Edafoclima del ecotono pinar de silvestre rebollar en los Montes de Valsaín (Segovia).

El objetivo central de este Trabajo de Fin de Carrera es el de caracterizar los regímenes de variación de las variables de estado edafoclimáticas bajo diferentes condiciones de cubierta forestal arbórea. La comparación de éstos permitirá identificar y evaluar el papel que juega el tipo de cubierta vegetal en la respuesta microclimatica observada. Para ello, a partir de los registros obtenidos de las variables de estado: a) Se procederá a un proceso de depuración y validación. b) Se analizará su comportamiento temporal a lo largo del periodo de observación. c) Se integrarán para caracterizar el comportamiento microclimático para cada tipo de cubierta, identificando las variables de estado que muestran un régimen de variación más trascendentes para la respuesta biológica observada (diferencias entre condiciones de cubierta). Se ha conseguido una aproximación empírica al conocimiento del comportamiento edafoclimático bajo diferentes condiciones de cubierta. Sucesivos intentos deben proporcionar una mayor disponibilidad de observaciones, con períodos suficientemente largos y continuos, de más de un año de duración, y con repeticiones en las localizaciones(un mínimo de dos unidades de medición por localización) que garanticen una mayor robustez estadística en los resultados a obtener

Efficacy of naloxegol on symptoms and quality of life related to opioid-induced constipation in patients with cancer: a 3-month follow-up analysis

Objectives: Opioid-induced constipation (OIC) can affect up to 63% of all patients with cancer. The objectives of this study were to assess quality of life as well as efficacy and safety of naloxegol, in patients with cancer with OIC. Methods: An observational study was made of a cohort of patients with cancer and with OIC exhibiting an inadequate response to laxatives and treated with naloxegol. The sample consisted of adult outpatients with a Karnofsky performance status score ≥50. The Patient Assessment of Constipation Quality of Life Questionnaire (PAC-QOL) and the Patient Assessment of Constipation Symptoms (PAC-SYM) were applied for 3 months. Results: A total of 126 patients (58.2% males) with a mean age of 61.3 years (range 34-89) were included. Clinically relevant improvements (>0.5 points) were recorded in the PAC-QOL and PAC-SYM questionnaires (p<0.0001) from 15 days of treatment. The number of days a week with complete spontaneous bowel movements increased significantly (p<0.0001) from 2.4 to 4.6 on day 15, 4.7 after 1 month and 5 after 3 months. Pain control significantly improved (p<0.0001) during follow-up. A total of 13.5% of the patients (17/126) presented some gastrointestinal adverse reaction, mostly of mild (62.5%) or moderate intensity (25%). Conclusions: Clinically relevant improvements in OIC-related quality of life, number of bowel movements and constipation-related symptoms were recorded as early as after 15 days of treatment with naloxegol in patients with cancer and OIC, with a good safety profile

Healthcare-Associated Pneumonia: Don't Forget About Respiratory Viruses!

Introduction: Healthcare-associated infections are an important cause of morbidity and mortality, are among the most common adverse events in healthcare, and of them, pneumonia is the most commonly reported. Our objective was to evaluate the incidence and clinical outcome of respiratory viruses in hospital-acquired pneumonia (HAP).Methods: This was a prospective cohort study, include patients aged between 0 and 18 who fulfilled Centers for Diseases Control and Prevention (CDC) criteria for HAP. Demographic and clinical data were obtained, and a nasopharyngeal swab specimen was taken for the detection of respiratory viruses. All included patients were monitored until discharge to collect data on the need for mechanical ventilation, intensive care unit (ICU) admission, and mortality. All-cause 30-day mortality was also ascertained.Results: Four thousand three hundred twenty-seven patients were followed for 42,658 patient-days and 5,150 ventilator-days. Eighty-eight patients (2.03%) met the CDC criteria for HAP, 63 patients were included, and clinical and epidemiological characteristics showed no statistically significant differences between patients with virus associated healthcare-associated pneumonia (VAHAP) and those with non-viral healthcare-associated pneumonia (NVHAP). At least one respiratory virus was detected in 65% [95% CI (53–77)] of episodes of HAP, with a single viral pathogen observed in 53.9% and coinfection with 2 viruses in 11.1% of cases. The outcome in terms of ICU admission, mechanical ventilation and the 30-day mortality did not show a significant difference between groups.Conclusions: In two-thirds of the patients a respiratory virus was identified. There was no difference in mortality or the rest of the clinical outcome variables. About half of the patients required mechanical ventilation and 10% died, which emphasizes the importance of considering these pathogens in nosocomial infections, since their identification can influence the decrease in hospital costs and be taken into account in infection control policies

Unraveling the effect of silent, intronic and missense mutations on VWF splicing: contribution of next generation sequencing in the study of mRNA

Large studies in von Willebrand disease patients, including Spanish and Portuguese registries, led to the identification of >250 different mutations. It is a challenge to determine the pathogenic effect of potential splice site mutations on VWF mRNA. This study aimed to elucidate the true effects of 18 mutations on VWF mRNA processing, investigate the contribution of next-generation sequencing to in vivo mRNA study in von Willebrand disease, and compare the findings with in silico prediction. RNA extracted from patient platelets and leukocytes was amplified by RT-PCR and sequenced using Sanger and next generation sequencing techniques. Eight mutations affected VWF splicing: c.1533+1G>A, c.5664+2T>C and c.546G>A (p.=) prompted exon skipping; c.3223-7_3236dup and c.7082-2A>G resulted in activation of cryptic sites; c.3379+1G>A and c.7437G>A) demonstrated both molecular pathogenic mechanisms simultaneously; and the p.Cys370Tyr missense mutation generated two aberrant transcripts. Of note, the complete effect of three mutations was provided by next generation sequencing alone because of low expression of the aberrant transcripts. In the remaining 10 mutations, no effect was elucidated in the experiments. However, the differential findings obtained in platelets and leukocytes provided substantial evidence that four of these would have an effect on VWF levels. In this first report using next generation sequencing technology to unravel the effects of VWF mutations on splicing, the technique yielded valuable information. Our data bring to light the importance of studying the effect of synonymous and missense mutations on VWF splicing to improve the current knowledge of the molecular mechanisms behind von Willebrand disease. clinicaltrials.gov identifier:02869074

Unraveling the effect of silent, intronic and missense mutations on VWF splicing : contribution of next generation sequencing in the study of mRNA

Large studies in von Willebrand disease patients, including Spanish and Portuguese registries, led to the identification of >250 different mutations. It is a challenge to determine the pathogenic effect of potential splice site mutations on VWF mRNA. This study aimed to elucidate the true effects of 18 mutations on VWF mRNA processing, investigate the contribution of next-generation sequencing to in vivo mRNA study in von Willebrand disease, and compare the findings with in silico prediction. RNA extracted from patient platelets and leukocytes was amplified by RT-PCR and sequenced using Sanger and next generation sequencing techniques. Eight mutations affected VWF splicing: c.1533+1G>A, c.5664+2T>C and c.546G>A (p.=) prompted exon skipping; c.3223-7_3236dup and c.7082-2A>G resulted in activation of cryptic sites; c.3379+1G>A and c.7437G>A) demonstrated both molecular pathogenic mechanisms simultaneously; and the p.Cys370Tyr missense mutation generated two aberrant transcripts. Of note, the complete effect of three mutations was provided by next generation sequencing alone because of low expression of the aberrant transcripts. In the remaining 10 mutations, no effect was elucidated in the experiments. However, the differential findings obtained in platelets and leukocytes provided substantial evidence that four of these would have an effect on VWF levels. In this first report using next generation sequencing technology to unravel the effects of VWF mutations on splicing, the technique yielded valuable information. Our data bring to light the importance of studying the effect of synonymous and missense mutations on VWF splicing to improve the current knowledge of the molecular mechanisms behind von Willebrand disease. identifier:02869074

Clonal chromosomal mosaicism and loss of chromosome Y in elderly men increase vulnerability for SARS-CoV-2

The pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2, COVID-19) had an estimated overall case fatality ratio of 1.38% (pre-vaccination), being 53% higher in males and increasing exponentially with age. Among 9578 individuals diagnosed with COVID-19 in the SCOURGE study, we found 133 cases (1.42%) with detectable clonal mosaicism for chromosome alterations (mCA) and 226 males (5.08%) with acquired loss of chromosome Y (LOY). Individuals with clonal mosaic events (mCA and/or LOY) showed a 54% increase in the risk of COVID-19 lethality. LOY is associated with transcriptomic biomarkers of immune dysfunction, pro-coagulation activity and cardiovascular risk. Interferon-induced genes involved in the initial immune response to SARS-CoV-2 are also down-regulated in LOY. Thus, mCA and LOY underlie at least part of the sex-biased severity and mortality of COVID-19 in aging patients. Given its potential therapeutic and prognostic relevance, evaluation of clonal mosaicism should be implemented as biomarker of COVID-19 severity in elderly people. Among 9578 individuals diagnosed with COVID-19 in the SCOURGE study, individuals with clonal mosaic events (clonal mosaicism for chromosome alterations and/or loss of chromosome Y) showed an increased risk of COVID-19 lethality

Molecular and clinical profile of von Willebrand disease in Spain (PCM-EVW-ES) : comprehensive genetic analysis by next-generation sequencing of 480 patients

Molecular diagnosis of patients with von Willebrand disease is pending in most populations due to the complexity and high cost of conventional molecular analyses. The need for molecular and clinical characterization of von Willebrand disease in Spain prompted the creation of a multicenter project (PCM-EVW-ES) that resulted in the largest prospective cohort study of patients with all types of von Willebrand disease. Molecular analysis of relevant regions of the VWF, including intronic and promoter regions, was achieved in the 556 individuals recruited via the development of a simple, innovative, relatively low-cost protocol based on microfluidic technology and next-generation sequencing. A total of 704 variants (237 different) were identified along VWF, 155 of which had not been previously recorded in the international mutation database. The potential pathogenic effect of these variants was assessed by in silico analysis. Furthermore, four short tandem repeats were analyzed in order to evaluate the ancestral origin of recurrent mutations. The outcome of genetic analysis allowed for the reclassification of 110 patients, identification of 37 asymptomatic carriers (important for genetic counseling) and re-inclusion of 43 patients previously excluded by phenotyping results. In total, 480 patients were definitively diagnosed. Candidate mutations were identified in all patients except 13 type 1 von Willebrand disease, yielding a high genotype-phenotype correlation. Our data reinforce the capital importance and usefulness of genetics in von Willebrand disease diagnostics. The progressive implementation of molecular study as the first-line test for routine diagnosis of this condition will lead to increasingly more personalized and effective care for this patient population

Estudios de no inferioridad de eficacia y seguridad: revisión e interpretación de aspectos metodológicos y estadísticos en ensayos clínicos y estudios observacionales con medicamentos

Non-inferiority studies are increasingly more common for introducing new medicines in the market. Despite being situations where the use of this study design is justified, there is not a common analytical approach on how to conduct them. Pursuing a rigorous methodology, both in the study conduction and in its disseminations, is critical to ensure robust results to enable regulatory agencies and clinicians to reach valid conclusions and decisions which ultimately will benefit clinical practice. Most of the published reviews focus on the efficacy outcomes of non-inferiority clinical trials. We are unaware of other reviews that goes beyond and includes specific aspects for non-interventional designs and for studies focused on safety. Moreover, this review provides a simple and practical perspective with a minimum mathematical content on this complex type of studies.Los estudios de no inferioridad son cada vez más frecuentes para introducir nuevos medicamentos en el mercado. Aunque existen situaciones en las que su uso está justificado, no existe un enfoque analítico único y conservador. Para arrojar resultados fiables y de calidad, deben seguir una estricta metodología, tanto en la ejecución como en la difusión de los resultados, la cual permita, tanto a las agencias reguladoras como a los clínicos, establecer conclusiones válidas y decisiones que repercutan en beneficio de la práctica clínica. La mayor parte de las revisiones publicadas se centran en los ensayos clínicos de no inferioridad de eficacia. En esta revisión se contemplan, además, los diseños observacionales y los aspectos específicos de los estudios de seguridad. Todo ello desde un punto de vista práctico y sencillo, con un contenido matemático mínimo

Hacia una escuela abierta : participación activa en Educación Infantil

Se pretende que los alumnos-as de la rama profesional de 'Jardín de Infancia' y ciclos formativos de Educación Infantil, pongan en práctica sus conocimientos en centros de Educación Infantil. Otros objetivos son también fomentar la motivación y el aprendizaje de técnicas útiles a los alumnos en sus estudios profesionales. La metodología parte de reuniones departamentales donde se proponen investigaciones sobre intervenciones en el campo de la Infancia. Se proponen además visitas a instituciones de animación infantil dentro del barrio, y tras una fase de documentación y desarrollo práctico de los temas se elabora una memoria como base para su evaluación. La valoración es positiva y con un alto grado de implicación por parte de alumnos y profesores..Madrid (Comunidad Autónoma). Consejería de Educación y CulturaMadridMadrid (Comunidad Autónoma). Subdirección General de Formación del Profesorado. CRIF Las Acacias; General Ricardos 179 - 28025 Madrid; Tel. + 34915250893ES