RESUMEN
BACKGROUND: POLE mutated endometrial carcinomas may represent a subspecific type of tumors harboring a more favorable prognosis. Grade 3 (G3 or high-grade) endometrioid endometrial carcinomas remain a clinical dilemma, with some tumors behaving as the low-grade counterparts and others presenting a more aggressive behavior. OBJECTIVES: To determine the association between POLE mutational status and the overall-survival (OS) and progression-free-survival (PFS) of patients with G3 endometrioid endometrial cancer (EC). We also aimed to determine the prevalence of POLE mutations in G3 endometrioid EC. METHODS: We conducted a systematic review in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines (PROSPERO No: CRD4202340008). We searched the following electronic databases: PubMed/Medline, EMBASE, Cochrane Library, Scopus, and Web of Science. For time-to-event data, the effect of POLE mutation in G3 EC was described using hazard ratios (HRs) and corresponding 95% confidence intervals (CIs). Individual patient data for each study was investigated if available from the study authors. If individual patient data were not available, information regarding time-to-event outcomes was extracted using an appropriate methodology. OS and PFS were analyzed using both one-stage and two-stage approaches, the Kaplan-Meier method, and Cox-proportional hazards models. RESULTS: This systematic review and meta-analysis included 19 studies with 3092 patients who had high-grade endometrioid EC. Patients with POLE mutations had lower risks of death (HR = 0.36, 95% CI 0.26 to 0.50, I2 = 0%, 10 trials) and disease progression (HR = 0.31, 95% CI 0.17 to 0.57, I2 = 33%, 10 trials). The pooled prevalence of POLE mutation was 11% (95% CI 9 to 13, I2 = 68%, 18 studies). CONCLUSION: POLE mutations in high-grade endometrioid EC are associated with a more favorable prognosis with increased OS and PFS.
Asunto(s)
Carcinoma Endometrioide , ADN Polimerasa II , Neoplasias Endometriales , Mutación , Clasificación del Tumor , Proteínas de Unión a Poli-ADP-Ribosa , Humanos , Femenino , Neoplasias Endometriales/genética , Neoplasias Endometriales/patología , Neoplasias Endometriales/mortalidad , Carcinoma Endometrioide/genética , Carcinoma Endometrioide/patología , ADN Polimerasa II/genética , Proteínas de Unión a Poli-ADP-Ribosa/genética , Pronóstico , Supervivencia sin ProgresiónRESUMEN
Musicians' body behaviour has a preponderant role in audience perception. We investigated how performers' motion is perceived depending on the musical style and musical expertise. To further explore the effect of visual input, stimuli were presented in audio-only, audio-visual and visual-only conditions. We used motion and audio recordings of expert saxophone players playing two contrasting excerpts (positively and negatively valenced). For each excerpt, stimuli represented five motion degrees with increasing quantity of motion (QoM) and distinct predominant gestures. In the experiment (online and in-person), 384 participants rated performance recordings for expressiveness, professionalism and overall quality. Results revealed that, for the positively valenced excerpt, ratings increased as a function of QoM, whilst for the negatively valenced, the recording with predominant flap motion was favoured. Musicianship did not have a significant effect in motion perception. Concerning multisensory integration, both musicians and non-musicians presented visual dominance in the positively valenced excerpt, whereas in the negatively valenced, musicians shifted to auditory dominance. Our findings demonstrate that musical style not only determines the way observers perceive musicians' movement as adequate, but also that it can promote changes in multisensory integration.
Asunto(s)
Percepción Auditiva , Percepción de Movimiento , Música , Humanos , Masculino , Femenino , Adulto , Percepción de Movimiento/fisiología , Adulto Joven , Percepción Auditiva/fisiología , Percepción Visual/fisiología , Movimiento/fisiología , Persona de Mediana Edad , Adolescente , Desempeño Psicomotor/fisiologíaRESUMEN
OBJECTIVES: To describe characteristics of women with aesthetically ideal buttocks and differentiate them from women with normal buttocks. METHODS: Case-control study comparing anatomy of women with ideal buttocks (buttocks models) to women with normal buttocks using magnetic resonance images, anthropometric measurements and photography. RESULTS: Comparing to normal women, buttocks models have a narrower waist, narrower iliac crest, wider C point, wider hips and bigger and thicker gluteus maximus muscle (GMM). A bigger GMM adds more projection to the C point, point of maximum projection in the lateral view is 2.7 cm higher than the pubic bone. The amount of subcutaneous fat was equal in models and controls. CONCLUSIONS: Our study provides new knowledge regarding the tridimensional aspects of the beauty of the buttocks area. A beautiful buttock is a conjunction of adequate bony shape, muscle development, subcutaneous fat layer, and tight skin. Comparing to normal women, buttocks models have a narrower waist, narrower iliac crest, wider C point, wider hips and bigger and thicker Gluteus Maximus Muscle. Accurate understanding of the aesthetic goals in a given patient can guide surgical technique. LEVEL OF EVIDENCE III: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .
Asunto(s)
Imagen por Resonancia Magnética , Humanos , Femenino , Nalgas/diagnóstico por imagen , Nalgas/cirugía , Estudios de Casos y Controles , Antropometría , EstéticaRESUMEN
Neural angiostrongyliasis is an emerging zoonosis caused by the rat lungworm, Angiostrongylus cantonensis. In humans, infection with this nematode often results in eosinophilic meningitis and other severe disorders of the central nervous system. Europe was deemed a nonendemic region until 2018, when A. cantonensis worms were detected on the Mediterranean island of Mallorca, Spain, a tourism hotspot. Since that time, a sentinel surveillance system and a molecular approach have been used to follow the invasion path of the rat lungworm on the island. A. cantonensis worms have been found in animals from 8 locations on the island over 3 consecutive years. Our preliminary results show a recognizable pattern of clinical signs in infected hedgehogs and a single mitochondrial haplotype circulating in Mallorca. We present strong evidence confirming that the rat lungworm has successfully established and colonized an island in Europe and discuss observations and possible strategies for its early detection across continental Europe.
Asunto(s)
Angiostrongylus cantonensis , Meningitis , Nematodos , Infecciones por Strongylida , Angiostrongylus cantonensis/genética , Animales , Ratas , España/epidemiología , Infecciones por Strongylida/epidemiología , Infecciones por Strongylida/veterinariaRESUMEN
The acanthocephalan parasite Plagiorhynchus cylindraceus has a global distribution and utilizes isopods and birds as intermediate and definitive hosts, respectively. Occasionally, mammals of various orders can act as paratenic hosts. In hedgehogs, severe cases have been reported in juvenile specimens due to secondary infections, as a consequence of complete penetrations of the intestinal wall by cystacanths. In a 66-month study period, we found seven larvae of this parasite encysted in both, the peritoneal cavity and intestine of the Algerian hedgehog, Atelerix algirus in Majorca. Morphology alone was insufficient to identify the species, due to the lack of previous reports and taxonomy-informative characters. In the present report, we combined the use of morphology and the DNA-barcoding approach to confirm to identify cystacanths as P. cylindraceus. This is the first report of this parasite in this hedgehog species. The epidemiological implications will be discussed, including the risk of zoonosis and the importance of using modern approaches to identify immature acanthocephalan larvae in wildlife hosts.
Asunto(s)
Acantocéfalos/clasificación , Acantocéfalos/genética , Código de Barras del ADN Taxonómico , Erizos/parasitología , Helmintiasis Animal/epidemiología , Intestinos/patología , Cavidad Peritoneal/parasitología , Acantocéfalos/anatomía & histología , Animales , Aves/parasitología , ADN/genética , Femenino , Helmintiasis Animal/parasitología , Larva/crecimiento & desarrollo , Masculino , Zoonosis/epidemiologíaRESUMEN
In October 2018, two Atelerix algirus hedgehogs were admitted to the Wildlife Rehabilitation Hospital in Mallorca (Balearic Islands, Spain) with signs of acute neurological disease. Necropsy detected immature, fully developed nematodes in the subarachnoid space of both hedgehogs, including a gravid female worm. DNA-based molecular tools confirmed the nematode as Angiostrongylus cantonensis, an important aetiological agent of eosinophilic meningitis in humans. So far this zoonotic parasite in has not been reported in western European wildlife.
Asunto(s)
Angiostrongylus cantonensis/aislamiento & purificación , Erizos/parasitología , Nematodos/genética , Infecciones por Nematodos/diagnóstico , Zoonosis/parasitología , Angiostrongylus cantonensis/genética , Animales , Enfermedades Transmisibles Emergentes , Infecciones por Nematodos/transmisión , Reacción en Cadena de la Polimerasa , Análisis de Secuencia , EspañaRESUMEN
The physiological function of Ataxin-3 (ATXN3), a deubiquitylase (DUB) involved in Machado-Joseph Disease (MJD), remains elusive. In this study, we demonstrate that ATXN3 is required for neuronal differentiation and for normal cell morphology, cytoskeletal organization, proliferation and survival of SH-SY5Y and PC12 cells. This cellular phenotype is associated with increased proteasomal degradation of α5 integrin subunit (ITGA5) and reduced activation of integrin signalling and is rescued by ITGA5 overexpression. Interestingly, silencing of ATXN3, overexpression of mutant versions of ATXN3 lacking catalytic activity or bearing an expanded polyglutamine (polyQ) tract led to partially overlapping phenotypes. In vivo analysis showed that both Atxn3 knockout and MJD transgenic mice had decreased levels of ITGA5 in the brain. Furthermore, abnormal morphology and reduced branching were observed both in cultured neurons expressing shRNA for ATXN3 and in those obtained from MJD mice. Our results show that ATXN3 rescues ITGA5 from proteasomal degradation in neurons and that polyQ expansion causes a partial loss of this cellular function, resulting in reduced integrin signalling and neuronal cytoskeleton modifications, which may be contributing to neurodegeneration.
Asunto(s)
Proteínas del Tejido Nervioso/metabolismo , Neuronas/metabolismo , Proteínas Nucleares/metabolismo , Péptidos/metabolismo , Proteínas Represoras/metabolismo , Factores de Transcripción/metabolismo , Animales , Ataxina-3 , Diferenciación Celular , Células Cultivadas , Ganglios Espinales/citología , Ganglios Espinales/metabolismo , Células HEK293 , Hipocampo/citología , Hipocampo/metabolismo , Humanos , Integrina alfa5/metabolismo , Ratones , Células PC12 , Complejo de la Endopetidasa Proteasomal/metabolismo , Ratas , Ratas WistarRESUMEN
BACKGROUND: Glioblastoma (GBM), the most malignant primary brain tumor, leads to poor and unpredictable clinical outcomes. Recent studies showed the tumor microenvironment has a critical role in regulating tumor growth by establishing a complex network of interactions with tumor cells. In this context, we investigated how GBM cells modulate resident glial cells, particularly their paracrine activity, and how this modulation can influence back on the malignant phenotype of GBM cells. METHODS: Conditioned media (CM) of primary mouse glial cultures unexposed (unprimed) or exposed (primed) to the secretome of GL261 GBM cells were analyzed by proteomic analysis. Additionally, these CM were used in GBM cells to evaluate their impact in glioma cell viability, migration capacity and activation of tumor-related intracellular pathways. RESULTS: The proteomic analysis revealed that the pre-exposure of glial cells to CM from GBM cells led to the upregulation of several proteins related to inflammatory response, cell adhesion and extracellular structure organization within the secretome of primed glial cells. At the functional levels, CM derived from unprimed glial cells favored an increase in GBM cell migration capacity, while CM from primed glial cells promoted cells viability. These effects on GBM cells were accompanied by activation of particular intracellular cancer-related pathways, mainly the MAPK/ERK pathway, which is a known regulator of cell proliferation. CONCLUSIONS: Together, our results suggest that glial cells can impact on the pathophysiology of GBM tumors, and that the secretome of GBM cells is able to modulate the secretome of neighboring glial cells, in a way that regulates the "go-or-grow" phenotypic switch of GBM cells.
Asunto(s)
Neoplasias Encefálicas/metabolismo , Proliferación Celular , Glioblastoma/metabolismo , Neuroglía/metabolismo , Fenotipo , Proteoma/metabolismo , Animales , Línea Celular Tumoral , Supervivencia Celular , Células Cultivadas , Medios de Cultivo Condicionados/farmacología , Sistema de Señalización de MAP Quinasas , Ratones , Ratones Endogámicos C57BL , Neuroglía/efectos de los fármacos , Neuroglía/fisiología , Comunicación ParacrinaRESUMEN
Quorum sensing (QS) is an important regulatory mechanism in biofilm formation and differentiation. Interference with QS can affect biofilm development and antimicrobial susceptibility. This study evaluates the potential of selected phytochemical products to inhibit QS. Three isothiocyanates (allylisothiocyanate - AITC, benzylisothiocyanate - BITC and 2-phenylethylisothiocyanate - PEITC) and six phenolic products (gallic acid - GA, ferulic acid - FA, caffeic acid - CA, phloridzin - PHL, (-) epicatechin - EPI and oleuropein glucoside - OG) were tested. A disc diffusion assay based on pigment inhibition in Chromobacterium violaceum CV12472 was performed. In addition, the mechanisms of QS inhibition (QSI) based on the modulation of N-acyl homoserine lactone (AHLs) activity and synthesis by the phytochemicals were investigated. The cytotoxicity of each product was tested on a cell line of mouse lung fibroblasts. AITC, BITC and PEITC demonstrated a capacity for QSI by modulation of AHL activity and synthesis, interfering the with QS systems of C. violaceum CviI/CviR homologs of LuxI/LuxR systems. The cytotoxic assays demonstrated low effects on the metabolic viability of the fibroblast cell line only for FA, PHL and EPI.
Asunto(s)
Incrustaciones Biológicas/prevención & control , Chromobacterium/efectos de los fármacos , Isotiocianatos/farmacología , Fenoles/farmacología , Fitoquímicos/farmacología , Percepción de Quorum/efectos de los fármacos , Animales , Biopelículas/efectos de los fármacos , Línea Celular , Chromobacterium/fisiología , Isotiocianatos/toxicidad , Ratones , Pruebas de Sensibilidad Microbiana , Fenoles/toxicidad , Fitoquímicos/toxicidad , Pruebas de ToxicidadRESUMEN
Background: Low fibrinogen levels are associated with an increased risk of perioperative bleeding. However, there is an ongoing debate over the ideal treatment threshold, the benefits of prophylactic supplementation with fibrinogen concentrate, and the best source of fibrinogen. While fibrinogen concentrate supplementation is being widely used to treat bleeding related to acquired haemostatic deficiencies, there is a lack of evidence regarding its dosage, effectiveness, and safety. This systematic review provides an up-to-date summary of the relationship between fibrinogen concentrate supplementation and safety measures in the perioperative care of non-trauma, non-obstetric adult patients. Methods: A comprehensive online search was conducted on PubMed/Medline, EMBASE, Scopus, Web of Science, the Cochrane Database of Systematic Reviews, and the Cochrane Central Register of Controlled Trials. Results: This systematic review and meta-analysis encompasses ten studies involving 1391 patients. There was a decreased risk of total thromboembolic events in patients treated with fibrinogen compared to the control (OR 0.65, 95% CI 0.43 to 0.98, I2 = 0%). In addition, when fibrinogen was used prophylactically, it resulted in shorter ICU stays (MD -1.50, 95% CI -2.64 to -0.36), when set against its therapeutic use. A sensitivity analysis on cardiovascular surgery studies did not reveal any statistically significant difference. Conclusions: The use of fibrinogen concentrate in the perioperative care of non-trauma and non-obstetric adult patients may lead to potential benefits.
RESUMEN
INTRODUCTION: The qualities of primary healthcare (PHC) make it a very relevant environment for research; however, there is still work to be done to enhance the research capabilities of family physicians in healthcare units. Considering there is no ongoing review that specifically addresses this objective, the proposed goal of this scoping review is to determine the depth of the literature on the current strategies that support research capacity building among family physicians in the context of PHC. METHODS AND ANALYSIS: The scoping review will include studies from PubMed, Scopus, Web of Science, Cochrane Library and grey literature, published from 2008 to 2023, that address strategies to promote research capacity building among family physicians in the context of PHC. Only studies published in English, Portuguese or Spanish will be considered. All study designs, including quantitative, qualitative and mixed-methods studies, will be eligible for inclusion. The literature search will be performed from January to March of 2024 and data charting will employ a descriptive-analytical method, systematically summarising study objectives, methodologies, findings and implications. This protocol follows the Preferred Reporting Items for Systematic Reviews and Meta-Analysis Protocols and the review will employ the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for scoping reviews. ETHICS AND DISSEMINATION: This review does not need ethical approval. Peer-reviewed publications, policy summaries, presentations at conferences and involvement with pertinent stakeholders are all part of our outreach approach.
Asunto(s)
Creación de Capacidad , Médicos de Familia , Humanos , Exactitud de los Datos , Etnicidad , Proyectos de Investigación , Atención Primaria de Salud , Revisiones Sistemáticas como Asunto , Literatura de Revisión como AsuntoRESUMEN
Introduction: The inflammatory response after spinal cord injury (SCI) is an important contributor to secondary damage. Infiltrating macrophages can acquire a spectrum of activation states, however, the microenvironment at the SCI site favors macrophage polarization into a pro-inflammatory phenotype, which is one of the reasons why macrophage transplantation has failed. Methods: In this study, we investigated the therapeutic potential of the macrophage secretome for SCI recovery. We investigated the effect of the secretome in vitro using peripheral and CNS-derived neurons and human neural stem cells. Moreover, we perform a pre-clinical trial using a SCI compression mice model and analyzed the recovery of motor, sensory and autonomic functions. Instead of transplanting the cells, we injected the paracrine factors and extracellular vesicles that they secrete, avoiding the loss of the phenotype of the transplanted cells due to local environmental cues. Results: We demonstrated that different macrophage phenotypes have a distinct effect on neuronal growth and survival, namely, the alternative activation with IL-10 and TGF-ß1 (M(IL-10+TGF-ß1)) promotes significant axonal regeneration. We also observed that systemic injection of soluble factors and extracellular vesicles derived from M(IL-10+TGF-ß1) macrophages promotes significant functional recovery after compressive SCI and leads to higher survival of spinal cord neurons. Additionally, the M(IL-10+TGF-ß1) secretome supported the recovery of bladder function and decreased microglial activation, astrogliosis and fibrotic scar in the spinal cord. Proteomic analysis of the M(IL-10+TGF-ß1)-derived secretome identified clusters of proteins involved in axon extension, dendritic spine maintenance, cell polarity establishment, and regulation of astrocytic activation. Discussion: Overall, our results demonstrated that macrophages-derived soluble factors and extracellular vesicles might be a promising therapy for SCI with possible clinical applications.
Asunto(s)
Interleucina-10 , Traumatismos de la Médula Espinal , Humanos , Animales , Ratones , Factor de Crecimiento Transformador beta1 , Proteómica , Secretoma , Traumatismos de la Médula Espinal/terapiaRESUMEN
Music performance requires high levels of motor control. Professional musicians use body movements not only to accomplish and help technical efficiency, but to shape expressive interpretation. Here, we recorded motion and audio data of twenty participants performing four musical fragments varying in the degree of technical difficulty to analyze how knee flexion is employed by expert saxophone players. Using a computational model of the auditory periphery, we extracted emergent acoustical properties of sound to inference critical cognitive patterns of music processing and relate them to motion data. Results showed that knee flexion is causally linked to tone expectations and correlated to rhythmical density, suggesting that this gesture is associated with expressive and facilitative purposes. Furthermore, when instructed to play immobile, participants tended to microflex (>1 Hz) more frequently compared to when playing expressively, possibly indicating a natural urge to move to the music. These results underline the robustness of body movement in musical performance, providing valuable insights for the understanding of communicative processes, and development of motor learning cues.
RESUMEN
In investigating the influence of body movement in multimodal perception, human motion displays are frequently used as a means of visual standardization and control of external confounders. However, no principle is established regarding the selection of an adequate display for specific study purposes. The aim of this study was to evaluate the effects of adopting 4 visual displays (point-light, stick figure, body mass, skeleton) on the observers' perception of music performances in 2 expressive conditions (immobile, projected expressiveness). Two hundred eleven participants rated 8 audio-visual samples in expressiveness, match between movement and music, and overall evaluation. The results revealed significant isolated main effects of visual display and expressive condition on the observers' ratings (in both, p < 0.001), and interaction effects between the two factors (p < 0.001). Displays closer to a human form (mostly skeleton, sometimes body mass) exponentiated the evaluations of expressiveness and music-movement match in the projected expressiveness condition, and of overall evaluation in the immobile condition; the opposite trend occurred with the simplified motion display (stick figure). Projected expressiveness performances were higher rated than immobile performances. Although the expressive conditions remained distinguishable across displays, the more complex ones potentiated the attribution of subjective qualities. We underline the importance of considering the variable display as an influencing factor in perceptual studies.
Asunto(s)
Percepción de Movimiento , Música , Humanos , Movimiento (Física) , Movimiento , Percepción Social , Percepción VisualRESUMEN
BACKGROUND: Clinical trials often use digital technologies to collect data continuously outside the clinic and use the derived digital endpoints as trial endpoints. Digital endpoints are also being developed to support diagnosis, monitoring, or therapeutic interventions in clinical care. However, clinical validation stands as a significant challenge, as there are no specific guidelines orienting the validation of digital endpoints. OBJECTIVE: This paper presents the protocol for a scoping review that aims to map the existing methods for the clinical validation of digital endpoints. METHODS: The scoping review will comprise searches from the electronic literature databases MEDLINE (PubMed), Scopus (including conference proceedings), Embase, IEEE (Institute of Electrical and Electronics Engineers) Xplore, ACM (Association for Computing Machinery) Digital Library, CENTRAL (Cochrane Central Register of Controlled Trials), Web of Science Core Collection (including conference proceedings), and Joanna Briggs Institute Database of Systematic Reviews and Implementation Reports. We will also include various sources of gray literature with search terms related to digital endpoints. The methodology will adhere to the Joanna Briggs Institute Scoping Review and the Guidance for Conducting Systematic Scoping Reviews. RESULTS: A search for reviews on the existing evidence related to this topic was conducted and has shown that no such review was previously undertaken. This review will provide a systematic assessment of the literature on methods for the clinical validation of digital endpoints and highlight any potential need for harmonization or reporting of methods. The results will include the methods for the clinical validation of digital endpoints according to device, digital endpoint, and clinical application goal of digital endpoints. The study started in January 2023 and is expected to end by December 2023, with results to be published in a peer-reviewed journal. CONCLUSIONS: A scoping review of methodologies that validate digital endpoints is necessary. This review will be unique in its breadth since it will comprise digital endpoints collected from several devices and not focus on a specific disease area. The results of our work should help guide researchers in choosing validation methods, identify potential gaps in the literature, or inform the development of novel methods to optimize the clinical validation of digital endpoints. Resolving these gaps is the key to presenting evidence in a consistent way to regulators and other parties and obtaining regulatory acceptance of digital endpoints for patient benefit. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): PRR1-10.2196/47119.
RESUMEN
Angiostrongylus cantonensis is an invasive nematode parasite that causes eosinophilic meningitis in many vertebrate hosts, including humans. This parasite is spreading rapidly through the six continents, with Europe being the final frontier. Sentinel surveillance may be a cost-effective strategy to monitor the pathogen's arrival to new geographical regions. Necropsy, followed by tissue digestion, is often used to recover helminth parasites from vertebrate host tissues, however, to detect brain parasites, this protocol is poorly utilized. Our brain digestion protocol is easily performed and 1) reduces false positivity and negativity, 2) provides accurate estimates of parasite burden and 3) helps establish a more precise prevalence. Early detection of A. cantonensis increases the efficacy of prevention, treatment, and disease control strategies for susceptible animal populations and humans.
Asunto(s)
Angiostrongylus cantonensis , Meningitis , Nematodos , Infecciones por Strongylida , Animales , Humanos , Meningitis/parasitología , Encéfalo/parasitología , Mamíferos , Infecciones por Strongylida/diagnóstico , Infecciones por Strongylida/veterinaria , Infecciones por Strongylida/epidemiologíaRESUMEN
Angiostrongylus cantonensis is the main etiological agent of eosinophilic meningitis, a disease that often leads to severe neurological manifestations in mammals and birds. In recent years, the prevalence of this zoonotic nematode has dramatically increased as it expands into new territories beyond its native range in Southeast Asia and the Pacific Basin.Its arrival to Europe, the last continent to be invaded, has raised many questions concerning the parasite's life cycle, particularly in the Mediterranean region, where it is now endemic. This study aims to collect evidence about intermediate hosts (snail and slug species) involved in the transmission of the A. cantonensis in Mallorca. We have conducted a systematic surveillance of gastropods within 2 km radius areas, surrounding the specific locations where infected hedgehogs were found. We employed a sequence-based detection approach that included a species-specific PCR amplification followed by DNA sequencing of the internal transcribed spacer I (ITS-1). This conservative approach was essential to avoid cross reactions with the numerous metastrongylid species known to be circulating in Mallorca. Overall, we collected and identified 398 gastropods belonging to 17 species, of which 11% tested positive for A. cantonensis. These gastropods were collected from touristic settlements to agricultural lands. Five gastropod species: Theba pisana, Cornu aspersum, Deroceras reticulatum, Milax gagates and Otala lactea, had been previously incriminated as A. cantonensis intermediate hosts, while 6 species: Papillifera papillaris, Cochlicella acuta, Eobania vermiculata, Ganula lanuginosa, Milax nigricans and Rumina decollata, are newly recorded hosts. The findings of this study have important epidemiological implications, and further measures are discussed to prevent neuroangiostrongylosis cases.
RESUMEN
Parkinson's disease (PD) is the most common movement disorder, characterized by the progressive loss of dopaminergic neurons from the nigrostriatal system. Currently, there is no treatment that retards disease progression or reverses damage prior to the time of clinical diagnosis. Mesenchymal stem cells (MSCs) are one of the most extensively studied cell sources for regenerative medicine applications, particularly due to the release of soluble factors and vesicles, known as secretome. The main goal of this work was to address the therapeutic potential of the secretome collected from bone-marrow-derived MSCs (BM-MSCs) using different models of the disease. Firstly, we took advantage of an optimized human midbrain-specific organoid system to model PD in vitro using a neurotoxin-induced model through 6-hydroxydopamine (6-OHDA) exposure. In vivo, we evaluated the effects of BM-MSC secretome comparing two different routes of secretome administration: intracerebral injections (a two-site single administration) against multiple systemic administration. The secretome of BM-MSCs was able to protect from dopaminergic neuronal loss, these effects being more evident in vivo. The BM-MSC secretome led to motor function recovery and dopaminergic loss protection; however, multiple systemic administrations resulted in larger therapeutic effects, making this result extremely relevant for potential future clinical applications.
Asunto(s)
Células Madre Mesenquimatosas , Enfermedad de Parkinson , Humanos , Enfermedad de Parkinson/tratamiento farmacológico , Secretoma , Encéfalo , Oxidopamina , OrganoidesRESUMEN
(1) Background: The aim of the present study was to contribute to the validation of the Portuguese version of the Kenny Music Performance Anxiety Inventory (K-MPAI) and to study its psychometric properties. (2) Methods: A sample of 164 undergraduate music students in Portugal (62.2% female; mean age = 22.63; SD = 4.36) completed an online survey composed of the K-MPAI Portuguese version, the State Trait Anxiety Inventory, and a sociodemographic questionnaire. The K-MPAI psychometric properties were examined using exploratory factor analyses, known-group differences, and Cronbach's alpha. (3) Results: A four-factor structure was identified, in line with recent validation of this measure in other countries: music performance anxiety-related symptoms, depression and hopelessness, parental support, and memory self-efficacy. Concurrent and known-group validity were established, and reliability scores were appropriate for the dimensions and total score. (4) Conclusions: The results provide initial evidence of the appropriateness of the Portuguese version of the K-MPAI.
RESUMEN
Adipose tissue derived stem cells (ASCs) are recognized to secret a myriad of molecules (secretome) know to modulate inflammatory response, promote axonal growth as well vascular remodeling and cellular survival. In previous works we have reported the benefit effects of ASCs transplanted to the injury site in a rat model of spinal cord injury (SCI). Emerging evidence have shown that the therapeutic actions of these cells are a consequence of their intense paracrine activity mediated by their secretome, which includes soluble bioactive molecules and vesicles. In this study, we intended to dissect the vesicular and protein individual function, comparing with whole secretome therapeutic effect. Therefore, we identified a beneficial effect of the whole secretome on neurite growth compared with protein or vesicular fraction alone and characterized their impact on microglia in vitro. Moreover, in a compression SCI mice model, from the motor tests performed, a statistical difference was found on beam balance test revealing differences in motor recovery between the use of the whole the secretome or their protein fraction. Finally, two different delivery methods, local or peripheral (IV), of ASC secretome were tested in vivo. Results indicate that when injected intravenously the secretome of ASCs has a beneficial effect on motor recovery of spinal cord injury animals compared with a single local injection and respective controls. Overall, our results showed that the whole secretome performed better than the fractions individually, raising ASC secretome mode of action as a synergy of proteic and vesicular fraction on SCI context. Also, when intravenously delivered, ASC secretome can promote SCI animal's motor recovery highlighting their therapeutic potential.