A generic musculoskeletal model of the juvenile lower limb for biomechanical analyses of gait

The aim of this study was to develop a generic musculoskeletal model of a healthy 10-year-old child and examine the effects of geometric scaling on the calculated values of lower-limb muscle forces during gait. Subject-specific musculoskeletal models of five healthy children were developed from in vivo MRI data, and these models were subsequently used to create a generic juvenile (GJ) model. Calculations of lower-limb muscle forces for normal walking obtained from two scaled-generic versions of the juvenile model (SGJ1 and SGJ2) were evaluated against corresponding results derived from an MRI-based model of one subject (SSJ1). The SGJ1 and SGJ2 models were created by scaling the GJ model using gait marker positions and joint centre locations derived from MRI imaging, respectively. Differences in the calculated values of peak isometric muscle forces and muscle moment arms between the scaled-generic models and MRI-based model were relatively small. Peak isometric muscle forces calculated for SGJ1 and SGJ2 were respectively 2.2% and 3.5% lower than those obtained for SSJ1. Model-predicted muscle forces for SGJ2 agreed more closely with calculations obtained from SSJ1 than corresponding results derived from SGJ1. These results suggest that accurate estimates of muscle forces during gait may be obtained by scaling generic juvenile models based on joint centre locations. The generic juvenile model developed in this study may be used as a template for creating subject-specific musculoskeletal models of normally-developing children in studies aimed at describing lower-limb muscle function during gait

Analysis of muscle coordination in crouch-gait of children with cerebral palsy

Zsfassung in dt. SpracheThe most common cause for childhood disability in Europe is cerebral palsy (CP). Permanent disturbances of movement, gait and posture are caused by this non-progressive neurologic disorder. Surgeries that correct deformities of muscles and bones of the lower limbs are a common treatment. The mobility of patients after these interventions can improve even more, if the individual muscle functions of a patient are known in advance. Goal of this dissertation is to investigate the crouched gait of children with CP on a level of individual muscle analyses according to biomechanical calculations using individual models based on radiology data. A secondary goal of this thesis is the development of methods that can help to pave the way for using muscle specific biomechanical analysis in clinical routine. Musculoskeletal lower-limb models of two children with cerebral palsy were created together with five models of a control group of normally developing children. Here a newly developed method was applied that facilitates the generation of models that incorporate of individual subject's geometry with the appropriate parameterization of the modelled muscles. The method and the generated models are validated by comparing simulated maximum isometric joint moments to dynamometric measurements. Additionally a combination of the data of the control group is used to describe the first available generic biomechanical model for children. The individual models are used to calculate the time histories of leg-muscle forces and their contribution towards joint moments as well as to joint and centre of mass accelerations. These results provide insight into muscle coordination during gait of normally developing children and of crouch gait in children with cerebral palsy. Analysis of particular muscle functions show the capability of such simulation methods to provide additional diagnostic information that can help to improve the treatment of children with cerebral palsy

Papillomavirus-like Particles in Equine Medicine

Papillomaviruses (PVs) are a family of small DNA tumor viruses that can induce benign lesions or cancer in vertebrates. The observation that animal PV capsid-proteins spontaneously self-assemble to empty, highly immunogenic virus-like particles (VLPs) has led to the establishment of vaccines that efficiently protect humans from specific PV infections and associated diseases. We provide an overview of PV-induced tumors in horses and other equids, discuss possible routes of PV transmission in equid species, and present recent developments aiming at introducing the PV VLP-based vaccine technology into equine medicine

Potential of a BPV1 L1 VLP vaccine to prevent BPV1- or BPV2-induced pseudo-sarcoid formation and safety and immunogenicity of EcPV2 L1 VLPs in the horse

We have previously shown that immunization of horses with BPV1 L1 virus-like particles (VLP) is safe and highly immunogenic, and that bovine papillomavirus types 1 and 2 (BPV1, BPV2) are closely related serotypes. Here we evaluated the protective potential of a BPV1 L1 VLP vaccine against experimental BPV1 and BPV2 challenge, and studied the safety and immunogenicity of a bivalent EcPV2/BPV1 L1 VLP vaccine. Fourteen healthy horses were immunized with BPV1 L1 VLPs (100 µg/injection) plus adjuvant on days 0 and 28, whilst seven remained unvaccinated. On day 42, all 21 horses were challenged intradermally at ten sites of the neck with 107 BPV1 virions per injection. In analogy, 14 horses immunized twice with EcPV2 plus BPV1 L1 VLPs (50 µg each) and seven control animals were challenged with 107 BPV2 virions/injection. Immunization with BPV1 L1 VLPs alone induced a robust antibody response (day-42 median titre: 12,800) and BPV1-inoculated skin remained unchanged in 13/14 vaccinated horses. Immunization with the bivalent vaccine was safe, resulted in lower median day-42 antibody titres of 400 for BPV1, and 1600 for EcPV2, and conferred significant yet incomplete cross-protection from BPV2-induced tumour formation, with 11/14 horses developing small, short-lived papules. Control horses developed pseudo-sarcoids at all inoculation sites. The monovalent BPV1 L1 VLP vaccine proved highly effective in protecting horses from BPV1-induced pseudo-sarcoid formation. Incomplete protection from BPV2-induced tumour development conferred by the bivalent vaccine is due to the poorer immune response by immune interference or lower cross-neutralization titres to heterologous BPV2 virions