http://hdl.handle.net/10366/4613 2026-08-23T12:07:11Z http://hdl.handle.net/10366/172424 [EN] Age-related hearing loss (ARHL, presbycusis) is one of the most prevalent sensory impairments in older adults and is characterized by progressive elevation of auditory thresholds, reduced frequency discrimination, and, in advanced stages, disabling hearing loss. Large multicenter studies indicate that ARHL is a major modifiable risk factor for cognitive decline and dementia. This condition reflects not only peripheral cochlear degeneration but also extensive reorganization of the central auditory system, including cortical hyperexcitability, excitation–inhibition imbalance, and age-associated neuroinflammatory processes (“inflammaging”). At the cochlear level, aging predominantly affects outer hair cells, whose degeneration is linked to mitochondrial dysfunction and oxidative stress, ultimately altering ascending sensory input. These peripheral changes, together with age-related epigenetic modifications in the auditory cortex, lead to reduced GABAergic inhibition and alterations in the extracellular matrix and perineuronal nets, thereby promoting a compensatory gain state characterized by hyperexcitability and impaired adaptive synaptic plasticity. Within this framework, cortical electrical stimulation has emerged as a promising therapeutic strategy. Anodal direct current stimulation can modulate neuronal excitability and enhance the molecular machinery underlying synaptic plasticity. Moreover, activation of the auditory cortex may exert downstream effects on the cochlea via corticofugal efferent pathways, potentially conferring otoprotective benefits. This thesis investigates whether repeated epidural anodal stimulation of the auditory cortex at the onset of aging can delay peripheral and central alterations in Wistar rats. Our results demonstrate that this intervention stabilizes auditory thresholds, preserves cochlear function, and maintains auditory-evoked responses. At the cortical level, stimulation preserves excitation–inhibition balance, prevents hyperexcitability, maintains inhibitory interneuron function, and sustains activity-dependent synaptic plasticity. These functional effects are accompanied by robust modulation of auditory cortex gene expression, assessed through transcriptomic sequencing. Transcriptomic analyses reveal that early aging induces widespread gene dysregulation affecting neurotransmission, synaptic plasticity, extracellular matrix remodeling, and inflammatory and preapoptotic pathways. In this context, electrical stimulation counteracts many of these changes, restoring a molecular profile more similar to that of the young auditory cortex. In particular, we observe stabilization of pathways related to inflammaging, oxidative stress, and neurodegeneration, as well as of genes involved in synaptic function and the structural support of interneurons (perineuronal nets). In conclusion, these findings demonstrate that auditory cortex electrical stimulation acts at both peripheral and central levels to slow the progression of presbycusis and the maladaptive reorganization of central auditory pathways. This approach not only preserves auditory function but also mitigates key cellular and molecular mechanisms underlying brain aging, underscoring its potential as a therapeutic strategy to prevent neurodegeneration associated with hearing loss.; [ES] La pérdida auditiva relacionada con la edad (presbiacusia, ARHL) es una de las alteraciones sensoriales más frecuentes en adultos mayores y se caracteriza por un aumento progresivo de los umbrales auditivos, deterioro en la discriminación de frecuencias y, en estadios avanzados, pérdida auditiva incapacitante. Más allá de sus efectos sobre la comunicación, la ARHL se ha identificado como un importante factor de riesgo modificable para el deterioro cognitivo y la demencia. A nivel coclear, el envejecimiento afecta principalmente a las células ciliadas externas, cuya degeneración se asocia con disfunción mitocondrial y estrés oxidativo. Estos cambios en el procesamiento del sonido de la cóclea alteran las entradas sensoriales ascendentes y desencadenan mecanismos de reorganización de la corteza auditiva. A consecuencia de la alteración de las entradas sensoriales y cambios epigenéticos inducidos por la edad en la corteza auditiva se produce una reducción de la inhibición GABA que junto con alteraciones en la matriz extracelular y en las redes perineuronales, lo que favorece un estado de ganancia compensatoria que cursa con hiperexcitabilidad y deterioro de la plasticidad sináptica adaptativa. En este contexto, la estimulación eléctrica cortical ha emergido como una posible estrategia terapéutica. Estudios previos han demostrado que la estimulación anódica de corriente continua puede modular la excitabilidad neuronal y promover plasticidad sináptica. La activación de la corteza auditiva puede influir sobre la cóclea a través de vías eferentes corticofugales, induciendo un potencial efecto otoprotector. La presente tesis evalúa si la estimulación epidural anódica repetida (multisesión) de la corteza auditiva, aplicada en fases tempranas de la presbiacusia, puede retrasar tanto los cambios periféricos como centrales asociados al envejecimiento auditivo en ratas Wistar. Nuestros resultados muestran que esta intervención estabiliza los umbrales y mantiene respuestas auditivas parecidas a las de animales jóvenes. A nivel cortical, la estimulación, mantiene el equilibrio excitación/inhibición, previene la hiperexcitabilidad manteniendo la plasticidad sináptica dependiente de la actividad. Estos resultados se correlacionan con la modificación de la expresión génica en la CA, que se analiza en esta tesis mediante técnicas de secuenciación. El análisis transcriptómico revela que el envejecimiento temprano induce una amplia desregulación génica asociada a neurotransmisión, plasticidad, remodelado de la matriz extracelular y procesos inflamatorios y preapoptóticos. En este contexto, la estimulación eléctrica contrarresta gran parte de estos cambios, restaurando un perfil molecular más similar al de la CA joven. En particular, se observa una estabilización en la expresión de las rutas relacionadas con inflammaging, estrés oxidativo y neurodegeneración, y de genes implicados en la función sináptica y el soporte estructural de interneuronas (perineuronal nets). En conjunto, estos hallazgos indican que la estimulación eléctrica de la corteza auditiva actúa a nivel tanto periférico como central retrasando el envejecimiento sensorial auditivo. A la vista de nuestros resultados este modelo de intervención podría ser una estrategia prometedora para prevenir la neurodegeneración asociada a la pérdida auditiva. 2026-01-01T00:00:00Z http://hdl.handle.net/10366/172390 [EN] To perceive the acoustic world, the auditory system must process a vast array of complex sound signals. Rather than being treated as single units, these signals are decomposed into multiple cues, such as frequency, intensity, timing, and phase differences, which are encoded in a distributed manner across circuits in the lower auditory brainstem (Brugge and Geisler, 1978; Covey and Casseday, 1995; Yin et al., 2002, 2019). This lower portion of the auditory pathway comprises three main relay stations: the cochlear nuclei (CN), the superior olivary complex (SOC), and the nuclei of the lateral lemniscus (NLL). The information encoded in these stations ends up converging in the inferior colliculus (IC), where auditory cues are further processed and integrated to generate more complex representations (Casseday et al., 2002; Malmierca, 2004; Ito and Malmierca, 2018). From the IC, this integrated auditory information is transmitted sequentially to the auditory thalamus and then to the auditory cortex. This prevailing, simplified view of the auditory pathway considers the IC a mandatory relay station for nearly all ascending auditory information originating in the lower auditory brainstem (e.g., Ito, 2020; Opoku-Baah et al., 2021; Sitek et al., 2022; Willett and Groh, 2022; Lee et al., 2024; Meeker et al., 2024; Mitchell and Carney, 2025; Sacco et al., 2025).; [ES] Para percibir el mundo acústico, el sistema auditivo debe procesar una amplia variedad de señales sonoras complejas. En lugar de ser tratadas como unidades únicas, estas señales se descomponen en múltiples pistas, como la frecuencia, la intensidad, el tiempo y las diferencias de fase, que se codifican de manera distribuida a través de circuitos en el tronco encefálico auditivo inferior (Brugge and Geisler, 1978; Covey and Casseday, 1995; Yin et al., 2002, 2019). Esta porción inferior de la vía auditiva comprende tres estaciones principales de relevo: los núcleos cocleares (CN), el complejo olivar superior (SOC) y los núcleos del lemnisco lateral (NLL). La información codificada en estas estaciones termina convergiendo en el colículo inferior (IC), donde las pistas auditivas se procesan e integran adicionalmente para generar representaciones más complejas (Casseday et al., 2002; Malmierca, 2004; Ito and Malmierca, 2018). Desde el IC, esta información auditiva integrada se transmite secuencialmente al tálamo auditivo y después a la corteza auditiva. Esta visión predominante y simplificada de la vía auditiva considera al IC una estación de relevo obligatoria para casi toda la información auditiva ascendente que se origina en el tronco encefálico auditivo inferior (p. ej., Ito, 2020; Opoku-Baah et al., 2021; Sitek et al., 2022; Willett and Groh, 2022; Lee et al., 2024; Meeker et al., 2024; Mitchell and Carney, 2025; Sacco et al., 2025) 2026-01-01T00:00:00Z http://hdl.handle.net/10366/172368 [EN] The second volume of the Research Topic entitled “Innovative approaches in glioma therapy: exploring new therapeutic frontiers,” together with the first volume (Marcos et al.), shows the large number of different strategies that exist to combat glioma. In the first volume, molecular targets (ADORA1, Fyn, metformin, ion channels, and clusterin), prognostic assessment (lysine crotonylation-related long non-coding RNAs), anti-glioma therapies (intraoperative radiotherapy, the combination of photodynamic, and tumor-treating fields therapies) and studies focused on pleomorphic xanthoastrocytoma and the involvement of the gut microbiota in glioma were published (Marcos et al.). Building on this, this second Research Topic expands our understanding of various aspects of glioma, ranging from original articles and patient studies to review articles that compile some of the available information on glioma from a multidisciplinary perspective. Both volumes considerably increase our knowledge on glioma from different approaches. 2026-01-01T00:00:00Z http://hdl.handle.net/10366/172367 [EN] Primary visual cortex (V1), traditionally considered a purely visual area, is increasingly recognized for its role in multisensory processing. According to predictive coding theory, cortical circuits generate expectations about sensory inputs (predictions) and signal deviations from them (prediction errors). To test whether V1 encodes auditory prediction errors, we recorded neuronal activity and LFP from layers IV–VI in urethane-anesthetized rats during auditory oddball and no-repetition control sequences. Recorded neurons from layers V–VI in our sample responded to tones, with many showing stronger responses to deviant than standard stimuli. Deviant responses primarily reflected prediction error rather than repetition suppression and were enhanced under temporally uncertain (random) conditions. Layer V neuronal responses were faster and more phasic, while in layer VI were broader and more sustained. These results reveal that infragranular circuits in V1 encode auditory prediction errors and contextual regularities, positioning V1 as a multimodal inference hub within predictive hierarchy. 2026-01-01T00:00:00Z http://hdl.handle.net/10366/172187 [EN] The visual system of teleost fish grows continuously, which is a useful model for studying regeneration of the central nervous system. Glial cells are key for this process, but their contribution is still not well defined. We followed oligodendrocytes in the visual system of adult zebrafish during regeneration of the optic nerve at 6, 24, and 72 hours post-lesion and at 7 and 14 days post-lesion via the sox10:tagRFP transgenic line and confocal microscopy. To understand the changes that these oligodendrocytes undergo during regeneration, we used Sox2 immunohistochemistry, a stem cell marker involved in oligodendrocyte differentiation. We also used the Click-iT™ Plus TUNEL assay to study cell death and a BrdU assay to determine cell proliferation. Before optic nerve crush, sox10:tagRFP oligodendrocytes are located in the retina, in the optic nerve head, and through all the entire optic nerve. Sox2-positive cells are present in the peripheral germinal zone, the mature retina, and the optic nerve. After optic nerve crush, sox10:tagRFP cells disappeared from the optic nerve crush zone, suggesting that they died, although they were not TUNEL positive. Concomitantly, the number of Sox2-positive cells increased around the crushed area, the optic nerve head, and the retina. Then, between 24 hours post-lesion and 14 days post-lesion, double sox10:tagRFP/Sox2-positive cells were detected in the retina, optic nerve head, and whole optic nerve, together with a proliferation response at 72 hours post-lesion. Our results confirm that a degenerating process may occur prior to regeneration. First, sox10:tagRFP oligodendrocytes that surround the degenerated axons stop wrapping them, change their “myelinating oligodendrocyte” morphology to a “nonmyelinating oligodendrocyte” morphology, and die. Then, residual oligodendrocyte progenitor cells in the optic nerve and retina proliferate and differentiate for the purpose of remyelination. As new axons arise from the surviving retinal ganglion cells, new sox10:tagRFP oligodendrocytes arise from residual oligodendrocyte progenitor cells to guide, nourish and myelinate them. Thus, oligodendrocytes play an active role in zebrafish axon regeneration and remyelination. 2024-10-22T00:00:00Z http://hdl.handle.net/10366/172096 [EN] Background & aims Lifestyle factors may influence disability trajectories in multiple sclerosis (MS), yet prospective data linking sustained dietary adherence to objective clinical outcomes remain limited. Homocysteine, a metabolite involved in one-carbon metabolism, represents a biologically plausible mediator between nutrition and neurodegeneration, although its longitudinal clinical relevance in MS is uncertain. This study aimed to investigate whether adherence to a structured dietary intervention is associated with longitudinal changes in plasma homocysteine levels and disability progression in patients with MS over 12 months. Methods In this prospective cohort study, 41 patients with MS were followed for 12 months. Dietary adherence was quantified using a structured follow-up scale (range 2–6). Plasma homocysteine levels and Expanded Disability Status Scale (EDSS) scores were assessed at baseline, 6 months, and 12 months. Associations between adherence, metabolic changes, and EDSS evolution were evaluated using correlation analyses and multivariate linear regression adjusting for age, sex, BMI, baseline EDSS, and treatment line. Results Baseline mean homocysteine was 10.91 ± 6.94 μmol/L and decreased to 8.24 ± 3.33 μmol/L at 6 months, remaining stable at 8.27 ± 2.42 μmol/L at 12 months. Between-group differences in homocysteine showed a trend toward significance at 12 months (ANOVA p = 0.059). Mean EDSS increased slightly from 1.14 to 1.23 in the overall cohort (p > 0.05). However, EDSS evolution differed according to dietary adherence (ANOVA p = 0.009): low-adherence patients showed a mean EDSS increase (+0.53 ± 0.72), whereas high-adherence patients showed a mean EDSS decrease (−0.56 ± 1.08). Given the low baseline EDSS, short follow-up, and small high-adherence subgroup, these changes should be interpreted as exploratory differences in short-term EDSS trajectory rather than confirmed clinical improvement and do not establish causality. Adherence score was inversely correlated with EDSS change (r = −0.57, p = 0.0006) and remained independently associated in multivariate analysis (β = −0.45, 95% CI −0.68 to −0.22, p = 0.0005). Conclusions Higher adherence to the dietary counselling programme was associated with a more favourable short-term disability trajectory over 12 months. However, causality cannot be inferred, and the clinical significance of these modest changes remains uncertain. Because the adherence score was not formally validated and may partly reflect broader health-related behaviours or engagement with care, and because the dietary intervention was individualized, the study cannot identify specific dietary components or dietary patterns associated with disability trajectories. These exploratory findings require confirmation in larger controlled studies using validated dietary assessment instruments. 2026-07-07T00:00:00Z http://hdl.handle.net/10366/172095 [EN] Introduction: Spain stands out as the European Union country with the highest life expectancy, reaching 83.2 years in 2022. This context is accompanied by population aging and an increase in chronic and degenerative diseases, which translates into greater medication use. In 2022, the National Health System (NHS) dispensed over 1,127.8 million packages. This study aims to evaluate the state of medication dispensation in La Rioja and its relationship with health determinants such as economic conditions, area of residence, age, and gender.Methods: We conducted an observational, retrospective, cross-sectional study between January 2016 and December 2023. A total of 4,108,656 raw e-dispensations (2016–2023) were recorded, from which 1,433,531 unique patient–ATC4–year records (26 frequent subgroups) were analyzed. We included patients aged 14 years and older with electronic dispensations. Variables analyzed included age, gender, socioeconomic level, type and number of dispensations, and the patient’s basic health zone. Statistical analyses employed Chi-square tests for categorical associations and Kruskal–Wallis tests to compare age distributions across ATC4 medication groups, with a significance level of p < 0.05.Results: Proton pump inhibitors (PPIs) were the most dispensed medications in La Rioja, with 82,195 dispensations between 2016 and 2023, followed by propionic acid derivative anti-inflammatory drugs. Antidepressant dispensations increased from 5,281 in 2016 to 7,486 in 2023. Regarding gender differences, women accounted for more dispensations (53.7%). The largest differences favoring women were observed in thyroid hormones, vitamin D, and antidepressant groups. Conversely, medication groups indicated for cardiovascular pathology—such as platelet aggregation inhibitors and angiotensin-converting enzyme inhibitors—showed a significant difference favoring men. Among the elderly, the most dispensed medications also corresponded to families indicated for cardiovascular diseases. By health zones, PPI dispensation was high and homogeneous in the Rioja 1 and Rioja 2 clusters, while anxiolytics and antidepressants stood out in the municipality of San Román and the Guindalera area of Logroño. In socioeconomic terms, pensioners with limited incomes (IHC 002) primarily consumed PPIs, paracetamol, and benzodiazepines, while low-income workers (IHC 003) showed notable dispensation of propionic acid derivatives, PPIs, and paracetamol.Discussion: Our findings align with national and European trends: PPIs and propionic acid derivative anti-inflammatories are the most frequently dispensed medications. Between 2016 and 2023, we observed an increase in the absolute number of unique users in ATC4 subgroup N06AX (Other antidepressants) (+41.8%) and, to a lesser extent, in N06AB (Selective serotonin reuptake inhibitors) (+25.5%), while the annual relative share of N06AB remained essentially stable. Socioeconomic determinants—such as low income and unemployment—appear to directly influence access to and dispensation of medications.Conclusion: Medication dispensation patterns in La Rioja mirror broader national and EU trends, with PPIs and propionic acid derivatives leading. Gender, age, geographic zone, and socioeconomic status are associated with distinct dispensation profiles. Targeted public health strategies should consider these determinants to optimize rational medication use and equity in access. 2025-11-03T00:00:00Z http://hdl.handle.net/10366/172094 [EN] Background: Patient safety is a fundamental pillar of health care quality. Simulation-based training provides a controlled environment for nursing students to develop safety competencies and error-recognition skills before clinical practice. Objective: This systematic review aimed to describe and characterize the simulation-based education features and modalities used to address patient safety outcomes in undergraduate nursing students, identifying the strategies that contribute to improvements in safety-related competencies. Methods: A systematic review was conducted following PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines across PubMed, Web of Science, Scopus, CINAHL, Cochrane, and Lilacs (2019‐2024). Inclusion criteria focused on original studies involving undergraduate nursing students and simulation interventions measuring patient safety outcomes. Studies in languages other than English, Spanish, or Portuguese were excluded. Two reviewers independently performed study selection and data extraction. Methodological quality was assessed using Joanna Briggs Institute tools, applying a 60% quality threshold for inclusion. Results were synthesized through a narrative approach. Results: A total of 20 studies from 12 countries were included. The methodological quality was high (n=14) and moderate (n=6). Findings revealed that high-fidelity simulation and virtual reality are the primary strategies used. Simulation proved effective in enhancing both technical skills (medication administration accuracy) and nontechnical skills (communication via SBAR [Situation, Background, Assessment, Recommendation] and ISBAR [Identification, Situation, Background, Assessment, Recommendation] tools, teamwork, and adverse event reporting). Key strategies contributing to safety included repetitive practice and interprofessional simulation, which significantly improved error detection and clinical judgment. Conclusions: Simulation is an essential pedagogical strategy for preparing nursing students to deliver safe care. Practical implications include the need to integrate structured simulation into nursing curricula to bridge the theory-practice gap. Future research should prioritize longitudinal designs to assess the retention of these safety skills in clinical settings and develop standardized metrics for measuring patient safety outcomes. 2026-05-26T00:00:00Z http://hdl.handle.net/10366/171999 [EN]Despite its established role in breast cancer treatment, Doxorubicin treatment remains subject to adaptive resistance mechanisms that extend beyond cancer cell intrinsic alterations ultimately reducing therapy efficacy. Our study in a MMTV-PyMT-driven mouse breast cancer model reveals that prolonged Doxorubicin (Dox) exposure triggers significant reprogramming of the tumour vasculature, substantially altering the angiocrine landscape and shaping treatment outcomes. Notably, tumours that initially respond, but later revert, display an endothelial cell subclustering with activation of proliferative and NF-κB-dependent cytokine pathways. We further identify a novel endothelial subpopulation characterised by higher expression of drug clearance and oxidative metabolism markers, suggesting an active role in mitigating Dox efficacy and angiogenesis promotion. These findings substantiate endothelial plasticity as a critical mediator of therapeutic failure. By uncovering these vascular adaptations, our work provides a new perspective on the underlying mechanisms of Dox resistance and the prolonged efficacy of chemotherapy in breast cancer. 2026-06-22T00:00:00Z http://hdl.handle.net/10366/171852 [ES]Introducción La imaginería motora (IM) es una herramienta ampliamente utilizada en campos como el deporte o la neurorrehabilitación ya que se ha demostrado que provoca una activación cerebral similar a la que se produce durante el movimiento. Sin embargo, la evidencia sobre su capacidad para inducir activación muscular periférica en el miembro inferior es limitada. El objetivo de este estudio fue analizar la actividad electromiográfica (EMG) durante diferentes condiciones de ejecución real e IM del miembro inferior. Materiales y métodos Participaron 17 adultos sanos, en los que se registró la actividad EMG superficial del recto y el bíceps femoral durante cuatro condiciones: ejecución real e IM guiada de un patrón motor simple (extensión de rodilla) y de un programa motor orientado a objetivo (golpeo de balón). Todos los participantes realizaron una única sesión experimental. La señal EMG se procesó de forma estandarizada y se normalizó respecto al máximo observado durante la ejecución real. Resultados La IM del patrón simple se asoció a incrementos subumbrales, pero significativos de la actividad EMG respecto al reposo, mientras que la IM del programa motor mostró mayor variabilidad interindividual y ausencia de diferencias consistentes frente al nivel basal. No se observaron correlaciones significativas entre la actividad EMG y la capacidad global de IM. Conclusión Estos resultados sugieren que la IM puede inducir activación muscular periférica de baja amplitud, especialmente en tareas motoras simples, mientras que el aumento de la complejidad funcional podría reducir la consistencia de dicha activación. 2026-01-01T00:00:00Z http://hdl.handle.net/10366/171838 [ES] Introducción: La esclerosis múltiple (EM) es una patología neurodegenerativa de carácter crónico, cuya fisiopatología se caracteriza por la presencia de procesos inflamatorios recurrentes y desmielinización a nivel del sistema nervioso central. En el abordaje terapéutico de esta enfermedad, las intervenciones de neurorehabilitación, como los métodos Vojta y Bobath, son comúnmente empleadas en la práctica clínica. No obstante, la evidencia científica disponible sobre su impacto en biomarcadores relacionados con la mielinización, así como en parámetros clínicos específicos, sigue siendo limitada, lo que pone de manifiesto la necesidad de investigaciones adicionales que permitan esclarecer su efectividad en este contexto. Objetivo: Comparar los efectos de la Terapia de Locomoción Refleja de Vojta frente al Método Bobath en sujetos con Esclerosis Múltiple, sobre la presión inspiratoria máxima (PIMax), el equilibrio, la espasticidad, el tiempo de reacción y el perfil lipidómico de ácidos grados relacionados con procesos neuroinflamatorios. Métodos: Se llevó a cabo un ensayo clínico aleatorizado con el objetivo de evaluar la eficacia comparativa de dos enfoques terapéuticos de neurorehabilitación en pacientes diagnosticados con EM. El estudio fue desarrollado en la Clínica de Fisioterapia Aymara Abreu, mientras que el análisis lipidómico se realizó en el Instituto de Neurociencias de Castilla y León (INCYL). La muestra estuvo compuesta por dos grupos: Un grupo de intervención, correspondiente al enfoque de locomoción refleja, el cual recibió sesiones individuales de fisioterapia (n = 16); y el segundo grupo “tratamiento habitual”, basado en el concepto Bobath (n = 12), que recibió un número equivalente de sesiones. Ambos grupos participaron en un programa de intervención de dos sesiones semanales durante un período de 12 meses. Las variables de resultado incluyeron: la Escala de Equilibrio de Berg, la Escala Tardieu, los tiempos de reacción (visual, auditivo y táctil) evaluados mediante el programa Cognifit, la presión inspiratoria máxima (PImax) y los biomarcadores lipídicos presentes en la lágrima. Resultados: La intervención basada en la Terapia de Locomoción Refleja de Vojta, en comparación con el enfoque terapéutico del concepto Bobath, evidenció mejoras significativas en diversos parámetros clínicos y fisiológicos. En particular, se observó un incremento en la presión inspiratoria máxima (PImax), una optimización de la estabilidad postural evaluada mediante la Escala de Equilibrio de Berg, y una disminución de la espasticidad, según los registros obtenidos a través de la Escala de Tardieu. Adicionalmente, se constató una reducción en la latencia de los tiempos de reacción visual, auditivo y táctil, medidos mediante el programa Cognifit. En el ámbito bioquímico, el análisis lipidómico de la lágrima reveló una disminución en los niveles de ácido araquidónico, lo cual podría indicar un menor proceso neuroinflamatorio. Conclusiones: La Terapia Vojta mostró una evolución funcional más consistente que el Método Bobath, observándose ligeras modificaciones en los ácidos grasos estudiados. Asimismo, se evidenciaron mejoras en parámetros fisiológicos funcionales como equilibrio, espasticidad, tiempo de reacción y PIMax. Su aplicación podría representar una estrategia terapéutica prometedora en la neurorrehabilitación. 2026-01-01T00:00:00Z http://hdl.handle.net/10366/171751 [EN]This study aims to design, build, and optimize the performance of a small-scale thermoacoustic engine (TAE) prototype hybrid (piezoelectric/thermoelectric) power generation. Independent variables are predicted using the quadratic model, which are selected based on ANOVA analysis for best fit of experimental data. A Box-Behnken Design (BBD) is applied with 20 treatments. The independent variables considered for evaluation included run time (5–15 min), hot-side heat exchanger (HX) temperature (400–600 °C), resonator length (0.402–0.604 m), cold-side HX temperature (0–27 °C) and working gas (air, N2, CO₂). The results show that the hot-side HX temperature had a significant impact on the total output power (P total), whereas the cold-side HX temperature and resonator length had a relatively mild effect on P total. The working gas type and run time also do not have a significant impact on P total. The optimal conditions for a maximum P total of 65 mW were achieved using nitrogen (N2) as the working gas, under a hot-side HX temperature of 585 °C, resonator length of 0.518 m, and cold-side HX temperature of 2.025 °C. The good fit between experimental and predicted values under optimal conditions confirms the accuracy of the model. Results demonstrate this TAE potential for industrial waste heat recovery application, despite long-term material stability at high temperatures need to be further investigated. 2026-05-01T00:00:00Z http://hdl.handle.net/10366/171673 Auditory mismatch responses—mismatch negativity (MMN) and mismatch fields (MMF)—are well established electrophys-iological markers of automatic auditory discrimination supported by short-term sensory memory. These responses, typicallyelicited using passive oddball paradigms, are increasingly used to investigate sensory and language processing in autism. Thissystematic review synthesizes findings from 55 studies comparing MMN and MMF responses in autistic and typically developing(TD) individuals across childhood, adolescence, and adulthood. Using the Synthesis Without Meta-analysis (SWiM) framework,we identified consistent evidence for smaller MMN amplitudes and reduced MMF power in autistic children and adolescentsrelative to TD peers, particularly in response to frequency, duration, and speech-based deviants. Studies also frequently reportedlonger mismatch latencies in autistic participants and associated these delays with language difficulties and heightened auditorysensitivity. Although some studies reported age-related convergence in MMN and MMF measures between autistic and TDgroups in later childhood or adolescence, greater right-hemisphere lateralization in autistic individuals emerged as a consistentfinding across both speech and non-speech paradigms, suggesting differences in hemispheric weighting for auditory process-ing of linguistic and non-linguistic cues. To explain interindividual and developmental variability in mismatch responses, wepropose a precision-weighted predictive coding account, in which divergent assignment of confidence to sensory predictionerrors may contribute to autism-related differences. While study quality was generally fair, methodological heterogeneity, un-derrepresentation of females, and limited cross-cultural sampling constrain generalizability. Future research should prioritizelongitudinal, sex-stratified, and culturally diverse designs, using standardized protocols and collaborative data practices. MMNand MMF responses hold promise as non-invasive translational biomarkers of early-stage sensory prediction and neurodevelop-mental variation in autism 2026-05-17T00:00:00Z http://hdl.handle.net/10366/171672 [EN] In autism, sensory differences have been linked to altered contextual processing and to how temporal structure supports the formation of regularities and predictions. Here, we examined how temporal and contextual auditory processing are shaped by sex, development, and prenatal valproic acid (VPA) exposure in the non-lemniscal inferior colliculus at low sound levels. Single-unit recordings from control and VPA-exposed rats were obtained using oddball and cascade paradigms, allowing dissociation of mismatch (iMM), repetition suppression (iRS), and prediction-error (iPE) components in both response magnitude and latency.In control animals, maturation selectively reorganized contextual and predictive processing in females, shifting responses toward reduced repetition suppression and increased prediction-error signaling. This shift was accompanied by longer response latencies, indicating a broader temporal integration window. Compared to male rats, adult females displayed prediction-driven, with reduced adaptation bias, of mismatch responses.In contrast, prenatal VPA exposure disrupted this sex- and age-dependent pattern, particularly in females, producing reduced response magnitude together with earlier response peaks. These findings reveal a female-specific reorganization of subcortical contextual processing and demonstrate that sex, age, and prenatal VPA exposure-related effects can dissociate response strength from temporal deployment. Collectively, our results highlight the role of temporal dynamics in contextual computation within the auditory midbrain and support the contribution of early subcortical circuits to autism-related sensory processing 2026-05-10T00:00:00Z http://hdl.handle.net/10366/171671 Brain-derived neurotrophic factor (BDNF) is a master regulator of neuronal differentiation and inhibitory circuit maturation in the mammalian brain. Yet, its downstream mediators in distinct neuronal populations remain incompletely defined. Here, we identify mitogen- and stress-activated kinase 1 (MSK1) as a critical mediator of BDNF signalling during postnatal striatal development. MSK1 expression predominates in GABAergic neurons across the cortex and striatum, with region-specific dynamics: MSK1 expression in cortical GABAergic interneurons declines from postnatal day 5 (P5) to day 30 (P30), while expression in striatal GABAergic medium spiny neurons (MSNs) persists into adulthood. Using a novel Msk1IV KO mouse model, generated by deleting exon IV of Msk1, we find that striatal volume and MSN dendritic complexity decrease by P60, without cortical neuron alterations, underscoring MSK1´s striatal-specific role. Mechanistically, MSK1 drives BDNF-induced MeCP2 phosphorylation at serine 421 in MSNs via MAPK/ERK, independently of CaMKII, forming a nuclear complex with MeCP2, thus amplifying MSK1´s role in transcriptional regulation. This MSK1-MeCP2 signalling is also involved in BDNF-dependent and independent morphological developmental processes of cultured striatal neurons. Accordingly, Msk1IV KO striatum shows dysregulated GABAergic (Gad1, Gabrg3) and dopaminergic (Drd1, Drd2, Drd3) gene expression, mirroring profiles in MeCP2 deficient models. Behaviourally, Msk1IV KO mice display hypersociability, impaired nest-building, and increased depressive-like behaviour in the forced swimming test, contributing to striatal circuit dysfunction. These findings link MSK1-mediated molecular disruptions to inhibitory circuit imbalances and behaviours reminiscent of psychiatric disorders, positioning MSK1 as a potential therapeutic target for neurodevelopmental and psychiatric disorders, including those associated with MeCP2 dysfunction. 2026-05-18T00:00:00Z http://hdl.handle.net/10366/171519 [EN]Nociception, the neural process underlying pain detection, is modulated by the NGF/TrkA signaling axis. Although anti-NGF antibodies can alleviate chronic pain, their clinical application is limited by adverse effects, underscoring the need to identify downstream regulators of this pathway. One such mechanism involves TrkA ubiquitination mediated by Nedd4 E3 ubiquitin ligases, whose activity is modulated by Nedd4 family interacting protein 2 (Ndfip2). Notably, Ndfip2 expression is regulated by TrkA signaling under pain conditions. Here, we characterize the physiological and molecular roles of Ndfip2 in sensory neurons. We demonstrate that Ndfip2 localizes to the endoplasmic reticulum and Golgi apparatus and interacts with TrkA in sensory neurons. Conditional deletion of Ndfip2 in TrkA-expressing cells selectively alters mechanical nociception. Mechanistically, loss of Ndfip2 decreases total TrkA protein levels, downstream activation, and cell-surface exposition, particularly in male-derived dorsal root ganglia neurons. Conversely, Ndfip2 expression reduces mature glycosylated TrkA and promotes the accumulation of non-glycosylated forms, consistent with impaired receptor maturation. Together, these findings identify Ndfip2 as a post-translational regulator of TrkA in TrkA-lineage sensory neurons and establish its in vivo role in mechanical nociception. 2026-03-31T00:00:00Z