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Safety of digoxin in nonagenarian patients with atrial fibrillation:lessons from the Spanish Multicenter Registry

Journal of Geriatric Cardiology 2021年第10期18卷 809-815页

作者： Pablo Domínguez-Erquicia Sergio Raposeiras-Roubín Emad Abu-Assi maría Cespón-Fernández David Alonso-Rodríguez Santiago Jesús Camacho-Freire Naiara Cubelos-Fernández Álvaro López-Masjuán Ríos maría melendo-viu AndrésÍñiguez-Romo Department of Cardiology University HospitalÁlvaro CunqueiroVigoSpain Health Research Institute Galicia Sur VigoSpain Department of Cardiology University Hospital of LeónLeónSpain Department of Cardiology University Hospital Juan Ramón JiménezHuelvaSpain

BACKGROUND The association between digoxin and mortality is an unclear issue.In older patients with atrial fibrillation(AF),where use of digoxin is frequent,the evidence of its safety is scarce.Our aim is to assess the safety of digoxin in nonagenarian patients with AF.METHODS We evaluated data from 795 nonagenarian patients with non-valvular AF from the Spanish Multicenter Registry.We analyzed the relationship between digoxin and all-cause mortality with the Cox proportional-hazards model.RESULTS Follow-up was 27.7±18.3 months.Mean age was 92.5±3.8 years,and 71%of nonagenarian patients were female.Digoxin was not associated with increased risk of mortality[adjusted hazard ratio(aHR)=1.16,95%CI:0.96−1.41,P=0.130].However,we found a significant increase in mortality in the subgroup with estimated glomerular filtration rate(eGFR)<30 mL/min per 1.73 m^(2)(aHR=2.01,95%CI:1.13−3.57,P=0.018),but not in the other subgroups of eGFR(30−59 mL/min per 1.73 m^(2) and≥60 mL/min per 1.73 m^(2)).When exploring the risk of mortality according to sex,male subgroup was associated with an in-crease in mortality(aHR=1.48,95%CI:1.02−2.14,P=0.041).This was not observed in females subgroup(aHR=1.03,95%CI:0.81−1.29,P=0.829).Based on the presence or absence of heart failure,we did not find significant differences(aHR=1.20,95%CI:0.87−1.65,P=0.268 vs.aHR=1.15,95%CI:0.90−1.47,P=0.273,respectively).CONCLUSIONS In our large registry of nonagenarian patients with AF,we did not find an association between digoxin and mortality in the total sample.However,in the subgroup analyses,we found an increase in mortality with the use of digoxin in men and in patients with an eGFR<30 mL/min per 1.73 m^(2).

关键词： patients digoxin fibrillation

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Experimental implementation of phase triplicator gratings in a spatial light modulator

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Chinese Optics Letters 2024年第2期22卷 64-69页

作者：高尚 maría del mar Sánchez-López Ignacio Moreno Instituto de Bioingeniería Universidad Miguel HernándezElche 03202Spain Departamento de Física Aplicada Universidad Miguel HernándezElche 03202Spain Departamento de Ciencia de Materiales Óptica y Tec.Electr´onicaUniversidad Miguel HernándezElche 03202Spain

In this work,we compare different methods for implementing a triplicator,a phase grating that generates three equiintense diffraction orders.The design with optimal efficiency features a continuous phase profile,which cannot be easily reproduced,and is typically affected by quantization.We compare its performance with binary and sinusoidal phase profiles.We also analyze the effect of quantizing the phase levels.Finally,a random approach is adopted to eliminate the additional harmonic orders.In all cases,a liquid-crystal-on-silicon spatial light modulator is employed to experimentally verify and compare the different approaches.

关键词： diffraction gratings phase modulation triplicator spatial light modulators

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Tracking the change in Spanish greenhouse gas emissions through an LMDI decomposition model:A global and sectoral approach

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Journal of Environmental Sciences 2024年第5期139卷 114-122页

作者： Paula Fernández González maría José Presno Manuel Landajo Department of Applied Economics University of OviedoAuda del Cristos/n 33011 OviedoSpain

The reduction of GHG emissions to reverse the greenhouse effect is one of the main challenges in this century.In this paper we pursue two objectives.First,we analyze the evolution of GHG emissions in Spain in 2008–2018,at both the global and sectoral levels,with the variation in emissions decomposed into a set of determining factors.Second,we propose several actions specifically oriented to more tightly controlling the level of emissions.Our results showed a remarkable reduction(18.44%)in GHG emissions,mainly due to the intensity effect,but also to the production-per-capita effect.We detected somewhat different patterns among the various sectors analyzed.While the intensity effect was the most influential one in the agricultural,transport,and others sectors,the production-per-capita effect was predominant in the case of industry.The carbonization effect was revealed as crucial in the commerce sector.The above findings highlight the importance of the energy efficiency measures taken in recent years in the Spanish economy,also pointing to the need to deepen those strategies and to propose new measures that entail greater efficiency in emissions.Additional efforts in areas like innovation,R&D,diffusion of more eco-friendly technologies,and a greater use of greener energies all prove to be essential reduction actions to fight the greenhouse effect.

关键词： LMDI Decomposition Spain GHG emissions

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A texture-modified dessert with high nutritional value designed for people with dysphagia:effect of refrigeration and frozen storage

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Food Science and Human Wellness 2024年第1期13卷 462-471页

作者： maría Cartagena Larisa Giura Diana Ansorena Iciar Astiasaran Department of Nutrition Food Science and PhysiologyFaculty of Pharmacy and NutritionUniversidad de NavarraC/Irunlarrea s/nPamplona 31008Spain Center for Nutrition Research University of Navarrac/Irunlarrea 1Pamplona 31008Spain Instituto de Investigación Sanitaria de Navarra IDISNAPamplona 31008Spain National Centre for Food Technology and Safety(CNTA)—Technology and Knowledge for Food Sector Competitiveness NavarreCrta-Na 134-km 53San Adrian 31570Spain

Dysphagia is commonly associated with malnutrition and an increased choking risk.To overcome these complications,food designed for people with dysphagia should have an appropriate texture and a high nutritional value.In this study,six formulations of a strawberry dessert enriched in protein(calcium caseinate)and fiber(wheat dextrin or inulin)were developed using different hydrocolloids(xanthan gum,carboxymethyl cellulose or modified starch)to provide desirable texture and stability.Nutritional value was calculated and total phenolic content and antioxidant activity of the samples were analyzed.Back-extrusion test,rheological measurements and sensory analysis were performed in refrigerated and frozen samples to characterize their textural and viscoelastic properties.The high content in protein(14.7 g/100 g)and fiber(7.9-8.7 g/100 g)made possible to use the claims“high protein”and“high fiber”.Phytochemicals supplied by strawberries contributed to the antioxidant properties of the dessert.Loss tangent ranged 0.28-0.35 for all the formulations,indicating a weak gel behavior,which could be considered safe to swallow.The formulations with dextrin in combination with carboxymethyl cellulose or xanthan gum seemed to be less susceptible to structural changes during frozen storage.This work provides insights for the development of a nutrient-dense dessert that meets the requirements of people with dysphagia.

关键词： Malnutrition Texture-modified-food Hydrocolloids Viscoelastic properties Food texture

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Omics-based biomarkers as useful tools in metabolic dysfunctionassociated steatotic liver disease clinical practice:How far are we?

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World Journal of Gastroenterology 2024年第14期30卷 1982-1989页

作者： Julieta Trinks maría F Mascardi Adrián Gadano Sebastián marciano Instituto de Medicina Traslacional e Ingeniería Biomédica-Consejo Nacional de Investigaciones Científicas y Técnicas-Instituto Universitario del Hospital Italiano-Hospital Italiano de Buenos Aires Ciudad Autónoma de Buenos Aires C1199ACLArgentina Consejo Nacional de Investigaciones Científicas y Técnicas Ciudad Autónoma de Buenos Aires C1425FQBArgentina Liver Unit Hospital Italiano de Buenos AiresCiudad Autónoma de Buenos Aires C1199DFArgentina Department of Research Hospital Italiano de Buenos AiresCiudad Autónoma de Buenos Aires C1199DFArgentina

Unmet needs exist in metabolic dysfunction-associated steatotic liver disease(MASLD)risk stratification.Our ability to identify patients with MASLD with advanced fibrosis and at higher risk for adverse outcomes is still limited.Incorporating novel biomarkers could represent a meaningful improvement to current risk predictors.With this aim,omics technologies have revolutionized the process of MASLD biomarker discovery over the past decades.While the research in this field is thriving,much of the publication has been haphazard,often using single-omics data and specimen sets of convenience,with many identified candidate biomarkers but lacking clinical validation and utility.If we incorporate these biomarkers to direct patients’management,it should be considered that the roadmap for translating a newly discovered omics-based signature to an actual,analytically valid test useful in MASLD clinical practice is rigorous and,therefore,not easily accomplished.This article presents an overview of this area’s current state,the conceivable opportunities and challenges of omics-based laboratory diagnostics,and a roadmap for improving MASLD biomarker research.

关键词： Metabolic dysfunction-associated steatotic liver disease Non-alcoholic steatohepatitis Biomarker Risk stratification Omics

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The immune system: uncharted pathways between senses and the brain

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Neural Regeneration Research 2024年第6期19卷 1173-1174页

作者： Noelia Casares mar Cuadrado-Tejedor Ana García-Osta Juan José Lasarte Immunology and Immunotherapy Program Centre for Applied Medical Research (CIMA) University of NavarraIDISNA Division of Gene Therapy for Neurological Disorders Centre for Applied Medical Research (CIMA) University of NavarraIDISNA Pathology Anatomy and Physiology Department School of Medicine University of NavarraIDISNA

Humans and animals use the classic five senses-sight, hearing, touch, smell, and taste-to detect and monitor their environment, with the sense of position and movement often referred to as the sixth sense. The perception of external signals through the senses is essential to an organism’s survival, transmitting signals to the central nervous system(CNS) and prompting physiological changes in other biological systems. In addition to the direct effects of sense-induced mediators in the brain,

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Impacts of PI3K/protein kinase B pathway activation in reactive astrocytes: from detrimental effects to protective functions

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Neural Regeneration Research 2025年第4期20卷 1031-1041页

作者： Ramón Pérez-Núñez maría Fernanda González Ana maría Avalos Lisette Leyton Cellular Communication Laboratory Programa de Biología Celular y MolecularCenter for Studies on ExerciseMetabolism and Cancer(CEMC)Instituto de Ciencias Biomédicas(ICBM)Facultad de MedicinaUniversidad de ChileSantiagoChile Advanced Center for Chronic Diseases(ACCDiS) Faculty of Chemical and Pharmaceutical Sciences&Faculty of MedicineUniversidad de ChileSantiagoChile Instituto de Ciencias Biomédicas Facultad de Ciencias de la SaludUniversidad Autónoma de ChileSantiagoChile

Astrocytes are the most abundant type of glial cell in the central nervous system.Upon injury and inflammation,astrocytes become reactive and undergo morphological and functional changes.Depending on their phenotypic classification as A1 or A2,reactive astrocytes contribute to both neurotoxic and neuroprotective responses,respectively.However,this binary classification does not fully capture the diversity of astrocyte responses observed across different diseases and injuries.Transcriptomic analysis has revealed that reactive astrocytes have a complex landscape of gene expression profiles,which emphasizes the heterogeneous nature of their reactivity.Astrocytes actively participate in regulating central nervous system inflammation by interacting with microglia and other cell types,releasing cytokines,and influencing the immune response.The phosphoinositide 3-kinase(PI3K)/protein kinase B(AKT)signaling pathway is a central player in astrocyte reactivity and impacts various aspects of astrocyte behavior,as evidenced by in silico,in vitro,and in vivo results.In astrocytes,inflammatory cues trigger a cascade of molecular events,where nuclear factor-κB serves as a central mediator of the pro-inflammatory responses.Here,we review the heterogeneity of reactive astrocytes and the molecular mechanisms underlying their activation.We highlight the involvement of various signaling pathways that regulate astrocyte reactivity,including the PI3K/AKT/mammalian target of rapamycin(mTOR),αvβ3 integrin/PI3K/AKT/connexin 43,and Notch/PI3K/AKT pathways.While targeting the inactivation of the PI3K/AKT cellular signaling pathway to control reactive astrocytes and prevent central nervous system damage,evidence suggests that activating this pathway could also yield beneficial outcomes.This dual function of the PI3K/AKT pathway underscores its complexity in astrocyte reactivity and brain function modulation.The review emphasizes the importance of employing astrocyte-exclusive models to understand their functions accurately and these models

关键词： inflammation integrins neuroprotective neurotoxic phosphatidylinositol 3-kinase reactive astrocytes signal transduction Thy-1(CD90)

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Disentangling the effects of management and climate change on habitat suitability for saproxylic species in boreal forests

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Journal of Forestry Research 2024年第2期35卷 121-133页

作者： Ellinoora Ekman maría Triviño Clemens Blattert Adriano Mazziotta maria Potterf Kyle Eyvindson Department of Biological and Environmental Science University of JyvaskylaP.O.Box 3540014 JyvaskylaFinland Institute for Atmospheric and Earth System Research(INAR)/Physics Faculty of ScienceUniversity of HelsinkiP.O.Box 6800014 HelsinkiFinland School of Resource Wisdom University of JyvaskylaP.O.Box 3540014 JyvaskylaFinland Natural Resources Institute Finland(LUKE) Latokartanonkaari 900790 HelsinkiFinland Ecosystem Dynamics and Forest Management Group Technical University of MunichHans‑Carl‑Von‑Carlowitz‑Platz 285354 FreisingGermany Faculty of Environmental Sciences and Natural Resource Management Norwegian University of Life SciencesP.O.Box 50031433ÅsNorway

Forest degradation induced by intensive forest management and temperature increase by climate change are resulting in biodiversity decline in boreal forests.Intensive forest management and high-end climate emission scenarios can further reduce the amount and diversity of deadwood,the limiting factor for habitats for saproxylic species in European boreal forests.The magnitude of their combined effects and how changes in forest management can affect deadwood diversity under a range of climate change scenarios are poorly understood.We used forest growth simulations to evaluate how forest management and climate change will individually and jointly affect habitats of red-listed saproxylic species in Finland.We simulated seven forest management regimes and three climate scenarios(reference,RCP4.5 and RCP8.5)over 100 years.Management regimes included set aside,continuous cover forestry,business-as-usual(BAU)and four modifications of BAU.Habitat suitability was assessed using a speciesspecific habitat suitability index,including 21 fungal and invertebrate species groups.“Winner”and“loser”species were identified based on the modelled impacts of forest management and climate change on their habitat suitability.We found that forest management had a major impact on habitat suitability of saproxylic species compared to climate change.Habitat suitability index varied by over 250%among management regimes,while overall change in habitat suitability index caused by climate change was on average only 2%.More species groups were identified as winners than losers from impacts of climate change(52%–95%were winners,depending on the climate change scenario and management regime).The largest increase in habitat suitability index was achieved under set aside(254%)and the climate scenario RCP8.5(>2%),while continuous cover forestry was the most suitable regime to increase habitat suitability of saproxylic species(up to+11%)across all climate change scenarios.Our results show that close-to-nature management regimes(e.g.,continuous cover fo

关键词： Biodiversity Simulations Finland Forest planning Habitat suitability Deadwood

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Interplay between mesenchymal stromal cells and the immune system after transplantation: implications for advanced cell therapy in the retina

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Neural Regeneration Research 2024年第3期19卷 542-547页

作者： maría Norte-Muñoz David García-Bernal Diego García-Ayuso Manuel Vidal-Sanz marta Agudo-Barriuso Grupo de Investigación Oftalmología Experimental Departamento de OftalmologíaOptometríaOtorrinolaringología y Anatomía PatológicaFacultad de MedicinaUniversidad de MurciaInstituto Murciano de Investigación Biosanitaria(IMIB)Campus de Ciencias de la Salud30120 MurciaSpain Grupo de Investigación Trasplante Hematopoyético y Terapia celular Departamento de Bioquímica e Inmunología.Facultad de MedicinaUniversidad de MurciaInstituto Murciano de Investigación Biosanitaria(IMIB)Campus de Ciencias de la Salud30120 MurciaSpain

Advanced mesenchymal stromal cell-based therapies for neurodegenerative diseases are widely investigated in preclinical models.Mesenchymal stromal cells are well positioned as therapeutics because they address the underlying mechanisms of neurodegeneration,namely trophic factor deprivation and neuroinflammation.Most studies have focused on the beneficial effects of mesenchymal stromal cell transplantation on neuronal survival or functional improvement.However,little attention has been paid to the interaction between mesenchymal stromal cells and the host immune system due to the immunomodulatory properties of mesenchymal stromal cells and the long-held belief of the immunoprivileged status of the central nervous system.Here,we review the crosstalk between mesenchymal stromal cells and the immune system in general and in the context of the central nervous system,focusing on recent work in the retina and the importance of the type of transplantation.

关键词： adaptive immunity cell therapy central nervous system immune system innate immunity mesenchymal stromal cells neuroregeneration preclinical studies retina transplantation

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Astrocytes, reactive astrogliosis, and glial scar formation in traumatic brain injury

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Neural Regeneration Research 2025年第4期20卷 973-989页

作者： maría Belén Cieri Alberto Javier Ramos Laboratorio de Neuropatología Molecular IBCN UBA-CONICETFacultad de MedicinaUniversidad de Buenos AiresBuenos AiresArgentina

Traumatic brain injury is a global health crisis,causing significant death and disability worldwide.Neuroinflammation that follows traumatic brain injury has serious consequences for neuronal survival and cognitive impairments,with astrocytes involved in this response.Following traumatic brain injury,astrocytes rapidly become reactive,and astrogliosis propagates from the injury core to distant brain regions.Homeostatic astroglial proteins are downregulated near the traumatic brain injury core,while pro-inflammatory astroglial genes are overexpressed.This altered gene expression is considered a pathological remodeling of astrocytes that produces serious consequences for neuronal survival and cognitive recovery.In addition,glial scar formed by reactive astrocytes is initially necessary to limit immune cell infiltration,but in the long term impedes axonal reconnection and functional recovery.Current therapeutic strategies for traumatic brain injury are focused on preventing acute complications.Statins,cannabinoids,progesterone,beta-blockers,and cerebrolysin demonstrate neuroprotective benefits but most of them have not been studied in the context of astrocytes.In this review,we discuss the cell signaling pathways activated in reactive astrocytes following traumatic brain injury and we discuss some of the potential new strategies aimed to modulate astroglial responses in traumatic brain injury,especially using cell-targeted strategies with miRNAs or lncRNA,viral vectors,and repurposed drugs.

关键词： astrocyte glial scar innate immunity neuroinflammation stab injury Toll-like receptors

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