Arqueología del vanguardismo histórico: introducción al caso hispanoamericano.

Sin resume

Effect of the residual doping on the performance of InN epilayers as saturable absorbers for ultrafast lasers at 1.55µm

We report on the improvement of performance of InN-based saturable absorbers in fiber lasers operating at 1.55 mum by reducing the residual doping, due to the lower Burstein-Moss effect. The improved tuning of the band-to-band transition with respect to the operation wavelength leads to an enhancement of nonlinear optical effects, resulting in 30 % of modulation depth. We introduce the development of an ultrafast mode-locked fiber laser using an improved InN-based saturable absorber that incorporates a buffer layer between the active layer and the substrate. The laser delivers output pulses with a temporal width of 220 fs, a repetition rate of 5.25 MHz, and high-pulse energy of 5.8 nJ.Ministerio de Economía, Industria y CompetitividadMinisterio de Ciencia, Innovación y UniversidadesComunidad de Madri

Clinical Value of Inflammatory and Neurotrophic Biomarkers in Bipolar Disorder: A Systematic Review and Meta-Analysis

Bipolar disorder (BD) is a multifactorial chronic psychiatric disease highly defined by genetic, clinical, environmental and social risk factors. The present systematic review and meta-analysis aimed to examine the relationship between inflammatory and neurotrophic factors and clinical, social and environmental factors involved in the development and the characterization of BD. Web of Science, PubMed, PsycINFO, Scopus and Science Direct were searched by two independent reviewers. The systematic review was registered in PROSPERO (CRD42020180626). A total of 51 studies with 4547 patients with a diagnosis of BD were selected for systematic review. Among them, 18 articles were included for meta-analysis. The study found some evidence of associations between BDNF and/or inflammatory factors and different stressors and functional and cognitive impairment, but limitations prevented firm conclusions. The main finding of the meta-analysis was a negative correlation between circulating levels of BDNF and depression severity score (standardized mean difference = −0.22, Confidence Interval 95% = −0.38, −0.05, p = 0.01). Evidence indicates that BDNF has a role in the depressive component of BD. However, the poor consistency found for other inflammatory mediators clearly indicates that highly controlled studies are needed to identity precise biomarkers of this disorder.This research was funded by Atención Primaria, Cronicidad y Promoción de la Salud: Red de Investigación en Atención Primaria de Adicciones (RIAPAd), Instituto de Salud Carlos III (ISCIII), Ministerio de Ciencia e Innovación and European Regional Development Funds-European Union (ERDF-EU), grant number RD21/0009/0003; ISCIII, ERDF-EU, grant number PI19/01577; Ministerio de Sanidad, Delegación de Gobierno para el Plan Nacional sobre Drogas, grant numbers PND 2019/040; and Consejería de Salud y Familia, Junta de Andalucía, grant numbers RIC-0111-2019. AV-N (CM19/00025) and CG-S-L (CM19/00240) hold “Rio Hortega” research contracts from the National System of Health, ISCIII, ERDF-EU. FM-C and JG-P has received funding from the Andalusia Government in the grants for human resources reinforcement in the research activity (Acción A de intensificación 2019 and Acción B de refuerzos de larga duración 2014). The funding sources had no further role in study design; in the collection, analysis and interpretation of data; in writing of the report; and in the decision to submit the paper for publication. Funding for open access charge: Universidad de Málaga/CBUA

Targeting the TWEAK–Fn14 pathway prevents dysfunction in cardiac calcium handling after acute kidney injury

Heart and kidney have a closely interrelated pathophysiology. Acute kidney injury (AKI) is associated with significantly increased rates of cardiovascular events, a relationship defined as cardiorenal syndrome type 3 (CRS3). The underlying mechanisms that trigger heart disease remain, however, unknown, particularly concerning the clinical impact of AKI on cardiac outcomes and overall mortality. Tumour necrosis factor-like weak inducer of apoptosis (TWEAK) and its receptor fibroblast growth factor-inducible 14 (Fn14) are independently involved in the pathogenesis of both heart and kidney failure, and recent studies have proposed TWEAK as a possible therapeutic target; however, its specific role in cardiac damage associated with CRS3 remains to be clarified. Firstly, we demonstrated in a retrospective longitudinal clinical study that soluble TWEAK plasma levels were a predictive biomarker of mortality in patients with AKI. Furthermore, the exogenous application of TWEAK to native ventricular cardiomyocytes induced relevant calcium (Ca2+) handling alterations. Next, we investigated the role of the TWEAK–Fn14 axis in cardiomyocyte function following renal ischaemia–reperfusion (I/R) injury in mice. We observed that TWEAK–Fn14 signalling was activated in the hearts of AKI mice. Mice also showed significantly altered intra-cardiomyocyte Ca2+ handling and arrhythmogenic Ca2+ events through an impairment in sarcoplasmic reticulum Ca2+-adenosine triphosphatase 2a pump (SERCA2a) and ryanodine receptor (RyR2) function. Administration of anti-TWEAK antibody after reperfusion significantly improved alterations in Ca2+ cycling and arrhythmogenic events and prevented SERCA2a and RyR2 modifications. In conclusion, this study establishes the relevance of the TWEAK–Fn14 pathway in cardiac dysfunction linked to CRS3, both as a predictor of mortality in patients with AKI and as a Ca2+ mishandling inducer in cardiomyocytes, and highlights the cardioprotective benefits of TWEAK targeting in CRS3This work was mainly supported by projects from the Instituto de Salud Carlos III (ISCIII) (PI20/00763, PI20/01482, CPII20/00022, FI18/00261, FI21/00212, CD19/00029, IFEQ21/00012, PI19/00588, PI22/00469) and co-funded by the European Union, Ministerio de Universidades (FPU20/03005), Ministerio de Ciencia e Innovaci on (RYR2019-026916-I), the Education and Research Council of Madrid (PEJ-2021- AI/SAL-21426), Biomedicine Network Comunidad de Madrid (P2022/BMD-7223 CIFRA_COR-CM), Spanish Network in Inflammasoma and Pyroptosis in Chronic Disease and Cancer (RED2022-134511-T), and the Spanish Society of Nephrology SEN/SENEFRO Foundatio

The anti-aging factor Klotho protects against acquired long QT syndrome induced by uremia and promoted by fibroblast growth factor 23

[Background]: Chronic kidney disease (CKD) is associated with increased propensity for arrhythmias. In this context, ventricular repolarization alterations have been shown to predispose to fatal arrhythmias and sudden cardiac death. Between mineral bone disturbances in CKD patients, increased fibroblast growth factor (FGF) 23 and decreased Klotho are emerging as important effectors of cardiovascular disease. However, the relationship between imbalanced FGF23-Klotho axis and the development of cardiac arrhythmias in CKD remains unknown. [Methods]: We carried out a translational approach to study the relationship between the FGF23–Klotho signaling axis and acquired long QT syndrome in CKD-associated uremia. FGF23 levels and cardiac repolarization dynamics were analyzed in patients with dialysis-dependent CKD and in uremic mouse models of 5/6 nephrectomy (Nfx) and Klotho deficiency (hypomorphism), which show very high systemic FGF23 levels. [Results]: Patients in the top quartile of FGF23 levels had a higher occurrence of very long QT intervals (> 490 ms) than peers in the lowest quartile. Experimentally, FGF23 induced QT prolongation in healthy mice. Similarly, alterations in cardiac repolarization and QT prolongation were observed in Nfx mice and in Klotho hypomorphic mice. QT prolongation in Nfx mice was explained by a significant decrease in the fast transient outward potassium (K+) current (Itof), caused by the downregulation of K+ channel 4.2 subunit (Kv4.2) expression. Kv4.2 expression was also significantly reduced in ventricular cardiomyocytes exposed to FGF23. Enhancing Klotho availability prevented both long QT prolongation and reduced Itof current. Likewise, administration of recombinant Klotho blocked the downregulation of Kv4.2 expression in Nfx mice and in FGF23-exposed cardiomyocytes. [Conclusion]: The FGF23–Klotho axis emerges as a new therapeutic target to prevent acquired long QT syndrome in uremia by minimizing the predisposition to potentially fatal ventricular arrhythmias and sudden cardiac death in patients with CKD.This work was supported by projects from the Instituto de Salud Carlos III, Ministry of Economy, Industry and Competitiveness (PI17/01093, PI17/01193, PI20/00763, CP15/00129, F18/00261, CPII20/00022, SAF2017-84777-R, PID2020-113238RB-I00), from the Sociedad Española de Cardiología (SEC), and from the Fundación Renal Íñigo Alvarez de Toledo (FRIAT), co-funded by the European Regional Development Fund (Fondos FEDER)

Neurosurgical emergency management during the lockdown period in health care regions in Spain with different COVID-19 impact: lessons learned to improve outcomes on the future waves

Background COVID-19 has overloaded health care systems, testing the capacity and response in every European region. Concerns were raised regarding the impact of resources’ reorganization on certain emergency pathology management. The aim of the present study was to assess the impact of the outbreak (in terms of reduction of neurosurgical emergencies) during lockdown in different regions of Spain. Methods We analyzed the impact of the outbreak in four different affected regions by descriptive statistics and univariate comparison with same period of two previous years. These regions differed in their incidence level (high/low) and in the time of excess mortality with respect to lockdown declaration. That allowed us to analyze their influence on the characteristics of neurosurgical emergencies registered for every region. Results 1185 patients from 18 neurosurgical centers were included. Neurosurgical emergencies that underwent surgery dropped 24.41% and 28.15% in 2020 when compared with 2019 and 2018, respectively. A higher reduction was reported for the most affected regions by COVID-19. Non-traumatic spine experienced the most significant decrease in number of cases. Life-threatening conditions did not suffer a reduction in any health care region. Conclusions COVID-19 affected dramatically the neurosurgical emergency management. The most significant reduction in neurosurgical emergencies occurred on those regions that were hit unexpectedly by the pandemic, as resources were focused on fighting the virus. As a consequence, life-threating and non-life-threatening conditions’ mortality raised. Results in regions who had time to prepare for the hit were congruent with an organized and sensible neurosurgical decision-making.Peer reviewe

A personalized intervention to prevent depression in primary care: cost-effectiveness study nested into a clustered randomized trial

Abstract Background: Depression is viewed as a major and increasing public health issue, as it causes high distress in the people experiencing it and considerable financial costs to society. Efforts are being made to reduce this burden by preventing depression. A critical component of this strategy is the ability to assess the individual level and profile of risk for the development of major depression. This paper presents the cost-effectiveness of a personalized intervention based on the risk of developing depression carried out in primary care, compared with usual care. Methods: Cost-effectiveness analyses are nested within a multicentre, clustered, randomized controlled trial of a personalized intervention to prevent depression. The study was carried out in 70 primary care centres from seven cities in Spain. Two general practitioners (GPs) were randomly sampled from those prepared to participate in each centre (i.e. 140 GPs), and 3326 participants consented and were eligible to participate. The intervention included the GP communicating to the patient his/her individual risk for depression and personal risk factors and the construction by both GPs and patients of a psychosocial programme tailored to prevent depression. In addition, GPs carried out measures to activate and empower the patients, who also received a leaflet about preventing depression. GPs were trained in a 10- to 15-h workshop. Costs were measured from a societal and National Health care perspective. Qualityadjustedlife years were assessed using the EuroQOL five dimensions questionnaire. The time horizon was 18 months.This work was supported by grants from the Spanish Ministry of Health, the Institute of Health Carlos III (ISCIII) and the European Regional Development Fund (ERDF) ’A way to build Europe’(grant references PS09/02272, PS09/02147, PS09/01095, PS09/00849 and PS09/00461); the Andalusian Council of Health (grant reference PI-0569-2010); the Spanish Network of Primary Care Research ’redIAPP’ (RD06/0018, RD12/0005/0001); the ’Aragón group’ (RD06/0018/0020, RD12/0005/0006); the ’Bizkaya group’ (RD06/0018/0018, RD12/0005/0010); the Castilla-León Group (RD06/0018/0027); the Mental Health (SJD) Barcelona Group (RD06/0018/0017, RD12/0005/0008); and the Mental-Health, Services and Primary Care (SAMSERAP) MálagaGroup (RD06/0018/0039, RD12/0005/0005)

Effectiveness of an intervention for improving drug prescription in primary care patients with multimorbidity and polypharmacy:Study protocol of a cluster randomized clinical trial (Multi-PAP project)

This study was funded by the Fondo de Investigaciones Sanitarias ISCIII (Grant Numbers PI15/00276, PI15/00572, PI15/00996), REDISSEC (Project Numbers RD12/0001/0012, RD16/0001/0005), and the European Regional Development Fund ("A way to build Europe").Background: Multimorbidity is associated with negative effects both on people's health and on healthcare systems. A key problem linked to multimorbidity is polypharmacy, which in turn is associated with increased risk of partly preventable adverse effects, including mortality. The Ariadne principles describe a model of care based on a thorough assessment of diseases, treatments (and potential interactions), clinical status, context and preferences of patients with multimorbidity, with the aim of prioritizing and sharing realistic treatment goals that guide an individualized management. The aim of this study is to evaluate the effectiveness of a complex intervention that implements the Ariadne principles in a population of young-old patients with multimorbidity and polypharmacy. The intervention seeks to improve the appropriateness of prescribing in primary care (PC), as measured by the medication appropriateness index (MAI) score at 6 and 12months, as compared with usual care. Methods/Design: Design:pragmatic cluster randomized clinical trial. Unit of randomization: family physician (FP). Unit of analysis: patient. Scope: PC health centres in three autonomous communities: Aragon, Madrid, and Andalusia (Spain). Population: patients aged 65-74years with multimorbidity (≥3 chronic diseases) and polypharmacy (≥5 drugs prescribed in ≥3months). Sample size: n=400 (200 per study arm). Intervention: complex intervention based on the implementation of the Ariadne principles with two components: (1) FP training and (2) FP-patient interview. Outcomes: MAI score, health services use, quality of life (Euroqol 5D-5L), pharmacotherapy and adherence to treatment (Morisky-Green, Haynes-Sackett), and clinical and socio-demographic variables. Statistical analysis: primary outcome is the difference in MAI score between T0 and T1 and corresponding 95% confidence interval. Adjustment for confounding factors will be performed by multilevel analysis. All analyses will be carried out in accordance with the intention-to-treat principle. Discussion: It is essential to provide evidence concerning interventions on PC patients with polypharmacy and multimorbidity, conducted in the context of routine clinical practice, and involving young-old patients with significant potential for preventing negative health outcomes. Trial registration: Clinicaltrials.gov, NCT02866799Publisher PDFPeer reviewe

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