Impact of leptin deficiency on male tibia and vertebral body 3D bone architecture independent of changes in body weight.

Leptin an adipokine with potent effects on energy balance and body weight plays an important role in defining bone architecture in growing mammals. However, major changes in body weight can also influence morphology of trabecular and cortical bone. Therefore, we examined the impact of leptin deficiency on tibia and vertebral body 3D bone architecture independent of changes in body weight. Furthermore, advances in computational 3D image analysis suggest that average morphological values may mask regional specific differences in trabecular bone thickness. The study utilized leptin-deficient Ob/Ob mice (n = 8) weight-paired to C57BL/6 (C57) control mice (n = 8) which were split into either lean or obese groups for 24 ± 2 weeks. Whole tibias and L3 vertebrae were fixed before high resolution microcomputed tomography (µCT) scanning was performed. Leptin deficiency independent of body weight reduced tibia cortical bone volume, trabecular bone volume/tissue volume, number, and mineral density. Mean tibia trabecular thickness showed no significant differences between all groups; however, significant changes in trabecular thickness were found when analyzed by region. This study demonstrates that leptin deficiency significantly impacts tibia and vertebral body trabecular and cortical bone 3D architecture independent of changes in body weight.

Controlled Release of Antimicrobial ClO2 Gas from a Two-Layer Polymeric Film System.

We report a two-component label system comprising a chlorite-containing polymer film and an acid-containing polymer film that can release antimicrobial ClO2 gas upon adhering the two films together to enable a reaction of the chlorite and acid under moisture exposure. The chlorite-containing film comprises a commercial acrylate-based pressure-sensitive adhesive polymer impregnated with sodium chlorite. The acid-containing film comprises a commercial poly(vinyl alcohol) polymer loaded with tartaric acid. Both of the films were prepared on low ClO2-absorbing substrate films from stable aqueous systems of the polymers with high reagent loading. Rapid and sustained releases of significant amounts of ClO2 gas from the label system were observed in an in situ quantification system using UV-vis spectroscopy. It was found that the ClO2 release is slower at a lower temperature and can be accelerated by moisture in the atmosphere and the films. Controlled release of ClO2 gas from the label system was demonstrated by tailoring film composition and thickness. A model was developed to extract release kinetics and revealed good conversions of the label system. This two-component system can potentially be applied as a two-part label without premature release for applications in food packaging.

Concealed effects of gene-environment interactions in genome-wide association.

Genome-wide association studies (GWAS) have been conducted on many complex diseases with the aim of identifying common genetic variants important in disease susceptibility. It is rare for these to consider environmental factors when calculating the odds ratios for variants associated with disease. We modelled the effect of an environmentally-dependent genetic risk locus and showed that, despite a relatively low overall odds ratio, environmental exposure was able to conceal a large true effect size on disease susceptibility in exposed individuals. This model was applied to vitamin D deficiency in multiple sclerosis and raised the possibility of large magnitudes of concealed effect in loci responsive to vitamin D in this disease. In the post-GWAS era, efforts should be made to elucidate potential gene-environment interactions involved in complex traits in order for true effects on disease risk to be realised.

Re-entrant phase behavior for systems with competition between phase separation and self-assembly.

In patchy particle systems where there is a competition between the self-assembly of finite clusters and liquid-vapor phase separation, re-entrant phase behavior can be observed, with the system passing from a monomeric vapor phase to a region of liquid-vapor phase coexistence and then to a vapor phase of clusters as the temperature is decreased at constant density. Here, we present a classical statistical mechanical approach to the determination of the complete phase diagram of such a system. We model the system as a van der Waals fluid, but one where the monomers can assemble into monodisperse clusters that have no attractive interactions with any of the other species. The resulting phase diagrams show a clear region of re-entrance. However, for the most physically reasonable parameter values of the model, this behavior is restricted to a certain range of density, with phase separation still persisting at high densities.

Smoking and multiple sclerosis: an updated meta-analysis.

BACKGROUND: Multiple sclerosis (MS) is a leading cause of disability in young adults. Susceptibility to MS is determined by environmental exposure on the background of genetic risk factors. A previous meta-analysis suggested that smoking was an important risk factor for MS but many other studies have been published since then. METHODS/PRINCIPAL FINDINGS: We performed a Medline search to identify articles published that investigated MS risk following cigarette smoking. A total of 14 articles were included in this study. This represented data on 3,052 cases and 457,619 controls. We analysed these studies in both a conservative (limiting our analysis to only those where smoking behaviour was described prior to disease onset) and non-conservative manner. Our results show that smoking is associated with MS susceptibility (conservative: risk ratio (RR) 1.48, 95% confidence interval (CI) 1.35-1.63, p < 10⁻¹5; non-conservative: RR 1.52, 95% CI 1.39-1.66, p < 10⁻¹9). We also analysed 4 studies reporting risk of secondary progression in MS and found that this fell just short of statistical significance with considerable heterogeneity (RR 1.88, 95% CI 0.98-3.61, p = 0.06). DISCUSSION: Our results demonstrate that cigarette smoking is important in determining MS susceptibility but the effect on the progression of disease is less certain. Further work is needed to understand the mechanism behind this association and how smoking integrates with other established risk factors.

An updated meta-analysis of risk of multiple sclerosis following infectious mononucleosis.

BACKGROUND: Multiple sclerosis (MS) appears to develop in genetically susceptible individuals as a result of environmental exposures. Epstein-Barr virus (EBV) infection is an almost universal finding among individuals with MS. Symptomatic EBV infection as manifested by infectious mononucleosis (IM) has been shown in a previous meta-analysis to be associated with the risk of MS, however a number of much larger studies have since been published. METHODS/PRINCIPAL FINDINGS: We performed a Medline search to identify articles published since the original meta-analysis investigating MS risk following IM. A total of 18 articles were included in this study, including 19390 MS patients and 16007 controls. We calculated the relative risk of MS following IM using a generic inverse variance with random effects model. This showed that the risk of MS was strongly associated with IM (relative risk (RR) 2.17; 95% confidence interval 1.97-2.39; p<10(-54)). DISCUSSION: Our results establish firmly that a history of infectious mononucleosis significantly increases the risk of multiple sclerosis. Future work should focus on the mechanism of this association and interaction with other risk factors.