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1.
Artículo en Inglés, Español | MEDLINE | ID: mdl-38521441

RESUMEN

INTRODUCTION AND OBJECTIVES: Most of the complications associated with acute and symptomatic bradyarrhythmia (ASB) occur in the time from diagnosis to permanent pacemaker implantation (PPI). We aimed to evaluate the outcomes of an urgent 24/7 PPI service (PPI-24/7) for patients with ASB. METHODS: A total of 664 patients undergoing first-time PPI for ASB were prospectively assessed during 2 periods of identical length (18 months): 341 patients who underwent the procedure during working hours only (PPI-WH), and 323 patients who underwent the procedure after the implementation of the PPI-24/7 service. The primary safety endpoint was established as the cumulative 180-day incidence of complications related to the index arrhythmia and device implant. The primary efficacy endpoint was determined as the average number of hospital stays per patient. RESULTS: The PPI-24/7 period was associated with a significant shortening of the time from diagnosis to implantation (median [interquartile range]): 3hours [2-6] vs 16 [5-21]). The cumulative incidence of patients with complications at 180 days was lower in the PPI-24/7 period: 9% vs 17% (adjusted odds ratio, 0.5; P=.002), due to a significant reduction in preimplant complications: 2.5% vs 12% (P <.001). The average number of hospital stays was reduced by 2 per patient in the PPI-24/7 period (nonparametric P <.001). PPI-24/7 implants performed outside working hours (n=178) were safe, with a 180-day cumulative incidence in procedure-related complications of 3.9%. CONCLUSIONS: Among patients with ASB, PPI-24/7 was associated with a significant reduction in patient morbidity and efficient hospital resource use.

2.
J Dual Diagn ; : 1-13, 2024 Mar 13.
Artículo en Inglés | MEDLINE | ID: mdl-38478999

RESUMEN

Objective: The aim of this work was to examine the profile and treatment outcomes of patients with dual pathology depending on whether the patients were attending addiction centers or are being treated in a coordinated model by mental health services. Methods: Data from 7225 dual diagnosis patients were used, of whom 2417 (33.5%) received treatment in the mental health coordinated modality. Clinical information was taken from the patients' electronic health record. Results: Differences were found in patients' sociodemographic and comorbidity profiles according to treatment modality. In general, coordinated care yielded favorable outcomes (higher attendance and lower dropout rates but no differences in retention). The logistic regression analysis identified predictors of patient profiles in coordinated care, emphasizing having a severe mental health disorder (OR = 3.878, 95% CI [3.443, 4.368]; p = .000), being referred by social/health services, or having retired status. Main differences were observed according to the comorbid diagnosis presented, particularly in cases in which the patient had impulse control, hyperkinetic, or cluster C personality disorder. Conclusions: While therapeutic outcomes are influenced by associated comorbidities, the disorders prognosis can be favorable with appropriate treatment. Furthermore, analysis of differences according to treatment modality allows for predicting the type of patient who will receive a particular service, which enables the development of tailored treatments.

3.
Psychol Health ; : 1-20, 2023 Dec 29.
Artículo en Inglés | MEDLINE | ID: mdl-38156463

RESUMEN

OBJECTIVES: Alcohol Protective Behavioral Strategies (PBS) have consistently shown to be effective in reducing alcohol use and its associated consequences. We aimed to examine the explanatory value of the Theory of Planned Behavior (TPB) for using five PBS, studying the role of habit, and its potential variation across genders. METHODS: Targeted sampling was used to recruit 339 young adults in the community (women = 50.7%; mean age = 2.21[SD = 2.21]), who completed baseline and 2-month follow-up questionnaires. RESULTS: The explained variance of the TPB ranged from 58-68% for intention to use PBS, and 18-50% for behavior. The inclusion of habit produced increases of 17-26% in explained variance in intention, while explained variance in behavior remained similar. Habit was the strongest predictor of intention to use PBS, followed by attitude. Except for one behavior (drinking slowly), habits did not moderate the intention-behavior relationship, and the explanatory value of the TPB did not differ across genders. CONCLUSIONS: Our findings support the utility of the TPB as an explanatory model of alcohol PBS, along with the need to include habits within the framework of dual-process models. Interventions aimed at promoting alcohol PBS could be optimized by targeting attitudes towards PBS and habits.

4.
Europace ; 25(9)2023 08 02.
Artículo en Inglés | MEDLINE | ID: mdl-37669318

RESUMEN

AIMS: Same-day discharge (SDD) is feasible after pulmonary vein isolation (PVI). We aim to compare prospectively cryoballoon (CRYO) vs. radiofrequency (RF) ablation in a systematic SDD programme. METHODS AND RESULTS: We prospectively analysed the 617 scheduled PVI performed consecutively at our institution (n = 377 CRYO, n = 240 RF) from 1 April 2019 to 31 December 2022 within a systematic programme of SDD. The feasibility of SDD, the 10-day incidence of urgent/unplanned medical care after discharge (UUC-10), and the cost per procedure due to hospital resource use were studied. The 100 procedures performed during the previous year, in which patients were systematically hospitalized, were used as a control group. Same-day discharge was achieved in 585/617 (95%) procedures, with a significant trend towards a higher monthly SDD rate from 2019 to 2022 (P = 0.03). The frequency of SDD was similar in CRYO (356/377; 94%) vs. RF (229/240; 95%). After SDD, the UUC-10 was 66/585 (11.3%), being similar for CRYO (41/356; 11.5%) and RF (25/229; 10.9%); P = 0.8 (log-rank test). Of these, 10 patients were re-hospitalized, with an identical rate in CRYO-treated (6/356; 1.7%) and RF-treated (4/229; 1.7%) patients and owing to similar causes (4 haematomas, 4 pericarditis, and 2 symptomatic sinus node dysfunction). Same-day discharge was associated with an average savings per procedure of 63% (P < 0.001), but no differences were found between the CRYO and RF (P = 0.8). CONCLUSION: In a systematic SDD programme, feasibility (95%, increasing over time), safety (11% UUC-10, 1.7% re-hospitalizations), and savings (63% per procedure) were similar for CRYO and RF ablation procedures.


Asunto(s)
Técnicas de Ablación , Venas Pulmonares , Ablación por Radiofrecuencia , Humanos , Alta del Paciente , Venas Pulmonares/cirugía , Hospitalización
5.
World J Psychiatry ; 13(6): 278-297, 2023 Jun 19.
Artículo en Inglés | MEDLINE | ID: mdl-37383280

RESUMEN

Measurement of externalizing disorders such as antisocial disorders, attention-deficit/hyperactivity disorder or borderline disorder have relevant implications for the daily lives of people with these disorders. While the Diagnostic and Statistical Manual of Mental Disorders (DSM) and the International Classification of Diseases (ICD) have provided the diagnostic framework for decades, recent dimensional frameworks question the categorical approach of psychopathology, inherent in traditional nosotaxies. Tests and instruments develop under the DSM or ICD framework preferentially adopt this categorical approach, providing diagnostic labels. In contrast, dimensional measurement instruments provide an individualized profile for the domains that comprise the externalizing spectrum, but are less widely used in practice. Current paper aims to review the operational definitions of externalizing disorders defined under these different frameworks, revise the different measurement alternatives existing, and provide an integrative operational definition. First, an analysis of the operational definition of externalizing disorders among the DSM/ICD diagnostic systems and the recent Hierarchical Taxonomy of Psychopathology (HiTOP) model is carried out. Then, in order to analyze the coverage of operational definitions found, a description of measurement instruments among each conceptualization is provided. Three phases in the development of the ICD and DSM diagnosis systems can be observed with direct implications for measurement. ICD and DSM versions have progressively introduced systematicity, providing more detailed descriptions of diagnostic criteria and categories that ease the measurement instrument development. However, it is questioned whether the DSM/ICD systems adequately modelize externalizing disorders, and therefore their measurement. More recent theoretical approaches, such as the HiTOP model seek to overcome some of the criticism raised towards the classification systems. Nevertheless, several issues concerning this model raise mesasurement challenges. A revision of the instruments underneath each approach shows incomplete coverage of externalizing disorders among the existing instruments. Efforts to bring nosotaxies together with other theoretical models of psychopathology and personality are still needed. The integrative operational definition of externalizing disorders provided may help to gather clinical practice and research.

6.
Am J Respir Crit Care Med ; 207(8): 998-1011, 2023 04 15.
Artículo en Inglés | MEDLINE | ID: mdl-36724365

RESUMEN

Rationale: Chronic obstructive pulmonary disease (COPD) is a disease characterized by persistent airway inflammation and disordered macrophage function. The extent to which alterations in macrophage bioenergetics contribute to impaired antioxidant responses and disease pathogenesis has yet to be fully delineated. Objectives: Through the study of COPD alveolar macrophages (AMs) and peripheral monocyte-derived macrophages (MDMs), we sought to establish if intrinsic defects in core metabolic processes drive macrophage dysfunction and redox imbalance. Methods: AMs and MDMs from donors with COPD and healthy donors underwent functional, metabolic, and transcriptional profiling. Measurements and Main Results: We observed that AMs and MDMs from donors with COPD display a critical depletion in glycolytic- and mitochondrial respiration-derived energy reserves and an overreliance on glycolysis as a source for ATP, resulting in reduced energy status. Defects in oxidative metabolism extend to an impaired redox balance associated with defective expression of the NADPH-generating enzyme, ME1 (malic enzyme 1), a known target of the antioxidant transcription factor NRF2 (nuclear factor erythroid 2-related factor 2). Consequently, selective activation of NRF2 resets the COPD transcriptome, resulting in increased generation of TCA cycle intermediaries, improved energetic status, favorable redox balance, and recovery of macrophage function. Conclusions: In COPD, an inherent loss of metabolic plasticity leads to metabolic exhaustion and reduced redox capacity, which can be rescued by activation of the NRF2 pathway. Targeting these defects, via NRF2 augmentation, may therefore present an attractive therapeutic strategy for the treatment of the aberrant airway inflammation described in COPD.


Asunto(s)
Factor 2 Relacionado con NF-E2 , Enfermedad Pulmonar Obstructiva Crónica , Humanos , Macrófagos/metabolismo , Factor 2 Relacionado con NF-E2/metabolismo , Estrés Oxidativo , Enfermedad Pulmonar Obstructiva Crónica/metabolismo , Enfermedad Pulmonar Obstructiva Crónica/fisiopatología , Malato Deshidrogenasa/metabolismo
8.
Psychol Assess ; 35(4): e1-e11, 2023 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-36656723

RESUMEN

The Externalizing Spectrum Inventory-Brief Form (ESI-BF) measures tendencies toward disinhibition, lack of control, aggression, and substance use. This study adapts the ESI-BF to the Spanish population and assesses its psychometric properties. The study included 742 community adults obtained by stratified random sampling with proportional allocation according to gender, age, and geographical area of the Spanish territory and a clinical sample consisting of 333 patients. All participants completed the Personality Inventory for Diagnostic and Statistical Manual of Mental Disorders, fifth edition (PID-5) and the Alcohol Substance Dependence Severity Scale, in addition to the Spanish version of the ESI-BF. Reliability was quantified using McDonald's omega and Cronbach's α reliability coefficients. Validity evidences were studied applying confirmatory factor analysis (CFA) and correlations. Results indicated adequate reliability of scores on the ESI-BF's general factors and most of its facets. Regarding internal structure, and in line with previous studies, both symmetric and S-1 hierarchical two-subfactor (bifactor) emerged as the best-fitting models. Considering both criticisms of symmetric models and parsimony, the S-1 bifactor model, which showed configural invariance across gender and samples, was retained. Validity evidence based on the relationship with other measures of personality and alcohol consumption show correlations values theoretically expected in both clinical and community samples. Findings suggest that the Spanish adaptation of the ESI-BF shows functional near-equivalence to the original version. Its effective psychometric properties make it useful instrument for further research related to the externalizing spectrum. (PsycInfo Database Record (c) 2023 APA, all rights reserved).


Asunto(s)
Trastornos de la Personalidad , Personalidad , Adulto , Humanos , Psicometría , Reproducibilidad de los Resultados , Inventario de Personalidad , Trastornos de la Personalidad/diagnóstico
9.
J Clin Med ; 12(2)2023 Jan 04.
Artículo en Inglés | MEDLINE | ID: mdl-36675339

RESUMEN

Background: Determining the mechanism of supraventricular tachycardias with prolongedP ventriculoatrial (VA) intervals is sometimes a challenge. Our objective is to analyse the determinants, time course and diagnostic accuracy (atypical atrioventricular nodal reentrant tachycardias [AVNRT] versus orthodromic reentrant tachycardias through an accessory pathway [ORT]) of spontaneous VA intervals variation in patients with narrow QRS tachycardias and prolonged VA. Methods: A total of 156 induced tachycardias were studied (44 with atypical AVNRT and 112 with ORT). Two sets of 10 measurements were performed for each patient­after tachycardia induction and one minute later. VA and VV intervals were determined. Results: The difference between the longest and the shortest VA interval (Dif-VA) correlates significantly with the diagnosis of atypical AVNRT (C coefficient = 0.95 and 0.85 after induction and at one minute, respectively; p < 0.001). A Dif-VA ≥ 15 ms presents a sensitivity and specificity for atypical AVNRT of 50% and 99%, respectively after induction, and of 27% and 100% one minute later. We found a robust and significant correlation between the fluctuations of VV and VA intervals in atypical AVNRTs (Coefficient Rho: 0.56 and 0.76, after induction and at one minute, respectively; p < 0.001 for both) but not in ORTs. Conclusions: The analysis of VA interval variability after induction and one minute later correctly discriminates atypical AVNRT from ORT in almost all cases.

10.
Int J Sex Health ; 35(2): 284-295, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-38595857

RESUMEN

Objectives: To explore the relationship between sexual orientation and specific sexual and risk behaviors, compare the number of sexual behaviors and attitudes among people of different sexual orientations, and test the mediating effect of attitudes toward sexual behaviors in the relationship between sexual orientation and the number of sexual behaviors. Methods: A total of 2288 participants completed a checklist of sexual behaviors, indicators of sexual risk behaviors, and a scale of attitudes toward sexual behaviors. Results: Bisexual women engaged in a greater number of sexual behaviors and had more positive attitudes toward sexual behaviors than heterosexual women. Homosexual men engaged in a greater number of sexual behaviors than heterosexual men, and homosexual and bisexual men had more positive attitudes toward sexual behaviors than heterosexuals. Finally, we show the mediating role of attitudes toward sexual behaviors in the relationship between sexual orientation and the number of sexual behaviors engaged in. Conclusions: The importance of considering sexual orientation when analyzing sexual behaviors and attitudes is highlighted.

12.
Int J Methods Psychiatr Res ; 31(4): e1929, 2022 12.
Artículo en Inglés | MEDLINE | ID: mdl-35765238

RESUMEN

INTRODUCTION: Treatment retention and adherence are used as outcomes in numerous randomized clinical trials and observational studies conducted in the addiction field. Although usual criteria are 3/6 months of treatment retention or number of sessions attended, there is not a methodological support for conclusions using these criteria. This study analyzed the usefulness of retention and adherence to predict therapeutic success. METHODS: Retrospective observational study using real-world data from electronic health records of 11,907 patients in treatment diagnosed with cocaine, alcohol, cannabis and opiate use disorders or harmful use. RESULTS: Moderate effect size relations were found between the different type of clinical discharge and months in retention (η2  = 0.12) and proportion of attendance (η2  = 0.10). No relationship was found with the number of sessions attended. Using cut-off points (i.e., 3 or 6 months in treatment or attending 6 therapy sessions) worsens the ability to predict the type of discharge. DISCUSSIONS/CONCLUSION: Treatment retention and adherence are indicators moderately related to therapeutic success. Research using these indicators to assess the effectiveness of therapies should complement their results with other clinical indicators and quality of life measures.


Asunto(s)
Calidad de Vida , Trastornos Relacionados con Sustancias , Humanos , Cumplimiento y Adherencia al Tratamiento
13.
Nat Immunol ; 23(6): 927-939, 2022 06.
Artículo en Inglés | MEDLINE | ID: mdl-35624205

RESUMEN

Hypoxemia is a defining feature of acute respiratory distress syndrome (ARDS), an often-fatal complication of pulmonary or systemic inflammation, yet the resulting tissue hypoxia, and its impact on immune responses, is often neglected. In the present study, we have shown that ARDS patients were hypoxemic and monocytopenic within the first 48 h of ventilation. Monocytopenia was also observed in mouse models of hypoxic acute lung injury, in which hypoxemia drove the suppression of type I interferon signaling in the bone marrow. This impaired monopoiesis resulted in reduced accumulation of monocyte-derived macrophages and enhanced neutrophil-mediated inflammation in the lung. Administration of colony-stimulating factor 1 in mice with hypoxic lung injury rescued the monocytopenia, altered the phenotype of circulating monocytes, increased monocyte-derived macrophages in the lung and limited injury. Thus, tissue hypoxia altered the dynamics of the immune response to the detriment of the host and interventions to address the aberrant response offer new therapeutic strategies for ARDS.


Asunto(s)
Lesión Pulmonar , Síndrome de Dificultad Respiratoria , Animales , Humanos , Hipoxia/etiología , Inflamación/complicaciones , Pulmón , Lesión Pulmonar/complicaciones , Ratones
14.
J Interv Card Electrophysiol ; 63(1): 165-174, 2022 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-33594661

RESUMEN

PURPOSE: Implantable cardiac defibrillator (ICD) is the only definitive therapy for prevention of sudden cardiac death in hypertrophic cardiomyopathy (HCM). Conventional transvenous ICDs can provide cardiac pacing unlike new subcutaneous ICD, but the usefulness of cardiac pacing in HCM patients is not well defined. We sought to assess the usefulness of ICD pacing in HCM. METHODS: We retrospectively analyzed 93 HCM patients who had undergone ICD implantation at our center. Usefulness of pacing was defined as follows: 1) need of pacing due to bradycardia or AV conduction disturbances, 2) improvement of LV outflow tract obstruction by sequential AV pacing, 3) need for CRT pacing, or 4) successful antitachycardia pacing without a subsequent shock. Independent predictors of useful pacing were investigated by multivariable analysis. RESULTS: During a mean follow-up of 91.3 ± 5.5 months, 43 patients (46.2%) reached the composite endpoint. Independent predictors of pacing usefulness were older age (HR 1.36; 95%CI: 1.088-1.709; p=0.007) and NYHA functional class ≥ II (HR 2.15; 95%CI: 1.083-4.301; p=0.029). Twenty-eight (30.1%) patients had appropriate ICD interventions, triggered by a monomorphic ventricular tachycardia (MVT) in 22 of them (78.5%). In 17 individuals with MVT (77%), antitachycardia pacing successfully treated MVT. CONCLUSIONS: In our HCM series of patients with ICD, 46% of individuals benefitted from cardiac pacing. MVT were documented in nearly 80% of the patients with ventricular arrhythmias and antitachycardia pacing successfully treated them in 77% of cases.


Asunto(s)
Cardiomiopatía Hipertrófica , Desfibriladores Implantables , Taquicardia Ventricular , Anciano , Arritmias Cardíacas , Cardiomiopatía Hipertrófica/complicaciones , Cardiomiopatía Hipertrófica/terapia , Muerte Súbita Cardíaca/prevención & control , Humanos , Estudios Retrospectivos , Taquicardia Ventricular/terapia
15.
Front Psychol ; 12: 748025, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-34690897

RESUMEN

Inventory of Depression and Anxiety Symptoms-II (IDAS-II) constitutes a useful measurement tool with demonstrated psychometric properties that is contributing to the advancement of knowledge of emotional disorders within transdiagnostic models. To implement its use in clinical settings it is important that the scores can be interpreted in order to guide clinical decisions. This study aims to develops normative data for the Spanish version of the IDAS-II. An anonymous online survey was applied to 1,072 subjects, recruited through a stratified random sampling procedure taking into account population gender, age, and geographical region of Spain. Results show that women tend to score higher than men, particularly on the Dysphoria, General Depression, Appetite Gain, and Lassitude scales. Largest effect sizes for differences in the scores according to age were found for Lassitude, Dysphoria, and General Depression. Therefore, normative data according to gender and age group for each IDAS-II scale is provided. The norms provided in this work complement those already available, facilitating the decision-making of clinical professionals. Evidence of unidimensionality is provided for the 19 IDAS-II scales that allows researchers and clinicians to use specific IDAS-II scales independently.

16.
Rev. Soc. Esp. Dolor ; 28(3): 154-168, May-Jun. 2021. tab, ilus, graf
Artículo en Inglés, Español | IBECS | ID: ibc-227826

RESUMEN

Introducción: El uso de radiofrecuencia de los nervios geniculados para el tratamiento del dolor crónico de la rodilla secundario a osteoartrosis inició en 2011, y desde entonces se han realizado varios estudios con diferentes metodologías. Sin embargo, continúan generándose muchas dudas con respecto a las dianas anatómicas, los criterios de selección y la evidencia de su efectividad. Materiales y métodos: Se realizó una búsqueda electrónica desde enero de 2011 hasta abril de 2020 en las siguientes bases de datos: PubMed®, Embase ®, Google Académico y Web of Science (WoS). La búsqueda inicial encontró 106 artículos, de los cuales tomamos 33 para realizar la presente revisión. Resultados: Después de analizar cinco ensayos clínicos abiertos, un estudio de corte transversal, cuatro estudios prospectivos observacionales, ocho estudios de neuroanatomía, tres estudios retrospectivos, cuatro casos clínicos, dos series de casos, tres revisiones de la literatura y tres ensayos clínicos aleatorizados, controlados y doble ciegos; encontramos que la radiofrecuencia de los nervios geniculados disminuye el dolor asociado a la osteoartrosis de rodilla, consiguiendo una mejoría funcional con una duración variable del efecto analgésico entre tres y doce meses. A pesar del avance científico en esta área, aún no hay un consenso en cuanto a la neuroanatomía de la cápsula articular de la rodilla, la ubicación de las dianas, los parámetros empleados en radiofrecuencia y la utilidad de los bloqueos diagnósticos. Conclusiones: Se necesitan más ensayos clínicos que estandaricen los parámetros utilizados y confirmen los resultados positivos de los estudios realizados con radiofrecuencia de los nervios geniculados...(AU)


Introduction: The use of genicular nerve radiofrequency procedures to treat chronic knee pain due to osteoarthritis has surged in 2011, though many questions remain regarding anatomical targets, selection criteria, and evidence for effectiveness. Materials and methods: An electronic search was performed from January 2011 to April 2020. Databases searched included PubMed®, Embase®, Google Scholar and Web of Science (WoS). The initial search found 106 articles. Thirty-three articles were taken for this review. Results: After analyzing five open clinical trials, one cross-sectional study, four prospective observational studies, eight neuroanatomy studies, three retrospective studies, four clinical cases, two case series, three literature reviews and three randomized, double blind, controlled trials; we found genicular nerve radiofrequency achieves a pain reduction and functional improvement with a variable duration, between three and twelve months. There is no consensus regarding the neuroanatomy of the knee joint capsule, the location of the targets, the radiofrequency parameters used and the usefulness of diagnostic blocks. Conclusion: More clinical trials are needed to standardize the parameters used and confirm the positive results of genicular nerve radiofrequency. Although lonthere are few cases of adverse events associated with radiofrequency of the geniculate nerves, more studies are needed to support the safety of this technique and its long-term side effects in osteoarthritis knee pain management associated that do not respond to other previous medical treatments.(AU)


Asunto(s)
Humanos , Masculino , Femenino , Dolor Crónico/tratamiento farmacológico , Osteoartritis de la Rodilla/tratamiento farmacológico , Terapia por Radiofrecuencia , Ablación por Radiofrecuencia , Desnervación , Ganglio Geniculado , Dolor/tratamiento farmacológico , Manejo del Dolor/métodos , Osteoartritis , Traumatismos de la Rodilla
17.
Sci Adv ; 7(19)2021 05.
Artículo en Inglés | MEDLINE | ID: mdl-33962944

RESUMEN

Unbalanced immune responses to pathogens can be life-threatening although the underlying regulatory mechanisms remain unknown. Here, we show a hypoxia-inducible factor 1α-dependent microRNA (miR)-210 up-regulation in monocytes and macrophages upon pathogen interaction. MiR-210 knockout in the hematopoietic lineage or in monocytes/macrophages mitigated the symptoms of endotoxemia, bacteremia, sepsis, and parasitosis, limiting the cytokine storm, organ damage/dysfunction, pathogen spreading, and lethality. Similarly, pharmacologic miR-210 inhibition improved the survival of septic mice. Mechanistically, miR-210 induction in activated macrophages supported a switch toward a proinflammatory state by lessening mitochondria respiration in favor of glycolysis, partly achieved by downmodulating the iron-sulfur cluster assembly enzyme ISCU. In humans, augmented miR-210 levels in circulating monocytes correlated with the incidence of sepsis, while serum levels of monocyte/macrophage-derived miR-210 were associated with sepsis mortality. Together, our data identify miR-210 as a fine-tuning regulator of macrophage metabolism and inflammatory responses, suggesting miR-210-based therapeutic and diagnostic strategies.


Asunto(s)
MicroARNs , Sepsis , Animales , Inflamación/genética , Inflamación/metabolismo , Macrófagos/metabolismo , Ratones , MicroARNs/genética , MicroARNs/metabolismo , Monocitos/metabolismo , Sepsis/genética , Sepsis/metabolismo
19.
Nat Commun ; 12(1): 3098, 2021 05 25.
Artículo en Inglés | MEDLINE | ID: mdl-34035282

RESUMEN

The human Alzheimer's disease (AD) brain accumulates angiogenic markers but paradoxically, the cerebral microvasculature is reduced around Aß plaques. Here we demonstrate that angiogenesis is started near Aß plaques in both AD mouse models and human AD samples. However, endothelial cells express the molecular signature of non-productive angiogenesis (NPA) and accumulate, around Aß plaques, a tip cell marker and IB4 reactive vascular anomalies with reduced NOTCH activity. Notably, NPA induction by endothelial loss of presenilin, whose mutations cause familial AD and which activity has been shown to decrease with age, produced a similar vascular phenotype in the absence of Aß pathology. We also show that Aß plaque-associated NPA locally disassembles blood vessels, leaving behind vascular scars, and that microglial phagocytosis contributes to the local loss of endothelial cells. These results define the role of NPA and microglia in local blood vessel disassembly and highlight the vascular component of presenilin loss of function in AD.


Asunto(s)
Enfermedad de Alzheimer/genética , Péptidos beta-Amiloides/genética , Vasos Sanguíneos/metabolismo , Encéfalo/metabolismo , Neovascularización Patológica/genética , Placa Amiloide/genética , Enfermedad de Alzheimer/metabolismo , Péptidos beta-Amiloides/metabolismo , Animales , Vasos Sanguíneos/patología , Encéfalo/irrigación sanguínea , Encéfalo/patología , Modelos Animales de Enfermedad , Células Endoteliales/metabolismo , Femenino , Perfilación de la Expresión Génica/métodos , Humanos , Ratones Endogámicos C57BL , Ratones Noqueados , Ratones Transgénicos , Neovascularización Patológica/metabolismo , Placa Amiloide/metabolismo , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa/métodos
20.
Wellcome Open Res ; 6: 38, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-33997298

RESUMEN

Background: Acute respiratory distress syndrome (ARDS) is a severe critical condition with a high mortality that is currently in focus given that it is associated with mortality caused by coronavirus disease 2019 (COVID-19). Neutrophils play a key role in the lung injury characteristic of non-COVID-19 ARDS and there is also accumulating evidence of neutrophil mediated lung injury in patients who succumb to infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Methods: We undertook a functional proteomic and metabolomic survey of circulating neutrophil populations, comparing patients with COVID-19 ARDS and non-COVID-19 ARDS to understand the molecular basis of neutrophil dysregulation. Results: Expansion of the circulating neutrophil compartment and the presence of activated low and normal density mature and immature neutrophil populations occurs in ARDS, irrespective of cause. Release of neutrophil granule proteins, neutrophil activation of the clotting cascade and upregulation of the Mac-1 platelet binding complex with formation of neutrophil platelet aggregates is exaggerated in COVID-19 ARDS. Importantly, activation of components of the neutrophil type I interferon responses is seen in ARDS following infection with SARS-CoV-2, with associated rewiring of neutrophil metabolism, and the upregulation of antigen processing and presentation. Whilst dexamethasone treatment constricts the immature low density neutrophil population, it does not impact upon prothrombotic hyperinflammatory neutrophil signatures. Conclusions: Given the crucial role of neutrophils in ARDS and the evidence of a disordered myeloid response observed in COVID-19 patients, this work maps the molecular basis for neutrophil reprogramming in the distinct clinical entities of COVID-19 and non-COVID-19 ARDS.

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