Triglycerides and glycated hemoglobin for screening insulin resistance in obese patients

International audienceOBJECTIVE: Assessment of insulin resistance (IR) is essential in non-diabetic patients with obesity. Thus study aims to identify the best determinants of IR and to propose an original approach for routine assessment of IR in obesity. DESIGN AND PATIENTS: All adult with obesity defined by a body mass index >=30kg/m2, evaluated in the Nutrition Department between January 2010 and January 2015 were included in this cross-sectional study. Patients with diabetes were excluded. IR was diagnosed according to the HOMA-IR. Based on a logistic regression, we determined a composite score of IR. We then tested the variables with a principal component analysis and a hierarchical clustering analysis. RESULTS: A total of 498 patients with obesity were included. IR was associated with grade III obesity (OR=2.6[1.6-4.4], p\textless0.001), HbA1c>=5.7% (OR=2.6[1.7-4.0], p\textless0.001), hypertriglyceridemia \textgreater1.7mmol/l (OR=3.0[2.0-4.5], p\textless0.001) and age (OR=0.98[0.96-0.99], p=0.002). Exploratory visual analysis using factor map and clustering analysis revealed that lipid and carbohydrates metabolism abnormalities were correlated with insulin resistance but not with excessive fat accumulation and low-grade inflammation. CONCLUSIONS: Our results highlight the interest of simple blood tests such as HbA1c and triglyceride determination, which associated with BMI, may be widely available tools for screening IR in obese patients

A longitudinal study of mental health before and during COVID-19 lockdown in the French population

BACKGROUND: The impact of general population lockdown implemented in the face of the COVID-19 epidemic needs to be evaluated. We describe here a longitudinal study on the mental health of adults in France. METHODS: We did a secondary analysis of a web-based cohort, initially set up to study home and leisure injuries, in order to measure the consequences of the national lockdown implemented in France from 17 March 2020 to 11 May 2020, and to assess potential vulnerability and resilience factors. Eligible participants were invited to answer an online questionnaire designed to assess their living conditions and health during lockdown. Comparisons were done with answers provided 4.8 years earlier on average. RESULTS: On 15th April 2020, we sent email invitations to 9598 participants recruited between November 2014 and December 2019 and 1237 volunteers took part in the study by completing the online questionnaire. The proportion of those with anxiety symptoms markedly increased from 17.3 to 20.1%. The average self-rated level of mental health decreased from 7.77 to 7.58. Women, the elderly and the youngest appeared to be more vulnerable. A small living space (less than 30 m(2)) was associated with an increase in depression symptoms (PHQ-9 score), and poorer self-rated physical health at recruitment was associated with an increase in anxiety symptoms (GAD-7 score). On the contrary, the average self-rated level of physical health markedly increased from 7.44 to 7.94 between recruitment and lockdown, and the proportion of those who reported a level of 9 or 10 jumped from 25.7% at recruitment to 43.1% during lockdown. CONCLUSIONS: Mental health deteriorated during lockdown in France during the 2020 COVID-19 crisis. Overall, self-rated physical health improved but those who experienced a worse physical health were more likely to report anxiety symptoms

Metabolic selection of a homologous recombination-mediated gene loss protects Trypanosoma brucei from ROS production by glycosomal fumarate reductase

The genome of trypanosomatids rearranges by using repeated sequences as platforms for amplification or deletion of genomic segments. These stochastic recombination events have a direct impact on gene dosage and foster the selection of adaptive traits in response to environmental pressure. We provide here such an example by showing that the phosphoenolpyruvate carboxykinase (PEPCK) gene knockout (Δpepck) leads to the selection of a deletion event between two tandemly arranged fumarate reductase (FRDg and FRDm2) genes to produce a chimeric FRDg-m2 gene in the Δpepck∗ cell line. FRDg is expressed in peroxisome-related organelles, named glycosomes, expression of FRDm2 has not been detected to date, and FRDg-m2 is nonfunctional and cytosolic. Re-expression of FRDg significantly impaired growth of the Δpepck∗ cells, but FRD enzyme activity was not required for this negative effect. Instead, glycosomal localization as well as the covalent flavinylation motif of FRD is required to confer growth retardation and intracellular accumulation of reactive oxygen species (ROS). The data suggest that FRDg, similar to Escherichia coli FRD, can generate ROS in a flavin-dependent process by transfer of electrons from NADH to molecular oxygen instead of fumarate when the latter is unavailable, as in the Δpepck background. Hence, growth retardation is interpreted as a consequence of increased production of ROS, and rearrangement of the FRD locus liberates Δpepck∗ cells from this obstacle. Interestingly, intracellular production of ROS has been shown to be required to complete the parasitic cycle in the insect vector, suggesting that FRDg may play a role in this proces

Genetics of venous thrombosis: insights from a new genome wide association study

Background: Venous Thrombosis (VT) is a common multifactorial disease associated with a major public health burden. Genetics factors are known to contribute to the susceptibility of the disease but how many genes are involved and their contribution to VT risk still remain obscure. We aimed to identify genetic variants associated with VT risk. Methodology/Principal Findings: We conducted a genome-wide association study (GWAS) based on 551,141 SNPs genotyped in 1,542 cases and 1,110 controls. Twelve SNPs reached the genome-wide significance level of 2.0×10−8 and encompassed four known VT-associated loci, ABO, F5, F11 and FGG. By means of haplotype analyses, we also provided novel arguments in favor of a role of HIVEP1, PROCR and STAB2, three loci recently hypothesized to participate in the susceptibility to VT. However, no novel VT-associated loci came out of our GWAS. Using a recently proposed statistical methodology, we also showed that common variants could explain about 35% of the genetic variance underlying VT susceptibility among which 3% could be attributable to the main identified VT loci. This analysis additionally suggested that the common variants left to be identified are not uniformly distributed across the genome and that chromosome 20, itself, could contribute to ∼7% of the total genetic variance. Conclusions/Significance: This study might also provide a valuable source of information to expand our understanding of biological mechanisms regulating quantitative biomarkers for VT

Biomedicines

Antibody-mediated rejection (ABMR) is the leading cause of allograft failure in kidney transplantation. Its histological hallmark is represented by lesions of glomerulitis i.e., inflammatory cells within glomeruli. Current therapies for ABMR fail to prevent chronic allograft damage i.e., transplant glomerulopathy, leading to allograft loss. We used laser microdissection of glomeruli from formalin-fixed allograft biopsies combined with mass spectrometry-based proteomics to describe the proteome modification of 11 active and 10 chronic active ABMR cases compared to 8 stable graft controls. Of 1335 detected proteins, 77 were deregulated in glomerulitis compared to stable grafts, particularly involved in cellular stress mediated by interferons type I and II, leukocyte activation and microcirculation remodeling. Three proteins extracted from this protein profile, TYMP, WARS1 and GBP1, showed a consistent overexpression by immunohistochemistry in glomerular endothelial cells that may represent relevant markers of endothelial stress during active ABMR. In transplant glomerulopathy, 137 proteins were deregulated, which favor a complement-mediated mechanism, wound healing processes through coagulation activation and ultimately a remodeling of the glomerular extracellular matrix, as observed by light microscopy. This study brings novel information on glomerular proteomics of ABMR in kidney transplantation, and highlights potential targets of diagnostic and therapeutic interest

Bone Biomarkers Help Grading Severity of Coronary Calcifications in Non Dialysis Chronic Kidney Disease Patients

BACKGROUND: Osteoprotegerin (OPG) and fibroblast growth factor-23 (FGF23) are recognized as strong risk factors of vascular calcifications in non dialysis chronic kidney disease (ND-CKD) patients. The aim of this study was to investigate the relationships between FGF23, OPG, and coronary artery calcifications (CAC) in this population and to attempt identification of the most powerful biomarker of CAC: FGF23? OPG? METHODOLOGY/PRINCIPAL FINDINGS: 195 ND-CKD patients (112 males/83 females, 70.8 [27.4-94.6] years) were enrolled in this cross-sectional study. All underwent chest multidetector computed tomography for CAC scoring. Vascular risk markers including FGF23 and OPG were measured. Logistic regression analyses were used to study the potential relationships between CAC and these markers. The fully adjusted-univariate analysis clearly showed high OPG (≥10.71 pmol/L) as the only variable significantly associated with moderate CAC ([100-400[) (OR = 2.73 [1.03;7.26]; p = 0.04). Such association failed to persist for CAC scoring higher than 400. Indeed, severe CAC was only associated with high phosphate fractional excretion (FEPO(4)) (≥38.71%) (OR = 5.47 [1.76;17.0]; p = 0.003) and high FGF23 (≥173.30 RU/mL) (OR = 5.40 [1.91;15.3]; p = 0.002). In addition, the risk to present severe CAC when FGF23 level was high was not significantly different when OPG was normal or high. Conversely, the risk to present moderate CAC when OPG level was high was not significantly different when FGF23 was normal or high. CONCLUSIONS: Our results strongly suggest that OPG is associated to moderate CAC while FGF23 rather represents a biomarker of severe CAC in ND-CKD patients

Odour Maps in the Brain of Butterflies with Divergent Host-Plant Preferences

Butterflies are believed to use mainly visual cues when searching for food and oviposition sites despite that their olfactory system is morphologically similar to their nocturnal relatives, the moths. The olfactory ability in butterflies has, however, not been thoroughly investigated. Therefore, we performed the first study of odour representation in the primary olfactory centre, the antennal lobes, of butterflies. Host plant range is highly variable within the butterfly family Nymphalidae, with extreme specialists and wide generalists found even among closely related species. Here we measured odour evoked Ca2+ activity in the antennal lobes of two nymphalid species with diverging host plant preferences, the specialist Aglais urticae and the generalist Polygonia c-album. The butterflies responded with stimulus-specific combinations of activated glomeruli to single plant-related compounds and to extracts of host and non-host plants. In general, responses were similar between the species. However, the specialist A. urticae responded more specifically to its preferred host plant, stinging nettle, than P. c-album. In addition, we found a species-specific difference both in correlation between responses to two common green leaf volatiles and the sensitivity to these compounds. Our results indicate that these butterflies have the ability to detect and to discriminate between different plant-related odorants

Human Herpesvirus 8 (HHV8) Sequentially Shapes the NK Cell Repertoire during the Course of Asymptomatic Infection and Kaposi Sarcoma

The contribution of innate immunity to immunosurveillance of the oncogenic Human Herpes Virus 8 (HHV8) has not been studied in depth. We investigated NK cell phenotype and function in 70 HHV8-infected subjects, either asymptomatic carriers or having developed Kaposi's sarcoma (KS). Our results revealed substantial alterations of the NK cell receptor repertoire in healthy HHV8 carriers, with reduced expression of NKp30, NKp46 and CD161 receptors. In addition, down-modulation of the activating NKG2D receptor, associated with impaired NK-cell lytic capacity, was observed in patients with active KS. Resolution of KS after treatment was accompanied with restoration of NKG2D levels and NK cell activity. HHV8-latently infected endothelial cells overexpressed ligands of several NK cell receptors, including NKG2D ligands. The strong expression of NKG2D ligands by tumor cells was confirmed in situ by immunohistochemical staining of KS biopsies. However, no tumor-infiltrating NK cells were detected, suggesting a defect in NK cell homing or survival in the KS microenvironment. Among the known KS-derived immunoregulatory factors, we identified prostaglandin E2 (PGE2) as a critical element responsible for the down-modulation of NKG2D expression on resting NK cells. Moreover, PGE2 prevented up-regulation of the NKG2D and NKp30 receptors on IL-15-activated NK cells, and inhibited the IL-15-induced proliferation and survival of NK cells. Altogether, our observations are consistent with distinct immunoevasion mechanisms that allow HHV8 to escape NK cell responses stepwise, first at early stages of infection to facilitate the maintenance of viral latency, and later to promote tumor cell growth through suppression of NKG2D-mediated functions. Importantly, our results provide additional support to the use of PGE2 inhibitors as an attractive approach to treat aggressive KS, as they could restore activation and survival of tumoricidal NK cells

Les nouvelles missions du pharmacien d’officine apportées par la loi Hôpital-Patient-Santé-Territoire, illustrées par l’entretien pharmaceutique des patients insuffisants respiratoires

La loi Hôpital-Patient-Santé-Territoire marque un changement sans précédent pour la profession de pharmacien d’officine. Le pharmacien se voit rajouter à ses obligations pré-existantes de nouvelles missions afin qu’il assure au mieux la prise en charge des patients en tant que professionnel de santé de proximité. Sa rémunération est aussi en cours de réforme. Le pharmacien ne sera plus payé au nombre de boîtes vendues mais en fonction de son activité, des services rendus à la population et selon des objectifs définis par les autorités. L’entretien pharmaceutique est l’une de ces nouveautés. Grâce à ce temps privilégié accordé aux patients, notamment ceux atteints de pathologies chroniques telles que l’asthme ou la broncho-pneumopathie chronique obstructive, le pharmacien aide l’insuffisant respiratoire à comprendre et contrôler au mieux sa maladie, afin qu’il en résulte un bénéfice pour le patient dans sa vie quotidienne et une économie pour le système de santé. La profession de pharmacien est donc appelée à évoluer pour qu’elle se tourne davantage vers le suivi du patient. C’est pourquoi l’officine doit se moderniser afin de s’adapter à tous ces changements et les intégrer au mieux dans son activité quotidienne