- ItemOpen AccessNext-Generation Proteomics of Brain Extracellular Vesicles in Schizophrenia Provide New Clues on the Altered Molecular Connectome(MDPI, 2024) Lorca, Cristina; Fernández-Rhodes, María; Sánchez Milán, José Antonio; Mulet, Maria; Elortza, Félix; Ramos-Miguel, Alfredo; Callado, Luis F.; Meana, J. Javier; Mur, Maria; Batalla, Iolanda; Vilella, Elisabet; Serra, Aida; Gallart-Palau, XavierExtracellular vesicles (EVs) are tiny membranous structures that mediate intercellular communication. The role(s) of these vesicles have been widely investigated in the context of neurological diseases; however, their potential implications in the neuropathology subjacent to human psychiatric disorders remain mostly unknown. Here, by using next-generation discovery-driven proteomics, we investigate the potential role(s) of brain EVs (bEVs) in schizophrenia (SZ) by analyzing these vesicles from the three post-mortem anatomical brain regions: the prefrontal cortex (PFC), hippocampus (HC), and caudate (CAU). The results obtained indicate that bEVs from SZ-affected brains contain region-specific proteins that are associated with abnormal GABAergic and glutamatergic transmission. Similarly, these vesicles from the analyzed regions were implicated in synaptic decay, abnormal brain immunity, neuron structural imbalances, and impaired cell homeostasis. Our findings also provide evidence, for the first time, that networks of molecular exchange (involving the PFC, HC, and CAU) are potentially active and mediated by EVs in non-diseased brains. Additionally, these bEV-mediated networks seem to have become partially reversed and largely disrupted in the brains of subjects affected by SZ. Taken as a whole, these results open the door to the uncovering of new biological markers and therapeutic targets, based on the compositions of bEVs, for the benefit of patients affected by SZ and related psychotic disorders.
- ItemOpen AccessSubpopulations of corticotropin-releasing factor containing neurons and internal circuits in the chicken central extended amygdala(Wiley, 2024) Pross, Alessandra; Hanafi-Metwalli, Alek; Abellán Ródenas, Antonio; Desfilis, Ester; Medina Hernández, Loreta MªIn mammals, the central extended amygdala is critical for the regulation of the stress response. This regulation is extremely complex, involving multiple subpopulations of GABAergic neurons and complex networks of internal and external connections. Two neuron subpopulations expressing corticotropin-releasing factor (CRF), located in the central amygdala and the lateral bed nucleus of the stria terminalis (BSTL), play a key role in the long-term component of fear learning and in sustained fear responses akin to anxiety. Very little is known about the regulation of stress by the amygdala in nonmammals, hindering efforts for trying to improve animal welfare. In birds, one of the major problems relates to the high evolutionary divergence of the telencephalon, where the amygdala is located. In the present study, we aimed to investigate the presence of CRF neurons of the central extended amygdala in chicken and the local connections within this region. We found two major subpopulations of CRF cells in BSTL and the medial capsular central amygdala of chicken. Based on multiple labeling of CRF mRNA with different developmental transcription factors, all CRF neurons seem to originate within the telencephalon since they express Foxg1, and there are two subtypes with different embryonic origins that express Islet1 or Pax6. In addition, we demonstrated direct projections from Pax6 cells of the capsular central amygdala to BSTL and the oval central amygdala. We also found projections from Islet1 cells of the oval central amygdala to BSTL, which may constitute an indirect pathway for the regulation of BSTL output cells. Part of these projections may be mediated by CRF cells, in agreement with the expression of CRF receptors in both Ceov and BSTL. Our results show a complex organization of the central extended amygdala in chicken and open new venues for studying how different cells and circuits regulate stress in these animals.
- ItemOpen AccessHuman lifespan and sex-specific patterns of resilience to disease: a retrospective population-wide cohort study(BCM, 2024-01-08) Sol, Joaquim; Ortega Bravo, Marta; Portero Otín, Manuel; Piñol Ripoll, Gerard; Ribas-Ripoll, Vicent; Artigues i Barberà, Eva María; Buti, Miquel; Pamplona Gras, Reinald; Jové Font, MarionaBackground: Slower paces of aging are related to lower risk of developing diseases and premature death. Therefore, the greatest challenge of modern societies is to ensure that the increase in lifespan is accompanied by an increase in health span. To better understand the differences in human lifespan, new insight concerning the relationship between lifespan and the age of onset of diseases, and the ability to avoid them is needed. We aimed to comprehensively study, at a population-wide level, the sex-specific disease patterns associated with human lifespan. Methods: Observational data from the SIDIAP database of a cohort of 482,058 individuals that died in Catalonia (Spain) at ages over 50 years old between the 1st of January 2006 and the 30th of June 2022 were included. The time to the onset of the first disease in multiple organ systems, the prevalence of escapers, the percentage of life free of disease, and their relationship with lifespan were evaluated considering sex-specific traits. Results: In the study cohort, 50.4% of the participants were women and the mean lifespan was 83 years. The results show novel relationships between the age of onset of disease, health span, and lifespan. The key findings include: Firstly, the onset of both single and multisystem diseases is progressively delayed as lifespan increases. Secondly, the prevalence of escapers is lower in lifespans around life expectancy. Thirdly, the number of disease-free systems decreases until individuals reach lifespans around 87-88 years old, at which point it starts to increase. Furthermore, long-lived women are less susceptible to multisystem diseases. The associations between health span and lifespan are system-dependent, and disease onset and the percentage of life spent free of disease at the time of death contribute to explaining lifespan variability. Lastly, the study highlights significant system-specific disparities between women and men. Conclusions: Health interventions focused on delaying aging and age-related diseases should be the most effective in increasing not only lifespan but also health span. The findings of this research highlight the relevance of Electronic Health Records in studying the aging process and open up new possibilities in age-related disease prevention that should assist primary care professionals in devising individualized care and treatment plans.
- ItemOpen AccessEducational interventions and identification of risk factors to prevent and reduce peritonitis in peritoneal dialysis: A scoping review(Wiley, 2024-02-20) Fernàndez Labadía, Elena; Masot, Olga; Tejero Vidal, Lorena Lourdes; Botigué, Teresa; Bielsa Gracia, SaraBackground: Peritonitis is a common and serious complication of peritoneal dialysis and is one of the main causes of peritoneal dialysis technique failure and long-term hemodialysis conversion. Objectives: The aim of the review was to identify and clarify peritonitis risk factors and learn about strategies employed at international level to prevent and reduce the occurrence of peritoneal dialysis associated infections and their complications. Design: A scoping review. Participants: Adults in pertitoneal dialysis. Measurements: The methodology framework of Arksey and O'Malley and PRISMA for Scoping Reviews guidelines were applied. A search was conducted of PubMed, Scopus and CINAHL using terms to identify peritoneal dialysis -associated risk factors and interventions carried out for the prevention and reduction of peritonitis in adult persons living at home. Results: The 17 studies selected were based on work carried out in nine different countries. Eleven articles analysed modifiable risk factors (low educational level, being a foreigner and low adherence to aseptic technique) and non-modifiable risk factors (age and comorbidities) that predispose to peritonitis in peritoneal dialysis. The other six studies applied an intervention to improve the prevalence of peritonitis considering educational practices adapted to patient characteristics and the application of retraining. Conclusions: Personalised patient training and the identification of risk factors for peritonitis are key to reducing complications and enhancing the survival of peritoneal dialysis patients and the effectiveness of the technique.
- ItemOpen AccessAutomatic Methods for Carotid Contrast-Enhanced Ultrasound Imaging Quantification of Adventitial Vasa Vasorum(Elsevier, 2018) Pereira, Tania; Muguruza, José; Virtu, Maria; Vilaprinyo Terré, Ester; Sorribas Tello, Albert; Fernández i Giráldez, Elvira; Fernández Armenteros, José Manuel; Baena-Fustegueras, Juan A; Rius, Ferran; Betriu i Bars, M. Àngels; Solsona Tehàs, Francesc; Alves, RuiAdventitial vasa vasorum are physiologic microvessels that nourish artery walls. In the presence of cardiovascular risk factors, these microvessels proliferate abnormally. Studies have reported that they are the first stage of atheromatous disease. Contrast-enhanced ultrasound (CEUS) of the carotid allows direct, quantitative and non-invasive visualization of the adventitial vasa vasorum. Hence, the development of computer-assisted methods that speed image analysis and eliminate user subjectivity is important. We developed methods for automatic analyses and quantification of vasa vasorum neovascularization in CEUS and tested these methods in a cohort of 186 individuals, 63 of whom were healthy volunteers. We implemented alternative automatic strategies for using the images to stratify patients according to their risk group and compare the strategies with respect to diagnostic performance. An automatic single-parameter strategy performs less effectively than the corresponding Arcidiacono method based on manual interpretation of the images (68 < area under the receiver operating characteristic curve [AUROC] for the manual Arcidiacono method < 82; 60 < AUROC for the automatic single-parameter strategy < 63). However, by use of additional image parameters, an automatic multiparameter strategy has significantly improved performance with respect to the manual Arcidiacono method (78 < AUROC < 90). The automatic multiparameter strategy is a valuable alternative to the manual Arcidiacono method, improving both diagnostic speed and diagnostic accuracy.