The Expression of AQP1 IS Modified in Lung of Patients With Idiopathic Pulmonary Fibrosis: Addressing a Possible New Target

Activation of the epithelial-mesenchymal transition process (EMT) by which alveolar cells in human lung tissue undergo differentiation giving rise to a mesenchymal phenotype (fibroblast/miofibroblasts) has been well recognized as a key element in the origin of idiopathic pulmonary fibrosis (IPF). Here we analyzed expression of AQP1 in lung biopsies of patients diagnosed with IPF, and compared it to biopsies derived from patients with diverse lung pneumonies, such as hypersensitivity pneumonitis, sarcoidosis or normal lungs. Immunostaining for AQP1 showed a clear increment of AQP1 localized in the alveolar epithelium in biopsies from IPF patients alone. Moreover, to examine the possible participation of AQP1 in the pathophysiology of IPF, we evaluated its role in the pro-fibrotic transformation induced by transforming growth factor (TGF-β) in vitro. Human alveolar epithelial cells (A549), and fibroblasts derived from an IPF patient (LL29), or fibroblasts from healthy normal lung tissue (MRC-5), were treated with TGF-β, and levels of expression of AQP1, as well as those of E-cadherin, vimentin, α-SMA and collagen were analyzed by RT-qPCR, western blot and immunohistochemistry. An increase of AQP1 mRNA and protein after TGF-β treatment (4-72h) was observed either in A549 or IPF fibroblast-LL29 but not in MRC-5 fibroblasts. A gradual reduction of E-cadherin, and increased expression of vimentin, with no changes in α-SMA levels were observed in A549. Whereas in LL29 and MRC-5, TGF-β1 elicited a large production of collagen and α-SMA that was significantly greater in IPF fibroblast-LL29. Changes observed are consistent with activation of EMT by TGF-β, but whether modifications in AQP1 expression are responsible or independent events occurring at the same time is still unknown. Our results suggest that AQP1 plays a role in the pro-fibrotic TGF-β action and contributes to the etiology and pathophysiology of IPF. Understanding AQP1's role will help us comprehend the fate of this disease.Fondos FEDER (UE)Fundación NeumosurFundación SEPARISCIII Instituto de Salud Carlos II

Follow-up of health-related quality of life and pain in a cohort of patients with rheumatoid arthritis before and after COVID-19

The foot is one of the anatomical structures of the body most affected in rheumatoid arthritis (RA), associated with the disability of patients, even more during COVID-19. The aim of this study was to analyse whether the period of physical inactivity during COVID-19 is an influential factor on health-related quality of life and foot pain in patients with RA. Methods: 162 patients with foot pain and RA, recruited from the Hospital Virgen de las Nieves, Granada (Spain) were included. Data was collected during two different periods: January - December 2018 in person and June - September 2021 by phone. Patients were asked to complete the Spanish adapted version of the 12-Item Short Form Survey (SF-12) and the Visual Analogue Scale (VAS). Results: The results from the SF-12 questionnaires were divided between its two subscales (i.e., mental, and physical component). The physical component shows an improvement between 2018 and 2021, from 32.05in 2018–35.18 in 2021 (p < 0.05). The opposite happened with the mental component, showing a dete- rioration, from 39.69 in 2018–34.48 in 2021 (p < 0.05). Regarding pain, VAS shows higher levels of pain with statistically significant differences, both in general pain (from 6 in 2018–7 in 2012) and in foot pain (from 5 to 7), (p < 0.05). Conclusion: Mental quality of life and pain, both general and foot pain, are influenced by the period of physical inactivity during COVID-19.Funding for open access charge: Universidad de Málaga / CBU

The stability and consolidation of the Francoist Regime. The case of Eastern Andalusia, 1936-50

The stabilisation and longevity of Franco’s regime can be explained by the interpenetration of society and the institutions of the ‘New State’ in three overlapping areas: firstly, in the sphere of the shared culture of the community of civil war victors; secondly, through repression, based on the decisive collaboration of those supporting Francoism, which cut short any possible opposition; thirdly, in the socio-economic sphere, where those making up the groups supporting the ‘New State’ would see their personal interests fulfilled. At the same time, the defeated would be ensnared in a maze of misery and silence, abandoning any political concerns and concentrating instead on survival. Accordingly, the regime proved able to win support from a broad range of social groups while also eliminating any signs of opposition.The Spanish Ministerio de Innovación y Ciencia funded the research drawn on for this article (reference HAR2009‐07487)

Oral contraceptives do not modify the risk of a second attack and disability accrual in a prospective cohort of women with a clinically isolated syndrome and early multiple sclerosis

Cohort study; Oral contraceptives; Second relapseEstudio de cohorte; Anticonceptivos orales; Segunda recaídaEstudi de cohorts; Anticonceptius orals; Segona recaigudaObjective: To evaluate whether oral contraceptive (OC) use is associated with the risk of a second attack and disability accrual in women with a clinically isolated syndrome (CIS) and early multiple sclerosis (MS). Methods: Reproductive information from women included in the Barcelona CIS prospective cohort was collected through a self-reported cross-sectional survey. We examined the relationship of OC exposure with the risk of a second attack and confirmed Expanded Disability Status Scale of 3.0 using multivariate Cox regression models, adjusted by age, topography of CIS, oligoclonal bands, baseline brain T2 lesions, body size at menarche, smoking, and disease-modifying treatment (DMT). OC and DMT exposures were considered as time-varying variables. Findings were confirmed with sensitivity analyses using propensity score models. Results: A total of 495 women were included, 389 (78.6%) referred to ever use OC and 341 (68.9%) started OC before the CIS. Exposure to OC was not associated with a second attack (adjusted hazard ratio (aHR) = 0.73, 95% confidence interval (CI) = 0.33–1.61) or disability accrual (aHR = 0.81, 95% CI = 0.17–3.76). Sensitivity analyses confirmed these results. Conclusion: OC use does not modify the risk of second attack or disability accrual in patients with CIS and early MS, once considered as a time-dependent exposure and adjusted by other potential confounders.The author(s) disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: This project was supported by FIS PI15/0070 from Ministry of Economy and Competitiveness of Spain

Impacto de la edad del donante-receptor en la supervivencia al trasplante cardiaco. Subanálisis del Registro Español de Trasplante Cardiaco

[Abstract] Introduction and objectives. The age of heart transplant recipients and donors is progressively increasing. It is likely that not all donor-recipient age combinations have the same impact on mortality. The objective of this work was to compare survival in transplant recipients according to donor-recipient age combinations. Methods. We performed a retrospective analysis of transplants performed between 1 January 1993 and 31 December 2017 in the Spanish Heart Transplant Registry. Pediatric transplants, retransplants and combined transplants were excluded (6505 transplants included). Four groups were considered: a) donor < 50 years for recipient < 65 years; b) donor < 50 years for recipient ≥ 65 years; c) donor ≥ 50 years for recipient ≥ 65 years, and d) donor ≥ 50 years for recipient < 65 years. Results. The most frequent group was young donor for young recipient (73%). There were differences in the median survival between the groups (P < .001): a) younger-younger: 12.1 years, 95%CI, 11.5-12.6; b) younger-older: 9.1 years, 95%CI, 8.0-10.5; c) older-older: 7.5 years, 95%CI, 2.8-11.0; d) older-younger: 10.5 years, 95%CI, 9.6-12.1. On multivariate analysis, independent predictors of mortality were the age of the donor and the recipient (0.008 and 0.001, respectively). The worst combinations were older-older vs younger-younger (HR, 1.57; 95%CI, 1.22-2.01; P < .001) and younger-older vs younger-younger (HR, 1.33; 95%CI, 1.12-1.58; P = .001). Conclusions. Age (of the donor and recipient) is a relevant prognostic factor in heart transplant. The donor-recipient age combination has prognostic implications that should be identified when accepting an organ for transplant.[Resumen] Introducción y objetivos. La edad de receptores y donantes cardiacos se está incrementando progresivamente. Es probable que no todas las combinaciones tengan el mismo impacto en la mortalidad. El objetivo de este trabajo es comparar la supervivencia de los pacientes trasplantados según la combinación de edades de donante y receptor. Métodos. Análisis retrospectivo del Registro Español de Trasplante Cardiaco de los trasplantes realizados entre el 1 de enero de 1993 y el 31 de diciembre de 2017. Se excluyeron los pediátricos, los retrasplantes y los trasplantes combinados (se incluyeron 6.505 trasplantes). Se consideraron 4 grupos: a) donante menor de 50 años para receptor menor de 65 años; b) donante menor de 50 años para receptor de edad ≥ 65 años; c) donante de edad ≥ 50 años para receptor de 65 o más, y d) donante de edad ≥ 50 años para receptor menor de 65. Resultados. El grupo más frecuente fue el de donante joven para receptor joven (73%). Hubo diferencias en la mediana de supervivencia entre los grupos (p < 0,001): a) joven-joven: 12,1 años (IC95%, 11,5-12,6); b) joven-mayor: 9,1 años (IC95%, 8,0-10,5); c) mayor-mayor: 7,5 años (IC95%, 2,8-11,0), y d) mayor-joven: 10,5 años (IC95%, 9,6-12,1). En el análisis multivariante, las edades del donante y del receptor resultaron predictoras independientes de la mortalidad (0,008 y 0,001 respectivamente). Las peores combinaciones fueron mayor-mayor frente a joven-joven (HR = 1,57; IC95%, 1,22-2,01; p < 0,001) y joven-mayor frente a joven-joven (HR = 1,33; IC95%, 1,12-1,58; p = 0,001). Conclusiones. La edad (del donante y del receptor) es un factor pronóstico relevante en el trasplante cardiaco. La combinación de edades de donante y receptor posee implicaciones pronósticas que se debe conocer a la hora de aceptar un órgano para trasplante

Deciphering multiple sclerosis disability with deep learning attention maps on clinical MRI

Deep learning; Disability; Structural MRIAprendizaje profundo; Discapacidad; Resonancia magnética estructuralAprenentatge profund; Discapacitat; Ressonància magnètica estructuralThe application of convolutional neural networks (CNNs) to MRI data has emerged as a promising approach to achieving unprecedented levels of accuracy when predicting the course of neurological conditions, including multiple sclerosis, by means of extracting image features not detectable through conventional methods. Additionally, the study of CNN-derived attention maps, which indicate the most relevant anatomical features for CNN-based decisions, has the potential to uncover key disease mechanisms leading to disability accumulation. From a cohort of patients prospectively followed up after a first demyelinating attack, we selected those with T1-weighted and T2-FLAIR brain MRI sequences available for image analysis and a clinical assessment performed within the following six months (N = 319). Patients were divided into two groups according to expanded disability status scale (EDSS) score: ≥3.0 and < 3.0. A 3D-CNN model predicted the class using whole-brain MRI scans as input. A comparison with a logistic regression (LR) model using volumetric measurements as explanatory variables and a validation of the CNN model on an independent dataset with similar characteristics (N = 440) were also performed. The layer-wise relevance propagation method was used to obtain individual attention maps. The CNN model achieved a mean accuracy of 79% and proved to be superior to the equivalent LR-model (77%). Additionally, the model was successfully validated in the independent external cohort without any re-training (accuracy = 71%). Attention-map analyses revealed the predominant role of frontotemporal cortex and cerebellum for CNN decisions, suggesting that the mechanisms leading to disability accrual exceed the mere presence of brain lesions or atrophy and probably involve how damage is distributed in the central nervous system.MS PATHS is funded by Biogen. This study has been possible thanks to a Junior Leader La Caixa Fellowship awarded to C. Tur (fellowship code is LCF/BQ/PI20/11760008) by “la Caixa” Foundation (ID 100010434). The salaries of C. Tur and Ll. Coll are covered by this award

Early Pleistocene faunivorous hominins were not kleptoparasitic, and this impacted the evolution of human anatomy and socio-ecology

Humans are unique in their diet, physiology and socio-reproductive behavior compared to other primates. They are also unique in the ubiquitous adaptation to all biomes and habitats. From an evolutionary perspective, these trends seem to have started about two million years ago, coinciding with the emergence of encephalization, the reduction of the dental apparatus, the adoption of a fully terrestrial lifestyle, resulting in the emergence of the modern anatomical bauplan, the focalization of certain activities in the landscape, the use of stone tools, and the exit from Africa. It is in this period that clear taphonomic evidence of a switch in diet with respect to Pliocene hominins occurred, with the adoption of carnivory. Until now, the degree of carnivorism in early humans remained controversial. A persistent hypothesis is that hominins acquired meat irregularly (potentially as fallback food) and opportunistically through klepto-foraging. Here, we test this hypothesis and show, in contrast, that the butchery practices of early Pleistocene hominins (unveiled through systematic study of the patterning and intensity of cut marks on their prey) could not have resulted from having frequent secondary access to carcasses. We provide evidence of hominin primary access to animal resources and emphasize the role that meat played in their diets, their ecology and their anatomical evolution, ultimately resulting in the ecologically unrestricted terrestrial adaptation of our species. This has major implications to the evolution of human physiology and potentially for the evolution of the human brain

RICORS2040 : The need for collaborative research in chronic kidney disease

Chronic kidney disease (CKD) is a silent and poorly known killer. The current concept of CKD is relatively young and uptake by the public, physicians and health authorities is not widespread. Physicians still confuse CKD with chronic kidney insufficiency or failure. For the wider public and health authorities, CKD evokes kidney replacement therapy (KRT). In Spain, the prevalence of KRT is 0.13%. Thus health authorities may consider CKD a non-issue: very few persons eventually need KRT and, for those in whom kidneys fail, the problem is 'solved' by dialysis or kidney transplantation. However, KRT is the tip of the iceberg in the burden of CKD. The main burden of CKD is accelerated ageing and premature death. The cut-off points for kidney function and kidney damage indexes that define CKD also mark an increased risk for all-cause premature death. CKD is the most prevalent risk factor for lethal coronavirus disease 2019 (COVID-19) and the factor that most increases the risk of death in COVID-19, after old age. Men and women undergoing KRT still have an annual mortality that is 10- to 100-fold higher than similar-age peers, and life expectancy is shortened by ~40 years for young persons on dialysis and by 15 years for young persons with a functioning kidney graft. CKD is expected to become the fifth greatest global cause of death by 2040 and the second greatest cause of death in Spain before the end of the century, a time when one in four Spaniards will have CKD. However, by 2022, CKD will become the only top-15 global predicted cause of death that is not supported by a dedicated well-funded Centres for Biomedical Research (CIBER) network structure in Spain. Realizing the underestimation of the CKD burden of disease by health authorities, the Decade of the Kidney initiative for 2020-2030 was launched by the American Association of Kidney Patients and the European Kidney Health Alliance. Leading Spanish kidney researchers grouped in the kidney collaborative research network Red de Investigación Renal have now applied for the Redes de Investigación Cooperativa Orientadas a Resultados en Salud (RICORS) call for collaborative research in Spain with the support of the Spanish Society of Nephrology, Federación Nacional de Asociaciones para la Lucha Contra las Enfermedades del Riñón and ONT: RICORS2040 aims to prevent the dire predictions for the global 2040 burden of CKD from becoming true

Registro Español de Trasplante Cardiaco. XXXI Informe Oficial de la Asociación de Insuficiencia Cardiaca de la Sociedad Española de Cardiología

Introducción y objetivos Se presentan las características clínicas y los resultados de los trasplantes cardiacos realizados en España con la actualización correspondiente a 2019. Métodos Se describen las características clínicas y los resultados de los trasplantes cardiacos realizados en 2019, así como las tendencias de estos en el periodo 2010-2018. Resultados En 2019 se realizaron 300 trasplantes (8.794 desde 1984; 2.745 entre 2010 y 2019). Respecto a años previos, los cambios más llamativos son el descenso hasta el 38% de los trasplantes realizados en código urgente, y la consolidación en el cambio de asistencia circulatoria pretrasplante, con la práctica desaparición del balón de contrapulsación (0, 7%), la estabilización del uso del oxigenador extracorpóreo de membrana (9, 6%) y el aumento de los dispositivos de asistencia ventricular (29%). La supervivencia en el trienio 2016-2018 es similar a la del trienio 2013-2015 (p = 0, 34), y ambas mejores que la del trienio 2010-2012 (p = 0, 002 y p = 0, 01 respectivamente). Conclusiones Se mantienen estables tanto la actividad del trasplante cardiaco en España como los resultados en supervivencia en los últimos 2 trienios. Hay una tendencia a realizar menos trasplantes urgentes, la mayoría con dispositivos de asistencia ventricular. Introduction and objectives: The present report describes the clinical characteristics and outcomes of heart transplants in Spain and updates the data to 2019. Methods: We describe the clinical characteristics and outcomes of heart transplants performed in Spain in 2019, as well as trends in this procedure from 2010 to 2018. Results: In 2019, 300 transplants were performed (8794 since 1984; 2745 between 2010 and 2019). Compared with previous years, the most notable findings were the decreasing rate of urgent transplants (38%), and the consolidation of the type of circulatory support prior to transplant, with an almost complete disappearance of counterpulsation balloon (0.7%), stabilization in the use of extracorporeal membrane oxygenation (9.6%), and an increase in the use of ventricular assist devices (29.0%). Survival from 2016 to 2018 was similar to that from 2013 to 2015 (P = .34). Survival in both these periods was better than that from 2010 to 2012 (P = .002 and P = .01, respectively). Conclusions: Heart transplant activity has remained stable during the last few years, as have outcomes (in terms of survival). There has been a trend to a lower rate of urgent transplants and to a higher use of ventricular assist devices prior to transplant