Cystatin C adaptation in the first month of life

Je-Hyan Lee et al. have published a study on cystatin C concentrations in the first 30 days of life in 127 pre-term and 119 term neonates in this edition of Pediatric Nephrology, thereby closing a knowledge gap of detailed cystatin C concentrations beyond 72 h of life by day of life and by post-conceptional age. While the study objective has merit and a large number of measurements were included, there are some methodological limitations that bring the validity of the data into question as pure reference intervals for children up to 1 month of age, mostly because of the inclusion of patients that potentially could have an impaired glomerular filtration rate (GFR), for instance due to exposure to nephrotoxic drugs. We discuss the strengths and weaknesses of the study and outline an approach to definitely close this knowledge gap. We call for a worldwide collaboration to use Box-Cox transformations similar to the methodology used with growth charts to calculate age-independent z-scores and percentiles of neonatal and infant markers of GFR. This could also lead to better definitions of acute kidney injury in infants if GFR markers cross the percentiles based on post-conceptional or chronological age. © 2013 IPNA

Comparison of clinical and biochemical markers of dehydration with the clinical dehydration scale in children: A case comparison trial

Background: The clinical dehydration scale (CDS) is a quick, easy-to-use tool with 4 clinical items and a score of 1-8 that serves to classify dehydration in children with gastroenteritis as no, some or moderate/severe dehydration. Studies validating the CDS (Friedman JN) with a comparison group remain elusive. We hypothesized that the CDS correlates with a wide spectrum of established markers of dehydration, making it an appropriate and easy-to-use clinical tool.Methods: This study was designed as a prospective double-cohort trial in a single tertiary care center. Children with diarrhea and vomiting, who clinically required intravenous fluids for rehydration, were compared with minor trauma patients who required intravenous needling for conscious sedation. We compared the CDS with clinical and urinary markers (urinary electrolytes, proteins, ratios and fractional excretions) for dehydration in both groups using receiver operating characteristic (ROC) curves to determine the area under the curve (AUC).Results: We enrolled 73 children (male = 36) in the dehydration group and 143 (male = 105) in the comparison group. Median age was 32 months (range 3-214) in the dehydration and 96 months (range 2.6-214 months, p \u3c 0.0001) in the trauma group. Median CDS was 3 (range 0-8) within the dehydration group and 0 in the comparison group (p \u3c 0.0001). The following parameters were statistically significant (p \u3c 0.05) between the comparison group and the dehydrated group: difference in heart rate, diastolic blood pressure, urine sodium/potassium ratio, urine sodium, fractional sodium excretion, serum bicarbonate, and creatinine measurements. The best markers for dehydration were urine Na and serum bicarbonate (ROC AUC = 0.798 and 0.821, respectively). CDS was most closely correlated with serum bicarbonate (Pearson r = -0.3696, p = 0.002).Conclusion: Although serum bicarbonate is not the gold standard for dehydration, this study provides further evidence for the usefulness of the CDS as a dehydration marker in children.Trial registration: Registered at ClinicalTrials.gov (NCT00462527) on April 18, 2007. © 2014 Tam et al.; licensee BioMed Central Ltd

Quantitative MRI in patients with gluteal tendinopathy and asymptomatic volunteers : initial results on T1- and T2*-mapping diagnostic accuracy and correlation with clinical assessment

Dans le cadre du programme SharedIt de Springer Nature, une version de l'article est accessible gratuitement, en lecture seule, à cette adresse : https://rdcu.be/cjHMSObjective To determine if T1- and T2*-mapping of the gluteal tendons can discriminate between participants with and without clinical findings of gluteal tendinopathy (GT) and if they correlate with clinical assessment. Materials and methods This prospective study was conducted between January and December 2016. MRI of the hip included spin echo, short-T1 inversion recovery, variable-flip angle, and variable echo-time gradient echo sequences. MRI studies were reviewed independently by two radiologists. Two other readers segmented the gluteal tendons and T1, mono- (T2*m) and biexponential T2* (short (T2*s) and long (T2*l) components) were computed. Results Ten participants with GT (median age; interquartile range: 63 (57–67) years, all women) and 9 participants without GT (57 (55–59) years, 8 women) (P = 0.06) were enrolled. The sensitivity and specificity of reader 1 for disease classification were 40% (95% confidence interval (CI): 17–61%) and 70% (CI: 47–91%), and those of reader 2 were 70% (CI: 43–86%) and 80% (CI: 53–96%), with fair inter-reader agreement (Kappa = .38). T1 values could not discriminate between the two groups. The gluteal tendons T2*m and T2*s showed diagnostic accuracy ranging from .80 to .89. The posterior gluteus medius tendon T2*m and T2*s respectively showed sensitivity and specificity of 90%, and strong correlation (Spearman’s rho = −.71; P = 0.02) with the Lower Extremity Functional Scale score. Conclusion Quantitative MRI could help gain new insight into healthy and diseased gluteal tendons to allow better diagnosis and treatment stratification for patients

Utilisation of Mucin Glycans by the Human Gut Symbiont Ruminococcus gnavus Is Strain-Dependent

Commensal bacteria often have an especially rich source of glycan-degrading enzymes which allow them to utilize undigested carbohydrates from the food or the host. The species Ruminococcus gnavus is present in the digestive tract of ≥90% of humans and has been implicated in gut-related diseases such as inflammatory bowel diseases (IBD). Here we analysed the ability of two R. gnavus human strains, E1 and ATCC 29149, to utilize host glycans. We showed that although both strains could assimilate mucin monosaccharides, only R. gnavus ATCC 29149 was able to grow on mucin as a sole carbon source. Comparative genomic analysis of the two R. gnavus strains highlighted potential clusters and glycoside hydrolases (GHs) responsible for the breakdown and utilization of mucin-derived glycans. Transcriptomic and functional activity assays confirmed the importance of specific GH33 sialidase, and GH29 and GH95 fucosidases in the mucin utilisation pathway. Notably, we uncovered a novel pathway by which R. gnavus ATCC 29149 utilises sialic acid from sialylated substrates. Our results also demonstrated the ability of R. gnavus ATCC 29149 to produce propanol and propionate as the end products of metabolism when grown on mucin and fucosylated glycans. These new findings provide molecular insights into the strain-specificity of R. gnavus adaptation to the gut environment advancing our understanding of the role of gut commensals in health and disease

Integrated immunovirological profiling validates plasma SARS-CoV-2 RNA as an early predictor of COVID-19 mortality.

peer reviewedDespite advances in COVID-19 management, identifying patients evolving toward death remains challenging. To identify early predictors of mortality within 60 days of symptom onset (DSO), we performed immunovirological assessments on plasma from 279 individuals. On samples collected at DSO11 in a discovery cohort, high severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) viral RNA (vRNA), low receptor binding domain–specific immunoglobulin G and antibody-dependent cellular cytotoxicity, and elevated cytokines and tissue injury markers were strongly associated with mortality, including in patients on mechanical ventilation. A three-variable model of vRNA, with predefined adjustment by age and sex, robustly identified patients with fatal outcome (adjusted hazard ratio for log-transformed vRNA = 3.5). This model remained robust in independent validation and confirmation cohorts. Since plasma vRNA’s predictive accuracy was maintained at earlier time points, its quantitation can help us understand disease heterogeneity and identify patients who may benefit from new therapies

SARS-CoV-2 susceptibility and COVID-19 disease severity are associated with genetic variants affecting gene expression in a variety of tissues

Variability in SARS-CoV-2 susceptibility and COVID-19 disease severity between individuals is partly due to genetic factors. Here, we identify 4 genomic loci with suggestive associations for SARS-CoV-2 susceptibility and 19 for COVID-19 disease severity. Four of these 23 loci likely have an ethnicity-specific component. Genome-wide association study (GWAS) signals in 11 loci colocalize with expression quantitative trait loci (eQTLs) associated with the expression of 20 genes in 62 tissues/cell types (range: 1:43 tissues/gene), including lung, brain, heart, muscle, and skin as well as the digestive system and immune system. We perform genetic fine mapping to compute 99% credible SNP sets, which identify 10 GWAS loci that have eight or fewer SNPs in the credible set, including three loci with one single likely causal SNP. Our study suggests that the diverse symptoms and disease severity of COVID-19 observed between individuals is associated with variants across the genome, affecting gene expression levels in a wide variety of tissue types

AVONET: morphological, ecological and geographical data for all birds

Functional traits offer a rich quantitative framework for developing and testing theories in evolutionary biology, ecology and ecosystem science. However, the potential of functional traits to drive theoretical advances and refine models of global change can only be fully realised when species‐level information is complete. Here we present the AVONET dataset containing comprehensive functional trait data for all birds, including six ecological variables, 11 continuous morphological traits, and information on range size and location. Raw morphological measurements are presented from 90,020 individuals of 11,009 extant bird species sampled from 181 countries. These data are also summarised as species averages in three taxonomic formats, allowing integration with a global phylogeny, geographical range maps, IUCN Red List data and the eBird citizen science database. The AVONET dataset provides the most detailed picture of continuous trait variation for any major radiation of organisms, offering a global template for testing hypotheses and exploring the evolutionary origins, structure and functioning of biodiversity

Health relevance of the modification of low grade inflammation in ageing (inflammageing) and the role of nutrition

Ageing of the global population has become a public health concern with an important socio-economic dimension. Ageing is characterized by an increase in the concentration of inflammatory markers in the bloodstream, a phenomenon that has been termed "inflammageing". The inflammatory response is beneficial as an acute, transient reaction to harmful conditions, facilitating the defense, repair, turnover and adaptation of many tissues. However, chronic and low grade inflammation is likely to be detrimental for many tissues and for normal functions. We provide an overview of low grade inflammation (LGI) and determine the potential drivers and the effects of the "inflamed" phenotype observed in the elderly. We discuss the role of gut microbiota and immune system crosstalk and the gut-brain axis. Then, we focus on major health complications associated with LGI in the elderly, including mental health and wellbeing, metabolic abnormalities and infections. Finally, we discuss the possibility of manipulating LGI in the elderly by nutritional interventions. We provide an overview of the evidence that exists in the elderly for omega-3 fatty acid, probiotic, prebiotic, antioxidant and polyphenol interventions as a means to influence LGI. We conclude that slowing, controlling or reversing LGI is likely to be an important way to prevent, or reduce the severity of, age-related functional decline and the onset of conditions affecting health and well-being; that there is evidence to support specific dietary interventions as a strategy to control LGI; and that a continued research focus on this field is warranted

A first update on mapping the human genetic architecture of COVID-19

peer reviewe

Regards croisés sur la rétroaction et le débriefing : accompagner, former et professionnaliser

Comprend des références bibliographique