Perspectives on in silico bone mechanobiology: computational modelling of multicellular systems.

Bone mechanobiology is the study of the physical, biological and mechanical processes that continuously affect the multiscale multicellular system of the bone from the organ to the molecular scale. Current knowledge derives from experimental studies, which are often limited to gathering qualitative data in a cross-sectional manner, up to a restricted number of time points. Moreover, the simultaneous collection of information about 3D bone microarchitecture, cell activity as well as protein distribution and level is still a challenge. In silico models can expand qualitative information with hypothetical quantitative systems, which allow quantification, testing and comparison to existing quantifiable experimental data. An overview of multiscale, multiphysics, agent-based and hybrid techniques and their applications to bone mechanobiology is provided in the present review. The study analysed how mechanical signals, cells and proteins can be modelled in silico to represent bone remodelling and adaptation. Hybrid modelling of bone mechanobiology could combine the methods used in multiscale, multiphysics and agent-based models into a single model, leading to a unified and comprehensive understanding of bone mechanobiology. Numerical simulations of in vivo multicellular systems aided in hypothesis testing of such in silico models. Recently, in silico trials have been used to illustrate the mechanobiology of cells and signalling pathways in clinical biopsies and animal bones, including the effects of drugs on single cells and signalling pathways up to the organ level. This improved understanding may lead to the identification of novel therapies for degenerative diseases such as osteoporosis.

The internal dose of passive smoking at home depends on the size of the dwelling.

As part of a longitudinal study two urine samples (survey 1 in 1991 and survey 2 in 1992) were collected from 602 elementary school children to investigate the relationship between urinary cotinine excretion (UCE) and the daily consumption of cigarettes at home (exposure). Size of the dwelling, educational level, and maternal smoking were taken into consideration as additional predictors. The history regarding parental smoking habits and confounding variables was ascertained by standardized questionnaires completed by the parents. Cotinine was measured using gas chromatography selected ion monitoring. UCE was expressed as cotinine/creatinine (ng/mg). In children with detectable UCE in survey 1 (35%) and in survey 2 (44%) the excretion ranged between 1.5 and 24.7 ng/mg (5-95%) and between 1.2 and 25.2 ng/mg, respectively. UCE measurements in both surveys were highly correlated (r = 0.65, P = 0.0001), and 59.6% of the UCE in survey 2 can be explained in linear regression by the UCE in survey 1. Using multiple linear regression, the categorized number of cigarettes reported to be consumed at home (20 cigarettes and more: 1991, P = 0.0001; 1992, P = 0.0003) and low educational level of the parents (P = 0.011 in 1991, P = 0.04 in 1992) were positively associated with UCE, whereas the size of the dwelling turned out to be negatively associated with UCE (P = 0.12 in 1991, P = 0.001 in 1992). In small dwellings (< or = 80 m2) the effect of exposure on UCE was much more pronounced. In conclusion, a single UCE measurement provides information which is widely stable within a yearly interval and is related to passive smoke history as well as to socio-economic status and the size of the dwelling. The latter variable should be considered as an effect modifier of exposure on internal dose and should be taken into account in future studies on passive smoke exposure.

Is serum beta 2-microglobulin a tumor marker in gastrointestinal cancer?

Serial determinations of serum beta 2-microglobulin (beta 2m) and carcinoembryogenic antigen (CEA) were performed in 314 patients with histologically confirmed gastrointestinal cancer. The data were correlated with a set of clinical parameters. Pre-operative serum beta 2m levels did not discriminate different classes of tumor extension nor different stages of resectability of tumors in contrast to CEA. During post-operative surveillance the correlation of the time courses of serum beta 2m and CEA with the clinical course of malignant disease was studied in a selected group of 165 patients with resected primary carcinoma of the gastrointestinal tract. During the follow-up 74/165 patients showed disease progression or recurrence. In the beta 2m follow-up 66% false negative indications (49/74) of malignant disease were observed, whereas in the CEA follow-up it was 5% (4/74). The ratio of correct positive/false positive indications was 25/10 in the beta 2m follow-up and 70/10 in the CEA follow-up. The data indicate that the formation of serum beta 2m is not directly tumor associated in gastrointestinal cancer.