Tridimensional evaluation and optimization of the orthotic treatment of adolescent idiopathic scoliosis

Adolescent idiopathic scoliosis involves complex tridimensional deformities of the spine, rib cage and pelvis. Moderate curves generally are treated using an orthosis. This paper presents different studies performed over the last fifteen years related to the biomechanical evaluation and optimization of the orthopedic treatment of scoliotic deformities. Patient specific 3D models of the spine, pelvis and rib cage are computed from calibrated radiographs, and are used to calculate 2D and 3D clinical indices. The torso shape is acquired using surface topography. With such internal and external 3D models, the efficacy of the most frequently used orthoses can be analyzed and new treatments can be developed. Pressures generated by a brace on the patient's trunk were measured using a flexible matrix of pressure sensors and displayed over the patient's internal geometry in order to analyze the brace efficacy. Patient specific finite element models have been developed, including the osseo-ligamentous structures as well as the muscles, the neuro-control, trunk growth and its adaptation to the stress. These models were used to analyze the effects of the Boston brace. The electro-myographic activity also was measured to analyze the < active > correction mechanisms. Adjustment techniques and software are used to help the orthotists with real time feedback when the brace is being fabricated and adjusted to the patient. Residual growth potential is also being added to the computer model to simulate the long term effect of a brace. The improvement of the orthotic treatments of scoliotic deformities is very encouraging. The exploitation of such tools is expected to allow reaching optimal treatment personalized to each patient. double dagger.     

Innate versus adaptive immunity in sticklebacks: evidence for trade-offs from a selection experiment

In vertebrates, the immune system consists of two arms of different characteristics: the innate and the acquired immune response. Parasites that are only shortly exposed to the immune system are most efficiently attacked by fast, constitutive innate immune mechanisms. Here, we experimentally selected within four fish families for high innate resistance versus susceptibility of three-spined sticklebacks (Gasterosteus aculeatus) against infection with the eye-fluke (Diplostomum pseudospathacaeum), a parasite whose metacercariae are protected from the immune system within the eye lens. We predicted that in families with high susceptibility, the adaptive immune system would be upregulated when challenged with infection. In accordance, we found that MHC class IIB expression is increased by approximately 50% in those lines selected for higher parasite load (i.e. low innate response). This suggests extensive genetic correlations between innate and adaptive immune system and/or crosstalk between both lines of defense. An efficient, specific innate immune response might reduce overall activation of the immune system and potentially alleviate associated effects of immunopathology.     

A vectored measles virus induces hepatitis B surface antigen antibodies while protecting macaques against measles virus challenge

Hepatitis B virus (HBV) acute and chronic infections remain a major worldwide health problem. Towards developing an anti-HBV vaccine with single-dose scheme potential, we engineered infectious measles virus (MV) genomic cDNAs with a vaccine strain background and expression vector properties. Hepatitis B surface antigen (HBsAg) expression cassettes were inserted into this cDNA and three MVs expressing HBsAg at different levels generated. All vectored MVs, which secrete HBsAg as subviral particles, elicited humoral responses in MV-susceptible genetically modified mice. However, small differences in HBsAg expression elicited vastly different HBsAg antibody levels. The two vectors inducing the highest HBsAg antibody levels were inoculated into rhesus monkeys (Macaca mulatta). After challenge with a pathogenic MV strain (Davis87), control naive monkeys showed a classic measles rash and high viral loads. In contrast, all monkeys immunized with vaccine or a control nonvectored recombinant vaccine or HBsAg-expressing vectored MV remained healthy, with low or undetectable viral loads. After a single vaccine dose, only the vector expressing HBsAg at the highest levels elicited protective levels of HBsAg antibodies in two of four animals. These observations reveal an expression threshold for efficient induction of HBsAg humoral immune responses. This threshold is lower in mice than in macaques. Implications for the development of divalent vaccines based on live attenuated viruses are discussed.     

Rate of treadmilling of actin filaments in vitro

Actin filaments capped at the barbed ends were formed by polymerizing monomeric actin onto a gelsolin-actin complex. The rate of depolymerization and polymerization of the pointed ends was determined by diluting gelsolin-capped actin filaments into various concentrations of monomeric actin. Under the conditions of the experiments (100 mM-KCl, 2 mM-MgCl2 at 37 degrees C) the rate constant of dissociation of subunits both from a shortening and a lengthening filament was found to be 0.21 s-1. As the rate of dissociation of subunits from the slow pointed end determines the rate of treadmilling, it is concluded that actin filaments treadmill with a rate of about 2 micron/h.     

Differential response of stress fibers and myofibrils to gelsolin

The actin-severing activity of human platelet gelsolin was analyzed on embryonic skeletal and cardiac myofibrils, and on stress fibers in non-muscle cells. These subcellular structures, although in all three cell types composed of contractile proteins arranged in sarcomeric units, were found to respond differently to gelsolin. The myofibrils in permeabilized myotubes or cardiac cells, as well as in living, microinjected muscle cells proved resistant to a wide concentration range of gelsolin. The same was found for the "mini-sarcomeres" which are seen in developing muscle cells. In contrast, stress fibers in microinjected fibroblasts or epithelial cells, as well as in permeabilized cells, were broken down rapidly by the platelet gelsolin. We conclude from these results that the mini-sarcomeres in embryonic myotubes and cardiac myocytes are not identical with stress fibers.     

Distinct mouse DNA sequences enable establishment and persistence of plasmid DNA polymers in mouse cells.

Distinct elements isolated from mouse genomic DNA confer on plasmid DNA the ability to persist at high copy numbers in mouse L fibroblasts (1). Field inversion gel electrophoresis demonstrated that - in contrast to our previous assumption - the persisting plasmid DNA does not exist extrachromosomally but as clusters of tandem repeats integrated into genomic DNA. Digestion with restriction endonucleases that do not cut within the plasmid DNA results in fragments of 50-300 kb in length indicating reiteration of 10-50 plasmid DNA molecules. Restriction with several enzymes that cut once or twice within the plasmid sequences lead to fragment(s) indicative for head-to-tail tandem repeats. In situ hybridization revealed signals for a long homogeneously staining region (HSR) in one or two chromosomes per cell nucleus. Possibilities how these elements could act in the establishment and/or maintenance of the head-to-tail polymers of plasmid DNA in mouse cells are discussed.