Influencia de la contaminación ambiental sobre las agudizaciones del asma bronquial en un área de baja contaminación

La hipótesis principal de la presente tesis es que el incremento de la concentración de los contaminantes se asocia con un aumento de las exacerbaciones por asma en un entorno con niveles bajos de contaminación ambiental. Estudio ecológico retrospectivo de series temporales. Se consideraron las visitas por asma de pacientes mayores de 14 años que acudieron a un servicio de urgencias de forma consecutiva entre 2010 y 2018 (3287 días). La asociación entre la concentración media de PM2,5, PM10,¬ NO2 y O3 y el número diario de VUA se estudió mediante un modelo lineal generalizado con regresión de Poisson y un análisis de casos cruzados. El incremento de la concentración ambiental de NO2 se ha asociado con un aumento del número de urgencias hospitalarias por exacerbación de asma en la población adulta en un entorno con niveles bajos de contaminación.Departamento de Anatomía Patológica, Microbiología, Medicina Preventiva y Salud Pública, Medicina Legal y ForenseDoctorado en Investigación en Ciencias de la Salu

Purification of Starch Granules from Arabidopsis Leaves and Determination of Granule-Bound Starch Synthase Activity

Starch constitutes the most important carbon reserve in plants and is composed of branched amylopectin and linear amylose. The latter is synthesized exclusively by the Granule-Bound Starch Synthase (GBSS, EC 2.4.1.21). Here we report a readily reproducible, specific and highly sensitive protocol, which includes the isolation of intact starch granules from Arabidopsis thaliana leaves and the subsequent determination of GBSS activity. We have applied this method to study GBSS activity in diurnal cycles in vegetative growth and during the photoperiodic transition to flowering in Arabidopsis (Tenorio et al., 2003; Ortiz-Marchena et al., 2014).España,MINECO CSD2007-00057, BIO2008-02292, and BIO2011-28847-C02-00España, Junta de Andalucía P06-CVI-01450 and P08-AGR-0358

Characterization of the sucrose phosphate phosphatase (SPP) isoforms from Arabidopsis thaliana and role of the S6PPc domain in dimerization

Sucrose-phosphate phosphatase (SPP) catalyses the final step in the sucrose biosynthesis pathway. Arabidopsis thaliana genome codifies four SPP isoforms. In this study, the four Arabidopsis thaliana genes coding for SPP isoforms have been cloned, expressed in Escherichia coli and the kinetic and regulatory properties of the purified enzymes analysed. SPP2 is the isoform showing the highest activity, with SPP3b and SPP3a showing lower activity levels. No activity was detected for SPP1. We propose that this lack of activity is probably due to the absence of an essential amino acid participating in catalysis and/or in the binding of the substrate, sucrose-6-phosphate (Suc6P). The expression patterns of Arabidopsis SPP genes indicate that SPP2 and SPP3b are the main isoforms expressed in different tissues and organs, although the non-catalytic SPP1 is the main isoform expressed in roots. Thus, SPP1 could have acquired new unknown functions. We also show that the three catalytically active SPPs from Arabidopsis are dimers. By generating a chimeric SPP composed of the monomeric cyanobacterial SPP fused to the higher plant non-catalytic S6PPc domain (from SPP2), we show that the S6PPc domain is responsible for SPP dimerization. This is the first experimental study on the functionality and gene expression pattern of all the SPPs from a single plant species.Ministerio de Economía y Competitividad TRANSPLANTA Consolider 28317Junta de Andalucía P08-AGR-03582 y CVI-28

Usefulness of Artificial Neural Networks in the Diagnosis and Treatment of Sleep Apnea-Hypopnea Syndrome

Sleep apnea-hypopnea syndrome (SAHS) is a chronic and highly prevalent disease considered a major health problem in industrialized countries. The gold standard diagnostic methodology is in-laboratory nocturnal polysomnography (PSG), which is complex, costly, and time consuming. In order to overcome these limitations, novel and simplified diagnostic alternatives are demanded. Sleep scientists carried out an exhaustive research during the last decades focused on the design of automated expert systems derived from artificial intelligence able to help sleep specialists in their daily practice. Among automated pattern recognition techniques, artificial neural networks (ANNs) have demonstrated to be efficient and accurate algorithms in order to implement computer-aided diagnosis systems aimed at assisting physicians in the management of SAHS. In this regard, several applications of ANNs have been developed, such as classification of patients suspected of suffering from SAHS, apnea-hypopnea index (AHI) prediction, detection and quantification of respiratory events, apneic events classification, automated sleep staging and arousal detection, alertness monitoring systems, and airflow pressure optimization in positive airway pressure (PAP) devices to fit patients’ needs. In the present research, current applications of ANNs in the framework of SAHS management are thoroughly reviewed

Assessment of nocturnal autonomic cardiac imbalance in positional obstructive sleep apnea. A multiscale nonlinear approach

Producción CientíficaPositional obstructive sleep apnea (POSA) is a major phenotype of sleep apnea. Supine-predominant positional patients are frequently characterized by milder symptoms and less comorbidity due to a lower age, body mass index, and overall apnea-hypopnea index. However, the bradycardia-tachycardia pattern during apneic events is known to be more severe in the supine position, which could affect the cardiac regulation of positional patients. This study aims at characterizing nocturnal heart rate modulation in the presence of POSA in order to assess potential differences between positional and non-positional patients. Patients showing clinical symptoms of suffering from a sleep-related breathing disorder performed unsupervised portable polysomnography (PSG) and simultaneous nocturnal pulse oximetry (NPO) at home. Positional patients were identified according to the Amsterdam POSA classification (APOC) criteria. Pulse rate variability (PRV) recordings from the NPO readings were used to assess overnight cardiac modulation. Conventional cardiac indexes in the time and frequency domains were computed. Additionally, multiscale entropy (MSE) was used to investigate the nonlinear dynamics of the PRV recordings in POSA and non-POSA patients. A total of 129 patients (median age 56.0, interquartile range (IQR) 44.8–63.0 years, median body mass index (BMI) 27.7, IQR 26.0–31.3 kg/m2) were classified as POSA (37 APOC I, 77 APOC II, and 15 APOC III), while 104 subjects (median age 57.5, IQR 49.0–67.0 years, median BMI 29.8, IQR 26.6–34.7 kg/m2) comprised the non-POSA group. Overnight PRV recordings from positional patients showed significantly higher disorderliness than non-positional subjects in the smallest biological scales of the MSE profile (τ = 1: 0.25, IQR 0.20–0.31 vs. 0.22, IQR 0.18–0.27, p < 0.01) (τ = 2: 0.41, IQR 0.34–0.48 vs. 0.37, IQR 0.29–0.42, p < 0.01). According to our findings, nocturnal heart rate regulation is severely affected in POSA patients, suggesting increased cardiac imbalance due to predominant positional apneas.Ministerio de Ciencia, Innovación y Universidades - Fondo Europeo de Desarrollo Regional (Proyects DPI2017-84280-R and RTC-2017-6516-1)Sociedad Española de Neumología y Cirugía Torácica (Proyects 649/2018 and 66/2016)Gerencia Regional de Salud de Castilla y León (Proyecto GRS 1950/A/19)Ministerio de Educación, Cultura y Deporte (Proyecto FPU16/02938)Gerencia Regional de Salud de Castilla y León - (Projecto INT/M/15/20

Effect of intravenous pulses of methylprednisolone 250 mg versus dexamethasone 6 mg in hospitalised adults with severe COVID ‐19 pneumonia: An open‐label randomised trial

Producción CientíficaBackground: The efficacy and safety of high versus medium doses of glucocorticoids for the treatment of patients with COVID-19 has shown mixed outcomes in controlled trials and observational studies. We aimed to evaluate the effectiveness of methylprednisolone 250 mg bolus versus dexamethasone 6 mg in patients with severe COVID-19. Methods: A randomised, open-label, controlled trial was conducted between February and August 2021 at four hospitals in Spain. The trial was suspended after the first interim analysis since the investigators considered that continuing the trial would be futile. Patients were randomly assigned in a 1:1 ratio to receive dexamethasone 6 mg once daily for up to 10 days or methylprednisolone 250 mg once daily for 3 days. Results: Of the 128 randomised patients, 125 were analysed (mean age 60 ± 17 years; 82 males [66%]). Mortality at 28 days was 4.8% in the 250 mg methylprednisolone group versus 4.8% in the 6 mg dexamethasone group (absolute risk difference, 0.1% [95% CI, −8.8 to 9.1%]; p = 0.98). None of the secondary outcomes (admission to the intensive care unit, non-invasive respiratory or high-flow oxygen support, additional immunosuppressive drugs, or length of stay), or prespecified sensitivity analyses were statistically significant. Hyperglycaemia was more frequent in the methylprednisolone group at 27.0 versus 8.1% (absolute risk difference, −18.9% [95% CI, −31.8 to - 5.6%]; p = 0.007). Conclusions: Among severe but not critical patients with COVID-19, 250 mg/d for 3 days of methylprednisolone compared with 6 mg/d for 10 days of dexamethasone did not result in a decrease in mortality or intubation

Modelos de riesgo para la predicción de mortalidad hospitalaria en ancianos con neumonía por COVID-19

Producción CientíficaObjetivo. Los objetivos son comparar la utilidad pronóstica de tres escalas de gravedad (Pneumonia Severity Index: PSI; CURB-65 scale; Severity Community Acquired Pneumonia Score: SCAP) y diseñar un nuevo modelo predictivo de mortalidad hospitalaria en pacientes mayores de 75 años ingresados por neumonía por COVID-19. Método. Estudio retrospectivo de pacientes mayores de 75 años ingresados por neumonía por COVID-19 desde el servicio de urgencias entre el 12 de marzo y el 27 de abril de 2020. Se recogieron variables demográficas (edad, sexo, institucionalización), clínicas (síntomas, comorbilidades, índice de Charlson) y analíticas (bioquímica en suero, gasometría, hematimetría, hemostasia). Se derivó un modelo de riesgo y se compararon las escalas de gravedad PSI, CURB-65 y SCAP para predecir la mortalidad intrahospitalaria por cualquier causa. Resultados. Se incluyeron 186 pacientes, con una mediana de edad de 85 años (RIC 80-89), un 44,1% varones. La mortalidad fue del 47,3%. Las escalas PSI, CURB-65 y SCAP tuvieron un área bajo la curva (ABC) de 0,74 (IC 95% 0,64-0,82), 0,71 (IC 95% 0,62-0,79) y 0,72 (IC 95% 0,63-0,81), respectivamente. El modelo predictivo compuesto por la ausencia o presencia de síntomas (tos y disnea), comorbilidad (índice de Charlson) y datos analíticos (aspartato-aminotransferasa, potasio, urea y lactato-deshidrogenasa) tuvo un ABC de 0,81 (IC 95% 0,73-0,88). Conclusión. Este estudio muestra que la escala PSI tiene una capacidad predictiva de mortalidad moderada, notablemente mejor que las escalas CURB-65 y SCAP. Se propone un nuevo modelo predictivo de mortalidad que mejora significativamente el rendimiento de estas escalas, siendo necesario verificar su validez externa.Junta de Castilla y León (project GRS COVID 09/A/2020)Ministerio de Ciencia e Innovación – Agencia Estatal de Investigación, cofinanciada por el Fondo Social Europeo (grant RYC2019-028566-I)Gerencia Regional de Salud de Castilla y León (grant INT/M/15/20

Viral RNA load in plasma is associated with critical illness and a dysregulated host response in COVID‑19

Background. COVID-19 can course with respiratory and extrapulmonary disease. SARS-CoV-2 RNA is detected in respiratory samples but also in blood, stool and urine. Severe COVID-19 is characterized by a dysregulated host response to this virus. We studied whether viral RNAemia or viral RNA load in plasma is associated with severe COVID-19 and also to this dysregulated response. Methods. A total of 250 patients with COVID-19 were recruited (50 outpatients, 100 hospitalized ward patients and 100 critically ill). Viral RNA detection and quantification in plasma was performed using droplet digital PCR, targeting the N1 and N2 regions of the SARS-CoV-2 nucleoprotein gene. The association between SARS-CoV-2 RNAemia and viral RNA load in plasma with severity was evaluated by multivariate logistic regression. Correlations between viral RNA load and biomarkers evidencing dysregulation of host response were evaluated by calculating the Spearman correlation coefficients. Results. The frequency of viral RNAemia was higher in the critically ill patients (78%) compared to ward patients (27%) and outpatients (2%) (p < 0.001). Critical patients had higher viral RNA loads in plasma than non-critically ill patients, with non-survivors showing the highest values. When outpatients and ward patients were compared, viral RNAemia did not show significant associations in the multivariate analysis. In contrast, when ward patients were compared with ICU patients, both viral RNAemia and viral RNA load in plasma were associated with critical illness (OR [CI 95%], p): RNAemia (3.92 [1.183–12.968], 0.025), viral RNA load (N1) (1.962 [1.244–3.096], 0.004); viral RNA load (N2) (2.229 [1.382–3.595], 0.001). Viral RNA load in plasma correlated with higher levels of chemokines (CXCL10, CCL2), biomarkers indicative of a systemic inflammatory response (IL-6, CRP, ferritin), activation of NK cells (IL-15), endothelial dysfunction (VCAM-1, angiopoietin-2, ICAM-1), coagulation activation (D-Dimer and INR), tissue damage (LDH, GPT), neutrophil response (neutrophils counts, myeloperoxidase, GM-CSF) and immunodepression (PD-L1, IL-10, lymphopenia and monocytopenia). Conclusions. SARS-CoV-2 RNAemia and viral RNA load in plasma are associated with critical illness in COVID-19. Viral RNA load in plasma correlates with key signatures of dysregulated host responses, suggesting a major role of uncontrolled viral replication in the pathogenesis of this disease.This work was supported by awards from the Canadian Institutes of Health Research, the Canadian 2019 Novel Coronavirus (COVID-19) Rapid Research Funding initiative (CIHR OV2 – 170357), Research Nova Scotia (DJK), Atlantic Genome/Genome Canada (DJK), Li-Ka Shing Foundation (DJK), Dalhousie Medical Research Foundation (DJK), the “Subvenciones de concesión directa para proyectos y programas de investigación del virus SARS‐CoV2, causante del COVID‐19”, FONDO–COVID19, Instituto de Salud Carlos III (COV20/00110, CIBERES, 06/06/0028), (AT) and fnally by the “Convocatoria extraordinaria y urgente de la Gerencia Regional de Salud de Castilla y León, para la fnanciación de proyectos de investigación en enfermedad COVID-19” (GRS COVID 53/A/20) (CA). DJK is a recipient of the Canada Research Chair in Translational Vaccinology and Infammation. APT was funded by the Sara Borrell Research Grant CD018/0123 funded by Instituto de Salud Carlos III and co-fnanced by the European Development Regional Fund (A Way to Achieve Europe programme). The funding sources did not play any role neither in the design of the study and collection, not in the analysis, in the interpretation of data or in writing the manuscript

Study of obesity in workers of a sanitary center

Artículos originales[ES] Hemos analizado a través de un estudio epidemiológico descriptivo con una muestra de 806 trabajadores, la prevalencia de sobrepeso/obesidad en un medio sanitario. Para ello utilizamos datos obtenidos de la historia clínico laboral de nuestros trabajadores y la obtención de datos antropométricos. Definimos como sobrepeso un IMC>25 y obesidad >30. Los resultados obtenidos en porcentajes generales de sobrepeso y obesidad son similares a los descritos en la literatura; por sexos, los hombres de la muestra presentan más obesidad que las mujeres a pesar de estandarizar por edad (en contra de lo publicado). Conclusiones: Existe una elevada prevalencia de obesidad/sobrepeso en nuestra muestra, al igual que en la población general, lo cual hace necesaria la participación del médico del trabajo desde los Servicios de Prevención para la identificación y seguimiento de los perfilies ponderales de los trabajadores y establecer estrategias adecuadas para reducir la prevalencia. [EN] We have analyzed through an epidemiological descriptive study with a sample of 806 workers, the prevalencia of overweight / obesity in a sanitary way. For it we use information obtained of the history clinical labour of our workers and the obtaining of information anthropometrics. We define as overweight an IMC> 25 and obesity> 30. Them proved obtained in general percentages of overweight and obesity they are similar to described in the literature; for sexes, the men of the sample present more obesity than the women in spite of standardizing for age (against it published). Conclusions: A high prevalence of obesity / overweight exists in our sample, as in the general population, which makes necessary the participation of the doctor of the work from the Services of Prevention for the identification and follow-up of the perfilies consider them of the workers and to establish strategies adapted to reduce the prevalence.N

Estudio de obesidad en el medio sanitario Study of obesity in workers of a sanitary center

Hemos analizado a través de un estudio epidemiológico descriptivo con una muestra de 806 trabajadores, la prevalencia de sobrepeso/obesidad en un medio sanitario. Para ello utilizamos datos obtenidos de la historia clínico laboral de nuestros trabajadores y la obtención de datos antropométricos. Definimos como sobrepeso un IMC>25 y obesidad >30. Los resultados obtenidos en porcentajes generales de sobrepeso y obesidad son similares a los descritos en la literatura; por sexos, los hombres de la muestra presentan más obesidad que las mujeres a pesar de estandarizar por edad (en contra de lo publicado). Conclusiones: Existe una elevada prevalencia de obesidad/sobrepeso en nuestra muestra, al igual que en la población general, lo cual hace necesaria la participación del médico del trabajo desde los Servicios de Prevención para la identificación y seguimiento de los perfilies ponderales de los trabajadores y establecer estrategias adecuadas para reducir la prevalencia.We have analyzed through an epidemiological descriptive study with a sample of 806 workers, the prevalencia of overweight / obesity in a sanitary way. For it we use information obtained of the history clinical labour of our workers and the obtaining of information anthropometrics. We define as overweight an IMC> 25 and obesity> 30. Them proved obtained in general percentages of overweight and obesity they are similar to described in the literature; for sexes, the men of the sample present more obesity than the women in spite of standardizing for age (against it published). Conclusions: A high prevalence of obesity / overweight exists in our sample, as in the general population, which makes necessary the participation of the doctor of the work from the Services of Prevention for the identification and follow-up of the perfilies consider them of the workers and to establish strategies adapted to reduce the prevalence