Solvent effects on de-excitation channels in the p-coumaric acid methyl ester anion, an analogue of the photoactive yellow protein (PYP) chromophore

En un intento por arrojar luz sobre los efectos ambientales en los canales de desactivación del cromóforo PYP, se comparan los mecanismos de desactivación radiativa y no radiactiva del éster metílico del ácido p- cúmico aniónico (pCE - ) en la fase gaseosa y la solución acuosa en el CASPT2 // CASSCF / cc-pVDZ nivel y, cuando sea necesario, a nivel CASPT2 // CASPT2 / cc-pVDZ. Encontramos que el solvente produce modificaciones dramáticas en el perfil de energía libre del estado S1. Dos estructuras retorcidas que son mínimas en la fase gaseosa no pudieron ser localizadas en solución acuosa. Además, la estabilidad relativa de los mínimos y las intersecciones cónicas (IC) se revierte con respecto a los valores de la fase gaseosa, lo que afecta a las rutas de desactivación prevalentes. Como consecuencia de estos cambios, se abren tres canales de de-excitación competitivos en solución acuosa: la emisión de fluorescencia desde un mínimo planar en S1, la fotoisomerización trans - cis a través de un IC que implica la rotación del doble enlace de vinilo y el no desvitación radiativa, no reactiva, a través de la IC asociada a la rotación del enlace simple adyacente al grupo fenilo. En la fase gaseosa, los mínimos son las estructuras con menor energía, mientras que en solución la estructura CI β , caracterizada por una gran separación de cargas, se estabiliza fuertemente mediante interacciones con moléculas de agua y se convierte en la estructura con la energía más baja en S1. Estos hechos explican la baja señal de fluorescencia de pCE - en solución acuosa y la presencia de fotoisomerización trans - cis parcial en este sistema.In an attempt to shed light on the environmental effects on the deactivation channels of the PYP chromophore, radiative and non-radiative deactivation mechanisms of the anionic p-coumaric acid methyl ester (pCE−) in the gas phase and water solution are compared at the CASPT2//CASSCF/cc-pVDZ level and, when necessary, at the CASPT2//CASPT2/cc-pVDZ level. We find that the solvent produces dramatic modifications on the free energy profile of the S1 state. Two twisted structures that are minima in the gas phase could not be localized in aqueous solution. Furthermore, the relative stability of minima and conical intersections (CIs) is reverted with respect to the gas phase values, affecting the prevalent de-excitation paths. As a consequence of these changes, three competitive de-excitation channels are open in aqueous solution: the fluorescence emission from a planar minimum on S1, the trans–cis photoisomerization through a CI that involves the rotation of the vinyl double bond and the non-radiative, non-reactive, de-excitation through the CI associated with the rotation of the single bond adjacent to the phenyl group. In the gas phase, the minima are the structures with lower energy, while in solution the CIβ structure, characterized by a large charge separation, is strongly stabilized by interactions with water molecules and becomes the structure with the lowest energy on S1. These facts explain the low fluorescence signal of pCE− in aqueous solution and the presence of partial trans–cis photoisomerization in this system.Trabajo financiado por: Gobierno de Extremadura. Consejería de Economía, Comercio e Innovación. Proyecto GR15169peerReviewe

Simulación clínica al servicio formativo. Percepción de los aprendices de técnico en enfermería

The objective of this article is to analyze the perception of a group of technical education apprentices in nursing, in the exercise of cardiopulmonary simulation. This activity was carried out at the Centro de Gestión Tecnológica de Servicios ending the year 2021. With the theoretical support of Pamela Jeffries, David Ausubel and others, the clinical simulation was oriented towards meaningful and experiential learning contexts. The qualitative methodology used, was based on the triangulation of instruments that included a survey, interviews and participant observation, applied to volunteers with intentional sampling, interested in carrying out learning activities, using high and low fidelity equipment. There are many investigations worldwide related to the students' perception of simulated practices, but this work addresses a differential aspect that implies the improvement of comprehensive professional training, with a didactic strategy with an experiential focus. Two of the most significant results were: the use of technology is relevant because the relationship established between instructors and apprentices allows sharing and deepening learning. Secondly, the use of these active didactic techniques strengthens integral training, in dialogue with the institutional educational plan.El objetivo de este artículo es analizar la percepción de un grupo de aprendices de educación técnica en enfermería, en el ejercicio de simulación cardiopulmonar. Esta actividad se realizó en el Centro de Gestión Tecnológica de Servicios finalizando el año 2021. Con el apoyo teórico de Pamela Jeffries, David Ausubel y otros, se orientó la simulación clínica hacia contextos de aprendizaje significativo y experiencial. La metodología cualitativa utilizada, se basó en la triangulación de instrumentos que incluyó una encuesta, entrevistas y observación participante, aplicada a voluntarios con muestreo intencional, interesados en ejecutar actividades de aprendizaje, usando equipos de alta y baja fidelidad. Existen muchas investigaciones a nivel mundial relacionadas con la percepción de los estudiantes de las prácticas simuladas, pero este trabajo aborda un aspecto diferencial que implica la mejora de la formación profesional integral, con una estrategia didáctica de enfoque experiencial. Dos de los resultados significativos fueron: el uso de tecnología es relevante porque la relación que se establece entre instructores y aprendices, permite compartir el aprendizaje y profundizarlo. En segundo lugar, el uso de estas técnicas didácticas activas, fortalece la formación integral, en diálogo con el plan educativo institucional

Investigación científica para el aprendizaje en ciencias de la salud y la educación. Una revisión bibliográfica

Introduction: scientific enquiry has multiple definitions referring to the competences and capacities oriented to scientific inquiry in the learning process, as well as to the set of procedures of scientific methodology and the strategies of teaching and learning school science.Objective: to argue the use and importance of scientific enquiry for learning health sciences and education. Methods: more than fifty articles indexed in Scopus and other recognized databases were reviewed.Development: the sources consulted provided more information in relation to ideas conceived around scientific enquiry, elucidating the inquiry process made up of a cycle of stages, demonstrating the benefits of implementing the enquiry approach, where scientific competence encompasses methodological, conceptual, attitudinal and integrated dimensions to other fields of science.The results show the preponderance of scientific enquiry in science teaching, however, despite its importance and recognition, teachers do not develop the enquiry approach in the expected proportion, requiring a programmatic intervention for its implementation by governing bodies in health and education.Conclusions: Inquiry-based learning or research is considered the best option for health sciences and education, as it generates multiple activities that begin with observation, formulation of questions and queries, identification of variables, hypothesis formulation, collection of information, experimentation to contrast, analysis and explanation of results and generalizations.Introducción: la indagación científica tiene múltiples definiciones haciendo referencia a las competencias y capacidades orientadas a investigar científicamente en el proceso de aprendizaje, así como al conjunto de procedimientos de la metodología científica y las estrategias de enseñar y aprender la ciencia escolar.Objetivo: argumentar el uso e importancia de la indagación científica para el aprendizaje ciencias de la salud y la educación.  Métodos: se revisó información mayor a cincuenta artículos indexados en Scopus y otras reconocidas bases de datos.Desarrollo: las fuentes consultadas aportaron mayor información en relación a ideas concebidas en torno a la indagación científica,  dilucidan el proceso indagatorio conformado por un ciclo de etapas evidenciando las bondades de implementar el enfoque de indagación, donde la competencia científica abarca dimensiones metodológicas, conceptuales, actitudinales e integrada a otros campos de la ciencia. Los resultados expresan preponderancia de la indagación científica en la enseñanza de las ciencias, sin embargo, a pesar de su trascendencia y reconocimiento, los docentes no desarrollan el enfoque de indagación en proporción esperada, requiriendo una intervención programática de su implementación por entes rectores en salud y educación.Conclusiones: el aprendizaje por indagación o investigación es considerado como la mejor opción para las ciencias de la salud y educación, genera múltiples actividades que inician con observación, formulación de preguntas y cuestionamientos, identificación de variables, planteamiento de hipótesis, acopio de información, experimentación para contrastar, análisis y, explicación de resultados y generalizaciones

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

Vaccine breakthrough hypoxemic COVID-19 pneumonia in patients with auto-Abs neutralizing type I IFNs

Life-threatening `breakthrough' cases of critical COVID-19 are attributed to poor or waning antibody response to the SARS- CoV-2 vaccine in individuals already at risk. Pre-existing autoantibodies (auto-Abs) neutralizing type I IFNs underlie at least 15% of critical COVID-19 pneumonia cases in unvaccinated individuals; however, their contribution to hypoxemic breakthrough cases in vaccinated people remains unknown. Here, we studied a cohort of 48 individuals ( age 20-86 years) who received 2 doses of an mRNA vaccine and developed a breakthrough infection with hypoxemic COVID-19 pneumonia 2 weeks to 4 months later. Antibody levels to the vaccine, neutralization of the virus, and auto- Abs to type I IFNs were measured in the plasma. Forty-two individuals had no known deficiency of B cell immunity and a normal antibody response to the vaccine. Among them, ten (24%) had auto-Abs neutralizing type I IFNs (aged 43-86 years). Eight of these ten patients had auto-Abs neutralizing both IFN-a2 and IFN-., while two neutralized IFN-omega only. No patient neutralized IFN-ss. Seven neutralized 10 ng/mL of type I IFNs, and three 100 pg/mL only. Seven patients neutralized SARS-CoV-2 D614G and the Delta variant (B.1.617.2) efficiently, while one patient neutralized Delta slightly less efficiently. Two of the three patients neutralizing only 100 pg/mL of type I IFNs neutralized both D61G and Delta less efficiently. Despite two mRNA vaccine inoculations and the presence of circulating antibodies capable of neutralizing SARS-CoV-2, auto-Abs neutralizing type I IFNs may underlie a significant proportion of hypoxemic COVID-19 pneumonia cases, highlighting the importance of this particularly vulnerable population

Métodos y técnicas de monitoreo y predicción temprana en los escenarios de riesgos socionaturales

Esta obra concentra los métodos y las técnicas fundamentales para el seguimiento y monitoreo de las dinámicas de los escenarios de riesgos socionaturales (geológicos e hidrometeorológicos) y tiene como objetivo general orientar, apoyar y acompañar a los directivos y operativos de protección civil en aterrizar las acciones y políticas públicas enfocadas a la gestión del riesgo local de desastre

Spatiotemporal Characteristics of the Largest HIV-1 CRF02_AG Outbreak in Spain: Evidence for Onward Transmissions

Background and Aim: The circulating recombinant form 02_AG (CRF02_AG) is the predominant clade among the human immunodeficiency virus type-1 (HIV-1) non-Bs with a prevalence of 5.97% (95% Confidence Interval-CI: 5.41–6.57%) across Spain. Our aim was to estimate the levels of regional clustering for CRF02_AG and the spatiotemporal characteristics of the largest CRF02_AG subepidemic in Spain.Methods: We studied 396 CRF02_AG sequences obtained from HIV-1 diagnosed patients during 2000–2014 from 10 autonomous communities of Spain. Phylogenetic analysis was performed on the 391 CRF02_AG sequences along with all globally sampled CRF02_AG sequences (N = 3,302) as references. Phylodynamic and phylogeographic analysis was performed to the largest CRF02_AG monophyletic cluster by a Bayesian method in BEAST v1.8.0 and by reconstructing ancestral states using the criterion of parsimony in Mesquite v3.4, respectively.Results: The HIV-1 CRF02_AG prevalence differed across Spanish autonomous communities we sampled from (p < 0.001). Phylogenetic analysis revealed that 52.7% of the CRF02_AG sequences formed 56 monophyletic clusters, with a range of 2–79 sequences. The CRF02_AG regional dispersal differed across Spain (p = 0.003), as suggested by monophyletic clustering. For the largest monophyletic cluster (subepidemic) (N = 79), 49.4% of the clustered sequences originated from Madrid, while most sequences (51.9%) had been obtained from men having sex with men (MSM). Molecular clock analysis suggested that the origin (tMRCA) of the CRF02_AG subepidemic was in 2002 (median estimate; 95% Highest Posterior Density-HPD interval: 1999–2004). Additionally, we found significant clustering within the CRF02_AG subepidemic according to the ethnic origin.Conclusion: CRF02_AG has been introduced as a result of multiple introductions in Spain, following regional dispersal in several cases. We showed that CRF02_AG transmissions were mostly due to regional dispersal in Spain. The hot-spot for the largest CRF02_AG regional subepidemic in Spain was in Madrid associated with MSM transmission risk group. The existence of subepidemics suggest that several spillovers occurred from Madrid to other areas. CRF02_AG sequences from Hispanics were clustered in a separate subclade suggesting no linkage between the local and Hispanic subepidemics

Mortality from gastrointestinal congenital anomalies at 264 hospitals in 74 low-income, middle-income, and high-income countries: a multicentre, international, prospective cohort study

Summary Background Congenital anomalies are the fifth leading cause of mortality in children younger than 5 years globally. Many gastrointestinal congenital anomalies are fatal without timely access to neonatal surgical care, but few studies have been done on these conditions in low-income and middle-income countries (LMICs). We compared outcomes of the seven most common gastrointestinal congenital anomalies in low-income, middle-income, and high-income countries globally, and identified factors associated with mortality. Methods We did a multicentre, international prospective cohort study of patients younger than 16 years, presenting to hospital for the first time with oesophageal atresia, congenital diaphragmatic hernia, intestinal atresia, gastroschisis, exomphalos, anorectal malformation, and Hirschsprung’s disease. Recruitment was of consecutive patients for a minimum of 1 month between October, 2018, and April, 2019. We collected data on patient demographics, clinical status, interventions, and outcomes using the REDCap platform. Patients were followed up for 30 days after primary intervention, or 30 days after admission if they did not receive an intervention. The primary outcome was all-cause, in-hospital mortality for all conditions combined and each condition individually, stratified by country income status. We did a complete case analysis. Findings We included 3849 patients with 3975 study conditions (560 with oesophageal atresia, 448 with congenital diaphragmatic hernia, 681 with intestinal atresia, 453 with gastroschisis, 325 with exomphalos, 991 with anorectal malformation, and 517 with Hirschsprung’s disease) from 264 hospitals (89 in high-income countries, 166 in middleincome countries, and nine in low-income countries) in 74 countries. Of the 3849 patients, 2231 (58·0%) were male. Median gestational age at birth was 38 weeks (IQR 36–39) and median bodyweight at presentation was 2·8 kg (2·3–3·3). Mortality among all patients was 37 (39·8%) of 93 in low-income countries, 583 (20·4%) of 2860 in middle-income countries, and 50 (5·6%) of 896 in high-income countries (p<0·0001 between all country income groups). Gastroschisis had the greatest difference in mortality between country income strata (nine [90·0%] of ten in lowincome countries, 97 [31·9%] of 304 in middle-income countries, and two [1·4%] of 139 in high-income countries; p≤0·0001 between all country income groups). Factors significantly associated with higher mortality for all patients combined included country income status (low-income vs high-income countries, risk ratio 2·78 [95% CI 1·88–4·11], p<0·0001; middle-income vs high-income countries, 2·11 [1·59–2·79], p<0·0001), sepsis at presentation (1·20 [1·04–1·40], p=0·016), higher American Society of Anesthesiologists (ASA) score at primary intervention (ASA 4–5 vs ASA 1–2, 1·82 [1·40–2·35], p<0·0001; ASA 3 vs ASA 1–2, 1·58, [1·30–1·92], p<0·0001]), surgical safety checklist not used (1·39 [1·02–1·90], p=0·035), and ventilation or parenteral nutrition unavailable when needed (ventilation 1·96, [1·41–2·71], p=0·0001; parenteral nutrition 1·35, [1·05–1·74], p=0·018). Administration of parenteral nutrition (0·61, [0·47–0·79], p=0·0002) and use of a peripherally inserted central catheter (0·65 [0·50–0·86], p=0·0024) or percutaneous central line (0·69 [0·48–1·00], p=0·049) were associated with lower mortality. Interpretation Unacceptable differences in mortality exist for gastrointestinal congenital anomalies between lowincome, middle-income, and high-income countries. Improving access to quality neonatal surgical care in LMICs will be vital to achieve Sustainable Development Goal 3.2 of ending preventable deaths in neonates and children younger than 5 years by 2030

Prevalence, associated factors and outcomes of pressure injuries in adult intensive care unit patients: the DecubICUs study

Funder: European Society of Intensive Care Medicine; doi: http://dx.doi.org/10.13039/501100013347Funder: Flemish Society for Critical Care NursesAbstract: Purpose: Intensive care unit (ICU) patients are particularly susceptible to developing pressure injuries. Epidemiologic data is however unavailable. We aimed to provide an international picture of the extent of pressure injuries and factors associated with ICU-acquired pressure injuries in adult ICU patients. Methods: International 1-day point-prevalence study; follow-up for outcome assessment until hospital discharge (maximum 12 weeks). Factors associated with ICU-acquired pressure injury and hospital mortality were assessed by generalised linear mixed-effects regression analysis. Results: Data from 13,254 patients in 1117 ICUs (90 countries) revealed 6747 pressure injuries; 3997 (59.2%) were ICU-acquired. Overall prevalence was 26.6% (95% confidence interval [CI] 25.9–27.3). ICU-acquired prevalence was 16.2% (95% CI 15.6–16.8). Sacrum (37%) and heels (19.5%) were most affected. Factors independently associated with ICU-acquired pressure injuries were older age, male sex, being underweight, emergency surgery, higher Simplified Acute Physiology Score II, Braden score 3 days, comorbidities (chronic obstructive pulmonary disease, immunodeficiency), organ support (renal replacement, mechanical ventilation on ICU admission), and being in a low or lower-middle income-economy. Gradually increasing associations with mortality were identified for increasing severity of pressure injury: stage I (odds ratio [OR] 1.5; 95% CI 1.2–1.8), stage II (OR 1.6; 95% CI 1.4–1.9), and stage III or worse (OR 2.8; 95% CI 2.3–3.3). Conclusion: Pressure injuries are common in adult ICU patients. ICU-acquired pressure injuries are associated with mainly intrinsic factors and mortality. Optimal care standards, increased awareness, appropriate resource allocation, and further research into optimal prevention are pivotal to tackle this important patient safety threat

Correction to: Prevalence, associated factors and outcomes of pressure injuries in adult intensive care unit patients: the DecubICUs study

The original version of this article unfortunately contained a mistake