Strategies to Improve Therapeutic Adherence in Polymedicated Patients over 65 Years: A Systematic Review and Meta-Analysis.

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.

Efficacy of Acetylcholinesterase Inhibitors on Cognitive Function in Alzheimer's Disease. Review of Reviews.

Alzheimer's disease (AD) is the most common form of dementia over the age of 65. It is estimated that 115.4 million people will be affected by AD by 2050. Acetylcholinesterase inhibitors (AChEI) are the only available and approved treatment for AD. The aim of the present study was to analyse the evidence on the efficacy of the AChEI in the treatment of cognitive symptoms of Alzheimer's disease. For that purpose, a review of review of the systematic reviews (SRs) on this topic was carried out by Web of Science, PubMed, and The Cochrane Library, among others, were searched until 24 September 2021. Thirteen of the 1773 articles evaluated the efficacy of AChEI on cognitive function and/or general condition and/or behavioural disturbances of patients with mild to moderate AD. Methodological quality and risk of bias were rated using the ROBIS scale. The quality of the identified studies was high for nine of them, unclear for two, and finally only in two of the 13 studies did we detect low quality. Overall, AChEI showed very low efficacy in improving cognition in patients with mild to moderate AD. Better results were obtained in improving global state, with donepezil being the most effective treatment. No improvements in behavioural disturbances were found. Few high-quality reviews provide clear evidence of the effects of AChEI on cognition, global change, behaviour, and mortality. The data suggest that AChEI stabilize or slow cognitive deterioration, improving global status. In addition, data indicate that the use of AChEI decreases mortality in patients with mild to moderate AD. However, there is no evidence that they improve patient behaviour. Donepezil is the best therapeutic alternative at a dose of 10 mg/day.

Trabajando la relación Universidad-sociedad. Abordaje multidisciplinar y difusión social / Working the University-Society relationship. Multidisciplinary approach and social diffusion

INTRODUCCIÓN: La transferencia del conocimiento a la sociedad es una de las funciones importantes de la Universidad, lo que implica el uso de un lenguaje y unos medios adecuados hacia los diferentes colectivos de la sociedad, atendiendo a grupos de edad y situaciones socioeconómicas diversas. MATERIALES Y MÉTODOS: A través de las competencias transversales de cada grado, competencias genéricas que se relacionan con la puesta en práctica de una forma integrada de aptitudes, conocimientos y valores adquiridos, se ha realizado este proyecto de innovación docente con alumnado de la Universidad del País Vasco/Euskal Herriko Unibertsitatea. En él se han trabajado las habilidades del alumnado en el uso de diferentes registros de comunicación oral y escritura según la audiencia hacia la que se dirigen. Este trabajo se ha realizado dentro de un equipo multidisciplinar, de forma que el alumnado ha podido conocer y afrontar problemas de salud que requieren una actuación conjunta con otros profesionales del ámbito sanitario y científico. RESULTADOS Y CONCLUSIÓN: Esta interacción entre alumnado de diferentes grados ha permitido su enriquecimiento, proporcionándoles una visión más amplia de lo que pueden aportar los diferentes profesionales frente al mismo problema o reto. Desde este proyecto se ha planteado, a través de metodologías activas, favorecer la interacción entre los futuros profesionales de diferentes disciplinas y concienciar de la importancia de la transmisión de conocimiento a la sociedad, creando redes que contribuyan a la innovación y transferencia

INTRODUCTION: The transfer of knowledge to society is one of the important functions of the university, which implies the use of an appropriate language and means towards the different groups of society, attending to age groups and diverse socio-economic situations. MATERIALS AND METHODS: Through the transversal competences of each Degree, generic competences that are related to the implementation of an integrated form of acquired skills, knowledge and values, this teaching innovation project has been carried out with students from the University of The Basque Country (UPV / EHU). Thus, the student's abilities in the use of different oral and written communication registers according to the target audience have been studied. This work has been carried out within a multidisciplinary team, in such a way that the student has been able to know and face health problems that require joint action with other professionals in the health and scientific field. RESULTS AND CONCLUSION: This interaction among students of different degrees has allowed their enrichment, providing them with a broader vision of what different professionals can contribute to the same problem or challenge. From this project, it has been proposed, through active methodologies, to promote interaction between future professionals from different disciplines, and to raise awareness of the importance of the transmission of knowledge to society, creating networks that contribute to innovation and transfer

Opioid Activity in the Locus Coeruleus Is Modulated by Chronic Neuropathic Pain.

Pain affects both sensory and emotional aversive responses, often provoking depression and anxiety-related conditions when it becomes chronic. As the opioid receptors in the locus coeruleus (LC) have been implicated in pain, stress responses, and opioid drug effects, we explored the modifications to LC opioid neurotransmission in a chronic constriction injury (CCI) model of short- and long-term neuropathic pain (7 and 30 days after nerve injury). No significant changes were found after short-term CCI, yet after 30 days, CCI provoked an up-regulation of cAMP (cyclic 5'-adenosine monophosphate), pCREB (phosphorylated cAMP response element binding protein), protein kinase A, tyrosine hydroxylase, and electrical activity in the LC, as well as enhanced c-Fos expression. Acute mu opioid receptor desensitization was more intense in these animals, measured as the decline of the peak current caused by [Met5]-enkephalin and the reduction of forskolin-stimulated cAMP produced in response to DAMGO. Sustained morphine treatment did not markedly modify certain LC parameters in CCI-30d animals, such as [Met5]-enkephalin-induced potassium outward currents or burst activity and c-Fos rebound after naloxone precipitation, which may limit the development of some typical opioid drug-related adaptations. However, other phenomena were impaired by long-term CCI, including the reduction in forskolin-stimulated cAMP accumulation by DAMGO after naloxone precipitation in morphine dependent animals. Overall, this study suggests that long-term CCI leads to changes at the LC level that may contribute to the anxiodepressive phenotype that develops in these animals. Furthermore, opioid drugs produce complex adaptations in the LC in this model of chronic neuropathic pain.

Ketamine promotes rapid and transient activation of AMPA receptor-mediated synaptic transmission in the dorsal raphe nucleus.

Accumulating evidence indicates that the antidepressant effects of ketamine are, in part, mediated by an increase in the AMPA receptor-mediated neurotransmission in depression related areas, such as the prefrontal cortex (PFC). Therefore, activity in PFC-projecting areas related to major depression, such as the dorsal raphe nucleus (DR), may also be modulated by ketamine. We used whole-cell patch-clamp recordings and western blot experiments to determine whether ketamine promotes acute and maintained alterations in glutamatergic transmission and mTOR pathway in the DR. Bath perfusion of ketamine, but not the NMDA receptor antagonist D-AP5, increased the frequency of AMPA receptor-mediated spontaneous EPSCs (sEPSCs) in DR neurons. However, ketamine did not affect evoked EPSCs or spontaneous inhibitory currents (sIPSCs). Pre-incubation of DR slices with the mTOR inhibitor PP242 decreased the frequency of sEPSCs and prevented the effect of ketamine. The results also show that while no electrophysiological effects were detected 24 h after ketamine administration, phosphorylation levels of mTOR were significantly increased in the DR. Nevertheless, expression levels of synaptic proteins were unaffected at that time. Altogether, the present data demonstrate that ketamine transiently increases spontaneous AMPA receptor-mediated neurotransmission in the DR.

The Neuroprotective Effect of Conditioned Medium from Human Adipose-Derived Mesenchymal Stem Cells is Impaired by N-acetyl Cysteine Supplementation.

Oxidative stress is a common feature in neurodegenerative diseases associated with neuroinflammation, and therefore, has been proposed as a key target for novel therapies for these diseases. Recently, adipose-derived stem cell (ASC)-based cell therapy has emerged as a novel strategy for neuroprotection. In this study, we evaluate the therapeutic role of ASC-conditioned medium (ASC-CM) against H2O2-induced neurotoxicity in a new in vitro model of ec23/brain-derived neurotrophic factor (BDNF)-differentiated human SH-SY5Y neuron-like cells (SH-SY5Yd). In the presence of ASC-CM, stressed SH-SY5Yd cells recover normal axonal morphology (with an almost complete absence of H2O2-induced axonal beading), electrophysiological features, and cell viability. This beneficial effect of ASC-CM was associated with its antioxidant capacity and the presence of growth factors, namely, BDNF, glial cell line-derived neurotrophic factor, and transforming growth factor ß1. Moreover, the neuroprotective effect of ASC-CM was very similar to that obtained from treatment with BDNF, an essential factor for SH-SY5Yd cell survival. Importantly, we also found that the addition of the antioxidant agent N-acetyl cysteine to ASC-CM abolished its restorative effect; this was associated with a strong reduction in reactive oxygen species (ROS), in contrast to the moderate decrease in ROS produced by ASC-CM alone. These results suggest that neuronal restorative effect of ASC-CM is associated with not only the release of essential neurotrophic factors, but also the maintenance of an appropriate redox state to preserve neuronal function.

Fast and Efficient Neural Conversion of Human Hematopoietic Cells.

A major challenge in regenerative medicine is the generation of functionally effective target cells to replace or repair damaged tissues. The finding that most somatic cells can be directly converted into cells of another lineage by the expression of specific transcription factors has paved the way to novel applications. Induced neurons (iNs) represent an alternative source of neurons for disease modeling, drug screening, and potentially, for cell replacement therapy. This unit describes methods for the efficient conversion of blood cells into iNs, including protocols to isolate cord blood CD133+ cells, infect them with Sendai virus vectors that express SOX2 and c-MYC, and differentiate the infected cells (PB-MNCs) into mature neurons. A method to reprogram peripheral blood mononuclear cells into iNs is also described. Support protocols describe how to culture rat astrocytes and characterize the electrophysiology of iNs. © 2016 by John Wiley & Sons, Inc.

Deletion of GIRK2 Subunit of GIRK Channels Alters the 5-HT1A Receptor-Mediated Signaling and Results in a Depression-Resistant Behavior.

BACKGROUND: Targeting dorsal raphe 5-HT1A receptors, which are coupled to G-protein inwardly rectifying potassium (GIRK) channels, has revealed their contribution not only to behavioral and functional aspects of depression but also to the clinical response to its treatment. Although GIRK channels containing GIRK2 subunits play an important role controlling excitability of several brain areas, their impact on the dorsal raphe activity is still unknown. Thus, the goal of the present study was to investigate the involvement of GIRK2 subunit-containing GIRK channels in depression-related behaviors and physiology of serotonergic neurotransmission. METHODS: Behavioral, functional, including in vivo extracellular recordings of dorsal raphe neurons, and neurogenesis studies were carried out in wild-type and GIRK2 mutant mice. RESULTS: Deletion of the GIRK2 subunit promoted a depression-resistant phenotype and determined the behavioral response to the antidepressant citalopram without altering hippocampal neurogenesis. In dorsal raphe neurons of GIRK2 knockout mice, and also using GIRK channel blocker tertiapin-Q, the basal firing rate was higher than that obtained in wild-type animals, although no differences were observed in other firing parameters. 5-HT1A receptors were desensitized in GIRK2 knockout mice, as demonstrated by a lower sensitivity of dorsal raphe neurons to the inhibitory effect of the 5-HT1A receptor agonist, 8-OH-DPAT, and the antidepressant citalopram. CONCLUSIONS: Our results indicate that GIRK channels formed by GIRK2 subunits determine depression-related behaviors as well as basal and 5-HT1A receptor-mediated dorsal raphe neuronal activity, becoming alternative therapeutic targets for psychiatric diseases underlying dysfunctional serotonin transmission.

Fast and efficient neural conversion of human hematopoietic cells.

Neurons obtained directly from human somatic cells hold great promise for disease modeling and drug screening. Available protocols rely on overexpression of transcription factors using integrative vectors and are often slow, complex, and inefficient. We report a fast and efficient approach for generating induced neural cells (iNCs) directly from human hematopoietic cells using Sendai virus. Upon SOX2 and c-MYC expression, CD133-positive cord blood cells rapidly adopt a neuroepithelial morphology and exhibit high expansion capacity. Under defined neurogenic culture conditions, they express mature neuronal markers and fire spontaneous action potentials that can be modulated with neurotransmitters. SOX2 and c-MYC are also sufficient to convert peripheral blood mononuclear cells into iNCs. However, the conversion process is less efficient and resulting iNCs have limited expansion capacity and electrophysiological activity upon differentiation. Our study demonstrates rapid and efficient generation of iNCs from hematopoietic cells while underscoring the impact of target cells on conversion efficiency.