain function, contributing to neurodegenerative processes and cognitive decline. In mice, peripheral surgery induces a systemic inflammatory response associated with changes in hippocampal synaptic plasticity and transient cognitive decline, however, the underlying mechanisms remain unknown. Here we investigated the effect of peripheral surgery on neuronal-glial function within hippocampal neuronal circuits of relevance to cognitive processing in male mice at 6, 24, and72hpostsurgery. At 6hwedetect theproinflammatorycytokineIL-6inthehippocampus, followedupbyalterations in them RNA and protein expression of astrocyticandneuronal proteinsnecessaryfor optimal energysupplytothebrainandfor thereuptakeandrecycling of glutamate in the synapse. Similarly, at 24 h postsurgery the mRNA expression of structural proteins (GFAP and AQP4) was compromised. At this time point, functional analysis in astrocytes revealed a decrease in resting calcium signaling. Examination of neuronal activity by whole-cell patch-clamp shows elevated levels of glutamatergic transmission and changes in AMPA receptor subunit composition at 72 h postsurgery. Finally, lactate, an essential energy substrate produced by astrocytes and critical for memory formation, decreases at 6 and 72 h after surgery. Based on temporal parallels with our previous studies, we propose that the previously reported cognitive decline observed at 72 h postsurgery in mice might be the consequence of temporal hippocampal metabolic, structural, and functional changes in astrocytes that lead to a disruption of the neuroglial metabolic coupling and consequently to a neuronal dysfunction.This work was supported by a “Ramón y Cajal” fellowship (RYC-2014-15792 to A.G.-C.) from Spanish “Ministerio de Economía y Competitividad”, the Swedish Research Council, the confocal microscope used in the study by Knut and Alice Wallenberg Foundation (Grant KAW2008.0149), and NIH/NIA R01AG057525 to N.T

Management of Primary Dysmenorrhea among University Students in the South of Spain and Family Influence.

The present study analyses the management of primary dysmenorrhea by university students in the south of Spain. In this cross-sectional observational study, 224 women participated, using an ad hoc self-report questionnaire about menstrual pain and self-care and including sociodemographic and gynecological variables. Some 76.8% of participants consumed analgesics and the majority self-medicated with non-steroidal anti-inflammatory drugs (NSAIDs) without consulting a health professional, with a correlation between pain intensity and the number of pills ingested during menstruation (r = 0.151, p < 0.05). The higher proportion of women who found their analgesia effective were those who took medication after being prescribed by a health care provider (60.8%) compared to those who self-medicated (40%; p < 0.01). Only 43.8% employed non-pharmaceutical methods, most commonly antalgic positions, massages and local heat. These choices were not related to the intensity of menstrual pain nor with the severity of the dysmenorrhea, nor did these most common methods prove to be the most effective. However, a higher percentage of women using non-pharmacological methods was identified in women with family members suffering from dysmenorrhea (73.2%) compared to those without (60%; p = 0.040), which may indicate that the choice of remedies is more related to learning self-care in the family context. This study identifies the need for education on self-care and management of menstrual pain.post-print338 K

Menstrual Migraine Among Spanish University Students.

Purpose:This study sought to determine the prevalence of menstrual migraine among female university studentsat the Nursing Faculty of Ciudad Real and to determine possible risk factors.Design and methods:A cross-sectional observational study was performed using a self-report questionnaire. Twohundred and ninety-nine femaleuniversity students participated inthestudy;all were enrolledin the2017/2018academic year at the Faculty of Nursing. Participants were over the age of 18 years and without any diagnosedgynecological pathology. The main measurement tools were menstrual migraine between days−2 and +3 ofthe menstrual cycle, over the previous six cycles.Results:The prevalence of menstrual migraine was 45.15%, identifying the following possible risk factors: dys-menorrhea (OR 9.19; 1.62–6.28% CI), use of hormonal contraceptive methods (OR 2.60; 95% CI 1.30–5.20), men-strual irritability (OR 2.34; 95% CI 1.25–4.40), menstrual dizziness (OR 2.05; 95% CI % 1.12–3.75) and dailyconsumption of cola beverages (OR 1.85; 95% CI % 1.04–3.32).Conclusions:The prevalence of this problem is high among our population and the approach is complex.Practice implications: It is necessary to continue to research the pharmacological measures and methods of phar-macological pain relief as well as interventions directed at lifestyle modifications considering the potential riskfactors involved in menstrual migrainepost-print393 K

Nursing process in a geriatric patient

Presentamos caso de varón de 81 años ingresado en una Residencia de ancianos, en el que elaboraremos un plan de cuidados estandarizados, con el objetivo de mantener su independencia funcional, mejorar su calidad de vida, disminuir la mortalidad y aumentar la esperanza de vida, proporcionando una atención individualizada al anciano y a su entorno. Realizaremos una valoración geriátrica integral y con ello valoraremos, mediante la taxonomía enfermera NANDA, NIC, NOC y la Escala Nutricional (MNA), sus necesidades alteradas siguiendo el modelo de Virginia Henderson. Con la presentación de este caso, pretendemos dar una serie de recomendaciones para la conservación de su salud e independencia funcional, por ser los aspectos más importantes de la promoción de la salud en los adultos de edad avanzada.We present the case of 78 year old man admitted to the Nursing Virgin of Africa, which will produce a standardized care plan, with the objective of maintaining functional independence, improve their quality of life, reduce mortality and increase life expectancy life, providing individualized care to the elderly and their environment. We will make a comprehensive geriatric assessment and thus will value, by nurse taxonomy NANDA, NIC, NOC and Nutritional Scale (MNA), altered their needs along the lines of Virginia Henderson. By presenting this case, we intend to give a series of recommendations for the preservation of health and functional independence, being the most important aspects of health promotion in older adults

Relationship between Diet, Menstrual Pain and other Menstrual Characteristics among Spanish Students.

This study sought to describe and compare adherence to the Mediterranean diet and consumption of local foods from the Huelva region among Spanish university women in relation to menstrual pain and other menstrual characteristics. This cross-sectional study included 311 health science students. The study variables were sociodemographic and gynecologic characteristics, adherence to the Mediterranean diet using the KIDMED questionnaire, alcohol consumption (SDU) and consumption of local food. A descriptive bivariate analysis and multiple binary regression were performed for menstrual pain. Up to 55.3% of participants had moderate adherence to the Mediterranean diet and only 29.6% had high adherence. Women with low adherence had longer menstrual cycles (p < 0.01). Eating less than two pieces of fruit per day (OR = 3.574; 95%CI = 1.474– 8.665; p < 0.05) and eating pulses more than one day a week (OR = 2.320; 95%CI = 1.006–5.348) raised the probability of suffering menstrual pain. A positive correlation between SDU and cycle length was identified (r = 0.119, p = 0.038), and menstrual bleeding was lower in women who consumed olive oil daily (p = 0.044). In conclusion, the Mediterranean diet, alcohol consumption and consuming typical foods from southern Spain appear to influence cycle length, menstrual flow and menstrual pain. Further research is necessary to confirm and expand these findings.post-print315 K

EmoCon: Emotions Analyzer in the Spanish Congress

EmoCon es un prototipo de un analizador de emociones en el Congreso de los Diputados. Su objetivo es analizar el perfil emocional a nivel de sesión parlamentaria y a nivel de cada diputado, a partir de las intervenciones realizadas durante las sesiones parlamentarias que tienen lugar en el Congreso de los Diputados. Para ello, la demo cuenta con tres módulos principales: i) descarga automática de los documentos de las sesiones y extracción de las intervenciones realizadas por cada diputado, ii) análisis de las emociones expresadas a nivel de sesión y a nivel de diputado y, iii) visualización de la información en una aplicación web.EmoCon is a prototype of an emotion analyzer in the Spanish Congress. Its objective is to analyze the emotions expressed by the deputies in the interventions made during the parliamentary sessions that take place in the Spanish Congress. To this end, the demo has three main modules: i) web scrapper for the session documents and processing, ii) emotions analyzer at the session level and at the deputy level, and iii) web application for visualization.Este trabajo ha sido parcialmente financiado por el Fondo Europeo de Desarrollo Regional (FEDER) y el proyecto LIVING-LANG (RTI2018-094653-B-C21) del Gobierno de España

Structural validation of ORTO-11-ES for the diagnosis of orthorexia nervosa

Purpose The ORTO-11-ES questionnaire is a tool to assess the pathological obsession displayed by some individuals regarding healthy eating. The aims of this study were (1) to confirm the factor structure of the Spanish version of ORTO-11-ES using confirmatory factor analysis (CFA) and (2) to examine the possible association between the ORTO-11-ES score, gender and body mass index (BMI). Methods The sample comprised 492 students from the University of Castilla la Mancha, Spain. Of these, 280 were women (56.9%). Participants were surveyed using the ORTO-11-ES questionnaire. Results The confirmatory factor analysis (CFA) supported the 11 elements and 3 domains of this tool as the better fitting model; for the Comparative Fit Index (CFI) and the Tucker–Lewis Index (TLI), the values were 0.94 and 0.91, respectively, and the Root Mean-Square Error of Approximation (RMSEA) was 0.058. The tendency towards orthorexic behavior is more associated with the female gender. The BMI had no influence on the tendency for ON. Conclusions This study is the first attempt to confirm the three-factor structure of a Spanish version of the ORTO-15 questionnaire. These findings suggest that the ORTO-11-ES may be a valuable tool for identifying subjects with specific eating behavior patterns. This information may be useful for health professionals involved in the research, development and implementation of interventions catered to individuals suffering from this eating disorder. Level of evidence Level V, descriptive cross-sectional study