A Proof of Concept of a Non-Invasive Image-Based Material Characterization Method for Enhanced Patient-Specific Computational Modeling.

PURPOSE: Computational models of cardiovascular structures rely on their accurate mechanical characterization. A validated method able to infer the material properties of patient-specific large vessels is currently lacking. The aim of the present study is to present a technique starting from the flow-area (QA) method to retrieve basic material properties from magnetic resonance (MR) imaging. METHODS: The proposed method was developed and tested, first, in silico and then in vitro. In silico, fluid-structure interaction (FSI) simulations of flow within a deformable pipe were run with varying elastic modules (E) between 0.5 and 32 MPa. The proposed QA-based formulation was assessed and modified based on the FSI results to retrieve E values. In vitro, a compliant phantom connected to a mock circulatory system was tested within MR scanning. Images of the phantom were acquired and post-processed according to the modified formulation to infer E of the phantom. Results of in vitro imaging assessment were verified against standard tensile test. RESULTS: In silico results from FSI simulations were used to derive the correction factor to the original formulation based on the geometrical and material characteristics. In vitro, the modified QA-based equation estimated an average E = 0.51 MPa, 2% different from the E derived from tensile tests (i.e. E = 0.50 MPa). CONCLUSION: This study presented promising results of an indirect and non-invasive method to establish elastic properties from solely MR images data, suggesting a potential image-based mechanical characterization of large blood vessels.

Morphine, a potential inhibitor of myeloperoxidase activity.

Morphine is an opioid alkaloid commonly used in clinical practice for its analgesic properties. The phenolic hydroxyl group of that phenanthrene derivative is pivotal for binding to opioid receptors but it may also be responsible for the antioxidant behavior of morphine reported in several in vitro experiments. In this study, we assessed the effect of morphine on myeloperoxidase (MPO), a hemic enzyme from azurophilic granules of polymorphonuclear neutrophils involved in the production of cytotoxic and microbicidal reactive oxidants during inflammatory response. Specific immunological extraction followed by enzyme detection (SIEFED) and molecular modeling (docking) were performed to study the potential anti-catalytic action of morphine on MPO in comparison with the inhibitory effects of reference antioxidant molecules quercetin, gallic acid and ascorbic acid. The reducing action of morphine on the MPO peroxidase cycle has been investigated using electron paramagnetic resonance (EPR) and UV-visible absorption spectroscopy. Morphine acted as a reducing substrate in the peroxidase cycle of MPO and therefore protected the enzyme against the suicide action of its natural substrate, hydrogen peroxide. The SIEFED experiments associated with the docking study, further demonstrated a lack of strong and sustained anti-catalytic activity of morphine. In summary, from the results of this study, it appears that morphine acts as a weak and reversible inhibitor of MPO that may nonetheless contribute to immunomodulatory and antioxidant effects of this opioid analgesic in vivo.

Metric field construction for anisotropic mesh adaptation with application to blood flow simulations.

The goal of this paper is to generate an anisotropic metric field suitable for cardiovascular geometries before a fluid simulation. Starting from a curvature map, an initial surface metric field is computed. This metric is used for anisotropic surface mesh adaptation and consecutively extended inside the volume in a frontal manner. The algorithm is based on the method proposed by Alauzet but replaces the metric intersection steps by an original metric 'blending'. This allows for a graded anisotropic volume mesh with a refinement layer close to the walls. The benefits of the resulting mesh are multiple: a reduced number of degrees of freedom, a priori refinement in areas with strong gradients of velocity and automatically increased resolution in regions with high surface curvature. The primal application of this method is in the domain of cardiovascular flows. Flow fields and derived quantities (wall shear stress) through a model bypass around a stenosed artery obtained on an adapted and standard isotropic mesh are compared. In addition, the mesh generation method is tested on a more complex patient-specific geometry. Values of computed wall shear stress are shown to be close to values obtained on anisotropic Hessian-adapted mesh, demonstrating the computational efficiency of the approach in comparison with adaptation based on error indicators derived from flow field.

Behavioral and adrenal responses to various stressors in mule ducks from different commercial genetic selection schemes and their respective parental genotypes.

The mule duck, a hybrid produced by crossing a Muscovy drake and a Pekin female, is reported to express inappropriate behavior such as collective avoidance of people, the resulting distress and physical consequences potentially compromising their welfare. The present study was carried out to characterize the responses of mule duck strains from different commercial selection schemes to various stressful conditions and to confirm previous data on the genetic cross effects observed in a specific genotype. Three independent experiments were conducted with ducks from 3 French breeding companies (A, B, and C). Each experiment compared 2 mule genotypes sharing one common parental origin (paternal for ducks from company A or maternal for ducks from companies B and C). Mule duck males from the 2 genotypes and their respective parental genotypes (Pekin and Muscovy) were subjected to a set of social and stressful physiological and behavioral tests. Previously reported differences in genetic cross effects on fear responses between the parental genotypes and the corresponding hybrid were confirmed in these commercial crosses. Both mule duck and Pekin genotypes showed more active physiological and behavioral responses to stress than Muscovy genotypes. The new finding of this study is that mule genotypes appear to be more sensitive to the social environment than both respective parental genotypes. Few differences were observed between the 2 mule genotypes from A and C. On the other hand, several traits of the 2 mule genotypes from B differed. In addition, A and C mule genotypes were characterized by the same adrenal and behavioral traits but contrasting responses. The B mule genotypes were characterized by a different set of behavioral traits, and only 1 of the 2 B mule ducks was characterized by a group of adrenal traits.

The 2.4-A crystal structure of the penicillin-resistant penicillin-binding protein PBP5fm from Enterococcus faecium in complex with benzylpenicillin.

Penicillin-binding proteins (PBPs) are membrane proteins involved in the final stages of peptidoglycan synthesis and represent the targets of beta-lactam antibiotics. Enterococci are naturally resistant to these antibiotics because they produce a PBP, named PBP5fm in Enterococcus faecium, with low-level affinity for beta-lactams. We report here the crystal structure of the acyl-enzyme complex of PBP5fm with benzylpenicillin at a resolution of 2.4 A. A characteristic of the active site, which distinguishes PBP5fm from other PBPs of known structure, is the topology of the loop 451-465 defining the left edge of the cavity. The residue Arg464, involved in a salt bridge with the residue Asp481, confers a greater rigidity to the PBP5fm active site. In addition, the presence of the Val465 residue, which points into the active site, reducing its accessibility, could account for the low affinity of PBP5fm for beta-lactam. This loop is common to PBPs of low affinity, such as PBP2a from Staphylococcus aureus and PBP3 from Bacillus subtilis. Moreover, the insertion of a serine after residue 466 in the most resistant strains underlines even more the determining role of this loop in the recognition of the substrates.

French multicenter randomized double-blind placebo-controlled trial on nebulized amiloride in cystic fibrosis patients. The Amiloride-AFLM Collaborative Study Group.

The effect of amiloride, a sodium channel blocker, has been evaluated in a multicenter randomized double-blind placebo-controlled trial in cystic fibrosis patients more than 5-years-old (n = 137) whose forced vital capacity (FVC), forced expiratory volume in 1 sec (FEV(1)), and forced mid-expiratory flow (FEF(25-75)) were not below 50%, 50%, and 30% of reference values, respectively. Patients were randomly allocated to two parallel groups. Sixty-four patients were chronically colonized with Pseudomonas aeruginosa; they received either amiloride or placebo as a nebulized solution three times daily for 6 months. Routine treatments were continued. Patients chronically colonized with Pseudomonas received nebulized colimycine twice a day for a month during the third and sixth months of treatment. Bronchopulmonary exacerbations were treated in the usual way. The effects of the amiloride treatment were assessed at the end of the 6-month treatment period. The effects on FVC and secondarily on FEV(1), FEF(25-75), the number of days on antibiotic therapy, the Shwachman score, a nutritional index (weight/height(2)), the change in sputum bacterial flora, and nocturnal cough were assessed. For the patients not chronically colonized with Pseudomonas, the effect of the treatment was also evaluated by counting chronic colonizations with pathogens appearing during the trial period. The present study failed to demonstrate any significant benefit of amiloride over placebo on FVC, FEV(1), and the other secondary endpoints in the studied population. Neither the chronically colonized, nor the noncolonized patients benefited. The confidence intervals of the differences between treatment groups indicated small differences that were most likely of no clinical significance. Complementary analyses taking into account the gender, the type of mutation, the subpopulations whose FVC and FEV(1) were below 80% of normal values at the beginning of the study, and also patients less than 10 years old, did not show any statistically or clinically significant improvements following amiloride therapy.

[Effectiveness and safety of hydroxyethyl-rutosides in the local treatment of symptoms of venous insufficiency during air travel]. / Etude d'efficacité et de tolérance des hydroxyethyl-rutosides dans le traitement local des symptômes d'insuffisance veineuse survenant au cours des transports aériens.

During air travel, the length of time spent in a sitting position and the absence of muscular activity in the calves severely slow the rate of blood flow in the lower limbs. The aim of this randomized, cross-over, double-blind study was to evaluate local application of Hydroxyethyl-rutosides (O-Beta-Hydroxyethylrutosides) in the treatment of symptoms of venous insufficiency including stasis-induced edema during extended air travel on flights exceeding 6 hours. Hydroxyethyl-rutosides or placebo was applied every 3 or 4 hours throughout the flight. In the 51 subjects evaluated (both males and females) the results show statistically significant differences favoring treatment with Hydroxyethyl-rutosides both with regard to objective signs of edema: change in minimum ankle circumference was less during trips in which Hydroxyethyl-rutosides was applied, whether compared with the maximum measurement (p = 0.04) or the last measurement made during the flights, and with regard to subjective signs: several symptoms occurred significantly less frequently when the subject applied Hydroxyethyl-rutosides during the flight [pain (p = 0.03), sensation of heavy and tired legs (p = 0.04) and sensation of swelling (p = 0.02)]. the patient's overall assessment of the treatment was also favorable after using Hydroxyethyl-rutosides Gel (p = 0.01). the number of subjects complaining of edema (pitting edema, marks of shoes, difficulties putting shoes back on) was significantly lower during periods of treatment with Hydroxyethyl-rutosides Gel (p = 0.001). Local application of Hydroxyethyl-rutosides, 3 to 4 times during 6 to 14 hours is thus effective in treating the main symptoms of venous insufficiency including stasis-induced edema caused by extended periods in the sitting position during long air flights.

Arthroscopic evaluation of post-traumatic patellofemoral chondropathy.

OBJECTIVE: To evaluate clinically and arthroscopically post-traumatic patellofemoral chondropathy. METHODS: Fifty-nine patients with post-traumatic patellofemoral chondropathy were included in a cross sectional study and 46 of them completed a 6 month longitudinal study. Evaluation of the disease, performed once in the cross sectional study and twice (at entry and after 6 months) in the longitudinal study, included clinical and arthroscopic variables evaluating disease activity and severity. Arthroscopy was performed under local anesthesia in an outpatient procedure using a small arthroscope. Chondropathy was evaluated by the overall assessment of the investigator using a visual analog scale, and by the Société Française d'Arthroscopie (SFA) scoring system (SFA score: 0-100). Synovitis was assessed by the "synovitis score," which represents a composite index taking into account intensity, extent and location of synovial abnormalities. RESULTS: In the cross sectional study, severity of chondropathy correlated with age, body mass index, disease duration, functional impairment (Lequesne's index and maximum number of steps descended), patellofemoral crepitus on active motion, limitation of flexion, and presence and amount of synovitis. Knee effusion correlated with the presence of synovitis, but no correlation was found between pain or functional impairment and presence or amount of synovitis. In the longitudinal study, no statistically significant change in chondropathy was observed after 6 months followup despite a statistically significant improvement in pain, function, and knee effusion after this period. However, a statistically significant correlation was found between the progression of patellofemoral chondropathy and the presence and amount of synovitis at baseline. Synovitis was present at baseline in 10 patients. Changes in SFA scores were 1.2 +/- 1.6 and -0.1 +/- 1.0 in the groups of patients with and without synovitis, respectively (p = 0.0062). CONCLUSION: These data suggest that synovitis might have a deleterious effect on the evolution of post-traumatic patellofemoral chondropathy or might be a marker for active cartilage breakdown.