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Introduction: Effective communication has been shown to improve patients' health outcomes. This study utilizes medical improvisation techniques to teach communication skills to different groups of health students (nurses, midwives, medical doctors, speech therapists). Objectives: Our objective was to design and compare an interprofessional workshop that incorporates applied improvisation to train different groups of healthcare students in communication skills, resilience, dealing with failure and empathy. Medical improvisation is an innovative concept to prepare healthcare students to be more effective communicators. Methods: Required medical improv workshops (using applied improvisational theater techniques) were held for first to third-year students in France and in Hungary. Workshop evaluations were obtained before and following the last session and at 3 months post-workshop for one cohort. The courses incorporated role plays, listening, storytelling and verbal/ nonverbal exercises to help students communicate with empathy and clarity. The two countries used the same questionnaires for assessment (Interpersonal Communication Questionnaire and Intolerance Uncertainty Scale) Results: 24 medical students participated in the Hungarian improvisation workshops, and 26 speech therapists students in the French improvisation workshops. In the finished Hungarian research over 90% of students rated the workshops as above average or excellent. Students reported a gain in insights regarding their role as a clinician (≥ 90%), an improvement in their ability to demonstrate effective communication (80–87%), and a positive impact on teamwork (91–93%). At 3 months post-workshop, students reported they had used at least 1 improvisation skill on their clinical wards. Both countries can claim promising results so far in their separate studies, our results comparing the French and Hungarian data using synchronized scales and questionnaires is currently in progress, and will be processed by the end of this year. Conclusions: This study demonstrates that medical improvisation exercises can be scaled to different fields of healthcare students in various years of their studies and that using improv in healthcare education is universal in its short and long-term effects. Further, we found that students felt that it improved their communication. This study also provides new insights regarding specific improvisation exercises that are most useful for the clinical environment. Keywords: Improvisation. Medical improvisation. Applied Improvisation. Medical education. Communication. Uncertainty tolerance. Soft skills training Disclosure of Interest: None Declared [ABSTRACT FROM AUTHOR]

The content of docosahexaenoic acid (DHA) in brain membranes is of crucial importance for the optimum development of brain functions. A lack of DHA accretion in the brain is accompanied by deficits in learning behavior linked to impairments in neurotransmission processes, which might result from alteration of brain fuel supply and hence energy metabolism. Experimental data we published support the hypothesis that n-3 fatty acids may modulate brain glucose utilization and metabolism. Indeed rats made deficient in DHA by severe depletion of total n-3 fatty acid intake have 1) a lower brain glucose utilization, 2) a decrease of the glucose transporter protein content GLUT1 both in endothelial cells and in astrocytes, 3) a repression of GLUT1 gene expression in basal state as well as upon neuronal activation. This could be due to the specific action of DHA on the regulation of GLUT1 expression since rat brain endothelial cells cultured with physiological doses of DHA had an increased GLUT1 protein content and glucose transport when compared to non-supplemented cells. These experimental data highlight the impact of n-3 fatty acids on the use of brain glucose, thereby constituting a key factor in the control of synaptic activity. This emerging role suggests that dietary intake of n-3 fatty acids can help to reduce the cognitive deficits in the elderly and possibly symptomatic cerebral metabolic alterations in Alzheimer disease by promoting brain glucose metabolism.

Docosahexaenoic acid (DHA, 22:6n-3) in membrane phospholipids originates from dietary intake of preformed DHA and from conversion of its essential precursor α-linolenic acid (ALA, 18:3n-3). Cultured cells, especially nervous cells, are increasingly used to explore the uptake, metabolism and gene transcription effects of n-3 fatty acids, raising the question of the specific metabolic fate of different fatty acids and of the physiological relevance of their concentrations in the culture medium. This paper reports experimental data that 1) compare the dose-dependent incorporation of preformed DHA into the ethanolamine phosphoglycerolipids (EPG) of neural and cerebral endothelial cells in culture with that of the developing rat brain, 2) evaluate the pathway of DHA synthesis from ALA, eicosapentaenoic acid (EPA, 20:5n-3) or n-3 docosapentaenoic acid (DPA, 22:5n-3) in a model of neuronal cells, the SH-5YSY human neuroblastoma cells, and 3) characterize in these cells the mRNA expression profile of genes involved in the fatty acid metabolism. The incorporation of preformed DHA in EPG followed, both in vivo and in vitro, a dose-response curve from which two parameters were drawn: the DHAmax, i.e. the plateau-value of the linearized dose-response curve (expressed in weight % of total fatty acids), and the DHA50, the concentration of DHA in the diet or in the culture medium corresponding to an incorporation of DHA in EPG equal to one-half the DHAmax. The ratio of DHAmax to DHA50 reflects the propensity (so-called the ‘avidity’ for DHA) of cells or tissues to incorporate the exogenous DHA. The DHAmax and the DHAmax/DHA50 ratio values of SH-SY5Y cells and of rat brain endothelial cells in culture were compared to those of the frontal cortex and hippocampus of rats chronically deficient in n-3 fatty acids and supplemented with preformed DHA. The same DHAmax/DHA50 ratio values were found in SH-SY5Y (5.2) cells and in rat brain areas (5.1-5.7) when the DHA doses were expressed in lmol DHA/liter of culture medium and in lmol DHA/10 g diet, respectively. The SH-SY5Y cells were able to produce neoformed EPA, DPA and DHA from supplemental ALA. The incorporation of neoformed EPA and DPA in EPG followed a dose-response saturating curve, while that of DHA was bell-shaped. The different pattern of neoformed DPA and neoformed DHA suggests that the conversion pathway was limited at the terminal step of DHA synthesis. The mRNA profile showed that two enzymes of the peroxisomal b-oxidation system, the L- and D-bifunctional proteins, were expressed at lower levels than those of the endoplasmic reticulum pathway (Δ6-desaturase). These data show that incorporation of preformed DHA in cultured neuroblastoma cells match physiological values, indicating that DHA uptake, acyl-CoA activation, and phospholipid acyltransferases are active. However, the synthesis and incorporation of newly formed DHA in SH-SY5Y cells responds to a critical concentration-window of precursors which could originate from the low basal expression level of peroxisomal enzymes.

Introduction: In humans, adversity in childhood exerts enduring effects on brain and increases the vulnerability to psychiatric diseases. It also leads to a higher risk of eating disorders and obesity. Maternal separation (MS) in mice has been used as a proxy of stress during infancy. We hypothesized that MS in mice affects motivation to obtain palatable food in adulthood and changes gene expression in reward system., Methods: Male and female pups from C57Bl/6J and C3H/HeN mice strains were subjected to a daily MS protocol from postnatal day (PND) 2 to PND14. At adulthood, their motivation for palatable food reward was assessed in operant cages., Results: Compared to control mice, male and female C3H/HeN mice exposed to MS increased their instrumental response for palatable food, especially when the effort required to obtain the reward was high. Importantly, this effect is shown in animals fed ad libitum . Transcriptional analysis revealed 375 genes differentially expressed in the nucleus accumbens of male MS C3H/HeN mice compared to the control group, some of these being associated with the regulation of the reward system (e.g., Gnas , Pnoc ). Interestingly, C57Bl/6J mice exposed to MS did not show alterations in their motivation to obtain a palatable reward, nor significant changes in gene expression in the nucleus accumbens., Conclusion: MS produces long-lasting changes in motivation for palatable food in C3H/HeN mice, but has no impact in C57Bl/6J mice. These behavioral alterations are accompanied by drastic changes in gene expression in the nucleus accumbens, a key structure in the regulation of motivational processes., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Benoit, Henry, Fneich, Mathou, Xia, Foury, Jouin, Junien, Capuron, Jouneau, Moisan, Delpierre, Gabory and Darnaudéry.)

Nutritional changes during developmental windows are of particular concern in offspring metabolic disease. Questions are emerging concerning the role of maternal weight changes before conception, particularly for weight loss, in the development of diet-related disorders. Understanding the physiological pathways affected by the maternal trajectories in the offspring is therefore essential, but a broad overview is still lacking. We recently reported both metabolic and behavioral negative outcomes in offspring born to obese or weight-loss mothers and fed a control of high-fat diet, suggesting long-term modeling of metabolic pathways needing to be further characterized. Using non-targeted LC-HRMS, we investigated the impact of maternal and post-weaning metabolic status on the adult male offspring's metabolome in three tissues involved in energy homeostasis: liver, hypothalamus and olfactory bulb. We showed that post-weaning diet interfered with the abundance of several metabolites, including 1,5-anhydroglucitol, saccharopine and βhydroxybutyrate, differential in the three tissues. Moreover, maternal diet had a unique impact on the abundance of two metabolites in the liver. Particularly, anserine abundance, lowered by maternal obesity, was normalized by a preconceptional weight loss, whatever the post-weaning diet. This study is the first to identify a programming long-term effect of maternal preconception obesity on the offspring metabolome., Competing Interests: The authors declare no conflict of interest.

According to the "developmental origins of health and disease" (DOHaD) concept, maternal obesity predisposes the offspring to non-communicable diseases in adulthood. While a preconceptional weight loss (WL) is recommended for obese women, its benefits on the offspring have been poorly addressed. We evaluated whether preconceptional WL was able to reverse the adverse effects of maternal obesity in a mouse model, exhibiting a modification of foetal growth and of the expression of genes encoding epigenetic modifiers in liver and placenta. We tracked metabolic and olfactory behavioural trajectories of offspring born to control, obese or WL mothers. After weaning, the offspring were either put on a control diet (CD) or a high-fat (HFD). After only few weeks of HFD, the offspring developed obesity, metabolic alterations and olfactory impairments, independently of maternal context. However, male offspring born to obese mother gained even more weight under HFD than their counterparts born to lean mothers. Preconceptional WL normalized the offspring metabolic phenotypes but had unexpected effects on olfactory performance: a reduction in olfactory sensitivity, along with a lack of fasting-induced, olfactory-based motivation. Our results confirm the benefits of maternal preconceptional WL for male offspring metabolic health but highlight some possible adverse outcomes on olfactory-based behaviours.

Background: Maternal obesity impacts fetal growth and pregnancy outcomes. To counteract the deleterious effects of obesity on fertility and pregnancy issue, preconceptional weight loss is recommended to obese women. Whether this weight loss is beneficial/detrimental for offspring remains poorly explored. Epigenetic mechanisms could be affected by maternal weight changes, perturbing expression of key developmental genes in the placenta or fetus. Our aim was to investigate the effects of chronic maternal obesity on feto-placental growth along with the underlying epigenetic mechanisms. We also tested whether preconceptional weight loss could alleviate these effects., Results: Female mice were fed either a control diet (CTRL group), a high-fat diet (obese (OB) group), or a high-fat diet switched to a control diet 2 months before conception (weight loss (WL) group). At mating, OB females presented an obese phenotype while WL females normalized metabolic parameters. At embryonic day 18.5 (E18.5), fetuses from OB females presented fetal growth restriction (FGR; -13 %) and 28 % of the fetuses were small for gestational age (SGA). Fetuses from WL females normalized this phenotype. The expression of 60 epigenetic machinery genes and 32 metabolic genes was measured in the fetal liver, placental labyrinth, and junctional zone. We revealed 23 genes altered by maternal weight trajectories in at least one of three tissues. The fetal liver and placental labyrinth were more responsive to maternal obesity than junctional zone. One third (18/60) of the epigenetic machinery genes were differentially expressed between at least two maternal groups. Interestingly, genes involved in the histone acetylation pathway were particularly altered (13/18). In OB group, lysine acetyltransferases and Bromodomain-containing protein 2 were upregulated, while most histone deacetylases were downregulated. In WL group, the expression of only a subset of these genes was normalized., Conclusions: This study highlights the high sensitivity of the epigenetic machinery gene expression, and particularly the histone acetylation pathway, to maternal obesity. These obesity-induced transcriptional changes could alter the placental and the hepatic epigenome, leading to FGR. Preconceptional weight loss appears beneficial to fetal growth, but some effects of previous obesity were retained in offspring phenotype.

The environment, defined broadly by all that is external to the individual, conditions the phenotype during development, particularly the susceptibility to develop non-communicable diseases. This notion, called Developmental Origins of Health and Disease (DOHaD), is based on numerous epidemiological studies as well as animal models. Thus, parental nutrition and obesity can predispose the offspring to develop metabolic and cardiovascular diseases in adulthood. The known underlying mechanisms include an altered development of tissues that adapt to maternal metabolic condition, and a placental dysfunction, which in turn impacts fetal growth and development. Epigenetic mechanisms modulate gene expression without affecting the DNA sequence itself. The main epigenetic marks are DNA methylation and histone post-translational modifications. These marks are erased and set-up during gametogenesis and development in order to ensure cellular identity. Therefore, they can lead to a memorisation of early environment and induce long-term alteration of cell and tissue functions, which will condition the susceptibility to non-communicable diseases. The placenta is a programming agent of adult disease. The environment, such as smoking or psychosocial stress, is able to modify epigenetic processes in placenta, such as small RNA expression and DNA methylation. We showed that placenta is sensitive to maternal obesity and maternal nutrition, in terms of histology, transcription and epigenetic marks. A clear sexual dimorphism is remarkable in the placental response to maternal environment. In adulthood, the phenotype is also different between males and females. Epigenetic mechanisms could underlie this differential response of males and females to the same environment. The DOHaD can no longer be ignored in Biology of Reproduction. The prevention of non-communicable diseases must take this new paradigm into account. Research will allow a better comprehension of the mechanisms of this early conditioning and the marked sexual dimorphism it is associated to., (© Société de Biologie, 2015.)

Specific mechanisms for maintaining docosahexaenoic acid (DHA) concentration in brain cells but also transporting DHA from the blood across the blood-brain barrier (BBB) are not agreed upon. Our main objective was therefore to evaluate the level of gene expression of fatty acid transport and fatty acid binding proteins in the cerebral cortex and at the BBB level during the perinatal period of active brain DHA accretion, at weaning, and until the adult age. We measured by real time RT-PCR the mRNA expression of different isoforms of fatty acid transport proteins (FATPs), long-chain acyl-CoA synthetases (ACSLs), fatty acid binding proteins (FABPs) and the fatty acid transporter (FAT)/CD36 in cerebral cortex and isolated microvessels at embryonic day 18 (E18) and postnatal days 14, 21 and 60 (P14, P21 and P60, respectively) in rats receiving different n-3 PUFA dietary supplies (control, totally deficient or DHA-supplemented). In control rats, all the genes were expressed at the BBB level (P14 to P60), the mRNA levels of FABP5 and ACSL3 having the highest values. Age-dependent differences included a systematic decrease in the mRNA expressions between P14-P21 and P60 (2 to 3-fold), with FABP7 mRNA abundance being the most affected (10-fold). In the cerebral cortex, mRNA levels varied differently since FATP4, ACSL3 and ACSL6 and the three FABPs genes were highly expressed. There were no significant differences in the expression of the 10 genes studied in n-3 deficient or DHA-supplemented rats despite significant differences in their brain DHA content, suggesting that brain DHA uptake from the blood does not necessarily require specific transporters within cerebral endothelial cells and could, under these experimental conditions, be a simple passive diffusion process., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

n-3 Polyunsaturated fatty acids (PUFA) support whole brain energy metabolism but their impact on neuroenergetics in specific brain areas and during neuronal activation is still poorly understood. We tested the effect of feeding rats as control, n-3 PUFA-deficient diet, or docosahexaenoic acid (DHA)-supplemented diet on the expression of key genes in fronto-parietal cortex and hippocampal neuroenergetics before and after neuronal stimulation (activated) by an enriched environment. Compared to control rats, n-3 deficiency specifically repressed GLUT1 gene expression in the fronto-parietal cortex in basal state and also during neuronal activation which specifically stimulated GLUT1. In contrast, in the CA1 area, n-3 deficiency improved the glutamatergic synapse function in both neuronal states (glutamate transporters, Na(+)/K(+) ATPase). DHA supplementation induced overexpression of genes encoding enzymes of the oxidative phosphorylation system and the F1F0 ATP synthase in the CA1 area. We conclude that n-3 deficiency repressed GLUT1 gene expression in the cerebral cortex, while DHA supplementation improved the mitochondrial ATP generation in the CA1 area of the hippocampus., (Copyright © 2012 Elsevier Ltd. All rights reserved.)

Omega-3 (ω3) polyunsaturated fatty acids (PUFA) are major components of brain cells membranes. ω3 PUFA-deficient rodents exhibit severe cognitive impairments (learning, memory) that have been linked to alteration of brain glucose utilization or to changes in neurotransmission processes. ω3 PUFA supplementation has been shown to lower anxiety and to improve several cognitive parameters in rodents, while very few data are available in primates. In humans, little is known about the association between anxiety and ω3 fatty acids supplementation and data are divergent about their impact on cognitive functions. Therefore, the development of nutritional studies in non-human primates is needed to disclose whether a long-term supplementation with long-chain ω3 PUFA has an impact on behavioural and cognitive parameters, differently or not from rodents. We address the hypothesis that ω3 PUFA supplementation could lower anxiety and improve cognitive performances of the Grey Mouse Lemur (Microcebus murinus), a nocturnal Malagasy prosimian primate. Adult male mouse lemurs were fed for 5 months on a control diet or on a diet supplemented with long-chain ω3 PUFA (n = 6 per group). Behavioural, cognitive and motor performances were measured using an open field test to evaluate anxiety, a circular platform test to evaluate reference spatial memory, a spontaneous locomotor activity monitoring and a sensory-motor test. ω3-supplemented animals exhibited lower anxiety level compared to control animals, what was accompanied by better performances in a reference spatial memory task (80% of successful trials vs 35% in controls, p<0.05), while the spontaneous locomotor activity was reduced by 31% in ω3-supplemented animals (p<0.001), a parameter that can be linked with lowered anxiety. The long-term dietary ω3 PUFA supplementation positively impacts on anxiety and cognitive performances in the adult mouse lemur. The supplementation of human food with ω3 fatty acids may represent a valuable dietary strategy to improve behavioural and cognitive functions.

Several in vivo studies suggest that docosahexaenoic acid (22:6 n-3), the main n-3 long-chain polyunsaturated fatty acids (LC-PUFA) of brain membranes, could be an important regulator of brain energy metabolism by affecting glucose utilization and the density of the two isoforms of the glucose transporter-1 (GLUT1) (endothelial and astrocytic). This study was conducted to test the hypothesis that 22:6 n-3 in membranes may modulate glucose metabolism in brain endothelial cells. It compared the impact of 22:6 n-3 and the other two main LC-PUFA, arachidonic acid (20:4 n-6) and eicosapentaenoic acid (20:5 n-3), on fatty acid composition of membrane phospholipids, glucose uptake and expression of 55-kDa GLUT1 isoform in two models of rat brain endothelial cells (RBEC), in primary culture and in the immortalized rat brain endothelial cell line RBE4. Without PUFA supplementation, both types of cerebral endothelial cells were depleted in 22:6 n-3, RBE4 being also particularly low in 20:4 n-6. After exposure to supplemental 20:4 n-6, 20:5 n-3 or 22:6 n-3 (15microM, i.e. a physiological dose), RBEC and RBE4 avidly incorporated these PUFA into their membrane phospholipids thereby resembling physiological conditions, i.e. the PUFA content of rat cerebral microvessels. However, RBE4 were unable to incorporate physiological level of 20:4 n-6. Basal glucose transport in RBEC (rate of [(3)H]-3-o-methylglucose uptake) was increased after 20:5 n-3 or 22:6 n-3 supplementation by 50% and 35%, respectively, whereas it was unchanged with 20:4 n-6. This increase of glucose transport was associated with an increased GLUT1 protein, while GLUT1 mRNA was not affected. The different PUFA did not impact on glucose uptake in RBE4. Due to alterations in n-6 PUFA metabolism and weak expression of GLUT1, RBE4 seems to be less adequate than RBEC to study PUFA metabolism and glucose transport in brain endothelial cells. Physiological doses of n-3 LC-PUFA have a direct and positive effect on glucose transport and GLUT1 density in RBEC that could partly explain decreased brain glucose utilization in n-3 PUFA-deprived rats.

The altered neuron activity of rats deficient in (n-3) PUFAs may be due in part to a decrease in brain glucose utilization and glucose transport. We measured the glucose transporter protein GLUT1 isoforms at the blood-brain barrier (55-kDa) and in astrocytes (45-kDa) by Western immunoblotting and their mRNA by real time RT-PCR analysis in the cerebral cortex of adult male rats fed diets lacking (n-3) fatty acids (1st generation). The neuron glucose transporter GLUT3 was also assayed. The fatty acids in the phosphatidylcholine (PC), ethanolamine phosphoglycerolipid (EPG), and phosphatidylserine (PS) fractions of isolated microvessels and homogenates of the cerebral cortex were determined. The levels of (n-6) PUFAs [mainly arachidonic acid, 20:4(n-6)] in the phospholipid fractions of microvessels were higher and the levels of (n-3) PUFAs [mainly docosahexaenoic acid, 22:6(n-3)] were lower than in cerebral cortex homogenates. The microvessels and cortex of rats fed the (n-3) PUFA-deficient diet had 50% of the control 22:6(n-3) contents; 22:6(n-3) was replaced by 22:5(n-6). The 55-kDa GLUT1 immunoreactivity in (n-3) PUFA-deficient microvessels was decreased (down 25%, P < 0.01), as was the 45 kDa-GLUT1 in the homogenate (down 30%, P < 0.01). But the amount of immunoreactivity of GLUT3 did not change. The amount of GLUT1 mRNA was not affected by the (n-3) PUFA-deficient diet. These results suggest that the decreased glucose utilization in the cerebral cortex of (n-3) PUFA-deficient rats is due to reduced amounts of the 2 isoforms of GLUT1, indicating post-transcriptional regulation of GLUT1 synthesis.

Collagen IV is a major structural component of basement membranes. In the glomerular basement membrane (GBM) of the kidney, the alpha3, alpha4, and alpha5(IV) collagen chains form a distinct network that is essential for the long-term stability of the glomerular filtration barrier, and is absent in most patients affected with Alport syndrome, a progressive inherited nephropathy associated with mutation in COL4A3, COL4A4, or COL4A5 genes. To investigate, in vivo, the regulation of the expression, assembly, and function of the alpha3alpha4alpha5(IV) protomer, we have generated a yeast artificial chromosome transgenic line of mice carrying the human COL4A3-COL4A4 locus. Transgenic mice expressed the human alpha3 and alpha4(IV) chains in a tissue-specific manner. In the kidney, when expressed onto a Col4a3(-/-) background, the human alpha3(IV) chain restored the expression of and co-assembled with the mouse alpha4 and alpha5(IV) chains specifically at sites where the human alpha3(IV) was expressed, demonstrating that the expression of all three chains is required for network assembly. The co-assembly of the human and mouse chains into a hybrid network in the GBM restores a functional GBM and rescues the Alport phenotype, providing further evidence that defective assembly of the alpha3-alpha4-alpha5(IV) protomer, caused by mutations in any of the three chains, is the pathogenic mechanism responsible for the disease. This line of mice, humanized for the alpha3(IV) collagen chain, will also provide a valuable model for studying the pathogenesis of Goodpasture syndrome, an autoimmune disease caused by antibodies against this chain.