Biomarkers in Exhaled Breath Condensate Are Not Predictive for Pulmonary Exacerbations in Children with Cystic Fibrosis: Results of a One-Year Observational Study

BackgroundCystic Fibrosis (CF) is characterized by chronically inflamed airways, and inflammation even increases during pulmonary exacerbations. These adverse events have an important influence on the well-being, quality of life, and lung function of patients with CF. Prediction of exacerbations by inflammatory markers in exhaled breath condensate (EBC) combined with early treatment may prevent these pulmonary exacerbations and may improve the prognosis.AimTo investigate the diagnostic accuracy of a set of inflammatory markers in EBC to predict pulmonary exacerbations in children with CF.MethodsIn this one-year prospective observational study, 49 children with CF were included. During study visits with an interval of 2 months, a symptom questionnaire was completed, EBC was collected, and lung function measurements were performed. The acidity of EBC was measured directly after collection. Inflammatory markers interleukin (IL)-6, IL-8, tumor necrosis factor α (TNF-α), and macrophage migration inhibitory factor (MIF) were measured using high sensitivity bead based flow immunoassays. Pulmonary exacerbations were recorded during the study and were defined in two ways. The predictive power of inflammatory markers and the other covariates was assessed using conditionally specified models and a receiver operating characteristic curve (SAS version 9.2). In addition, k-nearest neighbors (KNN) algorithm was applied (SAS version 9.2).ResultsSixty-five percent of the children had one or more exacerbations during the study. The conditionally specified models showed an overall correct prediction rate of 55%. The area under the curve (AUC) was equal to 0.62. The results obtained with the KNN algorithm were very similar.ConclusionAlthough there is some evidence indicating that the predictors outperform random guessing, the general diagnostic accuracy of EBC acidity and the EBC inflammatory markers IL-6, IL-8, TNF-α and MIF is low. At present it is not possible to predict pulmonary exacerbations in children with CF with the chosen biomarkers and the method of EBC analysis. The biochemical measurements of EBC markers should be improved and other techniques should be considered.     

The Enzymatic Paradox of Yeast Arginyl-tRNA Synthetase: Exclusive Arginine Transfer Controlled by a Flexible Mechanism of tRNA Recognition

Identity determinants are essential for the accurate recognition of transfer RNAs by aminoacyl-tRNA synthetases. To date, arginine determinants in the yeast Saccharomyces cerevisiae have been identified exclusively in vitro and only on a limited number of tRNA Arginine isoacceptors. In the current study, we favor a full cellular approach and expand the investigation of arginine determinants to all four tRNA Arg isoacceptors. More precisely, this work scrutinizes the relevance of the tRNA nucleotides at position 20, 35 and 36 in the yeast arginylation reaction. We built 21 mutants by site-directed mutagenesis and tested their functionality in YAL5, a previously engineered yeast knockout deficient for the expression of tRNA Arg CCG. Arginylation levels were also monitored using Northern blot. Our data collected in vivo correlate with previous observations. C35 is the prominent arginine determinant followed by G36 or U36 (G/U36). In addition, although there is no major arginine determinant in the D loop, the recognition of tRNA Arg ICG relies to some extent on the nucleotide at position 20. This work refines the existing model for tRNA Arg recognition. Our observations indicate that yeast Arginyl-tRNA synthetase (yArgRS) relies on distinct mechanisms to aminoacylate the four isoacceptors. Finally, according to our refined model, yArgRS is able to accommodate tRNA Arg scaffolds presenting N34, C/G35 and G/A/U36 anticodons while maintaining specificity. We discuss the mechanistic and potential physiological implications of these findings.     

Discrepancies between Patients’ Preferences and Educational Programs on Oral Anticoagulant Therapy: A Survey in Community Pharmacies and Hospital Consultations

Background

Oral anticoagulation therapy is increasingly used for the prevention and treatment of thromboembolic complications in various clinical situations. Nowadays, education programs for patients treated with anticoagulants constitute an integrated component of their management. However, such programs are usually based on the healthcare providers’ perceptions of what patients should know, rather than on patients’ preferences.

Objective

To investigate patients’ viewpoints on educational needs and preferred modalities of information delivery.

Methods

We conducted an observational study based on a self-administered questionnaire. To explore several profiles of patients, the study was designed for enrolling patients in two settings: during outpatient consultations in a cardiology department (Saint Antoine Hospital, Paris, France) and in community pharmacies throughout France.

Results

Of the 371 patients who completed the questionnaire, 187 (50.4%) were recruited during an outpatient consultation and 184 (49.6%) were recruited in community pharmacies. 84.1% of patients were receiving a vitamin K antagonist and 15.6% a direct oral anticoagulant. Patients ranked 16 of 21 (76.2%) questionnaire items on information about their treatment as important or essential; information on adverse effects of treatment was the highest ranked domain (mean score 2.38, 95% CI 2.30–2.46). Pharmacists (1.69, 1.58–1.80), nurses (1.05, 0.95–1.16), and patient associations (0.36, 0.29–0.44), along with group sessions (0.85, 0.75–0.95), the internet (0.77, 0.67–0.88), and delivery of material at the patient’s home (1.26, 1.14–1.38), were ranked poorly in terms of delivering educational material.

Conclusion

This study revealed substantial discrepancies between patient preferences and current educational programs. These findings should be useful for tailoring future educational programs that are better adapted to patients, with a potential associated enhancement of their effectiveness.     

Enzymatic degradation of the antibiotic sulfamethazine by using crude extracts of different halophytic plants

Abstract

The biodegradation of the antibiotic sulfamethazine (SMT) by using different crude extracts of halophytes was investigated. For this purpose, crude water extracts of the halophytes Chenopodium quinoa, Sesuvium portulacastrum, and Tripolium pannonicum were prepared. Different amounts of SMT were added to the different extracts (final concentration of 1, 2, and 5?mg L^?1) and incubated at 37?°C. Crude extracts of T. pannonicum were further used to evaluate the degradation rate over time. In order to evaluate the influence of endophytic or naturally plant-associated microorganisms on the biodegradation of SMT, extracts from plants grown in sterile and non-sterile conditions were compared. SMT was analyzed by liquid chromatography coupled to positive ion electrospray mass spectrometry (ESI LC-MS). Based on the findings, crude extracts of T. pannonicum have a high potential to biodegrade SMT with a decrease up to 85.4% (4.27?±?0.10?mg L^?1) from an initial concentration of 5?mg L^?1. The lowest activity was obtained using extracts of C. quinoa with degradation of 4.5%. Extracts of plants cultivated under sterile and non-sterile conditions do not have any significant difference in SMT degradation. Therefore, microorganisms and their enzymatic activities do not seem to play a significant role during this process.     

Invasive plants negatively impact native,but not exotic,animals

Despite our growing understanding of the impacts of invasive plants on ecosystem structure and function, important gaps remain, including whether native and exotic species respond differently to plant invasion. This would elucidate basic ecological interactions and inform management. We performed a meta‐analytic review of the effects of invasive plants on native and exotic resident animals. We found that invasive plants reduced the abundance of native, but not exotic, animals. This varied by animal phyla, with invasive plants reducing the abundance of native annelids and chordates, but not mollusks or arthropods. We found dissimilar impacts among “wet” and “dry” ecosystems, but not among animal trophic levels. Additionally, the impact of invasive plants increased over time, but this did not vary with animal nativity. Our review found that no studies considered resident nativity differences, and most did not identify animals to species. We call for more rigorous studies of invaded community impacts across taxa, and most importantly, explicit consideration of resident biogeographic origin. We provide an important first insight into how native and exotic species respond differently to invasion, the consequences of which may facilitate cascading trophic disruptions further exacerbating global change consequences to ecosystem structure and function.     

Ecomorphological convergence in Eleutherodactylus frogs: a case of replicate radiations in the Caribbean

Replicate radiations, the repeated multiplication of species associated with ecological divergence, have attracted much attention and generated as much debate. Due to the few well‐studied cases, it remains unclear whether replicate radiations are an exceptional result of evolution or a relatively common example of the power of adaptation by natural selection. We examined the case of Eleutherodactylus frogs, which radiated in the Caribbean islands resulting in more than 160 species that occupy very diverse habitats. A time‐calibrated phylogeny revealed that these frogs independently diversified on all larger islands producing species that occupy a broad range of microhabitats in different islands. Using phylogenetic comparative methods, we found an association between morphological traits and particular microhabitats, and for most microhabitats detected significant morphological convergence. Our results indicate Caribbean Eleutherodactylus are a novel example of replicate radiations, and highlight the predictability of evolutionary processes, as similar ecological opportunities can lead to similar outcomes.