Memetic Evolutionary Multi-Objective Neural Network Classifier to Predict Graft Survival in Liver Transplant Patients

In liver transplantation, matching donor and recipient is a problem that can be solved using machine learning techniques. In this paper we consider a liver transplant dataset obtained from eleven Spanish hospitals, including the patient survival or the rejection in liver transplantation one year after the surgery. To tackle this problem, we use a multi-objective evolutionary algorithm for training generalized radial basis functions neural networks. The obtained models provided medical experts with a mathematical value to predict survival rates allowing them to come up with a right decision according to the principles of justice, efficiency and equit

The risk of incident depression when assessed with the lifestyle and well-being index

Objectives: Novel findings indicate links between unhealthy lifestyles and depression based on active inflammatory processes. Thus, identifying participants with poor habits could reveal differences in trends of incident depression. This study aimed to examine the association between an objective lifestyle assessment, as measured by the Lifestyle and Well-Being Index (LWB-I), and incident depression in healthy participants of a Spanish cohort. Study design: This was a longitudinal analysis of a subsample of 10,063 participants from the Seguimiento Universidad de Navarra cohort study. Methods: Group comparisons and Cox proportional hazard models were conducted using the LWB-I, which categorizes the sample into groups with healthy and unhealthy lifestyles and well-being. The main outcome was incident depression as well as secondary outcomes. Results: Those classified to the transition category of LWB-I were associated with a hazard ratio of 0.67 (95% confidence interval: 0.52-0.87), and those in the excellent category showed a hazard ratio of 0.44 (95% confidence interval: 0.33-0.58), which in both groups reflects a significantly lower risk of incident depression compared with the group including those classified in the poor LWB-I level. Moreover, the available sensitivity analyses concerning time of depression diagnosis or antidepressant treatment further supported the role of nutrition and physical activity on incident depression. Interestingly, throughout the follow-up, incident depression was inversely related to healthier daily habits as measured by the LWB-I. Conclusions: A global assessment of lifestyles such as the LWB-I provides valuable insight into the complex relationship between lifestyle factors and their link to depression risk.Funding was received from the Spanish Government-Instituto de Salud Carlos III , the European Regional Development Fund (FEDER; RD 06/0045, CIBER-OBN, grants PI10/02658, PI10/02293, PI13/00615, PI14/01668, PI14/01798, PI14/01764, PI17/01795, PI20/00564 and G03/140), the Navarra Regional Government (27/2011, 45/2011, 122/2014), the National Plan on Drugs (2020/021), and the University of Navarra

Melatonin Enhances Cisplatin and Radiation Cytotoxicity in Head and Neck Squamous Cell Carcinoma by Stimulating Mitochondrial ROS Generation, Apoptosis, and Autophagy

Head and neck cancer is the sixth leading cancer by incidence worldwide. Unfortunately, drug resistance and relapse are the principal limitations of clinical oncology for many patients, and the failure of conventional treatments is an extremely demoralizing experience. It is therefore crucial to find new therapeutic targets and drugs to enhance the cytotoxic effects of conventional treatments without potentiating or offsetting the adverse effects. Melatonin has oncostatic effects, although the mechanisms involved and doses required remain unclear. The purpose of this study is to determine the precise underlying mitochondrial mechanisms of melatonin, which increase the cytotoxicity of oncological treatments, and also to propose new melatonin treatments in order to alleviate and reverse radio- and chemoresistant processes. We analyzed the effects of melatonin on head and neck squamous cell carcinoma (HNSCC) cell lines (Cal-27 and SCC-9), which were treated with 0.1, 0.5, 1, and 1.5mM melatonin combined with 8 Gy irradiation or 10 μM cisplatin. Clonogenic and MTT assays, as well as autophagy and apoptosis, involving flow cytometry and western blot, were performed in order to determine the cytotoxic effects of the treatments. Mitochondrial function was evaluated by measuring mitochondrial respiration, mtDNA content (RT-PCR), and mitochondrial mass (NAO). ROS production, antioxidant enzyme activity, and GSH/GSSG levels were analyzed using a fluorometric method. We show that high concentrations of melatonin potentiate the cytotoxic effects of radiotherapy and CDDP in HNSCC, which are associated with increased mitochondrial function in these cells. In HNSCC, melatonin induces intracellular ROS, whose accumulation plays an upstream role in mitochondria-mediated apoptosis and autophagy. Our findings indicate that melatonin, at high concentrations, combined with cisplatin and radiotherapy to improve its effectiveness, is a potential adjuvant agent.This study was partially supported by grants from the Ministerio de Economía y Competitividad, Spain, and the FEDER Regional Development Fund (nos. SAF2013-49019 and SAF2017-85903), from the Instituto de Salud Carlos III (no. CB/10/00238), and from the Consejería de Economía, Innovación, Ciencia y Empleo, Junta de Andalucía (CTS-101)

Longitudinal analysis of blood DNA methylation identifies mechanisms of response to tumor necrosis factor inhibitor therapy in rheumatoid arthritis

[Abstract] Background: Rheumatoid arthritis (RA) is a chronic, immune-mediated inflammatory disease of the joints that has been associated with variation in the peripheral blood methylome. In this study, we aim to identify epigenetic variation that is associated with the response to tumor necrosis factor inhibitor (TNFi) therapy. Methods: Peripheral blood genome-wide DNA methylation profiles were analyzed in a discovery cohort of 62 RA patients at baseline and at week 12 of TNFi therapy. DNA methylation of individual CpG sites and enrichment of biological pathways were evaluated for their association with drug response. Using a novel cell deconvolution approach, altered DNA methylation associated with TNFi response was also tested in the six main immune cell types in blood. Validation of the results was performed in an independent longitudinal cohort of 60 RA patients. Findings: Treatment with TNFi was associated with significant longitudinal peripheral blood methylation changes in biological pathways related to RA (FDR<0.05). 139 biological functions were modified by therapy, with methylation levels changing systematically towards a signature similar to that of healthy controls. Differences in the methylation profile of T cell activation and differentiation, GTPase-mediated signaling, and actin filament organization pathways were associated with the clinical response to therapy. Cell type deconvolution analysis identified CpG sites in CD4+T, NK, neutrophils and monocytes that were significantly associated with the response to TNFi. Interpretation: Our results show that treatment with TNFi restores homeostatic blood methylation in RA. The clinical response to TNFi is associated to methylation variation in specific biological pathways, and it involves cells from both the innate and adaptive immune systems

Hospital Virtual: Sistema de información clínica y telecuidado de pacientes VIH/SIDA basado en tecnologías Web 2.0

Este artículo describe el desarrollo de un nuevo sistema de información clínica y telecuidado de pacientes VIH/SIDA que se encuentra implantado en rutina clínica dentro del Servicio de Enfermedades Infecciosas del Hospital Clínic de Barcelona. El proyecto surge ante la necesidad de unificar el sistema de información departamental del servicio y un sistema de telemedicina instalado en el hospital en 2004. Para ello se han diseñado e implementado nuevas bases de datos y dos sistemas específicos para uso de profesionales y pacientes. Además, se ha realizado una integración con el Sistema de Información del Hospital (HIS) permitiendo el acceso a todos los datos requeridos de los pacientes desde una única aplicación. Este nuevo sistema está al servicio de más de 70 profesionales sanitarios que realizan una media de 150 consultas al día disponiendo de información clínica de más de 8000 pacientes

Inhaled Methoxyflurane Provides Greater Analgesia and Faster Onset of Action Versus Standard Analgesia in Patients With Trauma Pain: InMEDIATE: A Randomized Controlled Trial in Emergency Departments

Study objective: The objective of the InMEDIATE study was to evaluate the change in intensity of traumatic pain over the first 20 min in adult patients treated with methoxyflurane versus standard analgesic treatment in Spain. This the first randomized, active-controlled, multicenter trial of methoxyflurane in the emergency setting in Europe. Methods: This was a randomized, controlled study that enrolled adult patients with acute moderate to severe (score >= 4 on the 11-point Numeric Rating Scale) trauma-associated pain in 14 Spanish emergency departments. Patients were randomized 1:1 to methoxyflurane (up to 2x3 mL) or standard analgesic treatment. Coprimary endpoints were the change from baseline in Numeric Rating Scale pain intensity score during the first 20 minutes of treatment and time to first pain relief. Results: Three hundred five patients were randomized (methoxyflurane 156; standard analgesic treatment 149). Most patients in the standard analgesic treatment group (70%) received intravenous first-step analgesics and 9.4% of patients were treated with opioids. Mean decrease from baseline in Numeric Rating Scale pain intensity score was greater for methoxyflurane than standard analgesic treatment at all points, with a significant treatment difference overall up to 20 minutes (repeated-measures model 2.47 versus 1.39; treatment difference 1.00; 95% confidence interval 0.84 to 1.32). Median time to first pain relief was significantly shorter for methoxyflurane than standard analgesic treatment (3 versus 10 minutes). Methoxyflurane achieved better patient and clinician ratings for pain control and comfort of treatment than standard analgesic treatment and exceeded patient and clinician expectations of treatment in, respectively, 77% and 72% of cases compared with 38% and 19% for standard analgesic treatment. Conclusion: These results support consideration of methoxyflurane as a nonnarcotic, easy-to-administer, rapid-acting, first-line alternative to currently available analgesic treatments for trauma pain

Health care and societal costs of the management of children and adolescents with attention-deficit/hyperactivity disorder in Spain: a descriptive analysis

Background: Attention-deficit/hyperactivity disorder (ADHD) is a common neurodevelopmental condition in childhood (5.3% to 7.1% worldwide prevalence), with substantial overall financial burden to children/adolescents, their families, and society. The aims of this study were to describe the clinical characteristics of children and adolescents with ADHD in Spain, estimate the associated direct/indirect costs of the disorder, and assess whether the characteristics and financial costs differed between children/adolescents adequately responding to currently available pharmacotherapies compared with children/adolescents for whom pharmacotherapies failed. Methods: This was a multicenter, cross-sectional, descriptive analysis conducted in 15 health units representative of the overall Spanish population. Data on demographic characteristics, socio-occupational status, social relationships, clinical variables of the disease, and pharmacological and non-pharmacological treatments received were collected in 321 children and adolescents with ADHD. Direct and indirect costs were estimated over one year from both a health care system and a societal perspective. Results: The estimated average cost of ADHD per year per child/adolescent was €5733 in 2012 prices; direct costs accounted for 60.2% of the total costs (€3450). Support from a psychologist/educational psychologist represented 45.2% of direct costs and 27.2% of total costs. Pharmacotherapy accounted for 25.8% of direct costs and 15.5% of total costs. Among indirect costs (€2283), 65.2% was due to caregiver expenses. The total annual costs were significantly higher for children/adolescents who responded poorly to pharmacological treatment (€7654 versus €5517; P = 0.024), the difference being mainly due to significantly higher direct costs, particularly with larger expenses for non-pharmacological treatment (P = 0.012). Conclusions: ADHD has a significant personal, familial, and financial impact on the Spanish health system and society. Successful pharmacological intervention was associated with lower overall expenses in the management of the disorde

IEOOS: the Spanish Institute of Oceanography Observing System

En prens

The ALHAMBRA survey: reliable morphological catalogue of 22 051 early- and late-type galaxies

Advanced Large Homogeneous Area Medium Band Redshift Astronomical (ALHAMBRA) is photometric survey designed to trace the cosmic evolution and cosmic variance. It covers a large area of ~4 deg2 in eight fields, where seven fields overlap with other surveys, allowing us to have complementary data in other wavelengths. All observations were carried out in 20 continuous, medium band (30 nm width) optical and 3 near-infrared (JHK) bands, providing the precise measurements of photometric redshifts. In addition, morphological classification of galaxies is crucial for any kind of galaxy formation and cosmic evolution studies, providing the information about star formation histories, their environment and interactions, internal perturbations, etc. We present a morphological classification of >40 000 galaxies in the ALHAMBRA survey. We associate to every galaxy a probability to be early type using the automated Bayesian code GALSVM. Despite of the spatial resolution of theALHAMBRAimages (~1 arcsec), for 22 051 galaxies, we obtained the contamination by other type of less than 10 per cent. Of those, 1640 and 10 322 galaxies are classified as early-(down to redshifts ~0.5) and late-type (down to redshifts ~1.0), respectively, with magnitudes F613W ≤ 22.0. In addition, for magnitude range 22.0 < F613W ≤ 23.0, we classified other 10 089 late-type galaxies with redshifts ≤1.3.We show that the classified objects populate the expected regions in the colour-mass and colour-magnitude planes. The presented data set is especially attractive given the homogeneous multiwavelength coverage available in the ALHAMBRA fields, and is intended to be used in a variety of scientific applications. The low-contamination catalogue (<10 per cent) is made publicly available with this paper. © 2013 The Authors Published by Oxford University Press on behalf of the Royal Astronomical Society.This research was supported by the Junta de Andalucía through projects PO8-TIC-03531 and TIC114, the Spanish Ministry of Economy and Competitiveness (MINECO) through projects AYA2006-14046, AYA2010-15169, AYA2010-22111-C03-02, AYA2011-29517-C03-01, and the Generalitat Valenciana through project GV/Prometeo 2009/064. MP acknowledges financial support from JAE-Doc program of the Spanish National Research Council (CSIC), co-funded by the European Social Fund.Peer Reviewe

Adipose-derived mesenchymal stromal cells for the treatment of patients with severe SARS-CoV-2 pneumonia requiring mechanical ventilation. A proof of concept study

Background: Identification of effective treatments in severe cases of COVID-19 requiring mechanical ventilation represents an unmet medical need. Our aim was to determine whether the administration of adipose-tissue derived mesenchymal stromal cells (AT-MSC) is safe and potentially useful in these patients. Methods: Thirteen COVID-19 adult patients under invasive mechanical ventilation who had received previous antiviral and/or anti-inflammatory treatments (including steroids, lopinavir/ritonavir, hydroxychloroquine and/or tocilizumab, among others) were treated with allogeneic AT-MSC. Ten patients received two doses, with the second dose administered a median of 3 days (interquartile range-IQR- 1 day) after the first one. Two patients received a single dose and another patient received 3 doses. Median number of cells per dose was 0.98 × 106 (IQR 0.50 × 106) AT-MSC/kg of recipient's body weight. Potential adverse effects related to cell infusion and clinical outcome were assessed. Additional parameters analyzed included changes in imaging, analytical and inflammatory parameters. Findings: First dose of AT-MSC was administered at a median of 7 days (IQR 12 days) after mechanical ventilation. No adverse events were related to cell therapy. With a median follow-up of 16 days (IQR 9 days) after the first dose, clinical improvement was observed in nine patients (70%). Seven patients were extubated and discharged from ICU while four patients remained intubated (two with an improvement in their ventilatory and radiological parameters and two in stable condition). Two patients died (one due to massive gastrointestinal bleeding unrelated to MSC therapy). Treatment with AT-MSC was followed by a decrease in inflammatory parameters (reduction in C-reactive protein, IL-6, ferritin, LDH and d-dimer) as well as an increase in lymphocytes, particularly in those patients with clinical improvement. Interpretation: Treatment with intravenous administration of AT-MSC in 13 severe COVID-19 pneumonia under mechanical ventilation in a small case series did not induce significant adverse events and was followed by clinical and biological improvement in most subjects. Funding: None.We would like to acknowledge the Instituto de Salud Carlos III (ISCIII) through the project “RD16/0011: Red de Terapia Celular”, from the sub-program RETICS, integrated in the “Plan Estatal de I+D+I 2013-2016” and co-financed by the European Regional Development Fund “A way to make Europe”, groups RD16/0011/0001, -/0002, -/005, -/0013, -/0015, -/0029), the Centro en Red de Medicina Regenerativa y Terapia Celular de Castilla y León, Spain and AvanCell-CM (Red de Investigación de Terapia Celular de la Comunidad de Madrid, Spain), for supporting some personnel and networking activities