Airway epithelial specific deletion of Jun-N-terminal kinase 1 attenuates pulmonary fibrosis in two independent mouse models

© 2020 van der Velden et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. The stress-induced kinase, c-Jun-N-terminal kinase 1 (JNK1) has previously been implicated in the pathogenesis of lung fibrosis. However, the exact cell type(s) wherein JNK1 exerts its pro-fibrotic role(s) remained enigmatic. Herein we demonstrate prominent activation of JNK in bronchial epithelia using the mouse models of bleomycin- or AdTGFβ1-induced fibrosis. Furthermore, in lung tissues of patients with idiopathic pulmonary fibrosis (IPF), active JNK was observed in various regions including type I and type II pneumocytes and fibroblasts. No JNK activity was observed in adjacent normal tissue or in normal control tissue. To address the role of epithelial JNK1, we ablated Jnk1 form bronchiolar and alveolar type II epithelial cells using CCSP-directed Cre recombinase-mediated ablation of LoxP-flanked Jnk1 alleles. Our results demonstrate that ablation of Jnk1 from airway epithelia resulted in a strong protection from bleomycin- or adenovirus expressing active transforming growth factor beta-1 (AdTGFβ1)-induced fibrosis. Ablation of the Jnk1 allele at a time when collagen increases were already present showed a reversal of existing increases in collagen content. Epithelial Jnk1 ablation resulted in attenuation of mesenchymal genes and proteins in lung tissue and preserved expression of epithelial genes. Collectively, these data suggest that epithelial JNK1 contributes to the pathogenesis of pulmonary fibrosis. Given the presence of active JNK in lungs from patients with IPF, targeting JNK1 in airway epithelia may represent a potential treatment strategy to combat this devastating disease

First AMBER/VLTI observations of hot massive stars

AMBER is the first near infrared focal instrument of the VLTI. It combines three telescopes and produces spectrally resolved interferometric measures. This paper discusses some preliminary results of the first scientific observations of AMBER with three Unit Telescopes at medium (1500) and high (12000) spectral resolution. We derive a first set of constraints on the structure of the circumstellar material around the Wolf Rayet Gamma2 Velorum and the LBV Eta Carinae

Epidemiological characteristics of varicella from 2000 to 2008 and the impact of nationwide immunization in Taiwan

[[abstract]]Background: Varicella has an important impact on public health. Starting in 2004 in Taiwan, nationwide free varicella vaccinations were given to 1-year-old children.Methods: Our study investigated the epidemiological characteristics of varicella from 2000 to 2008, and assessed the change of varicella epidemiology after the mass varicella immunization. ICD-9-CM codes related to varicella or chickenpox (052, 052.1, 052.2, 052.7, 052.8, 052.9) were analyzed for all young people under 20 years of age through the National Health Insurance database of Taiwan from 2000 to 2008.Results: Case numbers of varicella or chickenpox significantly declined after the nationwide immunization in 2004. Winter, particularly January, was the epidemic season of varicella. We found a significant post-vaccination decrease in incidence among preschool children, especially 3 to 6 year-old children-- the peak incidence was 66 per thousand for 4 and 5 year-old children before the nationwide immunization (2000 to 2003), and the peak incidence was 23 per thousand for 6 year-old children in 2008 (p < 0.001). Varicella-related hospitalization also significantly decreased in children younger than 6 years after the nationwide immunization.Conclusion: The varicella annual incidence and varicella-related hospitalization markedly declined in preschool children after nationwide varicella immunization in 2004

Sensitivity of ICD coding for sepsis in children-a population-based study.

BACKGROUND International Classification of Diseases 10th edition (ICD-10) is widely used to describe the burden of disease. AIM To describe how well ICD-10 coding captures sepsis in children admitted to the hospital with blood culture-proven bacterial or fungal infection and systemic inflammatory response syndrome. METHODS Secondary analysis of a population-based, multicenter, prospective cohort study on children with blood culture-proven sepsis of nine tertiary pediatric hospitals in Switzerland. We compared the agreement of validated study data on sepsis criteria with ICD-10 coding abstraction obtained at the participating hospitals. RESULTS We analyzed 998 hospital admissions of children with blood culture-proven sepsis. The sensitivity of ICD-10 coding abstraction was 60% (95%-CI 57-63) for sepsis; 35% (95%-CI 31-39) for sepsis with organ dysfunction, using an explicit abstraction strategy; and 65% (95%-CI 61-69) using an implicit abstraction strategy. For septic shock, the sensitivity of ICD-10 coding abstraction was 43% (95%-CI 37-50). Agreement of ICD-10 coding abstraction with validated study data varied by the underlying infection type and disease severity (p < 0.05). The estimated national incidence of sepsis, inferred from ICD-10 coding abstraction, was 12.5 per 100,000 children (95%-CI 11.7-13.5) and 21.0 per 100,000 children (95%-CI 19.8-22.2) using validated study data. CONCLUSIONS In this population-based study, we found a poor representation of sepsis and sepsis with organ dysfunction by ICD-10 coding abstraction in children with blood culture-proven sepsis when compared against a prospective validated research dataset. Sepsis estimates in children based on ICD-10 coding may thus severely underestimate the true prevalence of the disease. SUPPLEMENTARY INFORMATION The online version contains supplementary material available at 10.1007/s44253-023-00006-1

Hospitalizations for varicella in children and adolescents in a referral hospital in Hong Kong, 2004 to 2008: A time series study

Background: Varicella accounts for significant morbidities and remains a public health issue worldwide. Climatic factors have been shown to associate with the incidence and transmission of various infectious diseases. We describe the epidemiology of varicella in paediatric patients hospitalized at a tertiary referral hospital in Hong Kong from 2004 to 2008, and to explore the possible association between the occurrence of varicella infection and various climatic factors. Methods. The hospital discharge database of Princess Margaret Hospital was retrospectively analyzed for admissions associated with varicella from 2004 to 2008. Meteorological data were obtained from the monthly meteorological reports from the Hong Kong Observatory website. Time series analysis was performed with Poisson regression using a Generalized Estimating Equation (GEE) approach. Results: During the study period, 598 children were hospitalized for varicella. The mean age on admission was 57.6 months, and the mean duration of hospitalization was 3.7 days. The overall complication rate was 47%. The mean monthly relative humidity, especially in cool seasons, was inversely correlated with the monthly varicella cases of the same month. Conclusions: Varicella can lead to serious complications and prolonged hospitalization, even in previously healthy children. Lower relative humidity in cool seasons is associated with higher number of paediatric varicella hospital admissions. These findings are useful for a better understanding of the pattern of paediatric varicella hospitalization in Hong Kong. © 2011 Chan et al; licensee BioMed Central Ltd.link_to_subscribed_fulltex

Sensitivity of ICD coding for sepsis in children-a population-based study

BACKGROUND International Classification of Diseases 10th edition (ICD-10) is widely used to describe the burden of disease. AIM To describe how well ICD-10 coding captures sepsis in children admitted to the hospital with blood culture-proven bacterial or fungal infection and systemic inflammatory response syndrome. METHODS Secondary analysis of a population-based, multicenter, prospective cohort study on children with blood culture-proven sepsis of nine tertiary pediatric hospitals in Switzerland. We compared the agreement of validated study data on sepsis criteria with ICD-10 coding abstraction obtained at the participating hospitals. RESULTS We analyzed 998 hospital admissions of children with blood culture-proven sepsis. The sensitivity of ICD-10 coding abstraction was 60% (95%-CI 57-63) for sepsis; 35% (95%-CI 31-39) for sepsis with organ dysfunction, using an explicit abstraction strategy; and 65% (95%-CI 61-69) using an implicit abstraction strategy. For septic shock, the sensitivity of ICD-10 coding abstraction was 43% (95%-CI 37-50). Agreement of ICD-10 coding abstraction with validated study data varied by the underlying infection type and disease severity (p < 0.05). The estimated national incidence of sepsis, inferred from ICD-10 coding abstraction, was 12.5 per 100,000 children (95%-CI 11.7-13.5) and 21.0 per 100,000 children (95%-CI 19.8-22.2) using validated study data. CONCLUSIONS In this population-based study, we found a poor representation of sepsis and sepsis with organ dysfunction by ICD-10 coding abstraction in children with blood culture-proven sepsis when compared against a prospective validated research dataset. Sepsis estimates in children based on ICD-10 coding may thus severely underestimate the true prevalence of the disease. SUPPLEMENTARY INFORMATION The online version contains supplementary material available at 10.1007/s44253-023-00006-1

Direct constraint on the distance of y2 Velorum from AMBER/VLTI observations

In this work, we present the first AMBER observations, of the Wolf-Rayet and O (WR+O) star binary system y2 Velorum. The AMBER instrument was used with the telescopes UT2, UT3, and UT4 on baselines ranging from 46m to 85m. It delivered spectrally dispersed visibilities, as well as differential and closure phases, with a resolution R = 1500 in the spectral band 1.95-2.17 micron. We interpret these data in the context of a binary system with unresolved components, neglecting in a first approximation the wind-wind collision zone flux contribution. We show that the AMBER observables result primarily from the contribution of the individual components of the WR+O binary system. We discuss several interpretations of the residuals, and speculate on the detection of an additional continuum component, originating from the free-free emission associated with the wind-wind collision zone (WWCZ), and contributing at most to the observed K-band flux at the 5% level. The expected absolute separation and position angle at the time of observations were 5.1&plusmn;0.9mas and 66&plusmn;15&deg; respectively. However, we infer a separation of 3.62+0.11-0.30 mas and a position angle of 73+9-11&deg;. Our analysis thus implies that the binary system lies at a distance of 368+38-13 pc, in agreement with recent spectrophotometric estimates, but significantly larger than the Hipparcos value of 258+41-31 pc

Organ Dysfunction in Children With Blood Culture-Proven Sepsis: Comparative Performance of Four Scores in a National Cohort Study.

OBJECTIVES Previous studies applying Sepsis-3 criteria to children were based on retrospective analyses of PICU cohorts. We aimed to compare organ dysfunction criteria in children with blood culture-proven sepsis, including emergency department, PICU, and ward patients, and to assess relevance of organ dysfunctions for mortality prediction. DESIGN We have carried out a nonprespecified, secondary analysis of a prospective dataset collected from September 2011 to December 2015. SETTING Emergency departments, wards, and PICUs in 10 tertiary children's hospitals in Switzerland. PATIENTS Children younger than 17 years old with blood culture-proven sepsis. We excluded preterm infants and term infants younger than 7 days old. INTERVENTIONS None. MEASUREMENTS AND MAIN RESULTS We compared the 2005 International Pediatric Sepsis Consensus Conference (IPSCC), Pediatric Logistic Organ Dysfunction-2 (PELOD-2), pediatric Sequential Organ Failure Assessment (pSOFA), and Pediatric Organ Dysfunction Information Update Mandate (PODIUM) scores, measured at blood culture sampling, to predict 30-day mortality. We analyzed 877 sepsis episodes in 807 children, with a 30-day mortality of 4.3%. Percentage with organ dysfunction ranged from 32.7% (IPSCC) to 55.3% (pSOFA). In adjusted analyses, the accuracy for identification of 30-day mortality was area under the curve (AUC) 0.87 (95% CI, 0.82-0.92) for IPSCC, 0.83 (0.76-0.89) for PELOD-2, 0.85 (0.78-0.92) for pSOFA, and 0.85 (0.78-0.91) for PODIUM. When restricting scores to neurologic, respiratory, and cardiovascular dysfunction, the adjusted AUC was 0.89 (0.84-0.94) for IPSCC, 0.85 (0.79-0.91) for PELOD-2, 0.87 (0.81-0.93) for pSOFA, and 0.88 (0.83-0.93) for PODIUM. CONCLUSIONS IPSCC, PELOD-2, pSOFA, and PODIUM performed similarly to predict 30-day mortality. Simplified scores restricted to neurologic, respiratory, and cardiovascular dysfunction yielded comparable performance

Near-Infrared interferometry of Eta Carinae with high spatial and spectral resolution using the VLTI and the AMBER instrument

We present the first NIR spectro-interferometry of the LBV Eta Carinae. The K band observations were performed with the AMBER instrument of the ESO Very Large Telescope Interferometer using three 8.2m Unit Telescopes with baselines from 42 to 89m. The aim of this work is to study the wavelength dependence of Eta Car's optically thick wind region with a high spatial resolution of 5 mas (11 AU) and high spectral resolution. The medium spectral resolution observations (R=1,500) were performed in the wavelength range around both the HeI 2.059 micron and the Br gamma 2.166 micron emission lines, the high spectral resolution observations (R=12,000) only in the Br gamma line region. In the K-band continuum, a diameter of 4.0 +/-0.2 mas (Gaussian FWHM, fit range 28-89m) was measured for Eta Car's optically thick wind region. If we fit Hillier et al. (2001) model visibilities to the observed AMBER visibilities, we obtain 50 % encircled-energy diameters of 4.2, 6.5 and 9.6mas in the 2.17 micron continuum, the HeI, and the Br gamma emission lines, respectively. In the continuum near the Br gamma line, an elongation along a position angle of 120+/-15 degrees was found, consistent with previous VLTI/VINCI measurements by van Boekel et al. (2003). We compare the measured visibilities with predictions of the radiative transfer model of Hillier et al. (2001), finding good agreement. Furthermore, we discuss the detectability of the hypothetical hot binary companion. For the interpretation of the non-zero differential and closure phases measured within the Br gamma line, we present a simple geometric model of an inclined, latitude-dependent wind zone. Our observations support theoretical models of anisotropic winds from fast-rotating, luminous hot stars with enhanced high-velocity mass loss near the polar regions.Comment: 22 pages, 14 figures, 2 tables; A&A in pres