New control strategies for neuroprosthetic systems

The availability of techniques to artificially excite paralyzed muscles opens enormous potential for restoring both upper and lower extremity movements with\ud neuroprostheses. Neuroprostheses must stimulate muscle, and control and regulate the artificial movements produced. Control methods to accomplish these tasks include feedforward (open-loop), feedback, and adaptive control. Feedforward control requires a great deal of information about the biomechanical behavior of the limb. For the upper extremity, an artificial motor program was developed to provide such movement program input to a neuroprosthesis. In lower extremity control, one group achieved their best results by attempting to meet naturally perceived gait objectives rather than to follow an exact joint angle trajectory. Adaptive feedforward control, as implemented in the cycleto-cycle controller, gave good compensation for the gradual decrease in performance observed with open-loop control. A neural network controller was able to control its system to customize stimulation parameters in order to generate a desired output trajectory in a given individual and to maintain tracking performance in the presence of muscle fatigue. The authors believe that practical FNS control systems must\ud exhibit many of these features of neurophysiological systems

Est-ce que le genre influence la tolérance myocardique à l'ischémie-reperfusion dans un modèle de rat prédiabétique ?

International audienceObjectifs : Le prédiabète est un facteur de risque de diabète de type 2 et de complications cardiovasculaires comme l'infarctus du myocarde [1, 2]. Cependant peu d'études explorent les effets du genre dans ce contexte. L'objectif de cette étude a été de comparer les effets d'un régime riche en graisse et en sucre (HFS) sur la sensibilité du myocarde à un épisode d'ischémie-reperfusion chez des rats mâles et femelles. Matériels et méthodes : Pendant cinq mois, des rats Wistar mâles et femelles ont reçu un régime HFS (M-HFS et F-HFS) ou standard (M-CTRL et F-CTRL). Ensuite, des expériences ex vivo sur le modèle du coeur isolé perfusé ont été réalisées afin d'évaluer la tolérance à un épisode d'ischémie-reperfusion. Les coeurs ont été perfusé avec un tampon physiologique contenant du palmitate pendant 24 minutes, avant de subir une ischémie à faible flux et une reperfusion de 32 minutes chacune. Le métabolisme énergétique (ATP, PCr, Pi) et le pH intracellulaire ont été mesurés pendant tout le protocole à l'aide de la SRM du phosphore-31, en simultané avec la mesure de la fonction cardiaque. A la fin des expériences, les coeurs ont été conservés à-80°C pour des analyses biochimiques ultérieures. Résultats : Après cinq mois, le régime HFS a induit une prise de poids uniquement chez les M-HFS vs. M-CTRL, mais pas chez les F-HFS vs. F-CTRL. Le pourcentage de masse grasse est significativement augmenté chez les M-HFS et F-HFS vs. leurs CTRL respectifs. Dans les deux sexes, une intolérance au glucose et une hyperglycémie modérée à jeun a été observée avec le régime HFS (vs. CTRL respectifs), avec une intolérance au glucose plus marquée chez les F-HFS vs. M-HFS. Le ratio poids du coeur / longueur du tibia, utilisé comme marqueur d'hypertrophie cardiaque, est augmenté uniquement chez les M-HFS vs. M-CTRL. Ex vivo, le régime HFS n'a pas induit d'altérations de la fonction cardiaque et du métabolisme énergétique en conditions basales. Cependant à la reperfusion, une altération de la fonction cardiaque et du métabolisme énergétique (ATP et PCr) a été observée chez les mâles et femelles HFS (vs. CTRL respectifs), sans effet du sexe. Afin d'approfondir les mécanismes impliqués dans les altérations induites par le régime HFS, nous étudierons dans les coeurs le pourcentage en eau, le stress oxydant (MDA), la fonction mitochondriale (citrate synthase) et la fonction endothéliale (voie du NO). Conclusion : Cinq mois de régime HFS a induit le développement d'un prédiabète chez des femelles et des mâles Wistar, avec des différences entre les sexes concernant la tolérance au glucose et l'hypertrophie cardiaque. Le régime HFS a également diminué la tolérance myocardique à un épisode d'ischémie-reperfusion, sans effet du sexe. Références : [1] Grundy S.M., Pre-diabetes, metabolic syndrome, and cardiovascular risk, J Am Col

Immunofluorescent localization of cyclic nucleotide-dependent protein kinases on the mitotic apparatus of cultured cells

Cyclic nucleotides and cyclic nucleotide-dependent protein kinases have been implicated in the regulation of cell motility and division, processes that depend on the cell cytoskeleton. To determine whether cyclic nucleotides or their kinases are physically associated with the cytoskeleton during cell division, fluorescently labeled antibodies directed against cyclic AMP, cyclic GMP, and the cyclic nucleotide- dpendent protein kinases were used to localize these molecules in mitotic PtK1 cells. Both the cyclic GMP-dependent protein kinase and the type II regulatory subunit of the cyclic AMP-dependent protein kinase were localized on the mitotic spindle. Throughout mitosis, their distribution closely resembled that of tubulin. Antibodies to cyclic AMP, cyclic GMP, and the type I regulatory and catalytic subunits of the cyclic AMP-dependent protein kinase did not label the mitotic apparatus. The association between specific components of the cyclic neucleotide system and the mitotic spindle suggests that cyclic nucleotide-dependent phosphorylation of spindle proteins, such as those of microtubules, may play a fundamental role in the regulation of spindle assembly and chromosome motion

Immunogenicity of chimeric haemagglutinin-based, universal influenza virus vaccine candidates: interim results of a randomised, placebo-controlled, phase 1 clinical trial.

BackgroundInfluenza viruses cause substantial annual morbidity and mortality globally. Current vaccines protect against influenza only when well matched to the circulating strains. However, antigenic drift can cause considerable mismatches between vaccine and circulating strains, substantially reducing vaccine effectiveness. Moreover, current seasonal vaccines are ineffective against pandemic influenza, and production of a vaccine matched to a newly emerging virus strain takes months. Therefore, there is an unmet medical need for a broadly protective influenza virus vaccine. We aimed to test the ability of chimeric H1 haemagglutinin-based universal influenza virus vaccine candidates to induce broadly cross-reactive antibodies targeting the stalk domain of group 1 haemagglutinin-expressing influenza viruses.MethodsWe did a randomised, observer-blinded, phase 1 study in healthy adults in two centres in the USA. Participants were randomly assigned to one of three prime-boost, chimeric haemagglutinin-based vaccine regimens or one of two placebo groups. The vaccine regimens included a chimeric H8/1, intranasal, live-attenuated vaccine on day 1 followed by a non-adjuvanted, chimeric H5/1, intramuscular, inactivated vaccine on day 85; the same regimen but with the inactivated vaccine being adjuvanted with AS03; and an AS03-adjuvanted, chimeric H8/1, intramuscular, inactivated vaccine followed by an AS03-adjuvanted, chimeric H5/1, intramuscular, inactivated vaccine. In this planned interim analysis, the primary endpoints of reactogenicity and safety were assessed by blinded study group. We also assessed anti-H1 haemagglutinin stalk, anti-H2, anti-H9, and anti-H18 IgG antibody titres and plasmablast and memory B-cell responses in peripheral blood. This trial is registered with ClinicalTrials.gov, number NCT03300050.FindingsBetween Oct 10, 2017, and Nov 27, 2017, 65 participants were enrolled and randomly assigned. The adjuvanted inactivated vaccine, but not the live-attenuated vaccine, induced a substantial serum IgG antibody response after the prime immunisation, with a seven times increase in anti-H1 stalk antibody titres on day 29. After boost immunisation, all vaccine regimens induced detectable anti-H1 stalk antibody (2·2-5·6 times induction over baseline), cross-reactive serum IgG antibody, and peripheral blood plasmablast responses. An unsolicited adverse event was reported for 29 (48%) of 61 participants. Solicited local adverse events were reported in 12 (48%) of 25 participants following prime vaccination with intramuscular study product or placebo, in 12 (33%) of 36 after prime immunisation with intranasal study product or placebo, and in 18 (32%) of 56 following booster doses of study product or placebo. Solicited systemic adverse events were reported in 14 (56%) of 25 after prime immunisation with intramuscular study product or placebo, in 22 (61%) of 36 after immunisation with intranasal study product or placebo, and in 21 (38%) of 56 after booster doses of study product or placebo. Disaggregated safety data were not available at the time of this interim analysis.InterpretationThe tested chimeric haemagglutinin-based, universal influenza virus vaccine regimens elicited cross-reactive serum IgG antibodies that targeted the conserved haemagglutinin stalk domain. This is the first proof-of-principle study to show that high anti-stalk titres can be induced by a rationally designed vaccine in humans and opens up avenues for further development of universal influenza virus vaccines. On the basis of the blinded study group, the vaccine regimens were tolerable and no safety concerns were observed.FundingBill & Melinda Gates Foundation

A História da Alimentação: balizas historiográficas

Os M. pretenderam traçar um quadro da História da Alimentação, não como um novo ramo epistemológico da disciplina, mas como um campo em desenvolvimento de práticas e atividades especializadas, incluindo pesquisa, formação, publicações, associações, encontros acadêmicos, etc. Um breve relato das condições em que tal campo se assentou faz-se preceder de um panorama dos estudos de alimentação e temas correia tos, em geral, segundo cinco abardagens Ia biológica, a econômica, a social, a cultural e a filosófica!, assim como da identificação das contribuições mais relevantes da Antropologia, Arqueologia, Sociologia e Geografia. A fim de comentar a multiforme e volumosa bibliografia histórica, foi ela organizada segundo critérios morfológicos. A seguir, alguns tópicos importantes mereceram tratamento à parte: a fome, o alimento e o domínio religioso, as descobertas européias e a difusão mundial de alimentos, gosto e gastronomia. O artigo se encerra com um rápido balanço crítico da historiografia brasileira sobre o tema

Male and Female Rats Have Different Physiological Response to High-Fat High-Sucrose Diet but Similar Myocardial Sensitivity to Ischemia-Reperfusion Injury

International audiencePrediabetes is a strong predictor of type 2 diabetes and its associated cardiovascular complications, but few studies explore sexual dimorphism in this context. Here, we aim to determine whether sex influences physiological response to high-fat high-sucrose diet (HFS) and myocardial tolerance to ischemia-reperfusion injury. Male and female Wistar rats were subjected to standard (CTRL) or HFS diet for 5 months. Then, ex-vivo experiments on isolated perfused heart model were performed to evaluate tolerance to ischemia-reperfusion injury. HFS diet induced fasting hyperglycemia and increased body fat percent to a similar level in both sexes. However, glucose intolerance was more pronounced in female HFS. Cholesterol was increased only in female while male displayed higher level of plasmatic leptin. We observed increased heart weight to tibia length ratio only in males, but we showed a similar decrease in tolerance to ischemia-reperfusion injury in female and male HFS compared with respective controls, characterized by impaired cardiac function, energy metabolism and coronary flow during reperfusion. In conclusion, as soon as glucose intolerance and hyperglycemia develop, we observe higher sensitivity of hearts to ischemia-reperfusion injury without difference between males and females

Reduced up-regulation of the nitric oxide pathway and impaired endothelial and smooth muscle functions in the female type 2 diabetic goto-kakizaki rat heart

Abstract Background Type 2 diabetes is associated with greater relative risk of cardiovascular diseases in women than in men, which is not well understood. Consequently, we have investigated if male and female displayed differences in cardiac function, energy metabolism, and endothelial function which could contribute to increased cardiovascular complications in type 2 diabetic female. Methods Male and female Control and type 2 diabetic Goto-Kakizaki (GK) isolated rat hearts were perfused during 28\ua0min with a physiological buffer before freeze-clamping for biochemical assays. High energy phosphate compounds and intracellular pH were followed using 31 P magnetic resonance spectroscopy with simultaneous measurement of contractile function. Nitric oxide (NO) pathway and endothelium-dependent and independent vasodilatations were measured as indexes of endothelial function. Results were analyzed via two-way ANOVA, p\u2009< \u20090.05 was considered as statistically significant. Results Myocardial function was impaired in male and female diabetic versus Control groups ( p\u2009< \u20090.05) without modification of energy metabolism. Coronary flow was decreased in both diabetic versus Control groups but to a higher extent in female GK versus male GK rat hearts ( p\u2009< \u20090.05). NO production was up-regulated in diabetic groups but to a less extent in female GK rat hearts ( p\u2009< \u20090.05). Endothelium-dependent and independent vasodilatations were impaired in female GK rat compared with male GK ( p\u2009< \u20090.05) and female Control ( p\u2009< \u20090.05) rat hearts. Conclusions We reported here an endothelial damage characterized by a reduced up-regulation of the NO pathway and impaired endothelial and smooth muscle functions, and coronary flow rates in the female GK rat hearts while energy metabolism was normal. Whether these results are related to the higher risk of cardiovascular complications among type 2 diabetic female needs to be further elicited in the future

Protective Effect of Resveratrol against Ischemia-Reperfusion Injury via Enhanced High Energy Compounds and eNOS-SIRT1 Expression in Type 2 Diabetic Female Rat Heart

Type 2 diabetic women have a high risk of mortality via myocardial infarction even with anti-diabetic treatments. Resveratrol (RSV) is a natural polyphenol, well-known for its antioxidant property, which has also shown interesting positive effects on mitochondrial function. Therefore, we aim to investigate the potential protective effect of 1 mg/kg/day of RSV on high energy compounds, during myocardial ischemia-reperfusion in type 2 diabetic female Goto-Kakizaki (GK) rats. For this purpose, we used 31P magnetic resonance spectroscopy in isolated perfused heart experiments, with a simultaneous measurement of myocardial function and coronary flow. RSV enhanced adenosine triphosphate (ATP) and phosphocreatine (PCr) contents in type 2 diabetic hearts during reperfusion, in combination with better functional recovery. Complementary biochemical analyses showed that RSV increased creatine, total adenine nucleotide heart contents and citrate synthase activity, which could be involved in better mitochondrial functioning. Moreover, improved coronary flow during reperfusion by RSV was associated with increased eNOS, SIRT1, and P-Akt protein expression in GK rat hearts. In conclusion, RSV induced cardioprotection against ischemia-reperfusion injury in type 2 diabetic female rats via increased high energy compound contents and expression of protein involved in NO pathway. Thus, RSV presents high potential to protect the heart of type 2 diabetic women from myocardial infarction

Intolérance au glucose et obésité abdominale associées à une modification de la morphologie et une altération de la fonction cardiaque dans un modèle de syndrome métabolique induit par un régime

International audienceIntroduction: Le syndrome métabolique est défini par de multiples facteurs de risque pouvant prédire le diabète de type 2 et ses complications cardiovasculaires telles que l’infarctus du myocarde, en particulier chez les femmes. Par conséquent, l'objectif de cette étude préliminaire était d'étudier in vivo et ex vivo les effets d'un régime riche en graisse et en sucre (HFHSD) sur le développement du syndrome métabolique, sur la morphologie et la fonction cardiaque de rats Wistar femelles. Matériel et méthodes: Des rats Wistar femelles, soumises à un régime HFHSD (FHFD) ou standard (FND) pendant 5 mois, ont été explorées chaque mois par résonance magnétique cardiovasculaire multimodale (CMR) pour déterminer in vivo la fonction, la morphologie et la teneur en triglycérides (TG) cardiaque. La teneur en TG du foie a également été évaluée par spectroscopie de résonance magnétique du proton (SRM 1H). Ensuite, les rats ont subi un test de tolérance au glucose en intrapéritonéal (IPGTT) pour déterminer leur statut glycémique, et des expériences ex vivo sur le cœur isolé perfusé ont été réalisées pour étudier dans des conditions basales la fonction cardiaque et le métabolisme énergétique par spectroscopie de résonance magnétique du Phosphore 31. Résultats: Chez les FHFD vs. FND, la CMR a montré une augmentation de l’épaisseur de la paroi en systole au cours du temps (p\textless0,05) et en diastole à 3 et 5 mois de régime HFHSD (p\textless0,01) ; la SRM 1H a montré que la teneur en TG était augmentée dans le foie (p\textless0.01) mais pas dans le cœur. L’IPGTT a montré une intolérance au glucose significative (p\textless0,001) et les acides gras libres dans le plasma étaient augmentés (p\textless0,05) chez les FHFD vs. FND. À 5 mois, le poids des animaux n'était pas différent entre les groupes, mais les FHFD présentaient une obésité abdominale avec une augmentation du tissu adipeux viscéral (p \textless0,05), du pourcentage de graisse (p\textless0,05) et du pourcentage de graisse viscérale (p\textless0,05) par rapport aux FND. Dans des conditions de base, la fonction myocardique ex vivo était altérée chez les FHFD vs FND (p\textless0,01). Conclusion: Le syndrome métabolique induit par le régime HFHSD était caractérisé par une intolérance au glucose, une obésité abdominale, un dépôt de graisse hépatique, associés à une modification de la morphologie et à une altération de la fonction myocardique ex vivo. Ces résultats pourraient être liés au risque plus élevé de complications cardiovasculaires chez les femmes obèses diabétiques de type 2