Reproducibility of diabetes quality of care indicators as reported by patients and physicians

Introduction: Self-report of diabetes care has moderate validity and is prone to under- and over-reporting. We assessed reproducibility of a range of processes and outcomes of diabetes care as reported by patients and physicians. Methods: In a Swiss community-based survey, patients with diabetes and physicians independently reported past 12 months processes of care (HbA1c, lipids, microalbuminuria, blood pressure, weight, foot and eye examinations) and last measured values of HbA1c, height, weight and blood pressure. For dichotomous variables, we assessed reliability by Cohen's kappa and agreement by uniform kappa. For continuous measures, we used Lin's concordance correlation coefficient and limits of agreement, respectively. Results: Mean age of the 210 patients was 65 years; 40% were women, and 51% had diabetes for >10 years. Agreement was good for recommended processes of care such as blood pressure (uniform kappa = 0.94), HbA1c (0.93), weight (0.88) and lipid (0.78), but lower for microalbuminuria, foot and eye examinations (all <0.50). Cohen's kappa values were all low (<0.25). Comparisons of reported continuous variables showed large limits of agreement for height (±6 cm) and weight (8-10 kg) despite high concordance correlation coefficients (0.93 and 0.97). Concordance correlation coefficients were smaller for HbA1c (0.72) and blood pressure (0.5-0.6), with large limits of agreement (±2% and ±25 mmHg). Conclusion: While agreement of routine processes of care was good, agreement was less satisfactory for microalbuminuria, foot and eye examinations. Reports of continuous outcomes yielded good reliability but too wide limits of agreement. Quality of care evaluation relying on self-report only should be made cautiousl

The phenome-wide distribution of genetic variance

A general observation emerging from estimates of additive genetic variance in sets of functionally or developmentally related traits is that much of the genetic variance is restricted to few trait combinations as a consequence of genetic covariance among traits. While this biased distribution of genetic variance among functionally related traits is now well documented, how it translates to the broader phenome and therefore any trait combination under selection in a given environment is unknown. We show that 8,750 gene expression traits measured in adult male Drosophila serrata exhibit widespread genetic covariance among random sets of five traits, implying that pleiotropy is common. Ultimately, to understand the phenome-wide distribution of genetic variance, very large additive genetic variance-covariance matrices (G) are required to be estimated. We draw upon recent advances in matrix theory for completing high-dimensional matrices to estimate the 8,750-trait G and show that large numbers of gene expression traits genetically covary as a consequence of a single genetic factor. Using gene ontology term enrichment analysis, we show that the major axis of genetic variance among expression traits successfully identified genetic covariance among genes involved in multiple modes of transcriptional regulation. Our approach provides a practical empirical framework for the genetic analysis of high-dimensional phenome-wide trait sets and for the investigation of the extent of high-dimensional genetic constraint

Attention deficit hyperactivity disorder symptoms and cannabis use after 1 year among students of the i-Share cohort

ADHD; Cannabis; StudentsTDAH; Canabis; EstudiantesTDAH; Cànnabis; EstudiantsBackground Cannabis use in university students is associated with academic achievement failure and health issues. The objective of the study was to evaluate the association between attention deficit hyperactivity disorder (ADHD) symptoms and cannabis use after 1 year among students according to previous cannabis use. Methods Students in France were recruited from February 2013 to July 2020 in the i-Share cohort. 4,270 participants were included (2,135 who never used cannabis at inclusion and 2,135 who did). The Adult ADHD Self-Report Scale (ASRS) was used to assess ADHD symptoms at inclusion. Cannabis use frequency was evaluated 1 year after inclusion. Multinomial regressions were conducted to assess the association between inclusion ADHD symptoms and cannabis use after 1 year. Results Increase in ASRS scores was linked with a greater probability to use cannabis after 1 year and to have a higher cannabis use frequency (once a year—once a month adjusted odds ratio [OR]: 1.24 (1.15–1.34), more than once a month adjusted OR: 1.43 (1.27–1.61)). Among participants who never used cannabis at inclusion, this association disappeared (once a year—once a month adjusted OR: 1.15 (0.95–1.39), more than once a month adjusted OR: 1.16 (0.67–2)) but remained in participants who ever used cannabis at inclusion (once a year—once a month adjusted OR: 1.17 (1.06–1.29), more than once a month adjusted OR: 1.35 (1.18–1.55)). Conclusions High levels of ADHD symptoms in students could lead to continued cannabis use rather than new initiations.The preparation and initiation of the i-Share project was funded by the program ‘Invest for future’ (reference ANR-10-COHO-05). The i-Share Project is currently supported by an unrestricted grant from the Nouvelle-Aquitaine Regional Council (Conseil Régional Nouvelle-Aquitaine) (grant number: 4370420) and by the Bordeaux ‘Initiatives d’excellence’ (IdEx) program of the University of Bordeaux (ANR-10-IDEX-03-02). It has also received grants from the Nouvelle-Aquitaine Regional Health Agency (Agence Régionale de Santé Nouvelle-Aquitaine, grant N°6066R-8 R-8), Public Health France (Santé Publique France, grant number: 19DPPP023–0), the National Cancer Institute (Insitut national du cancer, grant number: INCa_11502), and the Medical Research Foundation (Fondation pour la recherche)

An improved whole life cycle culture protocol for the hydrozoan genetic model Clytia hemisphaerica

The jellyfish species Clytia hemisphaerica (Cnidaria, Hydrozoa) has emerged as a new experimental model animal in the last decade. Favorable characteristics include a fully transparent body suitable for microscopy, daily gamete production and a relatively short life cycle. Furthermore, whole genome sequence assembly and efficient gene editing techniques using CRISPR/Cas9 have opened new possibilities for genetic studies. The quasi-immortal vegetatively-growing polyp colony stage provides a practical means to maintain mutant strains. In the context of developing Clytia as a genetic model, we report here an improved whole life cycle culture method including an aquarium tank system designed for culture of the tiny jellyfish form. We have compared different feeding regimes using Artemia larvae as food and demonstrate that the stage-dependent feeding control is the key for rapid and reliable medusa and polyp rearing. Metamorphosis of the planula larvae into a polyp colony can be induced efficiently using a new synthetic peptide. The optimized procedures detailed here make it practical to generate genetically modified Clytia strains and to maintain their whole life cycle in the laboratory

The effects of time-restricted eating and weight loss on bone metabolism and health: a 6-month randomized controlled trial.

OBJECTIVE This study explored the impact of time-restricted eating (TRE) versus standard dietary advice (SDA) on bone health. METHODS Adults with ≥1 component of metabolic syndrome were randomized to TRE (ad libitum eating within 12 hours) or SDA (food pyramid brochure). Bone turnover markers and bone mineral content/density by dual energy x-ray absorptiometry were assessed at baseline and 6-month follow-up. Statistical analyses were performed in the total population and by weight loss response. RESULTS In the total population (n = 42, 76% women, median age 47 years [IQR: 31-52]), there were no between-group differences (TRE vs. SDA) in any bone parameter. Among weight loss responders (≥0.6 kg weight loss), the bone resorption marker β-carboxyterminal telopeptide of type I collagen tended to decrease after TRE but increase after SDA (between-group differences p = 0.041), whereas changes in the bone formation marker procollagen type I N-propeptide did not differ between groups. Total body bone mineral content decreased after SDA (p = 0.028) but remained unchanged after TRE (p = 0.31) in weight loss responders (between-group differences p = 0.028). Among nonresponders (<0.6 kg weight loss), there were no between-group differences in bone outcomes. CONCLUSIONS TRE had no detrimental impact on bone health, whereas, when weight loss occurred, it was associated with some bone-sparing effects compared with SDA

Somaclonal variation in clonal crops: containing the bad, exploring the good

Somaclonal variation describes random cellular changes in plants regenerated through tissue culture. It occurs in certain crops that undergo micropropagation and has been recorded in different explant sources, from leaves and shoots to meristems and embryos. In banana (Musa spp.), a clonal crop conserved in vitro, somaclonal variation has been observed after prolonged periods in tissue culture, resulting from an increase in subcultures performed on a given clone. According to scientific literature, variants, or off-types, often show characteristics such as abnormal growth and flower or fruit defects in frequencies ranging from 1% to 32%. This variation poses a problem for gene bank managers, whose mandate is to maintain the genetic integrity of their collections for research and breeding. In the case of the Bioversity International Musa Germplasm Transit Centre (ITC), stress during the in vitro process is minimized by various techniques and plants are regenerated after 10 years, making it a long and costly process. Identifying somaclonal variation at an early stage would be an ideal solution; however, this requires suitable molecular markers. Recent studies revealed that techniques such as direct DNA sequencing and single nucleotide olymorphisms (SNPs) are able to detect the underlying factors of somaclonal variation and are becoming more accessible. On the other hand, somaclonal variation can be beneficial as it allows the natural development of new varieties and supplies genetic stocks used for future genetic studies. Harnessing the diversity of somaclones is easier, faster and cheaper compared with other methods of crop improvement, al though it is also less predictable. So far, variants of crops such as apple, strawberry, potato and banana have been successfully adopted into global markets. In this chapter, we will discuss how to minimize the adverse effects of somaclonal variation while maximizing its benefits for greater crop diversity, with a particular focus on banana

The Gut Microbiota Regulates Intestinal CD4 T Cells Expressing RORγt and Controls Metabolic Disease

SummaryA high-fat diet (HFD) induces metabolic disease and low-grade metabolic inflammation in response to changes in the intestinal microbiota through as-yet-unknown mechanisms. Here, we show that a HFD-derived ileum microbiota is responsible for a decrease in Th17 cells of the lamina propria in axenic colonized mice. The HFD also changed the expression profiles of intestinal antigen-presenting cells and their ability to generate Th17 cells in vitro. Consistent with these data, the metabolic phenotype was mimicked in RORγt-deficient mice, which lack IL17 and IL22 function, and in the adoptive transfer experiment of T cells from RORγt-deficient mice into Rag1-deficient mice. We conclude that the microbiota of the ileum regulates Th17 cell homeostasis in the small intestine and determines the outcome of metabolic disease

Handling the heterogeneity of genomic and metabolic networks data within flexible workflows with the PADMet toolbox

National audienceA main challenge of the era of fast and massive genome sequencing is to transform sequences into biological knowledge. The reconstruction of metabolic networks that include all biochemical reactions of a cell is a way to understand physiology interactions from genomic data. In 2010, Thiele and Palsson described a general protocol enabling the reconstruction of high-quality metabolic networks. Since then several approaches have been implemented for this purpose. They all rely mainly on drafting a first metabolic network from genome annotations and orthology information followed by a gap-filling step. More precisely, in the case of exotic species the lack of good annotations and poor biological information result in incomplete networks. Reference databases of metabolic reactions guide the filling process in order to check whether adding reactions to a network allows compounds of interest to be produced from a given growth media. As a final objective, as soon as the network is considered to be complete enough, functional studies are undergone, often relying on the constraint-based paradigm derived from the Flux Balance Analysis (FBA) framework (Orth et al., 2010). The high diversity of input files and tools required to run any metabolic networks reconstruction protocol represents an important drawback. In addition, most approaches require reference metabolic networks of a template organism. Dictionaries mapping the reference metabolic databases to the gene identifiers corresponding to the studied organism may be required. As a main issue, it appears very difficult to ensure that input files agree among them. Such a heterogeneity produces loss of information during the use of the protocols and generates uncertainty in the final metabolic model. Here we introduce the PADMet-toolbox which allows conciliating genomic and metabolic network information. The toolbox centralizes all this information in a new graph-based format: PADMet (PortAble Database for Metabolism) and provides methods to import, update and export information. For the sake of illustration, the toolbox was used to create a workflow, named AuReMe, aiming to produce high-quality genome-scale metabolic networks and eventually input files to feed most platforms involved in metabolic network analyses. We applied this approach to two exotic organisms and our results evidenced the need of combining approaches and reconciling information to obtain a functional metabolic network to produce biomass