Effect of Sex and Prior Exposure to a Cafeteria Diet on the Distribution of Sex Hormones between Plasma and Blood Cells

It is generally assumed that steroid hormones are carried in the blood free and/or bound to plasma proteins. We investigated whether blood cells were also able to bind/carry sex-related hormones: estrone, estradiol, DHEA and testosterone. Wistar male and female rats were fed a cafeteria diet for 30 days, which induced overweight. The rats were fed the standard rat diet for 15 additional days to minimize the immediate effects of excess ingested energy. Controls were always kept on standard diet. After the rats were killed, their blood was used for 1) measuring plasma hormone levels, 2) determining the binding of labeled hormones to washed red blood cells (RBC), 3) incubating whole blood with labeled hormones and determining the distribution of label between plasma and packed cells, discounting the trapped plasma volume, 4) determining free plasma hormone using labeled hormones, both through membrane ultrafiltration and dextran-charcoal removal. The results were computed individually for each rat. Cells retained up to 32% estrone, and down to 10% of testosterone, with marked differences due to sex and diet (the latter only for estrogens, not for DHEA and testosterone). Sex and diet also affected the concentrations of all hormones, with no significant diet effects for estradiol and DHEA, but with considerable interaction between both factors. Binding to RBC was non-specific for all hormones. Estrogen distribution in plasma compartments was affected by sex and diet. In conclusion: a) there is a large non-specific RBC-carried compartment for estrone, estradiol, DHEA and testosterone deeply affected by sex; b) Prior exposure to a cafeteria (hyperlipidic) diet induced hormone distribution changes, affected by sex, which hint at sex-related structural differences in RBC membranes; c) We postulate that the RBC compartment may contribute to maintain free (i.e., fully active) sex hormone levels in a way similar to plasma proteins non-specific binding

Effect of Sex and Prior Exposure to a Cafeteria Diet on the Distribution of Sex Hormones between Plasma and Blood Cells

It is generally assumed that steroid hormones are carried in the blood free and/or bound to plasma proteins. We investigated whether blood cells were also able to bind/carry sex-related hormones: estrone, estradiol, DHEA and testosterone. Wistar male and female rats were fed a cafeteria diet for 30 days, which induced overweight. The rats were fed the standard rat diet for 15 additional days to minimize the immediate effects of excess ingested energy. Controls were always kept on standard diet. After the rats were killed, their blood was used for 1) measuring plasma hormone levels, 2) determining the binding of labeled hormones to washed red blood cells (RBC), 3) incubating whole blood with labeled hormones and determining the distribution of label between plasma and packed cells, discounting the trapped plasma volume, 4) determining free plasma hormone using labeled hormones, both through membrane ultrafiltration and dextran-charcoal removal. The results were computed individually for each rat. Cells retained up to 32% estrone, and down to 10% of testosterone, with marked differences due to sex and diet (the latter only for estrogens, not for DHEA and testosterone). Sex and diet also affected the concentrations of all hormones, with no significant diet effects for estradiol and DHEA, but with considerable interaction between both factors. Binding to RBC was non-specific for all hormones. Estrogen distribution in plasma compartments was affected by sex and diet. In conclusion: a) there is a large non-specific RBC-carried compartment for estrone, estradiol, DHEA and testosterone deeply affected by sex; b) Prior exposure to a cafeteria (hyperlipidic) diet induced hormone distribution changes, affected by sex, which hint at sex-related structural differences in RBC membranes; c) We postulate that the RBC compartment may contribute to maintain free (i.e., fully active) sex hormone levels in a way similar to plasma proteins non-specific binding

Influence of machine parameters on Ti-6-Al-4V small sized specimens made by laser metal deposition

International audienceThe present work is focused on one Additive Manufacturing (AM) process – Laser powder Metal Deposition (LMD-p) – and on one metallic alloy – Ti-6Al-4V. State of the art on LMD-p on Ti-6Al-4V alloy shows that three kinds of process parameters influence mechanical properties of building parts: raw materials (powder and substrate), machine parameters (Laser Power (P), Powder Flow (F) and Building Speed (V)), and building strategies (part orientation, waiting time between layers, etc.). Thus, this paper relates to first manufacturing investigations on small sized specimens (bead, wall and block) with the aim of providing a better knowledge about the first steps of manufacturing. Particularly, this paper is dedicated to the study of machine parameters (P, F and V).First, the influence of each machine parameter on 28 beads is studied separately. The geometrical aspect (high, width, dilution) of each bead is microscopically measured. Similarly, combinations of parameters (P/F, Energy Density and Powder Density) are introduced to increase parameters degree of freedom. First results show that P, V and F have a major influence on the beads’ geometry. In addition, a window process map is plotted and allows determining functional areas of machine parameters. From this map, walls (vertical superposition of one bead) are manufactured and microscopically observed. Functional sets of parameters from walls are selected and blocks can be built

Influence of machine parameters on Ti-6Al-4V small sized specimens made by Laser Metal Powder Deposition

International audienc

Prédiction de la réponse à la chimiothérapie des ostéosarcomes à partir des données radiomiques issues des IRM diagnostiques

International audienceIntroduction > L'ostéosarcome est la tumeur osseuse maligne la plus fréquente avant 25 ans. La réponse à la chimiothérapie néo-adjuvante influe la suite du traitement et est un facteur pronostique majeur. Il n'existe pas, actuellement, de moyens fiables de l'évaluer précocement. L'objectif de cette étude est de développer une méthode de prédiction de cette réponse à partir des données radiomiques issues de l'IRM diagnostique. Méthodes > Les caractéristiques cliniques et radiologiques de patients traités pour un ostéosar-come localisé ou métastatique en région Rhône-Alpes entre 2007 et 2016 ont été recueillies. Sur les IRM initiales, chaque tumeur était segmentée par un radiologue expert puis 87 caractéristiques radiomiques étaient extraites automatiquement. Une analyse univariée était réalisée pour évaluer l'association des caractéristiques avec la réponse histologique à la chimiothérapie néo-adjuvante. Pour distinguer les bons des mauvais répondeurs, nous avons construit des modèles prédictifs basés sur des machines à vecteurs de support. Leur performance de classification était évaluée par l'aire sous la courbe sensibilité/spécificité (AUROC). Résultats > L'analyse a porté sur les examens IRM de 69 patients dont 55,1 % (38/69) étaient bons répondeurs. Le modèle de prédiction obtenu à partir des données radiomiques issues de l'IRM diagnostique obtenait une aire sous la courbe de 0,98 avec une sensibilité de 100 % (IC 95 % [100 %-100 %]) et spécificité de 86 % (IC 95 % [59,7 %-111 %]). Discussion > Les caractéristiques radiomiques de l'IRM diagnostique pourraient permettre de prédire la réponse à la chimiothérapie des patients présentant un ostéosarcome avant de débuter la chimiothérapie néo-adjuvante

Prediction of Histologic Neoadjuvant Chemotherapy Response in Osteosarcoma Using Pretherapeutic MRI Radiomics

International audienc

Rare predicted loss-of-function variants of type I IFN immunity genes are associated with life-threatening COVID-19

BackgroundWe previously reported that impaired type I IFN activity, due to inborn errors of TLR3- and TLR7-dependent type I interferon (IFN) immunity or to autoantibodies against type I IFN, account for 15-20% of cases of life-threatening COVID-19 in unvaccinated patients. Therefore, the determinants of life-threatening COVID-19 remain to be identified in similar to 80% of cases.MethodsWe report here a genome-wide rare variant burden association analysis in 3269 unvaccinated patients with life-threatening COVID-19, and 1373 unvaccinated SARS-CoV-2-infected individuals without pneumonia. Among the 928 patients tested for autoantibodies against type I IFN, a quarter (234) were positive and were excluded.ResultsNo gene reached genome-wide significance. Under a recessive model, the most significant gene with at-risk variants was TLR7, with an OR of 27.68 (95%CI 1.5-528.7, P=1.1x10(-4)) for biochemically loss-of-function (bLOF) variants. We replicated the enrichment in rare predicted LOF (pLOF) variants at 13 influenza susceptibility loci involved in TLR3-dependent type I IFN immunity (OR=3.70[95%CI 1.3-8.2], P=2.1x10(-4)). This enrichment was further strengthened by (1) adding the recently reported TYK2 and TLR7 COVID-19 loci, particularly under a recessive model (OR=19.65[95%CI 2.1-2635.4], P=3.4x10(-3)), and (2) considering as pLOF branchpoint variants with potentially strong impacts on splicing among the 15 loci (OR=4.40[9%CI 2.3-8.4], P=7.7x10(-8)). Finally, the patients with pLOF/bLOF variants at these 15 loci were significantly younger (mean age [SD]=43.3 [20.3] years) than the other patients (56.0 [17.3] years; P=1.68x10(-5)).ConclusionsRare variants of TLR3- and TLR7-dependent type I IFN immunity genes can underlie life-threatening COVID-19, particularly with recessive inheritance, in patients under 60 years old

Correction: Rare predicted loss-of-function variants of type I IFN immunity genes are associated with life-threatening COVID-19

International audienc