http://hdl.handle.net/10366/4615 Mon, 14 Sep 2026 23:32:12 GMT 2026-09-14T23:32:12Z http://hdl.handle.net/10366/172757 [EN] Introduction. In recent years, cannabidiol (CBD) has been used as an adjunct therapy to anti-seizure medications for the control of seizures in patients with drug-resistant epilepsy. In addition to its anticonvulsant effect, CBD also has well-defined anti-inflammatory properties. Since neuroinflammation can trigger various pro-epileptogenic mechanisms, CBD could play an inhibitory role in this process. Epileptogenesis is the process by which epilepsy becomes a chronic disease following a brain injury, and one of its main characteristics is an increased susceptibility to seizures due to a reduced seizure threshold. However, the role of CBD in modulating this susceptibility remains poorly understood. Methodology. We developed an experimental protocol to discretely measure the seizure threshold (DMST) 7 or 14 days after lithium-pilocarpine-induced status epilepticus (SE) through the administration of small intraperitoneal (i.p.) doses of pentylenetetrazol (15 mg/kg/every 10 min). Results. Using the DMST, we observed a significant decrease in the seizure threshold after SE associated with a hypersensitivity state characterized by irritability and marked weight loss. A separate cohort of rats was treated with CBD (20 mg/kg) for 14 days following SE. Conclusions. Treatment with CBD did not improve the seizure threshold; moreover, it worsened the hypersensitivity state and delayed recovery following SE. Our results suggest that orally administered CBD, at a human-equivalent therapeutic and safe dose, does not improve susceptibility to seizure development after SE. Tue, 11 Aug 2026 00:00:00 GMT http://hdl.handle.net/10366/172757 2026-08-11T00:00:00Z http://hdl.handle.net/10366/172646 [EN]Background: A high prevalence of somatisation is associated with a strong impairment of quality of life. Recent research suggests common underlying mechanism of central sensitisation in functional syndromes and chronic pain, with emotion regulation (ER) processes closely linked to somatic symptoms. This study examines the relationship between negative affect (NA) and anger rumination (AR) and its influence on somatisation. Methods: Five hundred seven individuals participated (mean age = 34.60 ± 13.22 years; 380 women). They completed the Patient Health Questionnaire, Negative Affect Scale, and Displaced Aggression Questionnaire. A crosssectional multivariate factorial relational design was used. Descriptive, multiple linear regression, and mediation analyses were conducted on the total and sex-separated samples. Results: Data analysis revealed a significant positive relationship between NA and AR (r = 0.55, p < 0.01), and both were significantly associated with somatisation (rumination: r = 0.37, p < 0.01; NA: r = 0.54, p < 0.01). Simple linear regressions confirmed that higher levels of NA and AR individually predicted increased somatic symptoms in both sexes. However, multiple regression analyses revealed that the effect of AR on somatisation was reduced in women and became non-significant in men when accounting for NA. Mediation analysis showed a significant indirect effect of AR on somatisation through negative affect (B = 0.005, 95% bootstrap confidence interval [0.004, 0.006]), accounting for 62.5% of the total effect. The mediation pattern was replicated in both women (indirect effect B = 0.005, 95% confidence interval [0.004, 0.007]) and men (indirect effect B = 0.004, 95% confidence interval [0.002, 0.006]). These findings indicated that part of the effect of AR on somatisation occurred under the influence of NA. Conclusions: NA and AR were associated with increased somatic symptoms. These findingssuggest the benefit of developing interventions that encourage the use of functional ER strategies. These can help to reduce NA, which in a prolonged form can constitute a vulnerability for organisms, especially in those people with a tendency to somatise. Thu, 01 Jan 2026 00:00:00 GMT http://hdl.handle.net/10366/172646 2026-01-01T00:00:00Z http://hdl.handle.net/10366/172480 [EN] Cholangiocarcinoma (CCA) is a biliary cancer with a poor prognosis and marked chemoresistance. The transcription factor SOX17, which is essential for cholangiocyte differentiation, is frequently downregulated in CCA, as is the case with several tumor suppressor genes. This study provides a proof-of-concept for further development of cellular therapeutic strategies to restore SOX17 expression in CCA cells. For this aim, we used EGI-1 cells as the target cell model derived from extrahepatic CCA. Recombinant Tat-SOX17 protein was first produced in bacteria and purified using Ni-NTA affinity columns and asymmetric flow-field-flow fractionation. Tat-SOX17 entered EGI-1 cells and reached their nucleus. The addition of the α-fetoprotein signal peptide (AFPsp) to the chimeric protein enabled the efficient secretion of the fusion protein formed by AFPsp, SOX17, and reverse Tat (TatR) by donor cells. For the production of secretome enriched in AFPsp-SOX17-TatR protein, HEK293T cells, derived from embryonic kidney, were used. In EGI-1 cells cultured in the presence of this secretome, target gene expression, cell cycle progression, apoptosis, proliferation, colony formation, and cell migration were assessed. Protein expression and localization were analyzed by Western blotting and immunofluorescence. AFPsp-SOX17-TatR enters EGI-1 cells, reaches their nucleus, and modulates the expression of SOX17-dependent genes, such as ABCB1 and ABCG2. Moreover, a marked reduction in proliferation and colony-forming ability was found. In contrast, no significant effect on cell cycle progression, apoptosis, or cell migration was observed. Similar treatment of immortalized human cholangiocytes also increased their SOX17 content, resulting in upregulation of the cholangiolar marker cytokeratin 7 (CK7), but did not affect their proliferation rate. In conclusion, using chimeric proteins such as AFPsp-SOX17-TatR, which contain components for secretion from donor cells and entry into target cancer cells, can provide a promising approach for treating tumors such as CCA, which are characterized by reduced expression of tumor suppressor genes, including SOX17. Thu, 01 Jan 2026 00:00:00 GMT http://hdl.handle.net/10366/172480 2026-01-01T00:00:00Z http://hdl.handle.net/10366/172475 [EN] Roughly one-third of patients with epilepsy remain drug resistant, underscoring the need for novel therapeutic strategies. Although cannabidiol (CBD) has recently been approved for specific epileptic encephalopathies, its anticonvulsant mechanisms and the influence of biological sex on treatment response remain incompletely understood. In this preclinical study, we evaluated the efficacy, tolerability, pharmacokinetics, and molecular effects of CBD in the GASH/Sal hamster, a genetic model of audiogenic generalized tonic–clonic seizures. Animals received intraperitoneal CBD (200 mg/kg) either acutely or chronically for 14 days. CBD concentrations were measured in serum and brain, while seizure severity, latency, and neuroethological parameters were assessed following acoustic seizure induction. Safety was evaluated through body weight, hematological, and biochemical analyses, and gene expression profiling was performed in the inferior colliculus, the primary epileptogenic focus. CBD achieved measurable systemic and brain exposure after both acute and chronic administration, despite substantial inter-individual variability and no significant sex differences in drug concentrations. CBD reduced audiogenic seizure severity in a time-dependent manner, with greater protection after chronic treatment. CBD also prolonged latency to seizure onset in both sexes (earlier in females). Although complete seizure suppression was more frequent in females than males (37.5% vs. 12.5% after chronic treatment), direct sex comparisons did not reach statistical significance. Notably, higher serum and brain CBD concentrations were associated with lower seizure severity. Chronic CBD administration was well tolerated in both sexes, affecting selected hematological parameters without altering body weight or liver function. Gene expression profiling revealed that transcriptional organization of the inferior colliculus was driven predominantly by biological sex rather than by seizure induction or CBD treatment. Marked sex-dependent differences were observed in serotonergic, endocannabinoid, purinergic, and Sigmar1-related neuroprotective pathways. Within this molecular context, seizure stimulation modulated Trpv1 and Slc29a1, whereas chronic CBD induced pathway-specific, sex-dependent changes involving 5-Htr1a, Adora1, and Cnr1, without eliciting widespread transcriptional remodeling. Collectively, these findings identify CBD as a well-tolerated anticonvulsant in the GASH/Sal model and suggest that pharmacokinetic exposure and the sex-specific molecular organization of the epileptogenic focus contribute to variability in treatment response, highlighting the importance of considering biological sex in cannabinoid-based epilepsy research. Fri, 07 Aug 2026 00:00:00 GMT http://hdl.handle.net/10366/172475 2026-08-07T00:00:00Z 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. Thu, 01 Jan 2026 00:00:00 GMT http://hdl.handle.net/10366/172368 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. Tue, 22 Oct 2024 00:00:00 GMT http://hdl.handle.net/10366/172187 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. Tue, 07 Jul 2026 00:00:00 GMT http://hdl.handle.net/10366/172096 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. Mon, 03 Nov 2025 00:00:00 GMT http://hdl.handle.net/10366/172095 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. Tue, 26 May 2026 00:00:00 GMT http://hdl.handle.net/10366/172094 2026-05-26T00:00:00Z 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. Thu, 01 Jan 2026 00:00:00 GMT http://hdl.handle.net/10366/171852 2026-01-01T00:00:00Z 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. Tue, 31 Mar 2026 00:00:00 GMT http://hdl.handle.net/10366/171519 2026-03-31T00:00:00Z http://hdl.handle.net/10366/171518 [EN]Cell therapy is a promising strategy for tackling neurodegenerative diseases. The most outstanding results with this approach usually involve neuroprotection of damaged neurons at risk of death, but only with limited success. Current therapies are often based on the idea of “one gene, one disease, one drug” for single targets, a concept that limits their actual effectiveness. In contrast, combining different strategies can establish an advanced cell therapy that can slow down neuronal degeneration. In this study, we took advantage of the combination of cell and gene therapy, by transplanting bone marrow stem cells genetically modified to overexpress insulin-like growth factor 1 (IGF1) into a model of selective neurodegeneration, the PCD mouse. This animal is characterized by progressive neuronal loss in the olfactory bulb and alterations in IGF1 levels, among other symptoms. Using different techniques (cell cultures, viral transduction, cell transplants, flow cytometry, qPCR, ELISA, immunohistochemistry, advanced image analysis), our findings showed that neuronal death was virtually blocked, even 130 days after cell transplantation, a result clearly more successful than previous studies. The effects of this transplant are based in part on the regulation of neuroinflammation, increasing the proportion of reactive microglia and reducing that of proinflammatory microglia. In addition, IGF1 overexpression dramatically reduced DNA damage in mutant animals via IGF binding protein 3 pathway: this enhances neuroprotection by complementing the basal effect of cell therapy itself. In summary, our work supports the idea that combining therapeutic approaches and their synergies is a more effective tactic for combating neuronal loss. Sat, 16 May 2026 00:00:00 GMT http://hdl.handle.net/10366/171518 2026-05-16T00:00:00Z http://hdl.handle.net/10366/171410 [EN] Experimental evidence indicates that a high seizure burden can induce cerebral overexpression of P-glycoprotein (P-gp) at the blood–brain barrier, a phenomenon associated with drug-resistant epilepsy under the “transporter hypothesis”, but also at the neuronal level, linked to a reduced seizure threshold, increased seizure severity (SS), status epilepticus (SE), and a high spontaneous death (SD) rate. In contrast, we recently described a progressive reduction in SS and the absence of SE and SD in GASH/Sal hamsters subjected to 45 audiogenic seizures. Here, we examined SS, SE, and the SD, and the expression of P-gp, erythropoietin receptor (EPO-R), hypoxia-inducible factor 1 alpha subunit (HIF-1α) and cyclooxygenase 2 (COX-2), in the brains of GASH/Sal hamsters following 20 audiogenic kindling stimulations (AUK-20). SS was evaluated using the midbrain and limbic severity scales; gene expression was assessed by RT-qPCR and P-gp protein levels were measured by immunohistochemistry and Western blot (IHC/WB) analysis. A modest decrease in midbrain SS was observed, without an increase in the already low limbic SS scores, and no SE or SD events occurred. P-gp levels remained low in both IHC and WB analyses. At the mRNA level, we detected increased EPO-R expression, decreased HIF-1α, and increased COX-2 without an accompanying increased in Abcb1b. Unlike findings from other experimental epilepsy models, AUK-20 in GASH/Sal hamsters does not enhance limbic SS, trigger SE or SD, or induce P-gp overexpression in the brain. Independently of the implications for drug resistance, the lack of cerebral P-gp overexpression without increased SS in the AUK-20-GASH/Sal model supports a potential role of P-gp in modulating seizure severity and epilepsy-associated mortality risk. Thu, 09 Apr 2026 00:00:00 GMT http://hdl.handle.net/10366/171410 2026-04-09T00:00:00Z http://hdl.handle.net/10366/171359 [EN]The cytoskeleton relies heavily on the dynamic nature of microtubules, regulated by posttranslational modifications such as polyglutamylation and deglutamylation. Disruption of its internal balance, particularly through the absence of cytosolic carboxypeptidase 1 (CCP1), leads to cytoskeletal collapse and cell death. An example of this occurrence exists in the Purkinje Cell Degeneration (PCD) mouse, a direct animal model for childhood-onset neurodegeneration with cerebellar atrophy (CONDCA) human disease. Both CONDCA patients and PCD mice suffer a dramatic degeneration of Purkinje cells. Intriguingly, lobe X appears less vulnerable to this insult. This study revealed in wild-type mice that lobe X expresses less Ccp1 compared to other lobes, correlating with its delayed degeneration in PCD mice. Further expression analysis of other deglutamylating enzymes (CCP4 and CCP6) and glutamylating enzymes (TTLL1) revealed distinctive patterns: Ccp4 showed minimal relevance in cerebellum, while Ccp6 displayed a compensatory increase during critical stages. Meanwhile, Ttll1 expression remained consistent across lobes, suggesting that the resistance of lobe X may be related to a more dynamic, hyperglutamylated cytoskeleton. Unraveling the neuroresistance mechanisms of Purkinje cells may help mitigate neuronal loss in CONDCA patients and may offer a glimmer of hope for alleviating the symptoms of other neurodegenerative diseases. Wed, 01 Jan 2025 00:00:00 GMT http://hdl.handle.net/10366/171359 2025-01-01T00:00:00Z http://hdl.handle.net/10366/171017 [EN] This study assesses the performance of no-fee GNSS augmentation systems for tractor guidance. Five no-fee augmentation systems: EGNOS, GLIDE, RTK, VRS-NRTK, and on-site RTK were evaluated in both static and guidance tests over short- and long‑term periods using three GNSS receiver types: low-cost Navilock NL8022MP, mid-range Novatel Smart2, and high-end Harxon TS108PRO. Static tests recorded 24 h of position data from 14 receiver-augmentation configurations on a fixed surface. Guidance tests recorded trajectory data from the 14 configurations during straight-line guidance using a tractor equipped with two GNSS receivers, one under test and one high-precision reference. Results found that: (i) unaugmented GNSS resulted in guidance errors of 2–3 m, reduced below 1 m in pass-to-pass intervals shorter than 15 min; (ii) EGNOS reduced these guidance errors by ∼41%; (iii) GLIDE reduced guidance errors to below 20 cm for pass-to-pass intervals shorter than 15 min, with no long-term improvement; (iv) RTK guidance error decreased as baseline length shortened: >100 km yielded > 17 cm, 20–100 km yielded 3–20 cm, and < 20 km yielded 2–3 cm; (v) VRS-NRTK slightly outperformed RTK with similar baseline lengths; and (vi) on-site RTK enabled 1 cm guidance error. In summary: low-cost receivers without augmentation or with EGNOS result in metre-level errors; mid-range receivers with GLIDE deliver decimetre-level guidance errors in the short term; and high-end receivers using on-site RTK or VRS-NRTK on baselines up to 100 km achieve centimetre-level errors, enabling farmers to replicate tractor trajectories consistently year to year. Tue, 24 Mar 2026 00:00:00 GMT http://hdl.handle.net/10366/171017 2026-03-24T00:00:00Z http://hdl.handle.net/10366/170643 [EN]This paper delves into the prosodic features of speech affected in AD and MD, the type of pathology they are associated with (aphasia, apraxia or aprosodia), as well as the contribution of these alterations to the neurolinguistic field (hemispheric specialization).We used a corpus of spontaneous speech from patients with AD (n=10) and MD (n=10), and a control group with HS (n=10). The results showed a discriminatory significance of VnPVI (in MD), and (Δ)f0 and %V; furthermore, %V is a strong variable to distinguish between speakers with and without pathology, as well as to discriminate between AD and MD along with other variables. There is, however, no correlation with verbal fluency (semantic and phonological) or with MMSE, which would imply a motor type deficit: apraxic type in AD and aprosodic type in MD. These results show certain phonological and typological conditioning, among other issues. Wed, 01 Jan 2025 00:00:00 GMT http://hdl.handle.net/10366/170643 2025-01-01T00:00:00Z