Impaired Vestibular Function and Low Bone Mineral Density: Data from the Baltimore Longitudinal Study of Aging

Animal studies have demonstrated that experimentally induced vestibular ablation leads to a decrease in bone mineral density, through mechanisms mediated by the sympathetic nervous system. Loss of bone mineral density is a common and potentially morbid condition that occurs with aging, and we sought to investigate whether vestibular loss is associated with low bone mineral density in older adults. We evaluated this question in a cross-sectional analysis of data from the Baltimore Longitudinal Study of Aging (BLSA), a large, prospective cohort study managed by the National Institute on Aging (N = 389). Vestibular function was assessed with cervical vestibular evoked myogenic potentials (cVEMPs), a measure of saccular function. Bone mineral density was assessed using dual-energy X-ray absorptiometry (DEXA). In two-way t test analysis, we observed that individuals with reduced vestibular physiologic function had significantly lower bone mineral density. In adjusted multivariate linear regression analyses, we observed that older individuals with reduced vestibular physiologic function had significantly lower bone mineral density, specifically in weight-bearing hip and lower extremity bones. These results suggest that the vestibular system may contribute to bone homeostasis in older adults, notably of the weight-bearing hip bones at greatest risk of osteoporotic fracture. Further longitudinal analysis of vestibular function and bone mineral density in humans is needed to characterize this relationship and investigate the potential confounding effect of physical activity.     

Bone Health Status in Indian Overweight/Obese Children

This cross-sectional study, to assess bone health in Indian overweight, obese children in comparison with healthy controls was conducted in 245 (126 girls) children and adolescents aged 6–17 y in Pune, India. It was found that total body bone mineral content, bone area and bone mineral density adjusted for Tanner stage and weight were significantly lower in obese children as compared to overweight children, which in turn, was significantly lower than normal weight children (p?<?0.05). Thus, overweight and obesity is negatively related to bone health in children and adolescents. Interventions need to be planned to increase peak bone mass accrual in overweight and obese children to reduce future risk of fracture and osteoporosis.     

A Multiscale Computational Approach to Dissect Early Events in the Erb Family Receptor Mediated Activation,Differential Signaling,and Relevance to Oncogenic Transformations

We describe a hierarchical multiscale computational approach based on molecular dynamics simulations, free energy-based molecular docking simulations, deterministic network-based kinetic modeling, and hybrid discrete/continuum stochastic dynamics protocols to study the dimer-mediated receptor activation characteristics of the Erb family receptors, specifically the epidermal growth factor receptor (EGFR). Through these modeling approaches, we are able to extend the prior modeling of EGF-mediated signal transduction by considering specific EGFR tyrosine kinase (EGFRTK) docking interactions mediated by differential binding and phosphorylation of different C-terminal peptide tyrosines on the RTK tail. By modeling signal flows through branching pathways of the EGFRTK resolved on a molecular basis, we are able to transcribe the effects of molecular alterations in the receptor (e.g., mutant forms of the receptor) to differing kinetic behavior and downstream signaling response. Our molecular dynamics simulations show that the drug sensitizing mutation (L834R) of EGFR stabilizes the active conformation to make the system constitutively active. Docking simulations show preferential characteristics (for wildtype vs. mutant receptors) in inhibitor binding as well as preferential enhancement of phosphorylation of particular substrate tyrosines over others. We find that in comparison to the wildtype system, the L834R mutant RTK preferentially binds the inhibitor erlotinib, as well as preferentially phosphorylates the substrate tyrosine Y1068 but not Y1173. We predict that these molecular level changes result in preferential activation of the Akt signaling pathway in comparison to the Erk signaling pathway for cells with normal EGFR expression. For cells with EGFR over expression, the mutant over activates both Erk and Akt pathways, in comparison to wildtype. These results are consistent with qualitative experimental measurements reported in the literature. We discuss these consequences in light of how the network topology and signaling characteristics of altered (mutant) cell lines are shaped differently in relationship to native cell lines. Electronic supplementary material The online version of this article (doi:) contains supplementary material, which is available to authorized users. These authors contributed equally     

New “epsilon” sign in “highly unstable” intertrochanteric fracture

European Journal of Orthopaedic Surgery & Traumatology -     

Primary motor cortex long‐term plasticity in multiple system atrophy

In humans, intermittent and continuous theta‐burst stimulation (iTBS and cTBS) elicit long‐term changes in motor‐evoked potentials (MEPs) reflecting long‐term potentiation (LTP)‐ and depression (LTD)‐like plasticity in the primary motor cortex (M1). In this study, we used TBS to investigate M1 plasticity in patients with MSA. We also assessed whether responses to TBS reflect M1 excitability as tested by short‐interval intracortical inhibition (SICI), intracortical facilitation (ICF), short‐interval intracortical facilitation (SICF), and the input/output curves. We studied 20 patients with MSA and 20 healthy subjects (HS). Patients were clinically evaluated with the Unified Multiple System Atrophy Rating Scale. The left M1 was conditioned with TBS. Twenty MEPs were recorded from the right first dorsal interosseous muscle before TBS and 5, 15, and 30 minutes thereafter. In a subgroup of 10 patients, we also tested MEPs elicited by SICI, ICF, SICF, and input/output curves, before TBS. Between‐group analysis of variance showed that at all time points after iTBS MEPs increased, whereas after cTBS they decreased only in HS. In both subgroups tested, patients with predominant parkinsonian and cerebellar features, iTBS and cTBS left MEPs unchanged. MSA patients had reduced SICI, but normal ICF, SICF, and input/output curves. No correlation was found between patients' clinical features and responses to TBS and M1 excitability variables. These findings suggest impaired M1 plasticity in MSA. © 2013 International Parkinson and Movement Disorder Society