The upcoming European Soil Monitoring Law: An effective instrument for the protection of terrestrial ecosystems?

Soils are a precious resource consistently placed under several threats and urgently in need of protection within a regulatory framework at the European level. Soils are central to the provision of environmental services as well as human existence on earth. The need to protect soil has been identified by several recent European strategies and fortunately, a specific European regulation for soil protection is on the way-the European Soil Monitoring Law (formerly: Soil Health Law). However, efforts need to ensure that the upcoming Soil Monitoring Law closes gaps between existing regulations for chemicals and acknowledges current European strategies for environmental protection and sustainability. This brief communication started from a fruitful discussion among SETAC Global Soils Interest Group members on a recent public consultation on the newly proposed Soil Monitoring Law of the European Commission and highlights critical points focusing on the chemical pollution of soils. We emphasize urgent needs such as the essential definition of a "healthy state" of soils; the implementation of a suitable set of indicators and quality standards for the description of physical, chemical, and biological states of soils; the enforcement of the "polluter-pays" principle; and the establishment of a Europe-wide monitoring program. Results from monitoring need to be fed back into regulatory frameworks, including the regulation of chemicals. Guidance documents for the risk assessment of chemicals are outdated and need to be updated. Finally, actions need to be taken to foster healthy soils, stop biodiversity decline, and ensure the functioning of ecosystem services for future generations. Integr Environ Assess Manag 2024;20:316-321. © 2023 The Authors. Integrated Environmental Assessment and Management published by Wiley Periodicals LLC on behalf of Society of Environmental Toxicology & Chemistry (SETAC).

Children with single ventricle heart disease have a greater increase in sRAGE after cardiopulmonary bypass.

INTRODUCTION: Reducing cardiopulmonary bypass (CPB) induced inflammatory injury is a potentially important strategy for children undergoing multiple operations for single ventricle palliation. We sought to characterize the soluble receptor for advanced glycation end products (sRAGE), a protein involved in acute lung injury and inflammation, in pediatric patients with congenital heart disease and hypothesized that patients undergoing single ventricle palliation would have higher levels of sRAGE following bypass than those with biventricular physiologies. METHODS: This was a prospective, observational study of children undergoing CPB. Plasma samples were obtained before and after bypass. sRAGE levels were measured and compared between those with biventricular and single ventricle heart disease using descriptive statistics and multivariate analysis for risk factors for lung injury. RESULTS: sRAGE levels were measured in 40 patients: 19 with biventricular and 21 with single ventricle heart disease. Children undergoing single ventricle palliation had a higher factor and percent increase in sRAGE levels when compared to patients with biventricular circulations (4.6 vs. 2.4, p = 0.002) and (364% vs. 181%, p = 0.014). The factor increase in sRAGE inversely correlated with the patient's preoperative oxygen saturation (Pearson correlation (r) = -0.43, p = 0.005) and was positively associated with red blood cell transfusion (coefficient = 0.011; 95% CI: 0.004, 0.017; p = 0.001). CONCLUSIONS: Children with single ventricle physiology have greater increase in sRAGE following CPB as compared to children undergoing biventricular repair. Larger studies delineating the role of sRAGE in children undergoing single ventricle palliation may be beneficial in understanding how to prevent complications in this high-risk population.

Transposition With Hypertrophic Cardiomyopathy and Persistent Pulmonary Hypertension of the Newborn.

The contemporaneous presentation of transposition of the great arteries and hypertrophic cardiomyopathy is rare and complicates optimal surgical timing. We present a newborn with transposition and severe hypertrophic cardiomyopathy with a postnatal course complicated by persistent pulmonary hypertension who was supported with extracorporeal membrane oxygenation until successful arterial switch operation on the day of life 8.

Serum Soluble Receptor for Advanced Glycation End Products in Infants With Bronchiolitis: Associations With Acute Severity and Recurrent Wheeze.

BACKGROUND: Although bronchiolitis contributes to substantial acute (eg, intensive care use) and chronic (eg, recurrent wheeze) morbidities in young children, the pathobiology remains uncertain. We examined the associations of serum soluble receptor for advanced glycation end products (sRAGE) with acute and chronic morbidities of bronchiolitis including recurrent wheeze. METHODS: A multicenter, multiyear, cohort study of infants hospitalized for bronchiolitis was analyzed. We measured the serum sRAGE level at hospitalization and its association with intensive care use (use of mechanical ventilation and/or admission to the intensive care unit) and development of recurrent wheeze by age 3 years. We performed causal mediation analysis to estimate indirect (mediation) and direct effects of sRAGE on recurrent wheeze. RESULTS: In 886 infants with bronchiolitis, the median age was 2.9 months. Overall, 15% underwent intensive care and 32% developed recurrent wheeze. In multivariable modeling adjusting for 11 confounders, a higher presenting sRAGE level was associated with lower risk of intensive care (odds ratio for each 1-log increment, 0.39; 95% confidence interval [CI], .16 -.91; P = .03) and significantly lower rate of recurrent wheeze (hazard ratio [HR], 0.58; 95% CI, .36 -.94; P = .03). In mediation analysis, the direct effect was significant (HR, 0.60; 95% CI, .37 -.97; P = .04), while the indirect effect was not (P = .30). CONCLUSIONS: Serum sRAGE levels were inversely associated with acute and chronic morbidities of bronchiolitis. The effect of sRAGE on development of recurrent wheeze is potentially driven through pathways other than acute severity of bronchiolitis.

High BAL sRAGE is Associated with Low Serum Eosinophils and IgE in Children with Asthma.

Asthma remains the most common chronic lung disease in childhood in the United States. The receptor for advanced glycation end products (RAGE) has been recognized as both a marker of and participant in pulmonary pathophysiology. While membrane-bound RAGE (mRAGE) perpetuates the type 2 immune response, the soluble form (sRAGE) may act as a decoy receptor for pro-inflammatory ligands. Bronchoalveolar samples from 45 pediatric patients with asthma were obtained. Patients were divided into high and low BAL sRAGE groups using median sRAGE. Descriptive statistical analysis and non-parametric testing were applied. Children in the "high" sRAGE group had a lower median serum eosinophil (0.27 [SE ± 0.04] vs. 0.57 [± 0.06] K/mcl, adjusted p = 0.003) and lower serum IgE level (194.4 [± 60.7] vs. 676.2 ± 140.5) IU/mL, adjusted p = 0.004) as compared to the "low" sRAGE group. When controlling for age and body mass index percentile, absolute eosinophil count (p = 0.03) and serum IgE (p = 0.043) remained significantly lower in the "high" sRAGE group. Children with asthma and high levels of BAL sRAGE have lower serum eosinophil and IgE levels. These findings are consistent with the hypothesis that sRAGE may act as a decoy receptor by binding ligands that normally interact with mRAGE.

A Quality Improvement Project to Improve Documentation and Awareness of Limitations of Life-Sustaining Therapies.

PURPOSE: Poor documentation and understanding of the limitations of life-sustaining therapies upon admission to the pediatric intensive care unit (PICU) can result in moral distress for both providers and families. Limitations of life-sustaining treatments are often not documented and/or understood by members of the health care team. METHODS: We performed a quality improvement initiative to improve the care teams' understanding and paper documentation of the limitations of life-sustaining therapies in the PICU of a quaternary children's hospital from January 2018 to March 2019. We implemented a series of plan-do-study-act cycles, including initiation of an updated rounding tool that included limitations of interventions, in-person and electronic information sessions, and implementation of a visual bedside tool to remind providers when limitations were present. Pre- and postintervention surveys were administered. RESULTS: Nursing paper documentation of limitations of life-sustaining therapies increased sequentially from 0% to 88% during plan-do-study-act cycles. Creating a specific area to document limitations on the nursing sheet resulted in the most significant increase in documentation (36.6 points). Nurses reported that they "always" document limitations, which increased from 10% to 38%. The percentage of nurses who understood patients' intervention limitations increased from 28% to 33%. CONCLUSIONS: Limitations of life-sustaining therapies in the PICU are nuanced and involve multiple stakeholders. Nursing education and designation of a section of intervention limitations in nursing daily goal paper documentation can increase comfort with therapeutic limitations in the PICU. Future studies should explore impacts on patient care and serve as a framework for the ultimate goal of improving documentation of care limitations and code status in the electronic medical record.

Retinoids regulate TGFbeta signaling at the level of Smad2 phosphorylation and nuclear accumulation.

Indirect regulation of transforming growth factor (TGF)-beta signaling by retinoids occurs on a long-term timescale, secondary to transcriptional events. Studies by our group show loss of retinoid X receptor (RXR) alpha results in increased TGFbeta2 in the midgestational heart, which may play a role in the cardiac defects seen in this model [S.W. Kubalak, D.R. Hutson, K.K. Scott and R.A. Shannon, Elevated transforming growth factor beta2 enhances apoptosis and contributes to abnormal outflow tract and aortic sac development in retinoic X receptor alpha knockout embryos, Development 129 (2002) 733-746.]. Acute and direct interactions between retinoid and TGFbeta signaling, however, are not clearly understood. Treatment of dispersed hearts and NIH3T3 cells for 1 h with TGFbeta and retinoids (dual treatment) resulted in increased phosphorylated Smad2 and Smad3 when compared to treatment with TGFbeta alone. Of all dual treatments, those with the RXR agonist Bexarotene, resulted in the highest level of phosphorylated Smad2, a 7-fold increase over TGFbeta2 alone. Additionally, during dual treatment phosphorylation of Smad2 occurs via the TGFbeta type I receptor but not by increased activation of the receptor. As loss of RXRalpha results in increased levels of Smad2 phosphorylation in response to TGFbeta treatment and since nuclear accumulation of phosphorylated Smad2 is decreased during dual treatment, we propose that RXRalpha directly regulates the activities of Smad2. These data show retinoid signaling influences the TGFbeta pathway in an acute and direct manner that has been unappreciated until now.

The expanding role for retinoid signaling in heart development.

The importance of retinoid signaling during cardiac development has long been appreciated, but recently has become a rapidly expanding field of research. Experiments performed over 50 years ago showed that too much or too little maternal intake of vitamin A proved detrimental for embryos, resulting in a cadre of predictable cardiac developmental defects. Germline and conditional knockout mice have revealed which molecular players in the vitamin A signaling cascade are potentially responsible for regulating specific developmental events, and many of these molecules have been temporally and spatially characterized. It is evident that intact and controlled retinoid signaling is necessary for each stage of cardiac development to proceed normally, including cardiac lineage determination, heart tube formation, looping, epicardium formation, ventricular maturation, chamber and outflow tract septation, and coronary arteriogenesis. This review summarizes many of the significant milestones in this field and particular attention is given to recently uncovered cross-talk between retinoid signaling and other developmentally significant pathways. It is our hope that this review of the role of retinoid signaling during formation, remodeling, and maturation of the developing heart will serve as a tool for future discoveries.

Evolutionary conservation of a functionally important backbone phosphate group critical for aminoacylation of histidine tRNAs.

All histidine tRNA molecules have an extra nucleotide, G-1, at the 5' end of the acceptor stem. In bacteria, archaea, and eukaryotic organelles, G-1 base pairs with C73, while in eukaryotic cytoplasmic tRNAHis, G-1 is opposite A73. Previous studies of Escherichia coli histidyl-tRNA synthetase (HisRS) have demonstrated the importance of the G-1:C73 base pair to tRNAHis identity. Specifically, the 5'-monophosphate of G-1 and the major groove amine of C73 are recognized by E. coli HisRS; these individual atomic groups each contribute approximately 4 kcal/mol to transition state stabilization. In this study, two chemically synthesized 24-nucleotide RNA microhelices, each of which recapitulates the acceptor stem of either E. coli or Saccharomyces cervisiae tRNAHis, were used to facilitate an atomic group "mutagenesis" study of the -1:73 base pair recognition by S. cerevisiae HisRS. Compared with E. coli HisRS, microhelixHis is a much poorer substrate relative to full-length tRNAHis for the yeast enzyme. However, the data presented here suggest that, similar to the E. coli system, the 5' monophosphate of yeast tRNA(His) is critical for aminoacylation by yeast HisRS and contributes approximately 3 kcal/mol to transition state stability. The primary role of the unique -1:73 base pair of yeast tRNAHis appears to be to properly position the critical 5' monophosphate for interaction with the yeast enzyme. Our data also suggest that the eukaryotic HisRS/tRNAHis interaction has coevolved to rely less on specific major groove interactions with base atomic groups than the bacterial system.