Estudio fenotipico y funcional linfocitario en pacientes con gastritis cronica autoinmune y anemia perniciosa

Tesis Univ. Complutense de Madrid, 1991En nuestro trabajo se demuestra que en los pacientes con gastritis autoinmune existe una alteracion funcional del sistema inmune, detectable a nivel de la poblacion linfoide T. En estas celulas se demuestra una deficientes respuesta en la via principal de activacion y proliferacion linfocitaria que es la dependiente de interleucina-2. Este hallazgo, a nivel sistemico, de alteraciones linfocitarias en una entidad nosologica con manifestaciones clinicas predominantes en un organo, refuerza la vision sistemica de las enfermedades autoinmunes.Fac. de MedicinaTRUEpu

Estudio fenotipico y funcional linfocitario en pacientes con gastritis cronica autoinmune y anemia perniciosa

En nuestro trabajo se demuestra que en los pacientes con gastritis autoinmune existe una alteracion funcional del sistema inmune, detectable a nivel de la poblacion linfoide T. En estas celulas se demuestra una deficientes respuesta en la via principal de activacion y proliferacion linfocitaria que es la dependiente de interleucina-2. Este hallazgo, a nivel sistemico, de alteraciones linfocitarias en una entidad nosologica con manifestaciones clinicas predominantes en un organo, refuerza la vision sistemica de las enfermedades autoinmunes

Optimal Design Model for a Residential PV Storage System an Application to the Spanish Case

Self-consumption of photovoltaic energy is being promoted as an effective way for energy consumption in residential households. The European Directive 944/2019 promotes the use of green energy and battery energy storage systems (BESS) for self-consumption and, in Spain, the 244/2019 Royal Decree of the Spanish electrical regulatory framework allows the self-consumption of energy with a photovoltaic (PV) facility for residential use, as well as the injection of the surplus energy into the grid for which compensation will be received. At the same time, new developments in PV and BESS technologies reduce the costs of facilities, a fact that can increase the profitability of self-consumption through PV energy. This study evaluates the profitability of a household PV facility with BESS using a model based on real market prices, hourly data from user smart meters, and their own location; especially, the model gives the best configuration of PV panels power and BESS capacity. The financial indicators taken as reference for the results and conclusions are the Net Present Value (NPV), Internal Rate of Return (IRR), and Investment Return (IR). Our method examines also the effect of the BESS and PV panel costs on the profitability of the facility. Unlike other studies, our model is based on actual (not simulated) demand and price data, and it can be easily extended to other locations and market prices

Predicting critical illness on initial diagnosis of COVID-19 based on easily obtained clinical variables: development and validation of the PRIORITY model

Objectives: We aimed to develop and validate a prediction model, based on clinical history and examination findings on initial diagnosis of coronavirus disease 2019 (COVID-19), to identify patients at risk of critical outcomes. Methods: We used data from the SEMI-COVID-19 Registry, a cohort of consecutive patients hospitalized for COVID-19 from 132 centres in Spain (23rd March to 21st May 2020). For the development cohort, tertiary referral hospitals were selected, while the validation cohort included smaller hospitals. The primary outcome was a composite of in-hospital death, mechanical ventilation, or admission to intensive care unit. Clinical signs and symptoms, demographics, and medical history ascertained at presentation were screened using least absolute shrinkage and selection operator, and logistic regression was used to construct the predictive model. Results: There were 10 433 patients, 7850 in the development cohort (primary outcome 25.1%, 1967/7850) and 2583 in the validation cohort (outcome 27.0%, 698/2583). The PRIORITY model included: age, dependency, cardiovascular disease, chronic kidney disease, dyspnoea, tachypnoea, confusion, systolic blood pressure, and SpO2 ≤93% or oxygen requirement. The model showed high discrimination for critical illness in both the development (C-statistic 0.823; 95% confidence interval (CI) 0.813, 0.834) and validation (C-statistic 0.794; 95%CI 0.775, 0.813) cohorts. A freely available web-based calculator was developed based on this model (https://www.evidencio.com/models/show/2344). Conclusions: The PRIORITY model, based on easily obtained clinical information, had good discrimination and generalizability for identifying COVID-19 patients at risk of critical outcomes.No funding was received for this work

The prognostic value of eosinophil recovery in COVID-19: A multicentre, retrospective cohort study on patients hospitalised in spanish hospitals

Artículo con numerosos autores sólo se mencionan el primero, los de la UAM y el grupo colectivoObjectives: A decrease in blood cell counts, especially lymphocytes and eosinophils, has been described in patients with serious Severe Acute Respiratory Syndrome Coronavirus 2 (SARSCoV- 2), but there is no knowledge of their potential role of the recovery in these patients’ prognosis This article aims to analyse the effect of blood cell depletion and blood cell recovery on mortality due to COVID-19. Design: This work was a retrospective, multicentre cohort study of 9644 hospitalised patients with confirmed COVID-19 from the Spanish Society of Internal Medicine’s SEMI-COVID-19 Registry. Setting: This study examined patients hospitalised in 147 hospitals throughout Spain. Participants: This work analysed 9644 patients (57.12% male) out of a cohort of 12,826 patients 18 years of age hospitalised with COVID-19 in Spain included in the SEMI-COVID-19 Registry as of 29 May 2020. Main outcome measures: The main outcome measure of this work is the effect of blood cell depletion and blood cell recovery on mortality due to COVID-19. Univariate analysis was performed to determine possible predictors of death, and then multivariate analysis was carried out to control for potential confounders. Results: An increase in the eosinophil count on the seventh day of hospitalisation was associated with a better prognosis, including lower mortality rates (5.2% vs. 22.6% in non-recoverers, OR 0.234; 95% CI, 0.154 to 0.354) and lower complication rates, especially regarding the development of acute respiratory distress syndrome (8% vs. 20.1%, p = 0.000) and ICU admission (5.4% vs. 10.8%, p = 0.000). Lymphocyte recovery was found to have no effect on prognosis. Treatment with inhaled or systemic glucocorticoids was not found to be a confounding factor. Conclusion: Eosinophil recovery in patients with COVID-19 who required hospitalisation had an independent prognostic value for all-cause mortality and a milder cours

Higher mortality of hospitalized haematologic patients with COVID-19 compared to non-haematologic is driven by thrombotic complications and development of ARDS: An age-matched cohorts study

Background and Objectives: The characteristics of COVID-19 in haematologic patients compared to non-haematologic patients have seldom been analyzed. Our aim was to analyze whether there are differences in clinical characteristics and outcome of haematologic patients with COVID-19 as compared to non-haematologic. Patients and methods: Retrospective cohort study in 2 University hospitals of patients admitted with laboratory-confirmed COVID-19 included in the SEMICOVID19 database. The cohort with underlying haematologic disease was compared to a cohort of age and date-of-COVID-19-matched controls without haematologic disease (1:2). Results: 71 cases and 142 controls were included from March-May 2020. Twenty (28.1%) had received recent chemotherapy. Twelve (16.9%) were stem cell transplant recipients (SCT). Eleven (15.5%) were neutropenic concurrently with COVID-19 diagnosis. Haematologic patients presented ARDS (58.5 vs 20.7%, p = 0.0001), thrombotic complications (15.7 vs 2.1%, p = 0.002), DIC (5.7 vs 0.0%, p = 0.011), heart failure (14.3 vs 4.9%, p = 0.029) and required ICU admission (15.5 vs 2.8%, p = 0.001), MV (14.1% vs 2.1%, p 0.001), steroid (64.8 vs 33.1%, p = 0.0001), tocilizumab (33.8 vs 8.5%, p = 0.0001) or anakinra treatment (9.9% vs 0%, p = 0.0001) more often. In-hospital mortality was significantly higher (38.0% vs 18.3%, p = 0.002). Conclusions: Our results suggest COVID-19 has worse outcomes in haematologic patients than in non-haematologic, independently of age, and that the development of ARDS and thrombotic complications drive the higher in-hospital mortalit

Transgenic Mouse Models of Alzheimer’s Disease: An Integrative Analysis

Alzheimer’s disease (AD) constitutes the most prominent form of dementia among elderly individuals worldwide. Disease modeling using murine transgenic mice was first initiated thanks to the discovery of heritable mutations in amyloid precursor protein (APP) and presenilins (PS) genes. However, due to the repeated failure of translational applications from animal models to human patients, along with the recent advances in genetic susceptibility and our current understanding on disease biology, these models have evolved over time in an attempt to better reproduce the complexity of this devastating disease and improve their applicability. In this review, we provide a comprehensive overview about the major pathological elements of human AD (plaques, tauopathy, synaptic damage, neuronal death, neuroinflammation and glial dysfunction), discussing the knowledge that available mouse models have provided about the mechanisms underlying human disease. Moreover, we highlight the pros and cons of current models, and the revolution offered by the concomitant use of transgenic mice and omics technologies that may lead to a more rapid improvement of the present modeling batterThis research was funded by INSTITUTO DE SALUD CARLOS III (ISCiii) of Spain, cofinanced by FEDER funds from European Union, through grants PI21/00915 (to AG) and PI21/00914 (to JV); by JUNTA DE ANDALUCIA CONSEJERÍA DE ECONOMÍA Y CONOCIMIENTO through grants UMA18-FEDERJA-211 (to AG), UMA20-FEDERJA-104 (to IMG), P18-RT-2233 (to AG) and US-1262734 (to JV) co-financed by Programa Operativo FEDER 2014–2020 and CONSEJERIA DE SALUD grant PI-0276-2018 (to JAGL); by SPANISH MINISTER OF SCIENCE AND INNOVATION grant PID2019-108911RA-100 (to DBV), BEATRIZ GALINDO PROGRAM BAGAL18/00052 (to DBV), Alzheimer Association AARG-22-928219 (to DBV), grant PID2019-107090RA-100 (to IMG) and RAMON Y CAJAL PROGRAM RYC-2017-21879 (to IMG); and by MALAGA UNIVERSITY grant B1-2019_07 (to ESM), grant B1-2020_04 (to JAGL), grant B1-2019_06 (to IMG) and NASARD grant 27565 2018 (to IMG). M.M.-O. held a predoctoral contract from Malaga University, J.J.F.-V. held a postdoctoral contract from Malaga University, and E.S.-M. a postdoctoral contract (DOC_00251) from Junta de Andalucia. Partial funding for open access charge: Universidad de Málaga

Animal and Cellular Models of Alzheimer’s Disease: Progress, Promise, and Future Approaches

Alzheimer’s disease (AD) is an incurable neurodegenerative disease affecting over 45 million people worldwide. Transgenic mouse models have made remarkable contributions toward clarifying the pathophysiological mechanisms behind the clinical manifestations of AD. However, the limited ability of these in vivo models to accurately replicate the biology of the human disease have precluded the translation of promising preclinical therapies to the clinic. In this review, we highlight several major pathogenic mechanisms of AD that were discovered using transgenic mouse models. Moreover, we discuss the shortcomings of current animal models and the need to develop reliable models for the sporadic form of the disease, which accounts for the majority of AD cases, as well as human cellular models to improve success in translating results into human treatments.Peer reviewe