Circulating pro-neurotensin levels predict bodyweight gain and metabolic alterations in children.

BACKGROUND AND AIMS: Neurotensin (NT) is an intestinal peptide released after fat ingestion, which regulates appetite and facilitates lipid absorption. Elevated plasma levels of its stable precursor pro-neurotensin (pro-NT) are associated with type 2 diabetes, obesity and cardiovascular mortality in adult populations; no data on pro-NT and metabolic disease are available in children. Aim of the study was to evaluate plasma pro-NT in relation to the presence of obesity in children, and to test if high pro-NT associates with the development of metabolic impairment later in life. METHODS AND RESULTS: For this longitudinal retrospective study, we studied 151 overweight/obese children undergoing metabolic evaluations at University of Cagliari, Italy. Pro-NT was also assessed in 46 normal-weight, age-, sex-comparable normal-weight children, selected as a reference group. At the baseline, pro-NT was comparable between overweight/obese and normal-weight children and correlated positively with age (p < 0.001), triglycerides (p < 0.001) and inversely with HDL levels (p = 0.008). Plasma pro-NT associated with high triglycerides with OR = 5.9 (95%CI: 1.24-28.1; p = 0.026) after adjustment for multiple confounders. At the 6.5-year follow-up, high basal pro-NT associated with impaired ß-cell function to compensate for insulin-resistance (disposition index: r = -0.19, p = 0.035) and predicted bodyweight increase, as indicated by percentage change of standard deviation score BMI (median(95%CI) = +20.8(+4.9-+27.5)% in the highest tertile), independently from age, sex, triglycerides and insulin-resistance (standardized ß = 0.24; p = 0.036). CONCLUSIONS: Elevated pro-NT levels in children are significantly associated with weight gain later in life and may represent a marker of susceptibility to metabolic impairment in presence of obesity.

A priori prediction of the probability of survival in vehicle crashes using anthropomorphic test devices and human body models.

Objective: In the development of restraint systems, anthropomorphic test devices (ATDs) and human body models (HBMs) are used to estimate occupant injury risks. Due to conflicting objectives, this approach limits an injury severity risk tradeoff between the different body regions. Therefore, we present and validate a protocol for the aggregation of injury risks of body regions to a probability of survival (PoS). Methods: Injuries were clustered in regions similar to ATD or HBM investigations and the most severe injury as rated by the Maximum Abbreviated Injury Scale (MAIS) per body region was determined. Each injury was transformed into a dichotomous variable with regard to the injury severity level (e.g., MAIS 3+) whose injury risk was computed using the German In-Depth Accident Study (GIDAS) and NASS-CDS databases. Without loss of generality, we focus on 2 body regions-Head/face/neck (HFN) and chest (C)-at the MAIS 3+ level. The PoS was calculated using injury outcomes from the databases. The method of predicting PoS was validated by stratifying the database by crash type and technical crash severity. Results: The PoS of occupants injured in both HFN and C at the AIS 3+ level was found to be lower, at a statistically significant level, than that of occupants with AIS 3+ injuries to just one of the body regions. Focusing on occupants with only one body region injured at the AIS 3+ level, HFN injuries tended to decrease PoS more than chest injuries. For the validation cases, observed PoS could be reproduced in the majority of cases. When comparing predicted to observed values, a correlation of R2 = 0.92 was observed when not taking the restraint system into account. Focusing on frontal crashes, the correlation was R2 = 0.89. Considering only belted occupants, R2 increased to 0.93, whereas for cases with deployed airbag systems the R2 decreased to 0.68. The PoS for side crashes is reproduced with R2= 0.97 independent of the restraint system; it was 0.95 with belted occupants and 0.55 when also factoring in airbag deployment. Conclusions: The method showed an excellent predictive capability when disregarding the restraint system, or restraint-specific subgroups, for the considered validation cases.

In silico investigation of vertebroplasty as a stand-alone treatment for vertebral burst fractures.

BACKGROUND: The use of percutaneous vertebroplasty as a stand-alone treatment for stable vertebral burst fractures has been investigated in vitro and in clinical studies. These studies present inconsistent results on the mechanical response of vertebroplasty-treated burst fractures. In addition, observations of the loss of sagittal alignment after vertebroplasty raise questions on the applicability of vertebroplasty for burst fractures. Therefore, the aim of this study was to investigate the mechanical stability of burst fractures after stand-alone treatment by vertebroplasty. METHODS: Finite element simulations were performed with models generated from two laboratory-induced burst fractures in human thoracolumbar specimens. The burst fracture models were virtually injected with various cement volumes using a unipedicular or bipedicular approach. The models were subjected to four individual loads (compression, lateral bending, extension and torsion) and a multi-axial load case in the physiological range. FINDINGS: All treated burst fractures showed improvements in stiffness and a reduction in inter-fragmentary displacements, thus potentially providing a suitable mechanical environment for fracture healing. However, large volumes of the trabecular bone (<43%), cement (<53%) and bone-cement composite (<58%) were predicted to experience strain levels exceeding the yield point. While damage was not specifically modeled, this implies a potential collapse of the treated vertebra due to local failure. INTERPRETATION: To improve the primary stability and to prevent the collapse of treated burst fractures, the use of posterior instrumentation is suggested as an adjunct to vertebroplasty.

Geometrical aspects of patient-specific modelling of the intervertebral disc: collagen fibre orientation and residual stress distribution.

Patient-specific modelling of the spine is a powerful tool to explore the prevention and the treatment of injuries and pathologies. Albeit several methods have been proposed for the discretization of the bony structures, the efficient representation of the intervertebral disc anisotropy remains a challenge, especially with complex geometries. Furthermore, the swelling of the disc's nucleus pulposus is normally added to the model after geometry definition, at the cost of changes of the material properties and an unrealistic description of the prestressed state. The aim of this study was to develop techniques, which preserve the patient-specific geometry of the disc and allow the representation of the system anisotropy and residual stresses, independent of the system discretization. Depending on the modelling features, the developed approaches resulted in a response of patient-specific models that was in good agreement with the physiological response observed in corresponding experiments. The proposed methods represent a first step towards the development of patient-specific models of the disc which respect both the geometry and the mechanical properties of the specific disc.

Nonlinear dynamics of the human lumbar intervertebral disc.

Systems with a quasi-static response similar to the axial response of the intervertebral disc (i.e. progressive stiffening) often present complex dynamics, characterized by peculiar nonlinearities in the frequency response. However, such characteristics have not been reported for the dynamic response of the disc. The accurate understanding of disc dynamics is essential to investigate the unclear correlation between whole body vibration and low back pain. The present study investigated the dynamic response of the disc, including its potential nonlinear response, over a range of loading conditions. Human lumbar discs were tested by applying a static preload to the top and a sinusoidal displacement at the bottom of the disc. The frequency of the stimuli was set to increase linearly from a low frequency to a high frequency limit and back down. In general, the response showed nonlinear and asymmetric characteristics. For each test, the disc had different response in the frequency-increasing compared to the frequency-decreasing sweep. In particular, the system presented abrupt changes of the oscillation amplitude at specific frequencies, which differed between the two sweeps. This behaviour indicates that the system oscillation has a different equilibrium condition depending on the path followed by the stimuli. Preload and amplitude of the oscillation directly influenced the disc response by changing the nonlinear dynamics and frequency of the jump-phenomenon. These results show that the characterization of the dynamic response of physiological systems should be readdressed to determine potential nonlinearities. Their direct effect on the system function should be further investigated.

Modelling the influence of heterogeneous annulus material property distribution on intervertebral disk mechanics.

Accurate modeling of the annulus fibrosus (AF) is a crucial aspect to study spine mechanics in silico. Numerical models require validation at both the microscale and organ level to be representative of the real system. Although the AF presents distributed material properties, its response is often modeled with a homogeneous stiffness distribution. The aim of this study was to investigate the influence of different modeling approaches on the numerical response of disk models, based on lamellae mechanics. A material mapping strategy was developed to define element-wise the local annulus material properties, based on prior findings of single-lamella mechanics and collagen distribution. Three modeling approaches were compared: homogeneous, radial and radial-circumferential distribution of material properties. The simulations showed a strong influence of the chosen modeling approach on the disk's tissue- and organ-scale mechanics. A homogeneous model with uniform, average lamellae stiffness predicted a substantially different internal stress distribution and organ-level response, compared to a model with heterogeneous material properties of the annulus lamellae. Finally, the study has indirectly highlighted that the organization of the mature disks could be a consequence of adaptation to the stresses induced by the applied loads, in order to evenly distribute the load over the entire structure.

Nonlinear numerical analysis of the structural response of the intervertebral disc to impact loading.

The analysis of intervertebral disc dynamics under impact loading, using computational simulation, is scarcely reported. In this study, the contribution of the characteristic structure of the disc to its dynamic response has been evaluated. The influence of several model features on the dynamic response was investigated. A hyperelastic large deformation formulation was used to describe the nonlinear behaviour of the soft tissues. The material parameters were determined by the fitting of experimental data from the literature. The model demonstrated pressure wave propagation and reflection through the disc, with a periodic oscillation of the system in response to a single impulse load, and highlighted a potential primary role played by the collagen fibre reinforcement. Their tensioning contributes to changing the stress propagation and oscillation, with a faster reduction in the internal pressure peak. The natural frequency of the disc was predicted to be approximately 9.8 Hz for the vertical oscillation.

A continuum description of the damage process in the arterial wall of abdominal aortic aneurysms.

In the present work, we develop a three-dimensional isotropic finite-strain damage model for abdominal aortic aneurysm (AAA) wall that considers both the characteristic softening of the material caused by damage and the spatial variation of the material properties. A strain energy function is formulated that accounts for a hyperelastic, slightly compressible, isotropic material behavior during the elastic phase, whereas the damage process only contributes to the material response when the elastic limit of the AAA wall is exceeded. Material and damage parameters are obtained by fitting the strain energy function to the experimental data obtained by uniaxial tensile tests of freshly harvested AAA wall samples. The damage model extends the validity of the material law to a strain range of up to 50%. Purely elastic material laws for AAA wall are only valid for a strain range of up to 17%. In a series of finite element simulations of patient-specific AAAs, serving as numerical examples, we investigate the applicability of the damage model. The use of the damage model does not yield a more distinct identification of rupture-prone AAAs than other computational-based risk indices. However, the benefit of the finite-strain damage model is the potential capability to trigger growth and remodeling processes in mechanobiological models.