Preventing Falls with Vitamin D

Falls are the number one cause for injury-related morbidity and mortality in West Virginia’s seniors. Multiple independent variables contribute to the risk of a fall: previous falls, alterations in balance and vision, impairments in gait and strength, and medications most highly correlate with the risk for a fall. Vitamin D supplementation is emerging as an easy, safe and well-tolerated fall reduction/prevention strategy due to the beneficial effects on the musculoskeletal system with improvements in strength, function and navigational abilities. From meta-analysis data, maximal fall reduction benefit in seniors is achieved when correcting vitamin D deficiency and when using adjunctive calcium supplementation. It is therefore recommended that practitioners in our state screen for fall risks and consider the addition of supplementation protocols that provide sufficient vitamin D and calcium to our seniors

Post-operative outcomes, including opioid utilization and length of stay, following total knee arthroplasty: A retrospective case matched series comparing conventional and robotic-assisted total knee arthroplasty

Keywords Total Knee Arthroplasty, robotic-assisted, opioid use Background With the rise of robotic arm-assisted total knee arthroplasty (TKA) cases, there is a need to determine if there are clinical benefits associated with this technology. The purpose of this study was to further evaluate if robotic-assisted TKAs result in improved inpatient post-operative outcomes compared to conventional TKAs. Materials and Methods After IRB approval, a retrospective chart review of 100 robotic-assisted primary TKAs and 100 matched controls undergoing conventional TKA was performed. Patients underwent primary TKA from 2016 to 2018 with minimum 6-month postoperative follow-up by a single fellowship-trained arthroplasty surgeon at a high-volume joint center. Exclusion criteria included 40. Demographics and post-operative outcomes, including length of stay (LOS), opioid consumption, duration of opioid use, and discharge status, were recorded. Results There were no significant differences in pre-operative demographics between the two groups. A decrease in LOS (1.58 vs. 2.18 days, p < 0.001) and morphine equivalents (73.52 vs. 102.50, p = 0.017) was reported for the robotic TKA group compared to the control group. The robotic group also reported fewer patients at six weeks postoperatively requiring opioids compared to the control group (37 vs. 61, p = 0.001). Average KOOS Jr at 6-months postoperatively was 81.73 for the control group and 78.22 in the robotic group (p = 0.039). Conclusion Robotic-assisted TKA patients experienced significantly decreased LOS, morphine equivalents, and opioid usage at 6-week postoperatively, indicating that there are early clinical benefits of robotic-assisted TKA. No significant differences between the robotic and control groups were reported in pre-operative KOOS Jr. Although average 6-month postoperative KOOS Jr was slightly higher for the control group, the difference was clinically insignificant. Our average KOOS Jr for both cohorts was higher than the national 1-year postoperative average, 76.8

Complex Unfolding Kinetics of Single-Domain Proteins in the Presence of Force

Single-molecule force spectroscopy is providing unique, and sometimes unexpected, insights into the free-energy landscapes of proteins. Despite the complexity of the free-energy landscapes revealed by mechanical probes, forced unfolding experiments are often analyzed using one-dimensional models that predict a logarithmic dependence of the unfolding force on the pulling velocity. We previously found that the unfolding force of the protein filamin at low pulling speed did not decrease logarithmically with the pulling speed. Here we present results from a large number of unfolding simulations of a coarse-grain model of the protein filamin under a broad range of constant forces. These show that a two-path model is physically plausible and produces a deviation from the behavior predicted by one-dimensional models analogous to that observed experimentally. We also show that the analysis of the distributions of unfolding forces (p[F]) contains crucial and exploitable information, and that a proper description of the unfolding of single-domain proteins needs to account for the intrinsic multidimensionality of the underlying free-energy landscape, especially when the applied perturbation is small

Unilateral heat accelerates bone elongation and lengthens extremities of growing mice

Linear growth failure results from a broad spectrum of systemic and local disorders that can generate chronic musculoskeletal disability. Current bone lengthening protocols involve invasive surgeries or drug regimens, which are only partially effective. Exposure to warm ambient temperature during growth increases limb length, suggesting that targeted heat could noninvasively enhance bone elongation. We tested the hypothesis that daily heat exposure on one side of the body unilaterally increases femoral and tibial lengths. Mice (N = 20) were treated with 40 °C unilateral heat for 40 min/day for 14 days post-weaning. Non-treated mice (N = 6) served as controls. Unilateral increases in ear (8.8%), hindfoot (3.5%), femoral (1.3%), and tibial (1.5%) lengths were obtained. Tibial elongation rate was \u3e 12% greater (15 μm/day) on the heat-treated side. Extremity lengthening correlated with temperature during treatment. Body mass and humeral length were unaffected. To test whether differences persisted in adults, mice were examined 7-weeks post-treatment. Ear area, hindfoot, femoral, and tibial lengths were still significantly increased ∼6%, 3.5%, 1%, and 1%, respectively, on the heat-treated side. Left-right differences were absent in non-treated controls, ruling out inherent side asymmetry. This model is important for designing noninvasive heat-based therapies to potentially combat a range of debilitating growth impediments in children

Refolding upon force quench and pathways of mechanical and thermal unfolding of ubiquitin

The refolding from stretched initial conformations of ubiquitin (PDB ID: 1ubq) under the quenched force is studied using the Go model and the Langevin dynamics. It is shown that the refolding decouples the collapse and folding kinetics. The force quench refolding times scale as tau_F ~ exp(f_q*x_F/k_B*T), where f_q is the quench force and x_F = 0.96 nm is the location of the average transition state along the reaction coordinate given by the end-to-end distance. This value is close to x_F = 0.8 nm obtained from the force-clamp experiments. The mechanical and thermal unfolding pathways are studied and compared with the experimental and all-atom simulation results in detail. The sequencing of thermal unfolding was found to be markedly different from the mechanical one. It is found that fixing the N-terminus of ubiquitin changes its mechanical unfolding pathways much more drastically compared to the case when the C-end is anchored. We obtained the distance between the native state and the transition state x_UF=0.24 nm which is in reasonable agreement with the experimental data.Comment: 35 pages, 15 figures, 1 tabl

SoxD Proteins Influence Multiple Stages of Oligodendrocyte Development and Modulate SoxE Protein Function

SummaryThe myelin-forming oligodendrocytes are an excellent model to study transcriptional regulation of specification events, lineage progression, and terminal differentiation in the central nervous system. Here, we show that the group D Sox transcription factors Sox5 and Sox6 jointly and cell-autonomously regulate several stages of oligodendrocyte development in the mouse spinal cord. They repress specification and terminal differentiation and influence migration patterns. As a consequence, oligodendrocyte precursors and terminally differentiating oligodendrocytes appear precociously in spinal cords deficient for both Sox proteins. Sox5 and Sox6 have opposite functions than the group E Sox proteins Sox9 and Sox10, which promote oligodendrocyte specification and terminal differentiation. Both genetic as well as molecular evidence suggests that Sox5 and Sox6 directly interfere with the function of group E Sox proteins. Our studies reveal a complex regulatory network between different groups of Sox proteins that is essential for proper progression of oligodendrocyte development