María Torrecilla

High-level athletic performance requires the implementation of personalized strategies based on the analysis of metabolic pathways involved in energy production: phosphagen, glycolytic, and oxidative pathways. In this context, mitochondria play an essential role as the central regulator of energy production, being closely linked to these three pathways. Exercise boosts cellular respiration, which can also be optimized by nutritional interventions and targeted supplementation, promoting mitochondrial biogenesis, reducing oxidative stress and increasing ATP production. These metabolic adaptations improve athletic performance, accelerate recovery processes, and reduce the risk of injury, adapting to the physiological characteristics of each athlete. Moreover, some of these metabolic adaptations converge on specific targets whose expression or activity is also altered in mental disorders. Therefore, the aim of this review is to analyze mitochondrial adaptations induced by exercise and supplementation, evaluating their impact on the phosphagen, glycolytic, and oxidative metabolic pathways, as well as their relationship with optimizing performance and recovery in high-level athletes, with special attention to their potential application to mental health.

Introduction: Treatment-resistant depression (TRD) is a major clinical challenge, and its neurobiological basis remains unclear. The locus coeruleus (LC), a key noradrenergic hub, shows altered activity in TRD models, and serotonergic 5-HT7 receptors have emerged as potential modulators of this circuit. Methods: We assessed the impact of 5-HT7 receptor activation on LC function in Wistar Kyoto rats, an established TRD model, using in vivo extracellular recordings, in vitro patch-clamp assays, and receptor expression analysis. Results: Systemic administration of AS19, a selective 5-HT7 receptor agonist, increased LC neuronal firing in both strains, with a significantly greater effect in Wistar Kyoto rats. This response was prevented by a 5-HT7 antagonist confirming receptor specificity. Glutamatergic blockade altered AS19 effects in a strain-dependent manner, whereas in vitro assays revealed no differential postsynaptic modulation and similar presynaptic inhibition across groups. Western blot analysis showed elevated 5-HT7 receptor expression in the LC, ventral hippocampus, and amygdala of Wistar Kyoto rats, alongside reduced expression in the prefrontal cortex. Conclusion: These findings indicate that 5-HT7 receptor activation exerts complex, circuit-dependent modulation of LC activity, influenced by glutamatergic and serotonergic inputs. Enhanced receptor expression in limbic regions and altered LC responsiveness may contribute to TRD pathophysiology and highlight 5-HT7 signaling as a promising target for novel therapeutic strategies.

Background: Stroke is commonly accompanied by motor disorders secondary to the initial injury, and at the mitochondrial level, there is an increase in oxidative stress, causing tissue damage and relating to alteration in motor function. Functional electrical stimulation (FES) therapies can be useful in stroke patients aimed at restoring motor function and improving life quality. Several studies have recently proposed that electrical stimulation modulates mitochondrial biogenesis and physiology; however, the effect of FES on individual complexes comprising the mitochondrial electron transport chain (mETC) remains unknown. Methods: To study the effect of FES therapy on the activity of the mETC, in vitro analyses were conducted using UV‐spectrophotometry of the activity of the complexes (I, II, and IV), glycerol‐3‐phosphate dehydrogenase (G3PDH), and monoamine oxidase (MAO) in peripheral blood mononuclear cells (PBMCs) obtained from stroke patients. Patients' activity of complex II and MAO was also determined in platelets. Analyses were measured before and after 12 rehabilitation sessions based on FES therapy combined with physical exercises. Results: The results showed that the activity of the mETC, G3PDH, and MAO was significantly reduced in pre‐intervention stroke patients compared to healthy volunteers, both in PBMCs and platelets, except for complex II in platelets and MAO in PBMCs. Interestingly, FES intervention increased the mETC, G3PDH, and MAO activity in both cell types of stroke patients. Conclusions: This preliminary study indicates that intervention can restore motor function and mitochondrial activity, which are damaged in stroke patients. However, more research is needed to determine if changes in mitochondrial activity can be used as biomarkers of the pathology and/or the efficacy of intervention.

Major Depressive Disorder (MDD) is one of the most disabling diseases in the world. MDD is traditionally diagnosed based on a patient’s symptoms, which can lead to misdiagnosis. Although the pathogenic mechanisms of MDD are unknown, several studies have identified mitochondrial dysfunction as a central factor in the onset and progression of MDD. In the context of MDD, alterations in mitochondrial metabolism can lead to imbalances in energy production and oxidative stress, contributing to the disorder´s underlying pathophysiological mechanisms. Consequently, the identification of mitochondrial dysfunction as a key biomarker for early and accurate diagnosis of MDD represents a significant challenge. Faced with the limits of traditional treatments with antidepressants, new pharmacological therapeutic targets are being investigated such as ketamine/esketamine, psychedelics, or anti-inflammatories. All of these drugs show potential antidepressant effects due to their speed of action and ability to modulate neuroplasticity and/or motor processing. In parallel, non-pharmacological therapeutic targets are studied, like Transcranial Magnetic Stimulation (TMS) and Deep Brain Stimulation (DBS), recognized for their ability to modulate neuronal activity and offer treatment alternatives. As cellular activity is directly related to mitochondrial respiration, the aim of this review is examining the link between mitochondrial dysfunction and MDD, assessing how mitochondrial biomarkers could provide a more objective and precise diagnostic tool, and exploring other treatments in addition to traditional antidepressants, with a specific focus on emerging therapeutic targets. Finally, a detailed analysis of the strengths, weaknesses, opportunities, and threats of these approaches was carried out, highlighting the key challenges that must be addressed.

Background: Part of the population over 65 years of age suffer from several pathologies and are therefore polymedicated. In this systematic review and metanalysis, we aimed to determine the efficacy of several strategies developed to improve adherence to pharmacological treatment in polymedicated elderly people. Design: Web Of Science, PubMed and the Cochrane Library were searched until 2 January 2024. In total, 17 of the 1508 articles found evaluated the efficacy of interventions to improve adherence to medication in polymedicated elderly patients. Methodological quality and the risk of bias were rated using the Cochrane risk of bias tool. Open Meta Analyst^® software was used to create forest plots of the meta-analysis. Results: In 11 of the 17 studies, an improvement in adherence was observed through the use of different measurement tools and sometimes in combination. The most frequently used strategy was using instructions and counselling, always in combination, in a single strategy used to improve adherence; one involved the use of medication packs and the other patient follow-up. In both cases, the results in improving adherence were positive. Five studies using follow-up interventions via visits and phone calls showed improved adherence on the Morisky Green scale compared to those where usual care was received [OR = 1.900; 95% CI = 1.104–3.270] (p = 0.021). Discussion: There is a high degree of heterogeneity in the studies analyzed, both in the interventions used and in the measurement tools for improving adherence to treatment. Therefore, we cannot make conclusions about the most efficacious strategy to improve medication adherence in polymedicated elderly patients until more evidence of single-intervention strategies is available.

Neuroinflammation has a significant impact on different pathologies, such as stroke or spinal cord injury, intervening in their pathophysiology: expansion, progression, and resolution. Neuroinflammation involves oxidative stress, damage, and cell death, playing an important role in neuroplasticity and motor dysfunction by affecting the neuronal connection responsible for motor control. The diagnosis of this pathology is performed using neuroimaging techniques and molecular diagnostics based on identifying and measuring signaling molecules or specific markers. In parallel, new therapeutic targets are being investigated via the use of bionanomaterials and electrostimulation to modulate the neuroinflammatory response. These novel diagnostic and therapeutic strategies have the potential to facilitate the development of anticipatory patterns and deliver the most beneficial treatment to improve patients’ quality of life and directly impact their motor skills. However, important challenges remain to be solved. Hence, the goal of this study was to review the implication of neuroinflammation in the evolution of motor function in stroke and trauma patients, with a particular focus on novel methods and potential biomarkers to aid clinicians in diagnosis, treatment, and therapy. A specific analysis of the strengths, weaknesses, threats, and opportunities was conducted, highlighting the key challenges to be faced in the coming years.

La Universidad, como institución académica de enseñanza superior e investigación, debe ser capaz de formar profesionales competentes en diferentes ámbitos de aplicación, preparados para afrontar problemas complejos que requieran un abordaje multidisciplinar. Así mismo, el conocimiento adquirido durante la fase de formación universitaria debe transmitirse de una forma clara y comprensible a la sociedad. En este sentido, las redes sociales pueden representar una interesante herramienta de divulgación para mejorar la comunicación y el acercamiento entre la universidad y la sociedad. Este trabajo planteó un escenario complejo dentro del ámbito sanitario, como es el aumento en la aparición de resistencias a los antibióticos, para que los equipos multidisciplinares formados por alumnado de distintos grados lo trabajasen desarrollando las competencias transversales y específicas de cada grado, estableciendo de esta manera sinergias de colaboración. Posteriormente, se desarrolló un blog en el aula, donde los diferentes equipos de trabajo multidisciplinar reflejaban sus soluciones a los escenarios planteados, utilizando un lenguaje divulgativo para acercar su conocimiento a la sociedad preocupada por el uso adecuado de los antibióticos. De esta manera, mediante la utilización de metodologías activas, el alumnado tomó conciencia de la importancia del trabajo multidisciplinar, así como de la difusión del conocimiento adquirido.

Information about the paper titled "INNOVATIVE ACTIVE LEARNING METHODOLOGIES APPLIED TO HEALTH AND AGING-RELATED BACHELOR’S THESES TO ACHIEVE SUSTAINABLE DEVELOPMENT GOALS: THE RESULTS OF IKASASUN-ODS PROJECT" at IATED Digital Library

Drug side effects are one of the main reasons for treatment withdrawal during clinical trials. Reactive oxygen species formation is involved in many of the drug side effects, mainly by interacting with the components of the cellular respiration. Thus, the early detection of these effects in the drug discovery process is a key aspect for the optimization of pharmacological research. To this end, the superoxide formation of a series of drugs and compounds with antidepressant, antipsychotic, anticholinergic, narcotic, and analgesic properties was evaluated in isolated bovine heart membranes and on cell membrane microarrays from a collection of human tissues, together with specific inhibitors of the mitochondrial electron transport chain. Fluphenazine and PB28 promoted similar effects to those of rotenone, but with lower potency, indicating a direct action on mitochondrial complex I. Moreover, nefazodone, a drug withdrawn from the market due to its mitochondrial hepatotoxic effects, evoked the highest superoxide formation in human liver cell membranes, suggesting the potential of this technology to anticipate adverse effects in preclinical phases.