- ItemOpen AccessBreathing cessation events that compose the apnea–hypopnea index are distinctively associated with the adverse outcomes in Alzheimer’s disease(BMC, 2023) Targa, Adriano; Benítez, Iván; Moncusí Moix, Anna; Dakterzada, Farida; Minguez Roure, Olga; Vaca, Rafaela; Dalmases, Mireia; Sánchez de la Torre, Manuel; Barbé Illa, Ferran; Piñol Ripoll, GerardBackground Previous studies challenge the impact of obstructive sleep apnea (OSA) once patients are diagnosed with Alzheimer’s disease (AD). Nevertheless, OSA recognizably disrupts sleep, and relevant associations between sleep, AD pathological markers, and cognition have been demonstrated. We aimed to further explore this, evaluating the associations between each breathing cessation event that compose the apnea–hypopnea index (AHI) and the sleep structure to finally investigate whether this was related to increased levels of AD markers and higher cognitive decline. Methods Observational, prospective study, including consecutive patients diagnosed with mild-moderate AD. The participants were submitted to overnight polysomnography followed by a cerebrospinal fluid collection for AD pathological markers levels determination. Neuropsychological assessment was performed at baseline and after 12 months of follow-up. Results The cohort was composed of 116 patients (55.2% females) with a median [p25;p75] age of 76.0 [72.0;80.0] years and an AHI of 25.9 [15.1;48.5], which was mainly defined by the presence of hypopneas and obstructive apneas. These were distinctively associated with the sleep structure, with obstructive apneas being related to arousals and sleep lightening and hypopneas being related to an increased number of arousals only. Despite having a lower frequency, mixed and central apneas also presented associations with the sleep structure, particularly increasing the time spent in the lighter sleep stages. In relation to AD pathological markers, obstructive and mixed apneas were related to an augment in neurofilament light levels while hypopneas were associated with a higher phosphorylated- tau/amyloid-beta protein ratio. Hypopneas were the most important event for an increased cognitive decline at the 12-month follow-up. Conclusions Our findings highlight the importance of a patient-centered approach, with a comprehensive and detailed analysis of the AHI to effectively predict the different outcomes and tailor the appropriate therapeutic strategies.
- ItemOpen AccessDifferential systemic decellularization in vivo to study molecular changes in each vasculature layer in murine models of disease(Cell Press, 2023) Gallart Palau, Xavier Ramon; Lorca, Cristina; Mulet, Maria; Sánchez Milán, José Antonio; Lisa, Julia; Cam Ngan, SoFong; Iyappan, Ranjith; Katoueezadeh, Maryam; Serra, Aida; Kwan Sze, SiuVascular dysfunction underlies the onset and progression of many life-threatening diseases, highlighting the need for improved understanding of its molecular basis. Here, we present differential systemic decellularization in vivo (DISDIVO), a protocol that enables systemic and independent study of the molecular changes in each vasculature layer in murine models of disease. We describe steps for anesthesia, perfusion surgery, and exsanguination. We then detail detachment and collection of glycocalyx and decellularization and collection of both endothelial and smooth muscle cells. For complete details on the use and execution of this protocol, please refer to Serra et al., Gallart-Palau et al., and Vinaiphat et al.
- ItemOpen AccessGATEKEEPER's Strategy for the Multinational Large-Scale Piloting of an eHealth Platform: Tutorial on How to Identify Relevant Settings and Use Cases(JMIR Publications, 2023) Batlle Garcia, Jordi de; Benítez, Iván; Moncusí Moix, Anna; Androutsos, Odysseas; Barbastro, Rosana Angles; Antonini, Alessio; Arana, Eunate; Cabrera-Umpierrez, Maria Fernanda; Cea, Gloria; Dafoulas, George Ε.; Folkvord, Frans; Fullaondo, Ane; Giuliani, Francesco; Huang, Hsiao-Ling; Innominato, Pasquale F.; Kardas, Przemyslaw; Lou, Vivian W.Q.; Manios, Yannis; Matsangidou, Maria; Mercalli, Franco; Mokhtari, Mounir; Pagliara, Silvio; Schellong, Julia; Stieler, Lisa; Votis, Konstantinos; Currás, Paula; Arredondo, Maria Teresa; Posada, Jorge; Guillén, Sergio; Pecchia, Leandro; Barbé Illa, Ferran; Torres, Gerard; Fico, GiuseppeBackground: The World Health Organization’s strategy toward healthy aging fosters person-centered integrated care sustained by eHealth systems. However, there is a need for standardized frameworks or platforms accommodating and interconnecting multiple of these systems while ensuring secure, relevant, fair, trust-based data sharing and use. The H2020 project GATEKEEPER aims to implement and test an open-source, European, standard-based, interoperable, and secure framework serving broad populations of aging citizens with heterogeneous health needs. Objective: We aim to describe the rationale for the selection of an optimal group of settings for the multinational large-scale piloting of the GATEKEEPER platform. Methods: The selection of implementation sites and reference use cases (RUCs) was based on the adoption of a double stratification pyramid reflecting the overall health of target populations and the intensity of proposed interventions; the identification of a principles guiding implementation site selection; and the elaboration of guidelines for RUC selection, ensuring clinical relevance and scientific excellence while covering the whole spectrum of citizen complexities and intervention intensities. Results: Seven European countries were selected, covering Europe’s geographical and socioeconomic heterogeneity: Cyprus, Germany, Greece, Italy, Poland, Spain, and the United Kingdom. These were complemented by the following 3 Asian pilots: Hong Kong, Singapore, and Taiwan. Implementation sites consisted of local ecosystems, including health care organizations and partners from industry, civil society, academia, and government, prioritizing the highly rated European Innovation Partnership on Active and Healthy Aging reference sites. RUCs covered the whole spectrum of chronic diseases, citizen complexities, and intervention intensities while privileging clinical relevance and scientific rigor. These included lifestyle-related early detection and interventions, using artificial intelligence–based digital coaches to promote healthy lifestyle and delay the onset or worsening of chronic diseases in healthy citizens; chronic obstructive pulmonary disease and heart failure decompensations management, proposing integrated care management based on advanced wearable monitoring and machine learning (ML) to predict decompensations; management of glycemic status in diabetes mellitus, based on beat to beat monitoring and short-term ML-based prediction of glycemic dynamics; treatment decision support systems for Parkinson disease, continuously monitoring motor and nonmotor complications to trigger enhanced treatment strategies; primary and secondary stroke prevention, using a coaching app and educational simulations with virtual and augmented reality; management of multimorbid older patients or patients with cancer, exploring novel chronic care models based on digital coaching, and advanced monitoring and ML; high blood pressure management, with ML-based predictions based on different intensities of monitoring through self-managed apps; and COVID-19 management, with integrated management tools limiting physical contact among actors. Conclusions: This paper provides a methodology for selecting adequate settings for the large-scale piloting of eHealth frameworks and exemplifies with the decisions taken in GATEKEEPER the current views of the WHO and European Commission while moving forward toward a European Data Space.
- ItemOpen AccessFungal corneal abscess caused by Exophiala dermatitidis(Sociedad Española de Quimioterapia, 2023) Mormeneo Bayo, Saray; Bellés Bellés, Alba; Prats Sánchez, Iván; López González, Éric; Aramburu, Jesus; Bernet Sánchez, Albert; Garcia Gonzalez, MercedesLetter to the Editor
- ItemOpen AccessChanging biosynthesis of terpenoid percursors in rice through synthetic biology(Frontiers Media SA, 2023) Basallo, Oriol; Pérez, Lucía; Lucido, Abel; Sorribas, Albert; Marin-Saguino, Alberto; Vilaprinyo Terré, Ester; Perez‑Fons, Laura; Albacete, Alfonso; Martínez-Andújar, Cristina; Fraser, Paul D.; Christou, Paul; Capell Capell, Teresa; Alves, RuiMany highly valued chemicals in the pharmaceutical, biotechnological, cosmetic, and biomedical industries belong to the terpenoid family. Biosynthesis of these chemicals relies on polymerization of Isopentenyl di-phosphate (IPP) and/or dimethylallyl diphosphate (DMAPP) monomers, which plants synthesize using two alternative pathways: a cytosolic mevalonic acid (MVA) pathway and a plastidic methyleritritol-4-phosphate (MEP) pathway. As such, developing plants for use as a platform to use IPP/DMAPP and produce high value terpenoids is an important biotechnological goal. Still, IPP/DMAPP are the precursors to many plant developmental hormones. This creates severe challenges in redirecting IPP/DMAPP towards production of non-cognate plant metabolites. A potential solution to this problem is increasing the IPP/DMAPP production flux in planta. Here, we aimed at discovering, understanding, and predicting the effects of increasing IPP/DMAPP production in plants through modelling. We used synthetic biology to create rice lines containing an additional ectopic MVA biosynthetic pathway for producing IPP/DMAPP. The rice lines express three alternative versions of the additional MVA pathway in the plastid, in addition to the normal endogenous pathways. We collected data for changes in macroscopic and molecular phenotypes, gene expression, isoprenoid content, and hormone abundance in those lines. To integrate the molecular and macroscopic data and develop a more in depth understanding of the effects of engineering the exogenous pathway in the mutant rice lines, we developed and analyzed data-centric, line-specific, multilevel mathematical models. These models connect the effects of variations in hormones and gene expression to changes in macroscopic plant phenotype and metabolite concentrations within the MVA and MEP pathways of WT and mutant rice lines. Our models allow us to predict how an exogenous IPP/DMAPP biosynthetic pathway affects the flux of terpenoid precursors. We also quantify the long-term effect of plant hormones on the dynamic behavior of IPP/DMAPP biosynthetic pathways in seeds, and predict plant characteristics, such as plant height, leaf size, and chlorophyll content from molecular data. In addition, our models are a tool that can be used in the future to help in prioritizing re-engineering strategies for the exogenous pathway in order to achieve specific metabolic goals