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In vitro analysis reported that annulus fibrosus lose its integrity in idiopathic scoliosis. Shear wave ultrasound elastography can be used for noninvasive measurement of shear wave speed in vivo in the annulus fibrosus, a parameter related to intervertebral disc (IVD) mechanical properties. The main aim was to assess shear wave speed in lumbar annulus fibrosus of scoliotic adolescents and compare it to asymptomatic patients. Methods: 300 lumbar IVDs in one hundred patients were measured: 34 patients without spinal pathologies, 44 adolescent idiopathic scoliosis (25 patients in a mild stage, 19 severe) and 22 in postoperative. We studied the three last mobile levels in every patient. Results: in patients without spinal pathologies, average shear wave speed was 3,1 m/s ± 0,37 (2,2-3,8 m/s) whereas, in scoliosis group, mean value was significantly higher at 3,627 m/s ± 0,538 (2,83-4,4) (p

International audience; To compare tendon elastic and structural properties of healthy individuals with those with Achilles or patellar tendinopathy. Sixty-seven participants (22 Achilles tendinopathy, 17 patellar tendinopathy, and 28 healthy controls) were recruited between March 2015 and March 2016. Shear wave velocity (SWV), an index of tissue elastic modulus, and tendon thickness were measured bilaterally at mid-tendon and insertional regions of Achilles and patellar tendons by an examiner blinded to group. Analysis of covariance, adjusted for age, body mass index, and sex was used to compare differences in tendon thickness and SWV between the two tendinopathy groups (relative to controls) and regions. Tendon thickness was included as a covariate for analysis of SWV. Compared to controls, participants with Achilles tendinopathy had lower SWV at the distal insertion (Mean difference MD; 95% CI: -1.56; -2.49 to -0.62 m/s; P

International audience; Several studies have suggested that evolving mechanical stresses and strains drive atherosclerotic plaque development and vulnerability. Especially, stress distribution in the plaque fibrous capsule is an important determinant for the risk of vulnerable plaque rupture. Knowledge of the stiffness of atherosclerotic plaque components is therefore of critical importance. In this work, force mapping experiments using atomic force microscopy (AFM) were conducted in apolipoprotein E-deficient (ApoE(-/-)) mouse, which represents the most widely used experimental model for studying mechanisms underlying the development of atherosclerotic lesions. To obtain the elastic material properties of fibrous caps and lipidic cores of atherosclerotic plaques, serial cross-sections of aortic arch lesions were probed at different sites. Atherosclerotic plaque sub-structures were subdivided into cellular fibrotic, hypocellular fibrotic and lipidic rich areas according to histological staining. Hertz's contact mechanics were used to determine elasticity (Young's) moduli that were related to the underlying histological plaque structure. Cellular fibrotic regions exhibit a mean Young modulus of 10.4±5.7kPa. Hypocellular fibrous caps were almost six-times stiffer, with average modulus value of 59.4±47.4kPa, locally rising up to ∼250kPa. Lipid rich areas exhibit a rather large range of Young's moduli, with average value of 5.5±3.5kPa. Such precise quantification of plaque stiffness heterogeneity will allow investigators to have prospectively a better monitoring of atherosclerotic disease evolution, including arterial wall remodeling and plaque rupture, in response to mechanical constraints imposed by vascular shear stress and blood pressure.

Aim: Atomic force microscopy nanoindentation of myofibers was used to assess and quantitatively diagnose muscular dystrophies from human patients. Materials & methods: Myofibers were probed from fresh or frozen muscle biopsies from human dystrophic patients and healthy volunteers, as well as mice models, and Young’s modulus stiffness values were determined. Results: Fibers displaying abnormally low mechanical stability were detected in biopsies from patients affected by 11 distinct muscle diseases, and Young’s modulus values were commensurate to the severity of the disease. Abnormal myofiber resistance was also observed from consulting patients whose muscle condition could not be detected or unambiguously diagnosed otherwise. Discussion & conclusion: This study provides a proof-of-concept that atomic force microscopy yields a quantitative read-out of human muscle function from clinical biopsies, and that it may thereby complement current muscular dystrophy diagnosis.

International audience; BACKGROUND: Because of the lack of reliable echocardiographic parameters to predict recovery after surgery, the optimal timing of surgery for severe mitral regurgitation remains controversial. The aim of this study was to determine whether global longitudinal strain (GLS) recorded preoperatively could help in predicting left ventricular (LV) ejection fraction (LVEF) postoperatively. METHODS: A total of 88 patients (mean age, 63 ± 13 years; 59 men) with severe degenerative mitral regurgitation were included prospectively in this study. Rest echocardiography was performed before and 6 ± 1 months after mitral valve surgery. Patients were divided into two groups: group A (postoperative LVEF ≥ 50%) and group B (postoperative LVEF < 50%). RESULTS: In group B, patients had larger preoperative LV end-systolic diameters (21.6 ± 2.6 vs 19.2 ± 3.7 mm/m(2), P = .02) and impaired preoperative GLS (-17 ± 2.8% vs -19.6 ± 3.6%, P = .01), whereas there was no difference in preoperative LVEF. Preoperative LV end-systolic diameter ≥ 22 mm/m(2) and GLS < -18% were independent predictors of postoperative LV dysfunction. CONCLUSIONS: LV end-systolic diameter is a well-recognized prognostic marker. In addition, this study demonstrates the additive and independent predictive value of preoperative GLS for predicting postoperative LV dysfunction.

Hepatitis C virus (HCV) p7 is a membrane-associated oligomeric protein harboring ion channel activity. It is essential for effective assembly and release of infectious HCV particles and an attractive target for antiviral intervention. Yet, the self-assembly and molecular mechanism of p7 ion channelling are currently only partially understood. Using molecular dynamics simulations (aggregate time 1.2 µs), we show that p7 can form stable oligomers of four to seven subunits, with a bias towards six or seven subunits, and suggest that p7 self-assembles in a sequential manner, with tetrameric and pentameric complexes forming as intermediate states leading to the final hexameric or heptameric assembly. We describe a model of a hexameric p7 complex, which forms a transiently-open channel capable of conducting ions in simulation. We investigate the ability of the hexameric model to flexibly rearrange to adapt to the local lipid environment, and demonstrate how this model can be reconciled with low-resolution electron microscopy data. In the light of these results, a view of p7 oligomerization is proposed, wherein hexameric and heptameric complexes may coexist, forming minimalist, yet robust functional ion channels. In the absence of a high-resolution p7 structure, the models presented in this paper can prove valuable as a substitute structure in future studies of p7 function, or in the search for p7-inhibiting drugs., Author Summary Hepatitis C remains a serious global health problem affecting more than 2% of the world's population, and current therapies are effective in only a subset of patients, necessitating an ongoing search for new treatments. The p7 viroporin is considered to be an attractive possible drug target, but rational drug design is hampered by the absence of a high-resolution p7 structure. In this paper, we explore possible structures of oligomeric p7 channels, and discuss the strengths and shortcomings of these models with respect to experimentally determined properties, such as pore-lining residues, ion conductance, and compatibility with low-resolution electron microscopy images. Our results present an image of p7 as a rudimentary, minimalistic ion channel, capable of existing in multiple oligomeric states but exhibiting a bias towards hexamers and heptamers. We believe that the work presented here will be valuable for future research by providing plausible 3-dimensional atomic-resolution models for the visualization of the p7 viroporin and serve as a basis for future computational studies.

International audience; BACKGROUND: The risk stratification of patients with left ventricular (LV) dysfunction can be performed using echocardiographic parameters such as the ejection fraction (EF). Recently, new technologies based on deformation measurements have been shown to identify early myocardial dysfunction before EF decrease. Consequently, tools such as two-dimensional strain have been incorporated into echocardiographic systems, allowing for fast, reliable, and reproducible calculation of longitudinal components of LV systolic deformation. The hypothesis in this study was that as a more sensitive marker of LV dysfunction, longitudinal strain would allow for the risk stratification of patients with heart failure. METHODS: This multicenter study included 147 patients with heart failure with LV EFs ≤ 45% (mean age, 64 ± 14 years; 74% men; mean LV EF, 29.9 ± 8.9%). Conventional echocardiographic parameters as well as global and segmental longitudinal strain were measured and compared with these values in a control population. Patients were monitored for cardiac events, defined as a composite criterion, over 12 months. RESULTS: Clinical events were observed in 20% of patients during the 12-month follow-up period. On receiver operating characteristic curve analysis, global longitudinal strain had the highest prognostic value (area under the curve, 0.83) and the highest combination of sensitivity (73%) and specificity (83%), using a cutoff value of -7%. CONCLUSION: Strain assessment is highly feasible and reliable in patients with LV dysfunction and allows for cardiovascular risk stratification in patients with heart failure with greater accuracy than LV EF.

International audience; Peak cap stress amplitude is recognized as a good indicator of vulnerable plaque (VP) rupture. However, such stress evaluation strongly relies on a precise, but still lacking, knowledge of the mechanical properties exhibited by the plaque components. As a first response to this limitation, our group recently developed, in a previous theoretical study, an original approach, called iMOD (imaging modulography), which reconstructs elasticity maps (or modulograms) of atheroma plaques from the estimation of strain fields. In the present in vitro experimental study, conducted on polyvinyl alcohol cryogel arterial phantoms, we investigate the benefit of coupling the iMOD procedure with the acquisition of intravascular ultrasound (IVUS) measurements for detection of VP. Our results show that the combined iMOD-IVUS strategy: (1) successfully detected and quantified soft inclusion contours with high positive predictive and sensitivity values of 89.7 ± 3.9% and 81.5 ± 8.8%, respectively, (2) estimated reasonably cap thicknesses larger than ∼300 µm, but underestimated thinner caps, and (3) quantified satisfactorily Young's modulus of hard medium (mean value of 109.7 ± 23.7 kPa instead of 145.4 ± 31.8 kPa), but overestimated the stiffness of soft inclusions (mean Young's moduli of 31.4 ± 9.7 kPa instead of 17.6 ± 3.4 kPa). All together, these results demonstrate a promising benefit of the new iMOD-IVUS clinical imaging method for in vivo VP detection.

International audience; Bovine testis hyaluronidase (btHyal) had been shown to have direct effects on cancer cells and to be a useful adjuvant in several medicines. Furthermore this enzyme had been found to be membrane-associated. Thus, in this work, the interactions between btHyal and membranes were analyzed by using lipid monolayers at the air-water interface as a biomimetic membrane system. This allowed us to define the btHyal interactions with two residues of hyaluronic acid (a btHyal substrate), GlcNAc and carboxylic group, which are present in cholesteryl-triethoxy-N-acetylglucosamine (Chol-E3-GlcNAc) and in DPPS, respectively. btHyal bound preferentially Chol-E3-GlcNAc monolayers and showed a decreasing affinity for Chol-E3-GlcNAc-DPPC monolayers containing decreasing amount of glycolipid, suggesting a crucial role of the glycolipid GlcNAc. Furthermore the significant btHyal binding to DPPS was not affected by the presence of free GlcNAc in the subphase. These results and the absence of significant binding of btHyal to pure DPPC monolayer suggest that the protein interacts with the lipid monolayer by mimicking the enzyme-substrate interactions or by electrostatic interactions.

International audience; This study aims at improving the understanding of mechanisms responsible for cell sensitivity to extracellular environment. We explain how substrate mechanical properties can modulate the force regulation of cell sensitive elements primarily adhesion sites. We present a theoretical and experimental comparison between two radically different approaches of the force regulation of adhesion sites that depends on their either stationary or dynamic behavior. The most classical stationary model fails to predict cell sensitivity to substrate stiffness whereas the dynamic model predicts extracellular stiffness dependence. This is due to a time dependent reaction force in response to actomyosin traction force exerted on cell sensitive elements. We purposely used two cellular models, i.e., alveolar epithelial cells and alveolar macrophages exhibiting respectively stationary and dynamic adhesion sites, and compared their sensitivity to theoretical predictions. Mechanical and structural results show that alveolar epithelial cells exhibit significant prestress supported by evident stress fibers and lacks sensitivity to substrate stiffness. On the other hand, alveolar macrophages exhibit low prestress and exhibit sensitivity to substrate stiffness. Altogether, theory and experiments consistently show that adhesion site dynamics and cytoskeleton prestress control cell sensitivity to extracellular environment with an optimal sensitivity expected in the intermediate range.

International audience; It is now recognized that prediction of the vulnerable coronary plaque rupture requires not only an accurate quantification of fibrous cap thickness and necrotic core morphology but also a precise knowledge of the mechanical properties of plaque components. Indeed, such knowledge would allow a precise evaluation of the peak cap-stress amplitude, which is known to be a good biomechanical predictor of plaque rupture. Several studies have been performed to reconstruct a Young's modulus map from strain elastograms. It seems that the main issue for improving such methods does not rely on the optimization algorithm itself, but rather on preconditioning requiring the best estimation of the plaque components' contours. The present theoretical study was therefore designed to develop: 1) a preconditioning model to extract the plaque morphology in order to initiate the optimization process, and 2) an approach combining a dynamic segmentation method with an optimization procedure to highlight the modulogram of the atherosclerotic plaque. This methodology, based on the continuum mechanics theory prescribing the strain field, was successfully applied to seven intravascular ultrasound coronary lesion morphologies. The reconstructed cap thickness, necrotic core area, calcium area, and the Young's moduli of the calcium, necrotic core, and fibrosis were obtained with mean relative errors of 12%, 4% and 1%, 43%, 32%, and 2%, respectively.

International audience; Usual imaging after endovascular aneurysm repair (EVAR) of abdominal aortic aneurysm (AAA) consists of AAA diameter monitoring and endoleak detection. Among additional predictor parameters previously proposed to help clinicians in better identifying subgroups of AAA still at risk of rupture, AAA wall motion after EVAR has been studied, but its value was not clearly established. Tissue Doppler imaging (TDI) is an ultrasonographic modality which allows wall motion measurements along an arterial segment. The aim of the current study was to analyze AAA wall motion with TDI before and after EVAR and to describe its evolution in patients with more than 1 month of follow-up. Twenty-five consecutive patients undergoing EVAR between February 2005 and June 2007 gave informed consent to be prospectively investigated with the TDI system before EVAR and at each visit during follow-up. The mean (SD) follow-up was 13.7 (9.7) months. Maximum mean segmental dilation (MMSD), segmental compliance, dilation at maximum diameter, pressure strain elastic modulus (Ep), and stiffness were compared between three periods (before stenting, before discharge, and at last follow-up), and their relation with AAA diameter was analyzed. A significant decrease in AAA compliance was immediately observed after successful EVAR and remained stable during later follow-up. On the other hand, AAA diameter progressively decreased along time and was statistically lower at the last control compared to the initial value. MMSD, segmental compliance, and dilation at maximum diameter were positively related to AAA diameter. This means that the larger the AAA diameter after stenting, the higher the value for these parameters can be expected. On the contrary, percentage of AAA diameter decrease and percentage of MMSD decrease were not related after successful EVAR. There was no parallelism between loss in compliance and diameter decrease along time, and there is not a unique pattern of AAA diameter and compliance evolution after EVAR. Even if comparison between patients without and with endoleak was weak due to the small sample of the latter group (five patients with endoleak), compliance tended to be greater in case of endoleak. AAA wall motion after successful EVAR reflects complex interactions between all the components of the stented aneurysm which evolve over time, including true compliance of the aneurysm wall itself; intra-aneurysm sac pressure with possible different effects for peak, mean, and pulse pressures; remodeling of the thrombus; stiffness characteristics of the graft; and systemic pressure. Combining simultaneous MMSD records with actual intrasaccular pressure measurements in patients with and without endoleak would improve our understanding of the clinical pulsatility mechanism within AAA after EVAR.

International audience; This study aims at improving the understanding of mechanisms responsible for cell sensitivity to extracellular environment. We explain how substrate mechanical properties can modulate the force regulation of cell sensitive elements primarily adhesion sites. We present a theoretical and experimental comparison between two radically different approaches of the force regulation of adhesion sites that depends on their either stationary or dynamic behavior. The most classical stationary model fails to predict cell sensitivity to substrate stiffness whereas the dynamic model predicts extracellular stiffness dependence. This is due to a time dependent reaction force in response to actomyosin traction force exerted on cell sensitive elements. We purposely used two cellular models, i.e., alveolar epithelial cells and alveolar macrophages exhibiting respectively stationary and dynamic adhesion sites, and compared their sensitivity to theoretical predictions. Mechanical and structural results show that alveolar epithelial cells exhibit significant prestress supported by evident stress fibers and lacks sensitivity to substrate stiffness. On the other hand, alveolar macrophages exhibit low prestress and exhibit sensitivity to substrate stiffness. Altogether, theory and experiments consistently show that adhesion site dynamics and cytoskeleton prestress control cell sensitivity to extracellular environment with an optimal sensitivity expected in the intermediate range.

The present study was designed to determine whether fatigue alters the ability to estimate an index of individual muscle force from shear elastic modulus measurements ( experiment I), and to test the ability of this technique to highlight changes in load sharing within a redundant muscle group during an isometric fatiguing task ( experiment II). Twelve subjects participated in experiment I, which consisted of smooth linear torque ramps from 0 to 80% of maximal voluntary contraction (MVC) performed before and after an isometric fatigue protocol, beginning at 40% of MVC and stopped when the force production dropped below 30% of MVC. Although the relationships between modulus and torque were very similar for pre- and postfatigue [root mean square deviation (RMSdeviation) = 3.7 ± 2.6% of MVC], the relationships between electromyography activity level and torque were greatly altered by fatigue (RMSdeviation = 10.3 ± 2.6% of MVC). During the fatiguing contraction, shear elastic modulus provided a significantly lower RMSdeviation between measured torque and estimated torque than electromyography activity level (5.7 ± 0.9 vs. 15.3 ± 3.8% of MVC). Experiment II performed with eight participants consisted of an isometric knee extension at 25% of MVC sustained until exhaustion. Opposite changes in shear elastic modulus were observed between synergists (vastus medialis, vastus lateralis, and rectus femoris) of some participants, reflecting changes in load sharing. In conclusion, despite the fact that we did not directly estimate muscle force (in Newtons), this is the first demonstration of an experimental technique to accurately quantify relative changes in force in an individual human muscle during a fatiguing contraction.