Melodic Intonation Therapy in Post-Stroke Non-Fluent Aphasia and Its Effects on Brain Plasticity

Melodic Intonation Therapy (MIT) is one of the most well-known therapies for the rehabilitation of speech in patients with non-fluent aphasia and which is thought to promote right-hemisphere involvement in language processing. This review focuses on the study of language lateralization and/or neuroplastic reorganization with neuroimaging and/or neurophysiological techniques in non-fluent aphasic patients post-stroke during or after MIT. A systematic search was carried out according to the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) in databases (PubMed, Scopus, EMBASE, Dialnet, Web of Science, Cochrane) with the keywords melodic intonation therapy, neuroimaging, functional magnetic resonance, and positron emission tomography and the boolean operators AND and OR. Articles including patients of all ages and either sex with any type of aphasia post-stroke and in any language, which studied language lateralization and/or neuroplastic reorganization after or during MIT were included. Articles which did not achieve the objectives, revisions and conferences were excluded. Different results were obtained from the 16 studies included in the review: predominantly greater activation of the right hemisphere but also of the left hemisphere or both. MIT is an effective therapy to rehabilitate non-fluent aphasic patients post-stroke. It involves different neurobiological mechanisms and depends on multiple individual factors. Studies with larger samples are necessary.Open access funding provided by University of Málaga and PAIDI Group CTS 159

Biomechanical Assessments in Woodwind Musicians: A Systematic Review.

Biomechanical methods are frequently used to provide information about the kinematics and kinetics of posture and movement during musical performance. The aim of this review was to identify and analyze the biomechanical methods performed on woodwind musicians to understand their musculoskeletal demands. A systemic review was carried out following the guidelines of the document Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). It was registered in PROSPERO (code 430304).The databases PubMed, Cochrane, CINAHL, Scopus, and Web of Science were consulted between January 2000 and March 2022. The search in the databases identified 1625 articles, and 16 different studies were finally included in the review, with a sample size of 390 participants. Pressure sensors, surface electromyography, infrared thermography, goniometry in two dimensions, and ultrasound topometry in three dimensions were biomechanical methods useful to broaden the knowledge of musculoskeletal demands during musical practice. Piezoresistive pressure sensors were the most widely used method. The great heterogeneity of the studies limited the comparability of the results. The findings raised the need to increase both the quantity and the quality of studies in future research.Partial funding for open access charge: Universidad de Málag

Psychosocial interventions reduce cortisol in breast cancer patients: systematic review and meta-analysis

IntroductionCancer initiation, progression and recurrence are intricate mechanisms that depend on various components: genetic, psychophysiological, or environmental. Exposure to chronic stress includes fear of recurrence that can affect biological processes that regulate immune and endocrine systems, increase cancer risk, and influence the survival rate. Previous studies show that psychological interventions might influence the level of cortisol that has been extensively used as a biomarker for measuring hypothalamic-pituitary-adrenal axis functioning and body's immunity response. This meta-analysis aimed to provide a quantitative scrutiny of the effect of certain types of psychosocial interventions on cortisol as a neuroendocrine biomarker in saliva or blood and might predict breast cancer (BC) progression.MethodsA literature search was performed in the following databases: PubMed, The Cohrane Library, Scopus, WOS, PsychInfo, Google Scholar, Ovid Science Direct. After methodical selection of originally generated 2.021 studies, the search yielded eight articles that met inclusion criteria. All these studies explored effects of psychosocial interventions that measured cortisol in total of 366 participants with BC, stages 0-IV, in randomized control trial or quasi experimental study design setting. We applied random effects model to conduct meta-analyses on the parameters of salivary and plasma cortisol and used PRISMA Guidelines as validated methodology of investigation to report the results.ResultsEight studies selected for meta-analysis have shown the reduction of cortisol level due to applied psychosocial intervention. The random effects model showed that interventions produced large effect sizes in reductions of cortisol in blood (Cohen's d = −1.82, 95% Confidence Interval (CI): −3.03, −0.60) and slightly less in saliva (d = −1.73, 95%CI: −2.68, −0.78) with an overall effect of d = −1.76 (95%CI: −2.46, −1.07).ConclusionOur study concluded that certain types of psychosocial interventions reduce cortisol (indicator of chronic stress) in patients with BC. Application of specific psychosocial support as adjuvant non-invasive therapy for affected females with BC at all phases of treatment could contribute to more cost-effective health care

Stability study over time of clinical solutions of ziv-aflibercept prepared in infusion bags using a proper combination of physicochemical and functional strategies

The study was entirely funded by Project FIS: PI-17/00547(Instituto Carlos III, Ministerio de Economia y Competitividad, Spain), which means that it was also partially supported by European Regional Development Funds (ERDF).A range of biopharmaceutical products are used to target Vascular Endothelial Growth Factor (VEGF), including Eylea (R) (aflibercept, AFL) and Zaltrap (R) (ziv-aflibercept, ziv-AFL). The first is indicated for ophthalmological diseases such as neovascular (wet) age-related macular degeneration, while the second is used in the treatment of metastatic colorectal cancer. The stability of AFL in prefilled syringes has been widely studied; however, no research has yet been done on the stability of ziv-AFL in polyolefin infusion bags. Therefore, the purpose of the present research is to evaluate the stability of ziv-AFL (Zaltrap (R)) clinical solutions prepared under aseptic conditions in polyolefin infusion bags at two different concentrations, i.e. 4.0 and 0.6 mg/mL, and stored refrigerated in darkness at 2-8 degrees C for 14 days. With that aim, the ziv-AFL clinical solutions were assessed by analysing changes in its physicochemical and functional properties. The distribution of the particulates was studied over a range of 0.001-10 mu m by Dynamic Light Scattering (DLS); oligomers were analysed by Size-Exclusion High-Performance Chromatography with Diode Array Detection (SE/HLPC-DAD); the secondary structure of the protein was studied by far UV Circular Dichroism (CD) and the tertiary structure by Intrinsic Tryptophan Fluorescence (IT-F) and Intrinsic Protein Fluorescence (IP-F); charge variants were assessed by Strong Cation Exchange Ultra High-Performance Chromatography with UV detection (SCX/UHPLC-UV); functionality was evaluated by ELISA by measuring the biological activity as manifested in the extension of the immunological reaction of the ziv-AFL with its antigen (VEGF). Neither aggregation nor oligomerization were detected by the techniques mentioned above. Secondary and tertiary structures remained unchanged over the 14-day period, as did charge variants. The functionality observed initially was maintained along time. Therefore, it could be proposed that the ziv-AFL clinical solutions studied showed great physicochemical and functional stability over a period of two weeks, regardless of the concentration, i.e. 4 or 0.6 mg/mL.Project FIS (Instituto Carlos III, Ministerio de Economia y Competitividad, Spain) PI-17/00547European Commissio

Comprehensive biophysical and functional study of ziv-aflibercept: characterization and forced degradation

This study was entirely funded by Project FIS: PI-17/00547 (Instituto Carlos III, Ministerio de Economia y Competitividad, Spain), which means that it was also partially supported by European Regional Development Funds (ERDF).Aflibercept (AFL) is an Fc fusion protein used in the treatment of colorectal cancers and different ophthalmological diseases. There are two medicines in which AFL is the active substance: Zaltrap and Eylea, referred as ziv-AFL and AFL respectively. No proper accelerated degradation studies were published on either AFL or ziv-AFL. These studies are essential during research, development and manufacturing stages. Here, we characterized ziv-AFL and submitted it to different stress conditions: light, 60 °C, freeze-thaw cycles, changes in pH, high hypertonic solution and strong denaturing conditions. We used an array of techniques to detect aggregation (SE-HPLC/DAD and DLS), changes in secondary structure (Far-UV circular dichroism), changes in conformation or tertiary structure (Intrinsic tryptophan fluorescence) and alterations in functionality (ELISA). Results indicate that aggregation is common degradation pathway. Two different types of aggregates were detected: dimers and high molecular weight aggregates attributed to β-amyloid-like structures. Secondary structure was maintained in most of the stress tests, while conformation was altered by almost all the tests except for the freeze-thaw cycles. Functionality, evaluated by its immunochemical reaction with VEGF, was found to be stable but with decrease when exposed to light and with likely partial inactivation of the drug when pH was altered.European Union (EU) FIS: PI-17/0054

Neuropeptide Y receptor 1 and galanin receptor 2 (NPY1R-GALR2) interactions in the dentate gyrus and their relevance for neurogenesis and cognition

Introduction: This study may unveil novel insights into the interactions between neuropeptide Y receptor 1 (NPY1R) and galanin receptor 2 (GALR2), in the dentate gyrus of the dorsal hippocampus, shedding light on their role in neurogenesis and cognitive functions. Existing literature highlights the potential of these interactions in enhancing learning and memory, yet detailed mechanisms remain underexplored. Methods: Utilizing intracerebroventricular injections of GALR2 and NPY1R agonists in Sprague-Dawley male rats, we examined neurogenesis via markers PCNA and DCX, and memory consolidation through the object-in-place task over a three-week period. Results: Significant increases in NPY1R-GALR2 co-localization and neuroblast proliferation were observed, alongside enhanced memory consolidation. These findings suggest a synergistic effect of NPY1R and GALR2 activation on cognitive functions. Discussion: Our findings may foster the development of novel heterobivalent or multitargeting drugs, affecting NPY1R-GALR2 interaction, and suggest a future pharmacogical strategy for improving learning and memory found in many brain diseases. Further research is encouraged to explore these mechanisms in pathological models.The author(s) declare financial support was received for the research, authorship, and/or publication of this article. This research was funded by the UMA18-FEDERJA-100 and ProyExcel_00613, Junta de Andalucía, Spain, to MN. Beca de Iniciación a la investigación de la Universidad de Málaga to PA. Funding for open access charge: Universidad de Málaga/CBUA. Additional funding support came from Cátedra Imbrain: Neurociencia Integrada y Bionestar to MN. This work also received support from Stiftelsen Olle Engkvist Byggmästare in 2018 and 2021, as well as from the Swedish Medical Research Council (Grant No. 62X-00715-50-3) awarded to KF and DB-E. Additionally, funding was provided by Hjärnfonden (Grants F02018-0286 and F02019-0296), Karolinska Institutet Forskningsstiftelser 2022, EMERGIA 2020-39318 (Plan Andaluz de Investigación, Desarrollo e Innovación 2020), and CONSOLIDACION INVESTIGADORA (CNS2022-136008, Programa Estatal para Desarrollar, Atraer y Retener Talento, del Plan Estatal de Investigación Científica, Técnica y de Innovación 2021-2023) awarded to DB-E. DB-E is affiliated with the Academia de Biólogos Cubanos and the Observatorio Cubano de Neurociencias (Yaguajay, Cuba)

Galanin and Neuropeptide Y Interaction Enhances Proliferation of Granule Precursor Cells and Expression of Neuroprotective Factors in the Rat Hippocampus: Role in depression and memory

Neuropeptide Y(NPY) Y1 receptor (Y1R) and galanin (GAL) receptor 2 (GALR2) interact in brain regions responsible for mood control and learning and memory processes, emphasizing the hippocampus. The current study assesses the sustained memory performance and antidepressive-like effects induced by GALR2 and NPYY1R agonists coadministration and their neurochemical hippocampal correlates. Object-in-place task and forced swimming test were conducted together with in situ proximity ligation assay (PLA) to manifest the formation of GALR2/Y1R heteroreceptor complexes. We evaluated cell proliferation through a 5-Bromo-2’-deoxyuridine (BrdU) and PCNA expression study within the hippocampus. The GalR2 agonist M1145 and GAL were demonstrated to act with the Y1R agonist to improve memory retrieval and antidepressive-like actions at 24 hours in both tasks, enhancing the cell proliferation in the DG of the hippocampus through BrdU and PCNA expression and the GALR2/Y1R heteroreceptor complexes upon agonist coactivation. Our results may provide the basis for developing heterobivalent agonist pharmacophores targeting Y1R-GALR2 heterocomplexes. It involves especially the neuronal precursor cells of the dentate gyrus in the hippocampus for the novel treatment of Alzheimer’s disease or depression.Supported by the UMA18-FEDERJA-100 and Proyecto Jovenes Investigadores (B1-2019_04) and Proyecto Puente (B4-2021) UMA , Spain to MN. Universidad de Málaga. Campus de Excelencia Internacional Andalucía Tech

Long- term enhancements in antidepressant efficacy and neurogenesis: Effects of intranasal co- administration of neuropeptide Y 1 receptor (NPY1R) and galanin receptor 2 (GALR2) agonists in the ventral hippocampus

This study evaluates the sustained antidepressant- like effects and neurogenic potential of a 3- day intranasal co- administration regimen of galanin receptor 2 (GALR2) agonist M1145 and neuropeptide Y Y1 receptor (NPY1R) agonist [Leu31, Pro34]NPY in the ventral hippocampus of adult rats, with outcomes ana-lyzed 3 weeks post- treatment. Utilizing the forced swimming test (FST), we found that this co- administration significantly enhances antidepressant- like behaviors, an effect neutralized by the GALR2 antagonist M871, highlighting the syner-gistic potential of these neuropeptides in modulating mood- related behaviors. In situ proximity ligation assay (PLA) indicated a significant increase in GALR2/NPYY1R heteroreceptor complexes in the ventral hippocampal dentate gyrus, suggesting a molecular basis for the behavioral outcomes observed. Moreover, proliferating cell nuclear antigen (PCNA) immunolabeling revealed increased cell proliferation in the subgranular zone of the dentate gyrus, specifically in neuroblasts as evidenced by co- labeling with doublecortin (DCX), without affect-ing quiescent neural progenitors or astrocytes. The study also noted a significant uptick in the number of DCX- positive cells and alterations in dendritic morphol-ogy in the ventral hippocampus, indicative of enhanced neuronal differentiation and maturation.Funding for open access charge: Universidad de Málaga/CBU

Galanin and Neuropeptide Y Interaction Enhances Proliferation of Granule Precursor Cells and Expression of Neuroprotective Factors in the Rat Hippocampus with Consequent Augmented Spatial Memory

Dysregulation of hippocampal neurogenesis is linked to several neurodegenereative diseases, where boosting hippocampal neurogenesis in these patients emerges as a potential therapeutic approach. Accumulating evidence for a neuropeptide Y (NPY) and galanin (GAL) interaction was shown in various limbic system regions at molecular-, cellular-, and behavioral-specific levels. The purpose of the current work was to evaluate the role of the NPY and GAL interaction in the neurogenic actions on the dorsal hippocampus. We studied the Y1R agonist and GAL effects on: hippocampal cell proliferation through the proliferating cell nuclear antigen (PCNA), the expression of neuroprotective and anti-apoptotic factors, and the survival of neurons and neurite outgrowth on hippocampal neuronal cells. The functional outcome was evaluated in the object-in-place task. We demonstrated that the Y1R agonist and GAL promote cell proliferation and the induction of neuroprotective factors. These effects were mediated by the interaction of NPYY1 (Y1R) and GAL2 (GALR2) receptors, which mediate the increased survival and neurites’ outgrowth observed on neuronal hippocampal cells. These cellular effects are linked to the improved spatial-memory effects after the Y1R agonist and GAL co-injection at 24 h in the object-in-place task. Our results suggest the development of heterobivalent agonist pharmacophores, targeting Y1R–GALR2 heterocomplexes, therefore acting on the neuronal precursor cells of the DG in the dorsal hippocampus for the novel therapy of neurodegenerative cognitive-affecting diseasesThis research was funded by the UMA18-FEDERJA-100 (Junta de Andalucía), Proyecto Jovenes Investigadores (B1-2019-04), Proyecto puente (B4-2021-06), Universidad de Málaga, Spain, to M.N. Swedish Medical Research Council, Sweden (62X-00715-50-3), to K.F., by Stiftelsen Olle Engkvist Byggmästare to K.F., and by Hjärnfonden, Sweden (F02018-0286), Hjärnfonden, Sweden (F02019-0296), and Karolinska Institutet Forskningsstiftelser, Sweden, to D.O.B.-E. D.O.B.-E. belongs to the “Academia de Biólogos Cubanos” group, Cuba. Partial funding for open access charge: Universidad de Málag

Intranasal Delivery of Galanin 2 and Neuropeptide Y1 Agonists Enhanced Spatial Memory Performance and antidepressant e!ects through Neuronal Precursor Cells Proliferation in the hippocampus

Neuropeptide Y(NPY) Y1 receptor (Y1R) and galanin (GAL) receptor 2 (GALR2) interact in brain regions responsible for learning and memory processes, emphasizing the hippocampus. The current study assesses the sustained memory performance and antidepressive-like e!ects induced by GALR2 and NPYY1R agonists intranasal coadministration and their neurochemical hippocampal correlates. Object-in-place task and forced swimming test were conducted together with in situ proximity ligation assay (PLA) to manifest the formation of GALR2/Y1R heteroreceptor complexes. We evaluated cell proliferation through a 5-Bromo-2’-deoxyuridine (BrdU) expression study within the hippocampus. The GalR2 agonist M1145 was demonstrated to act with the Y1R agonist to improve memory retrieval and antidepressive-like actions at 24 hours in both tasks, enhancing the cell proliferation in the DG of the hippocampus through BrdU expression and the GALR2/Y1R heteroreceptor complexes upon agonist coactivation. Our results may provide the basis for developing heterobivalent agonist pharmacophores targeting GALR2- Y1R heterocomplexes. It involves especially the neuronal precursor cells of the dentate gyrus in the hippocampus for the novel treatment of Alzheimer’s disease or depression. The work was supported by the UMA18-FEDERJA-100 and Proyecto Jovenes Investigadores (B1-2019_04) and Proyecto Puente (B4-2021) UMA , Spain to MN. Special mention to Grupo Vithas.The work was supported by the UMA18-FEDERJA-100 and Proyecto Jovenes Investigadores (B1-2019_04) and Proyecto Puente (B4-2021) UMA , Spain to MN. Special mention to Grupo Vithas. Universidad de Málaga. Campus de Excelencia Internacional Andalucía Tech