Electroacupuncture alleviates myocardial ischemia-reperfusion injury by inhibiting hypothalamic paraventricular nucleus neurons projecting to the rostral ventrolateral medulla.

Accumulating evidence suggests that electroacupuncture (EA) has obvious therapeutic effects and unique advantages in alleviating myocardial ischemia-reperfusion injury (MIRI), while the underlying neuromolecular mechanisms of EA intervention for MIRI have not been fully elucidated. The aim of the study is to investigate the role of the neural pathway of hypothalamic paraventricular nucleus (PVN) neurons projecting to the rostral ventrolateral medulla (RVLM) in the alleviation of MIRI rats by EA preconditioning. MIRI models were established by ligating the left anterior descending coronary artery for 30 min followed by reperfusion for 2 h. Electrocardiogram recording, chemogenetics, enzyme-linked immunosorbent assay, multichannel physiology recording and haematoxylin-eosin and immunofluorescence staining methods were conducted to demonstrate that the firing frequencies of neurons in the PVN and the expression of c-Fos decreased by EA pretreatment. Meanwhile, EA preconditioning significantly reduced the levels of creatine kinase isoenzymes (CK-MB), cardiac troponin I (cTnI) and lactic dehydrogenase (LDH). Virus tracing showed a projection connection between PVN and RVLM. The inhibition of the PVN-RVLM neural pathway could replicate the protective effect of EA pretreatment on MIRI rats. However, the activation of the pathway weakened the effect of EA preconditioning. EA pretreatment alleviated MIRI by regulating PVN neurons projecting to RVLM. This work provides novel evidence of EA pretreatment for alleviating MIRI.

Electron Accumulation Induced by Electron Injection-Incomplete Discharge on NiFe LDH for Enhanced Oxygen Evolution Reaction.

Optimizing the local electronic structure of electrocatalysts can effectively lower the energy barrier of electrochemical reactions, thus enhancing the electrocatalytic activity. However, the intrinsic contribution of the electronic effect is still experimentally unclear. In this work, the electron injection-incomplete discharge approach to achieve the electron accumulation (EA) degree on the nickel-iron layered double hydroxide (NiFe LDH) is proposed, to reveal the intrinsic contribution of EA toward oxygen evolution reaction (OER). Such NiFe LDH with EA effect results in only 262 mV overpotential to reach 50 mA cm-2, which is 51 mV-lower compared with pristine NiFe LDH (313 mV), and reduced Tafel slope of 54.8 mV dec-1 than NiFe LDH (107.5 mV dec-1). Spectroscopy characterizations combined with theoretical calculations confirm that the EA near concomitant Vo can induce a narrower energy gap and lower thermodynamic barrier to enhance OER performance. This study clarifies the mechanism of the EA effect on OER activity, providing a direct electronic structure modulation guideline for effective electrocatalyst design.

Nitrogen-Site Engineering in Covalent Organic Frameworks for H2O2 Photogeneration via Dual Channels of Indirect Two-Electron O2 Reduction.

Photocatalytic H2O2 production is a green and sustainable route, but far from meeting the increasing demands of industrialization due to the rapid recombination of the photogenerated charge carriers and the sluggish reaction kinetics. Effective strategies for precisely regulating the photogenerated carrier behavior and catalytic activity to construct high-performance photocatalysts are urgently needed. Herein, a nitrogen-site engineering strategy, implying elaborately tuning the species and densities of nitrogen atoms, is applied for H2O2 photogeneration performance regulation. Different nitrogen heterocycles, such as pyridine, pyrimidine, and triazine units, are polymerized with trithiophene units, and five covalent organic frameworks (COFs) with distinct nitrogen species and densities on the skeletons are obtained. Fascinatingly, they photocatalyzed H2O2 production via dominated two-electron O2 reduction processes, including O2-O2 •‒-H2O2 and O2-O2 •‒-O2 1-H2O2 dual pathways. Just in the air and pure water, the multicomponent TTA-TF-COF with the maximum nitrogen densities triazine nitrogen densities exhibited the highest H2O2 production rate of 3343 µmol g-1 h-1, higher than most of other reported COFs. The theoretical calculation revealed the higher activity is due to the easy formation of O2 •‒ and O2 1 in different catalytic process. This study gives a new insight into designing photocatalysis at atomic level.

Diastolic function assessment with four-dimensional flow cardiovascular magnetic resonance using automatic deep learning E/A ratio analysis.

BACKGROUND: Diastolic left ventricular (LV) dysfunction is a powerful contributor to the symptoms and prognosis of patients with heart failure. In patients with depressed LV systolic function, the E/A ratio, the ratio between the peak early (E) and the peak late (A) transmitral flow velocity, is the first step to defining the grade of diastolic dysfunction. Doppler echocardiography (echo) is the preferred imaging technique for diastolic function assessment, while cardiovascular magnetic resonance (CMR) is less established as a method. Previous four-dimensional (4D) Flow-based studies have looked at the E/A ratio proximal to the mitral valve, requiring manual interaction. In this study, we compare an automated, deep learning-based and two semi-automated approaches for 4D Flow CMR-based E/A ratio assessment to conventional, gold-standard echo-based methods. METHODS: Ninety-seven subjects with chronic ischemic heart disease underwent a cardiac echo followed by CMR investigation. 4D Flow-based E/A ratio values were computed using three different approaches; two semi-automated, assessing the E/A ratio by measuring the inflow velocity (MVvel) and the inflow volume (MVflow) at the mitral valve plane, and one fully automated, creating a full LV segmentation using a deep learning-based method with which the E/A ratio could be assessed without constraint to the mitral plane (LVvel). RESULTS: MVvel, MVflow, and LVvel E/A ratios were strongly associated with echocardiographically derived E/A ratio (R2 = 0.60, 0.58, 0.72). LVvel peak E and A showed moderate association to Echo peak E and A, while MVvel values were weakly associated. MVvel and MVflow EA ratios were very strongly associated with LVvel (R2 = 0.84, 0.86). MVvel peak E was moderately associated with LVvel, while peak A showed a strong association (R2 = 0.26, 0.57). CONCLUSION: Peak E, peak A, and E/A ratio are integral to the assessment of diastolic dysfunction and may expand the utility of CMR studies in patients with cardiovascular disease. While underestimation of absolute peak E and A velocities was noted, the E/A ratio measured with all three 4D Flow methods was strongly associated with the gold standard Doppler echocardiography. The automatic, deep learning-based method performed best, with the most favorable runtime of ∼40 seconds. As both semi-automatic methods associated very strongly to LVvel, they could be employed as an alternative for estimation of E/A ratio.

Patterns of recovery in extant and extirpated seabirds after the world's largest multipredator eradication.

Eradicating invasive predators from islands can result in substantial recovery of seabirds, but the mechanisms that drive population changes remain poorly understood. Meta-analyses have recently revealed that immigration is surprisingly important to the recovery of philopatric seabirds, but it is not known whether dispersal and philopatry interact predictably to determine rates of population growth and changes of distribution. We used whole-island surveys and long-term monitoring plots to study the abundance, distribution, and trends of 4 burrowing seabird species on Macquarie Island, Australia, to examine the legacy impacts of invasive species and ongoing responses to the world's largest eradication of multiple species of vertebrates. Wekas (Gallirallus australis) were eradicated in 1988; cats (Felis catus) in 2001; and rabbits (Oryctolagus cuniculus), black rats (Rattus rattus), and mice (Mus mus) in 2011-2014. We compared surveys from 1976-1979 and 2017-2018 and monitoring from the 1990s and 2000s onward. Antarctic prions (Pachyptila desolata) and white-headed petrels (Pterodroma lessonii) increased ∼1% per year. Blue petrels (Halobaena caerulea) and gray petrels (Procellaria cinerea) recolonized following extirpation from the main island in the 1900s but remained spatially and numerically rare in 2018. However, they increased rapidly at 14% and 10% per year, respectively, since cat eradication in 2001. Blue and gray petrel recolonization occurred on steep, dry, west-facing slopes close to ridgelines at low elevation (i.e., high-quality petrel habitat). They overlapped <5% with the distribution of Antarctic prion and white-headed petrels which occurred in suboptimal shallow, wet, east-facing slopes at high elevation. We inferred that the speed of population growth of recolonizing species was related to their numerically smaller starting size compared with the established species and was driven by immigration and selection of ideal habitat.

Patrones de recuperación en aves marinas existentes y extirpadas después de la mayor erradicación mundial de multidepredadores Resumen La erradicación de depredadores invasores en las islas puede derivar en la recuperación sustancial de aves marinas, aunque entendemos muy poco los mecanismos que causan los cambios poblacionales. Los metaanálisis recientes han revelado que la inmigración es de gran importancia para la recuperación de aves marinas filopátricas, aunque no sabemos si la dispersión y la filopatría interactúan de forma predecible para poder determinar las tasas de crecimiento poblacional y los cambios en la distribución. Aplicamos censos de isla completa y parcelas de monitoreo a largo plazo para estudiar la abundancia, distribución y tendencias de cuatro especies de aves marinas cavadoras en la Isla Macquarie, Australia, para analizar los impactos heredados de las especies invasoras y la respuesta continua a la mayor erradicación mundial de varias especies de vertebrados. El rascón weka (Gallirallus australis) se erradicó en 1988; los gatos (Felis catus) en 2001; y los conejos (Oryctolagus cuniculus), ratas (Rattus rattus) y ratones (Mus mus) entre 2011 y 2014. Comparamos los censos de 1976­1979 y 2017­2018 y el monitoreo realizado en los 90s y del año 2000 en adelante. El pato petrel antártico (Pachyptila desolata) y el petrel cabeciblanco (Pterodroma lessonii) incrementaron ∼1% por año. El petrel azulado (Halobaena caerulea) y la pardela gris (Procellaria cinerea) recolonizaron la isla después de su extirpación en la década de 1900, pero todavía eran especies raras espacial y numéricamente en 2018. Sin embargo, esta especie incrementó rápidamente en un 14% y 10% por año respectivamente desde que se erradicaron los gatos en 2001. La recolonización ocurrió desde las laderas empinadas, secas y con orientación al oeste en los sistemas montañosos de baja elevación (es decir, hábitats de gran calidad para los petreles). La distribución del petrel azulado y la pardela gris ocurrió en laderas someras subóptimas y húmedas con orientación al este a altas elevaciones. Esta distribución se traslapó menos del 5% con la del pato petrel antártico y la del petrel cabeciblanco. Inferimos que la velocidad del crecimiento poblacional de las especies que recolonizaron estuvo relacionada con el menor tamaño inicial en comparación con las especies establecidas y fue causada por la inmigración y la selección del hábitat ideal.

Review of hyperdispersal in wildlife translocations.

Species translocation is a common tool to reverse biodiversity loss, but it has a high failure rate. One factor that contributes to failure is postrelease hyperdispersal, which we define as the long-distance movement of individuals resulting in their failure to contribute to population establishment. We reviewed reported incidences of hyperdispersal and compared rates of hyperdispersal among taxa, population demographics, release cohorts, and success of mitigation techniques. Of 151 conservation translocations (reinforcements and reintroductions) in which animals were tracked, hyperdispersal was confirmed in 52.1% of programs. The prevalence of hyperdispersal (percentage of studies) was relatively consistent across taxa (42.9-60%), but hyperdispersal rates in birds were likely underestimated because 76.9% of bird translocations showed incidences in which birds could not be located after release, but hyperdispersal was unable to be confirmed. Eutherians exhibited a higher average incidence of hyperdispersal (percentage of hyperdispersing individuals in a cohort) of 20.2% than birds, reptiles, and marsupials (10.4%, 15.7%, and 10.3%, respectively). No significant trends were observed for sex, source population, or translocation type, but there were nonsignificant trends for males to hyperdisperse more than females and for higher incidences of hyperdispersal in reinforcements relative to reintroduction programs. Mitigation techniques included temporary confinement, supplementation of resources, and releasing animals in social groups, but only half of studies examining mitigation techniques found them useful. Hyperdispersal incidence was variable within taxa, and we advise against forming translocations strategies based on results from other species. Hyperdispersal is a significant welfare, economic, and conservation issue in translocations, and we suggest definitions, reporting, and experimental strategies to address it.

Revisión de la hiperdispersión en las reubicaciones de fauna Resumen La reubicación de especies se usa muy seguido como herramienta para revertir la pérdida de la biodiversidad a pesar de tener una tasa elevada de fracaso. Un factor que contribuye a este fracaso es la hiperdispersión posterior a la liberación, la cual definimos como el movimiento de larga distancia de los individuos que resulta en su fracaso para contribuir al establecimiento de la población. Revisamos las incidencias reportadas de la hiperdispersión y comparamos las tasas de hiperdispersión entre los taxones, las poblaciones, demografías, grupos de edad liberados y el éxito de las técnicas de mitigación. Confirmamos la hiperdispersión en 52.1% de 151 reubicaciones de conservación (reforzamiento y reintroducciones) en las cuales se rastreó a los animales. La prevalencia de la hiperdispersión (el porcentaje de estudios) tuvo una coherencia relativa en todos los taxones (42.9-60%), aunque probablemente se subestimaron las tasas de hiperdispersión de las aves porque el 76.9% de sus reubicaciones mostraron incidencias en las que no se pudieron ubicar a los individuos después de la liberación, pero tampoco se pudo confirmar la hiperdispersión. Los euterios exhibieron un promedio de incidencia de hiperdispersión (porcentaje de individuos con hiperdispersión dentro de un grupo de edad) del 20.2%, mayor que el de las aves, reptiles y marsupiales (10.4%, 15.7% y 10.3% respectivamente). No observamos tendencias significativas para el sexo, la población original o el tipo de reubicación, aunque sí hubo tendencias no significativas de mayor hiperdispersión en los machos que en las hembras y de mayor incidencia de hiperdispersión en los reforzamientos en relación con los programas de reintroducción. Las técnicas de mitigación incluyeron el confinamiento temporal, el suplemento de recursos y la liberación de animales en grupos sociales, pero sólo la mitad de los estudios que examinaban estas técnicas las encontraron útiles. La incidencia de la hiperdispersión varió en cada taxón, por lo que aconsejamos no estructurar las estrategias de reubicación con base en los resultados de otras especies. La hiperdispersión es un tema importante para el bienestar, la conservación y la economía de las reubicaciones y sugerimos estrategias de definición, reporte y experimentación para abordarla.

Effects of agriculture and nature reserves on avian behavior in northwestern Costa Rica.

Behavioral changes are often animals' first responses to environmental change and may act as a bellwether for population viability. Nonetheless, most studies of habitat conversion focus on changes in species occurrences or abundances. We analyzed >14,000 behavioral observations across 55 bird species in communities in northwestern Costa Rica to determine how land use affects reproductive, foraging, and other passive kinds of behaviors not associated with either foraging or reproduction. Specifically, we quantified differences in behaviors between farms, privately owned forests, and protected areas and implemented a novel modeling framework to account for variation in detection among behaviors. This framework entailed estimating abundances of birds performing different behaviors while allowing detection probabilities of individuals to vary by behavior. Birds were 1.2 times more likely to exhibit reproductive behaviors in forest than in agriculture and 1.5 times more likely to exhibit reproductive behaviors in protected areas than in private forests. Species were not always most abundant in the habitats where they were most likely to exhibit foraging or reproductive behaviors. Finally, species of higher conservation concern were less abundant in agriculture than in forest. Together, our results highlight the importance of behavioral analyses for elucidating the conservation value of different land uses.

Efectos de la agricultura y las reservas naturales sobre el comportamiento de las aves en el noroeste de Costa Rica Resumen Los cambios conductuales suelen ser la primera respuesta de los animales ante el cambio ambiental y pueden funcionar como un barómetro para la viabilidad poblacional. Sin embargo, la mayoría de los estudios sobre la conversión del hábitat se enfocan en cambios en la presencia o abundancia de las especies. Analizamos más de 14,000 observaciones conductuales en las comunidades de 55 especies de aves del noroeste de Costa Rica para determinar cómo el uso de suelo afectó el comportamiento reproductivo, de forrajeo y otras formas pasivas no asociadas con las dos anteriores. En específico, cuantificamos las diferencias en el comportamiento entre granjas, bosques de propiedad privada y áreas protegidas e implementamos un marco novedoso de modelado para justificar la variación en la detección entre los comportamientos. Este marco implicó estimar la abundancia de aves que realizaban diferentes comportamientos mientras permitía que variaran las probabilidades de detección de individuos según el comportamiento. Fue 1.2 veces más probable que las aves exhibieran comportamiento reproductivo en el bosque que en las zonas agrícolas y 1.5 veces más probable que exhibieran estos comportamientos en las áreas protegidas que en los bosques privados. Las especies no siempre fueron las más abundantes en los hábitats en donde era más probable que exhibieran comportamientos reproductivos o de forrajeo. Por último, las especies de mayor preocupación para la conservación fueron menos abundantes en las zonas agrícolas que en los bosques. En conjunto, nuestros resultados resaltan la importancia del análisis conductual para ilustrar el valor de conservación de los diferentes usos de suelo.

Quantitative support for the benefits of proactive management for wildlife disease control.

Finding effective pathogen mitigation strategies is one of the biggest challenges humans face today. In the context of wildlife, emerging infectious diseases have repeatedly caused widespread host morbidity and population declines of numerous taxa. In areas yet unaffected by a pathogen, a proactive management approach has the potential to minimize or prevent host mortality. However, typically critical information on disease dynamics in a novel host system is lacking, empirical evidence on efficacy of management interventions is limited, and there is a lack of validated predictive models. As such, quantitative support for identifying effective management interventions is largely absent, and the opportunity for proactive management is often missed. We considered the potential invasion of the chytrid fungus, Batrachochytrium salamandrivorans (Bsal), whose expected emergence in North America poses a severe threat to hundreds of salamander species in this global salamander biodiversity hotspot. We developed and parameterized a dynamic multistate occupancy model to forecast host and pathogen occurrence, following expected emergence of the pathogen, and evaluated the response of salamander populations to different management scenarios. Our model forecasted that taking no action is expected to be catastrophic to salamander populations. Proactive action was predicted to maximize host occupancy outcomes relative to wait-and-see reactive management, thus providing quantitative support for proactive management opportunities. The eradication of Bsal was unlikely under all the evaluated management options. Contrary to our expectations, even early pathogen detection had little effect on Bsal or host occupancy outcomes. Our results provide quantitative support that proactive management is the optimal strategy for promoting persistence of disease-threatened salamander populations. Our approach fills a critical gap by defining a framework for evaluating management options prior to pathogen invasion and can thus serve as a template for addressing novel disease threats that jeopardize wildlife and human health.

Apoyo cuantitativo para los beneficios de la gestión proactiva del control de enfermedades silvestres Resumen Uno de los mayores retos en la actualidad es encontrar estrategias eficaces de mitigación de patógenos. En el contexto de la fauna silvestre, las enfermedades infecciosas emergentes han causado en varias ocasiones una morbilidad generalizada de los hospedadores y el declive de las poblaciones de numerosos taxones. En zonas aún no afectadas por un patógeno, un enfoque de gestión proactivo tiene el potencial de minimizar o prevenir la mortalidad de los hospederos. Sin embargo, en general se carece de información crítica sobre la dinámica de la enfermedad en el nuevo sistema huésped, las pruebas empíricas sobre la eficacia de las intervenciones de gestión son limitadas y faltan modelos predictivos validados. Por lo tanto, no existe un apoyo cuantitativo para identificar intervenciones de gestión eficaces y a menudo se pierde la oportunidad de una gestión proactiva. Consideramos la posible invasión del hongo quitridio Batrachochytrium salamandrivorans (Bsal), cuya aparición prevista en América del Norte supone una grave amenaza para cientos de especies de salamandras en este punto caliente de la biodiversidad mundial de salamandras. Desarrollamos y parametrizamos un modelo dinámico de ocupación multiestado para predecir la presencia de hospederos y patógenos, tras la aparición esperada del patógeno, y evaluamos la respuesta de las poblaciones de salamandras a diferentes escenarios de gestión. Nuestro modelo predijo que no tomar ninguna medida sería catastrófico para las poblaciones de salamandras. También predijo que la acción proactiva maximizaría los resultados de ocupación de hospederos en relación con la gestión reactiva de esperar y ver, proporcionando así un apoyo cuantitativo a las oportunidades de gestión proactiva. La erradicación de Bsal fue improbable bajo todas las opciones de gestión evaluadas. Contrariamente a nuestras expectativas, incluso la detección temprana del patógeno tuvo poco efecto sobre los resultados de ocupación de Bsal o del hospedador. Nuestros resultados apoyan cuantitativamente a la gestión proactiva como la estrategia óptima para promover la persistencia de poblaciones de salamandras amenazadas por la enfermedad. Nuestro enfoque llena un vacío crítico al definir un marco para evaluar las opciones de gestión antes de la invasión de patógenos y, por lo tanto, puede servir como plantilla para hacer frente a nuevas amenazas de enfermedades que ponen en peligro la vida silvestre y la salud humana.

Designing celebrity-endorsed behavioral interventions in conservation.

The use of celebrity endorsement in environmental conservation interventions aiming to influence human behavior has increased in recent decades. Although good practice in designing, implementing, and evaluating behavioral interventions is outlined in recent publications, guidance on developing conservation interventions with celebrity endorsement remains limited. To fill this gap, we devised a guide for decision-making relating to celebrity-endorsed behavioral interventions based on the behavioral, project design, and celebrity endorsement literatures. The guide advises conducting research to understand the behavior system in question; defining endorser selection models and celebrities based on the research; developing an endorsement strategy with the appropriate communication channels; testing the celebrity, channels, and strategy with the target audience and making adjustments as needed; and, finally, evaluating the intervention after implementation. We applied this strategy to a case study, the aim of which was to design a celebrity-endorsed intervention to reduce consumption of wild meat in Ho Chi Minh City, Vietnam. Following our guide, we found that employing evidence-based decision-making substantially enhanced our ability to understand the complexity and potential cost associated with using celebrity endorsements in behavioral interventions.

Diseño de intervenciones conductuales para la conservación apoyadas por celebridades Resumen En las últimas décadas se ha incrementado el uso del apoyo de celebridades en las intervenciones de conservación ambiental que buscan influir sobre la conducta humana. Aunque las publicaciones recientes describen las buenas prácticas en el diseño, implementación y evaluación de las intervenciones conductuales, todavía son limitadas las directrices sobre el desarrollo de intervenciones de conservación apoyadas por celebridades. Para llenar este vacío, diseñamos una guía para decidir en relación con las intervenciones conductuales apoyadas por celebridades con base en la literatura sobre las conductas, diseño de proyectos y apoyo de celebridades. La guía recomienda investigar para entender el sistema conductual en cuestión; definir los modelos de selección de patrocinadores y celebridades con base en esta investigación; desarrollar una estrategia de apoyo con los canales adecuados de comunicación; probar los canales, estrategia y celebridades con el público objetivo y realizar los ajustes necesarios; y, por último, la evaluación de la intervención posterior a la implementación. Aplicamos esta estrategia a un estudio de caso, cuyo objetivo era diseñar una intervención con apoyo de celebridades para reducir el consumo de fauna en Ciudad Ho Chi Minh, Vietnam. Con nuestra guía encontramos que el uso de decisiones basadas en evidencias mejoró sustancialmente nuestra capacidad para entender la complejidad y el costo potencial asociado con el uso de apoyo de celebridades en las intervenciones conductuales.

Predictors of length of hospital stay after pediatric Ebstein anomaly corrective surgery: a retrospective cohort study.

BACKGROUND: The remarkable advancements in surgical techniques over recent years have shifted the clinical focus from merely reducing mortality to enhancing the quality of postoperative recovery. The duration of a patient's hospital stay serves as a crucial indicator in evaluating postoperative recovery and surgical outcomes. This study aims to identify predictors of the length of hospital stay for children who have undergone corrective surgery for Ebstein Anomaly (EA). METHODS: We conducted a retrospective cohort study on children (under 18 years of age) diagnosed with EA who were admitted for corrective surgery between January 2009 and November 2021 at Fuwai Hospital. The primary outcome was the Time to Hospital Discharge (THD). Cox proportional hazard models were utilized to identify predictors of THD. In the context of time-to-event analysis, discharge was considered an event. In cases where death occurred before discharge, it was defined as an extended THD, input as 100 days (exceeding the longest observed THD), and considered as a non-event. RESULTS: A total of 270 children were included in this study, out of which three died in the hospital. Following the Cox proportional hazard analysis, six predictors of THD were identified. The hazard ratios and corresponding 95% confidence intervals were as follows: age, 1.030(1.005,1.055); C/R > 0.65, 0.507(0.364,0.707); Carpentier type C or D, 0.578(0.429,0.779); CPB time, 0.995(0.991,0.998); dexamethasone, 1.373(1.051,1.795); and transfusion, 0.680(0.529,0.875). The children were categorized into three groups based on the quartile of THD. Compared to children in the ≤ 6 days group, those in the ≥ 11 days group were associated with a higher incidence of adverse outcomes. Additionally, the duration of mechanical ventilation and ICU stay, as well as hospital costs, were significantly higher in this group. CONCLUSION: We identified six predictors of THD for children undergoing corrective surgery for EA. Clinicians can utilize these variables to optimize perioperative management strategies, reduce adverse complications, improve postoperative recovery, and reduce unnecessary medical expenses.

Recurrent high-impact mutations at cognate structural positions in class A G protein-coupled receptors expressed in tumors.

G protein-coupled receptors (GPCRs) are the largest family of human proteins. They have a common structure and, signaling through a much smaller set of G proteins, arrestins, and effectors, activate downstream pathways that often modulate hallmark mechanisms of cancer. Because there are many more GPCRs than effectors, mutations in different receptors could perturb signaling similarly so as to favor a tumor. We hypothesized that somatic mutations in tumor samples may not be enriched within a single gene but rather that cognate mutations with similar effects on GPCR function are distributed across many receptors. To test this possibility, we systematically aggregated somatic cancer mutations across class A GPCRs and found a nonrandom distribution of positions with variant amino acid residues. Individual cancer types were enriched for highly impactful, recurrent mutations at selected cognate positions of known functional motifs. We also discovered that no single receptor drives this pattern, but rather multiple receptors contain amino acid substitutions at a few cognate positions. Phenotypic characterization suggests these mutations induce perturbation of G protein activation and/or ß-arrestin recruitment. These data suggest that recurrent impactful oncogenic mutations perturb different GPCRs to subvert signaling and promote tumor growth or survival. The possibility that multiple different GPCRs could moonlight as drivers or enablers of a given cancer through mutations located at cognate positions across GPCR paralogs opens a window into cancer mechanisms and potential approaches to therapeutics.

Luteolin Inhibits Indoxyl Sulfate-Induced ICAM-1 and MCP-1 Expression by Inducing HO-1 Expression in EA.hy926 Human Endothelial Cells.

In patients with chronic kidney disease, the uremic toxin indoxyl sulfate (IS) accelerates kidney damage and the progression of cardiovascular disease. IS may contribute to vascular diseases by inducing inflammation in endothelial cells. Luteolin has documented antioxidant and anti-inflammatory properties. This study aimed to investigate the effect of luteolin on IS-mediated reactive oxygen species (ROS) production and intercellular adhesion molecule (ICAM-1) and monocyte chemoattractant protein (MCP-1) expression in EA.hy926 cells and the possible mechanisms involved. IS significantly induced ROS production (by 6.03-fold, p < 0.05), ICAM-1 (by 2.19-fold, p < 0.05) and MCP-1 protein expression (by 2.18-fold, p < 0.05), and HL-60 cell adhesion (by 31%, p < 0.05), whereas, luteolin significantly decreased IS-induced ROS production, ICAM-1 and MCP-1 protein expression, and HL-60 cell adhesion. Moreover, luteolin attenuated IS-induced nuclear accumulation of p65 and c-jun. Luteolin dose-dependently increased heme oxygenase-1 (HO-1) expression and the maximum fold induction of HO-1 by luteolin was 3.68-fold (p < 0.05), whereas, HO-1 knockdown abolished the suppression of ICAM-1 and MCP-1 expression by luteolin. Luteolin may protect against IS-induced vessel damage by inducing HO-1 expression in vascular endothelial cells, which suppresses nuclear factor kappa B (NF-κB) and activator protein 1 (AP-1) mediated ICAM-1 and MCP-1 expression.

Ductus arteriosus diameters in fetuses with early- and late-onset fetal growth restriction.

PURPOSE: Fetal growth restriction (FGR) is a common pregnancy complication that can be associated with several adverse perinatal outcomes. One of these negative outcomes is ductus arteriosus, especially in preterm babies. In this study, intrauterine heart function and ductus diameter were evaluated in babies with FGR. METHODS: Thirty-seven fetuses with FGR were compared with 37 normal-weight fetuses at the same gestational week. In our study, ventricular diameters, aorta, pulmonary artery, ductus arteriosus (DA), aortic arch diameter, and flow traces were examined. In addition, the aorta and aortic isthmus diameters were proportioned to the ductus diameter, and the left ventricular myocardial performance index (MPI) [(ICT + IRT)/ET] was evaluated. RESULTS: There was no difference in DA diameters between the patient and control groups. The intragroup comparison of the cases with early- and late-onset FGR revealed no statistically significant difference between DA diameters. However, the ratios of the aortic annulus diameter/ductus diameter (AOD/DAD) and aortic isthmus diameter/ductus diameter (AID/DAD) were significantly lower in early-onset FGR because the diameter of the DA was greater. In addition, the mod-MPI values were higher in the patient group. CONCLUSIONS: In our study, although the ductal diameters did not change significantly in the patient group, the ductal diameter was greater in the early-onset intrauterine growth restriction (FGR) group compared with other cardiac measurements. The mod-MPI value, a cardiac function indicator, was higher in fetuses with FGR. These findings may be useful for evaluating postnatal cardiac functions in FGR.

Multifunctional Sr,Mg-Doped Mesoporous Bioactive Glass Nanoparticles for Simultaneous Bone Regeneration and Drug Delivery.

Mesoporous bioactive glass nanoparticles (MBGNs) doped with therapeutical ions present multifunctional systems that enable a synergistic outcome through the dual delivery of drugs and ions. The aim of this study was to evaluate influence of co-doping with strontium and magnesium ions (SrMg-MBGNs) on the properties of MBGNs. A modified microemulsion-assisted sol-gel synthesis was used to obtain particles, and their physicochemical properties, bioactivity, and drug-loading/release ability were evaluated. Indirect biological assays using 2D and 3D cell culture models on human bone marrow-derived mesenchymal stem cells (hBM-MSCs) and endothelial EA.hy926 cells, respectively, were used to determine biocompatibility of MBGNs, their influence on alkaline phosphatase (ALP) production, calcium deposition, and cytoskeletal organization. Results showed that Sr,Mg-doping increased pore volume and solubility, and changed the mesoporous structure from worm-like to radial-dendritic, which led to a slightly accelerated drug release compared to pristine MBGNs. Biological assays confirmed that particles are biocompatible, and have ability to slightly induce ALP production and calcium deposition of hBM-MSCs, as well as to significantly improve the proliferation of EA.hy926 compared to biochemical stimulation via vascular endothelial growth factor (VEGF) administration or regular media. Fluorescence staining revealed that SrMg-MBGNs had a similar effect on EA.hy926 cytoskeletal organization to the VEGF group. In conclusion, Sr,Mg-MBGNs might be considered promising biomaterial for biomedical applications.

A decision methodology for site-level ecosystem accounting.

The United Nations System of Environmental-Economic Accounting Ecosystem Accounting (SEEA EA) framework is the international standard for ecosystem accounting. To date, application of SEEA EA has been predominantly at large scales, usually at landscape and national levels. However, many environmental management decisions are taken locally, in site-specific contexts. While the use of SEEA EA continues to develop at all scales, there is currently no widely endorsed methodology for employing SEEA EA at local scales, such as the site level. We present a methodology for developing site-level ecosystem accounts, describing the important decisions at each step of the process. We also provide two case studies that demonstrate the context-dependent nature of the decision-making process of ecosystem accounting at small scales. The two major challenges for site-level accounting are stakeholder engagement and data availability. As the use of SEEA EA continues to increase in policy and decision-making processes worldwide, there is a need for local-scale case studies that adapt this methodology across a broad range of contexts. Our case studies provide some of the first published examples of the application of SEEA EA at the site level and are intended to promote consistent implementation of ecosystem accounting across scales.

Tracheoesophageal Fistula With Esophageal Atresia: A Case Series.

Tracheoesophageal fistula (TEF) with or without esophageal atresia (EA) results from maldevelopment of the trachea and esophagus during maturation of the primitive foregut. EA/TEF commonly presents shortly after birth because of increased oral secretions and the inability to advance a nasogastric or orogastric tube to the proper depth. Given that prenatal diagnosis is uncommon and early intervention is important to reduce morbidity and mortality risk, early recognition and diagnosis are imperative. We present a case series of two neonates diagnosed with EA/TEF, type "C" and type "E," born at low-acuity centers, who required transport to a tertiary center for surgical support. The pathophysiology as well as types of TEFs, symptomology, stabilization goals, corrective treatment, and long-term implications will be examined. Finally, the educational needs of parents and caregivers will be discussed.

Testing reliability and validity of practitioner-rated parental sensitivity: A novel tool for practice.

Improving parental sensitivity is an important objective of interventions to support families. This study examined reliability and validity of parental sensitivity ratings using a novel package of an e-learning tool and an interactive decision tree provided through a mobile application, called the OK! package. Independent raters assessed parental sensitivity using the OK! package (N = 11 raters) and the NICHD Parental Sensitivity rating scales (N = 22 raters) on the basis of videotaped mother-child interactions at 10- or 12-months-old (N = 294) and at 24-months-old (N = 204) from the Dutch longitudinal cohort study Generation2 . Mothers reported on children's externalizing and internalizing problems and social competence when children were 4 and 7 years old. Results showed excellent single interrater reliability for raters using the OK! package (mean ICC = .79), and strong evidence for convergent validity at 10- or 12-month-old (r = .57) and 24-month-old (r = .65). Prospective associations of neither parental sensitivity rated using the OK! package or the NICHD Parental Sensitivity rating scales with child developmental outcomes were statistically significant (p > .05), with overlapping 95% confidence intervals for both measures. The OK! package provides a promising direction for testing alternatives to current training and instruction modalities.

Mejorar la sensibilidad de progenitores es un objetivo importante de intervenciones para ayudar a las familias. Este estudio examinó la confiabilidad y validez de los puntajes de sensibilidad de progenitores usando un novedoso paquete de una herramienta de e-aprendizaje y un árbol interactivo de decisión, ofrecido a través de una aplicación móvil llamada ¡Paquete OK! Calificadores independientes evaluaron la sensibilidad de progenitores usando el ¡Paquete OK! (N = 11 calificadores) y las escalas de puntajes de Sensibilidad del Progenitor de NICHD (N = 22 calificadores) sobre la base de las interacciones madre-niño grabadas en video a los 10 o 12 meses de edad (N = 294) y a los 24 meses de edad (N = 204) del grupo holandés de estudio longitudinal Generación 2. Las madres reportaron sobre los problemas de externalización e internalización de los niños y la competencia social cuando los niños tenían 4 y 7 años. Los resultados muestran una excelente sola confiabilidad entre calificadores para los calificadores que usaron el ¡Paquete OK! (media ICC = .79), y una fuerte evidencia para la validez convergente a los 10 o 12 meses de edad (r = .57) y a los 24 meses de edad (r = .65). Las asociaciones probables, ni de la sensibilidad del progenitor evaluada usando el ¡Paquete OK! ni de las escalas de puntajes de Sensibilidad del Progenitor NICHD, con los resultados del desarrollo del niño, fueron estadísticamente significativas (p > .05), con intervalos de confiabilidad que coincidían 95% para ambas medidas. El ¡Paquete OK! Ofrece una prometedora directriz para examinar alternativas al entrenamiento y modalidades de instrucción actuales.

L'amélioration de la sensibilité parentale est un objectif important d'interventions pour soutenir les familles. Cette étude a examiné la fiabilité et la validité de la sensibilité parentale utilisant une nouvelle approche combinant un outil de formation en ligne et un arbre de décision interactif offert au travers d'une application mobile, appelée l'approche OK!. Des évaluateurs indépendants ont évalué la sensibilité parentale en utilisant l'approche OK! (N = 11 évaluateurs) et les échelles d'évaluation de le sensibilité parentale NICHD (N = 22 évaluateurs) sur la base d'interactions mère-enfant filmées à la vidéo à 10- ou 12 mois N = 294) et à 24 mois (N-204) de l'étude de cohorte longitudinale hollandaise Generation2. Les mères ont signalé les problèmes d'externalisation et d'internalisation des enfants et leur compétence sociale lorsque les enfants avaient 4 et 7 ans. Les résultats ont démontré une excellente fiabilité entre les évaluateurs pour les évaluateurs utilisant l'approche OK! (moyenne ICC = ,79(, et de fortes preuves d'une validité convergente à 10 ou 12 mois (r = ,57) et à 24 mois (r = ,65). Les associations prospectives d'aucune sensibilité parentale évaluée en utilisant l'approche OK! ou les échelles d'évaluation de la sensibilité parentale NICHD ave des résultats développementaux de l'enfant étaient statistiquement significatives (p . ,05) avec un chevauchement des intervalles de confiance de 95% pour les deux mesures. L'approche OK! offre une direction prometteuse d'alternatives des tests aux modalités de formation et d'instruction actuelles.

Challenging diagnosis of Wilson's disease: A case report.

Wilson's disease is arare inherited disorder of copper met abolism. If le f t untre ated, i t can turn into a multi systemic disease with copper deposition in the liver, brain, a nd other tissues. Diagnosi s of Wilson's is delayed in Pak ist an by many ye a rs on average due to va riabl e presen tations. In ad olescents, the initial s igns a re more likely to b e neuropsychiatric. Here we present a case of Wilso n's disease that pre sented initially with he patic symptoms and did not have signs specific to the di sea s e such as Kayser-Fleischer rings. Our case was diagnosed to be Wilson's Disease on ly on further investigat ions and s ubsequently the patient was treated with chela tion therapy using D-Penicillamine.Wilson's Disease should be kept in mind as a differential diagno sis in adolesce nt patients that present with unexplained acute liver failure and cytopenias without any neurological symptoms, as a missed diagnosis can prove to be fatal.

OneMax is not the Easiest Function for Fitness Improvements.

We study the (1:s+1) success rule for controlling the population size of the (1,λ)- EA. It was shown by Hevia Fajardo and Sudholt that this parameter control mechanism can run into problems for large s if the fitness landscape is too easy. They conjectured that this problem is worst for the ONEMAX benchmark, since in some well-established sense ONEMAX is known to be the easiest fitness landscape. In this paper we disprove this conjecture. We show that there exist s and ɛ such that the self-adjusting (1,λ)-EA with the (1:s+1)-rule optimizes ONEMAX efficiently when started with ɛn zero-bits, but does not find the optimum in polynomial time on DYNAMIC BINVAL. Hence, we show that there are landscapes where the problem of the (1:s+1)-rule for controlling the population size of the (1,λ)-EA is more severe than for ONEMAX. The key insight is that, while ONEMAX is the easiest function for decreasing the distance to the optimum, it is not the easiest fitness landscape with respect to finding fitness-improving steps.

Effects of CDDO-EA in sepsis-induced acute lung injury: mouse model of endotoxaemia.

OBJECTIVE: Aim: The aim of this research is to clarify the potential effect of CDDO-EA against experimentally sepsis induced lung injury in mice. PATIENTS AND METHODS: Materials and Methods: Mice have divided into four groups: Sham group CLP group, Vehicle-treatment group, CDDO-EA-treated group: mice in this group received CDDO-EA 2mg/kg intraperitoneally, 1hr before CLP, then the animals were sacrificed 24hr after CLP. After exsAngpuinations, tissue samples of lung were collected, followed by markers measurement including, TNF-α, IL-1ß, VEGF, MPO, caspase11, Angp-1and Angp-2 by ELISA, gene expression of TIE2 and VE-cadherin by qRT-PCR, in addition to histopathological study. RESULTS: Results: A significant elevation (p<0.05) in TNF-α, IL-1ß, MPO, ANGP-2, VEGF, CASPASE 11 in CLP and vehicle groups when compared with sham group. CDDO-EA group showed significantly lower levels p<0.05, level of ANGP-1 was significantly lower p<0.05 in the CLP and vehicle groups as compared with the sham group. Quantitative real-time PCR demonstrated a significant decrement in mRNA expression of TIE2&ve-cadherin genes p<0.05 in sepsis & vehicle. CONCLUSION: Conclusions: CDDO-EA has lung protective effects due to its anti-inflammatory and antiAngpiogenic activity, additionally, CDDO-EA showes a lung protective effect as they affect tissue mRNA expression of TIE2 and cadherin gene. Furthermore, CDDO-EA attenuate the histopathological changes that occur during polymicrobial sepsis thereby lung protection effect.