How effective are pictograms in communicating risk about driving-impairing medicines?

Objectives: To evaluate and compare the effectiveness of 2 pictograms in communicating risk in terms of respondents' level of understanding, estimated level of driving risk, and intention to change driving behavior. The added value of a side-text was also investigated.

Methods: Two experiments were conducted among 270 drivers visiting a pharmacy.

Simulations of trabecular remodeling and fatigue: is remodeling helpful or harmful?

Microdamage-targeted resorption is paradoxal, because it entails the removal of bone from a region that was already overloaded. Under continued intense loading, resorption spaces could potentially cause more damage than they remove. To investigate this problem, we incorporated damage algorithms in a computer-simulation model for trabecular remodeling.

A sclerostin-based theory for strain-induced bone formation.

Bone formation responds to mechanical loading, which is believed to be mediated by osteocytes. Previous theories assumed that loading stimulates osteocytes to secrete signals that stimulate bone formation. In computer simulations this 'stimulatory' theory successfully produced load-aligned trabecular structures.

Effects of vibration treatment on tibial bone of ovariectomized rats analyzed by in vivo micro-CT.

Daily low-amplitude, high-frequency whole-body vibration (WBV) treatment can increase bone formation rates and bone volume in rodents. Its effects vary, however, with vibration characteristics and study design, and effects on 3D bone microstructure of ovariectomized animals over time have not been documented. Our goal was to determine the effects of WBV on tibial bone of ovariectomized, mature rats over time using an in vivo micro-CT scanner.

Comparison of bone loss induced by ovariectomy and neurectomy in rats analyzed by in vivo micro-CT.

We hypothesized that osteoporosis due to estrogen deficiency progresses faster than due to disuse and that at the same amount of bone loss, disuse leads to less favorable bone structure and mechanical properties than estrogen deficiency. Adult rats were either ovariectomized (OVX) (n = 9) or neurectomized (NX) (n = 8). At week 0, 1, 2, 3, and 4, in vivo micro-CT scans were made of the proximal tibia.

Effects of PTH treatment on tibial bone of ovariectomized rats assessed by in vivo micro-CT.

Unlabelled: Using in vivo microcomputed tomography (micro-CT), we found in parathyroid hormone (PTH)-treated osteopenic rats linear increases in cortical and trabecular, due to increased trabecular thickness and number, bone mass. Bone was formed in cavities, leading to restoral of nearly cleaved trabeculae. For the first time, effects in PTH-treated rats were analyzed longitudinally.

Residual periosteum tension is insufficient to directly modulate bone growth.

Periosteal incision is one of the less severe interventions used to correct mild long bone growth pathologies. The mechanism responsible for this growth modulation is still unclear. A generally adopted hypothesis is that incision releases compressive force created by tensioned periosteum.

Remodeling of fracture callus in mice is consistent with mechanical loading and bone remodeling theory.

During the remodeling phase of fracture healing in mice, the callus gradually transforms into a double cortex, which thereafter merges into one cortex. In large animals, a double cortex normally does not form. We investigated whether these patterns of remodeling of the fracture callus in mice can be explained by mechanical loading.

Determining the most important cellular characteristics for fracture healing using design of experiments methods.

Computational models are employed as tools to investigate possible mechanoregulation pathways for tissue differentiation and bone healing. However, current models do not account for the uncertainty in input parameters, and often include assumptions about parameter values that are not yet established. The objective of this study was to determine the most important cellular characteristics of a mechanoregulatory model describing both cell phenotype-specific and mechanobiological processes that are active during bone healing using a statistical approach.

Relating osteon diameter to strain.

Osteon diameter is generally smaller in bone regions that experience larger strains. A mechanism relating osteon diameter to strain is as yet unknown. We propose that strain-induced osteocyte signals inhibit osteoclastic bone resorption.

Micro-finite element simulation of trabecular-bone post-yield behaviour--effects of material model, element size and type.

Micro-finite element (micro-FE) analysis became a standard tool for the evaluation of trabecular bone mechanical properties. The accuracy of micro-FE models for linear analyses is well established. However, the accuracy of recently developed nonlinear micro-FE models for simulations of trabecular bone failure is not known.

Indirect determination of trabecular bone effective tissue failure properties using micro-finite element simulations.

Trabecular bone strength is marked not only by the onset of local yielding, but also by post-yield behavior. To study and predict trabecular bone elastic and yield properties, micro-finite element (micro-FE) models were successfully applied. However, trabecular bone strength predictions require micro-FE models incorporating post-yield behavior of trabecular bone tissue.

Collagen orientation in periosteum and perichondrium is aligned with preferential directions of tissue growth.

A feedback mechanism between different tissues in a growing bone is thought to determine the bone's morphogenesis. Cartilage growth strains the surrounding tissues, eliciting alterations of its matrix, which in turn, creates anisotropic stresses, guiding directionality of cartilage growth. The purpose of this study was to evaluate this hypothesis by determining whether collagen fiber directions in the perichondrium and periosteum align with the preferential directions of long bone growth.

A mechano-regulatory bone-healing model incorporating cell-phenotype specific activity.

Phenomenological computational models of tissue regeneration and bone healing have been only partially successful in predicting experimental observations. This may be a result of simplistic modeling of cellular activity. Furthermore, phenomenological models are limited when considering the effects of combined physical and biological interventions.

Bone degeneration and recovery after early and late bisphosphonate treatment of ovariectomized wistar rats assessed by in vivo micro-computed tomography.

Bisphosphonates are antiresorptive drugs commonly used to treat osteoporosis. It is not clear, however, what the influence of the time point of treatment is. Recently developed in vivo micro-computed tomographic (CT) scanners offer the possibility to study such effects on bone microstructure in rats.

A unified theory for osteonal and hemi-osteonal remodeling.

The process of bone remodeling is carried out by 'basic multicellular units' of osteoclasts and osteoblasts. Osteoclasts excavate a resorption space that is subsequently filled with new bone by osteoblasts. In cortical bone osteoclasts dig tunnels through solid bone, in cancellous bone they dig trenches across the trabecular surface.

Load distribution in the healthy and osteoporotic human proximal femur during a fall to the side.

Due to remodeling of bone architecture, an optimal structure is created that minimizes bone mass and maximizes strength. In the case of osteoporotic vertebral bodies, however, this process can create over-adaptation, making them vulnerable for non-habitual loads. In a recent study, micro-finite element models of a healthy and an osteoporotic human proximal femur were analyzed for the stance phase of gait.

No effects of in vivo micro-CT radiation on structural parameters and bone marrow cells in proximal tibia of wistar rats detected after eight weekly scans.

Recently developed in vivo animal high-resolution micro-CT scanners offer the possibility to monitor longitudinal changes in bone microstructure of small rodents, but may impose high radiation doses that could damage bone tissue. The goal of this study was to determine the effects on the bone of 8 weeks of in vivo scanning of the proximal tibia in female Wistar rats. Eight weekly CT scans were made of the right proximal tibia of nine female, 30-week-old, retired-breeder, Wistar rats.

Additional weight bearing during exercise and estrogen in the rat: the effect on bone mass, turnover, and structure.

Mechanical loading and estrogen play important roles in bone homeostasis. The aim of this study was to evaluate the effects of mechanical loading on trabecular bone in the proximal femur of ovariectomized rats. We hypothesized that mechanical loading suppresses bone resorption and increases bone formation, which differs from the suppressive effects of estrogen on both resorption and formation.

Bone regeneration during distraction osteogenesis: mechano-regulation by shear strain and fluid velocity.

Corroboration of mechano-regulation algorithms is difficult, partly because repeatable experimental outcomes under a controlled mechanical environment are necessary, but rarely available. In distraction osteogenesis (DO), a controlled displacement is used to regenerate large volumes of new bone, with predictable and reproducible outcomes, allowing to computationally study the potential mechanisms that stimulate bone formation. We hypothesized that mechano-regulation by octahedral shear strain and fluid velocity can predict the spatial and temporal tissue distributions seen during experimental DO.

Finite element-based preclinical testing of cemented total hip implants.

We developed a finite element model to preclinically test cemented hip implants for damage accumulation, including cement crack formation, creep, and stem migration. Using this model, we simulated the mechanical failure processes of four cemented total hip arthroplasty implants (Lubinus SPII, Mueller Curved, Exeter and Charnley, all with known clinical results) during cyclic normal walking and stair-climbing loads. These four implants were selected to ascertain whether the simulation predicted greater damage development around clinically inferior stems, whether clinically inferior designs could be identified by an initial stress analysis without the prediction of cement damage, and whether the simulation could predict high implant subsidence rates in combination with minimal cement damage.

The PTHrP-Ihh feedback loop in the embryonic growth plate allows PTHrP to control hypertrophy and Ihh to regulate proliferation.

Growth plate and long bone development is governed by biochemical signaling pathways of which the PTHrP-Ihh system is the best known. Other factors, such as BMPs, FGFs and mechanical loading, may interact with this system. This study aims at elucidating the relative importance of PTHrP and Ihh for controlling proliferation, and hypertrophy in fetal growth plate cartilage.

Corroboration of mechanoregulatory algorithms for tissue differentiation during fracture healing: Comparison with in vivo results.

Several mechanoregulation algorithms proposed to control tissue differentiation during bone healing have been shown to accurately predict temporal and spatial tissue distributions during normal fracture healing. As these algorithms are different in nature and biophysical parameters, it raises the question of which reflects the actual mechanobiological processes the best. The aim of this study was to resolve this issue by corroborating the mechanoregulatory algorithms with more extensive in vivo bone healing data from animal experiments.

Causes of mechanically induced collagen damage in articular cartilage.

Osteoarthritis (OA) is a multifactorial disease, associated with articular cartilage degeneration and eventually joint destruction. The phases of the disease have been described in detail, and mechanical factors play an important role in the initiation of OA, but many questions remain about its etiology. Swelling of cartilage, one of the earliest signs of damage, is proportional to the amount of collagen damage.

Cortical bone development under the growth plate is regulated by mechanical load transfer.

Longitudinal growth of long bones takes place at the growth plates. The growth plate produces new bone trabeculae, which are later resorbed or merged into the cortical shell. This process implies transition of trabecular metaphyseal sections into diaphyseal sections.