Background: In order to maintain nonweightbearing restrictions of the lower extremity, an assistive device must be utilized. Currently most devices require the restricted limb to be held in a static position while the contralateral extremity provides forward propulsion. Atrophy and disuse conditions ensue rapidly, slowing healing and prolonging recovery. A hands-free single crutch (HFSC) utilizes both lower extremities, potentially reducing atrophy. The purpose of this study was to examine the electromyographic (EMG) differences between an HFSC and standard axillary crutches (SAC). Methods: A prospective, crossover study was performed using 21 healthy volunteers from an active duty foot and ankle clinic. Demographic data were obtained and then subjects were fitted with an HFSC and SAC. Wireless surface EMG sensors were applied to the belly of the rectus femoris (RF), vastus lateralis (VL), lateral gastrocnemius (LG), and the gluteus maximus (GM) by a board-certified orthopedic surgeon. Subjects then ambulated at a self-selected velocity for 30 m while 15 seconds of the gait cycle were recorded for each device. Mean muscle activity and the maximum voluntary isometric contraction (MVIC) were recorded. Results: The RF, GM, and LG showed significantly increased levels of muscle activity while using the HFSC compared to SAC (respectively P = .05, P = .03, P = .03). The VL did not show significantly higher muscle activity while using the HFSC ( P = .051). The RF, GM, and VL showed statistically significant higher MVIC percentages while using the HFSC compared with SAC (respectively P = .005, P = .005, P = .013). The LG did not show significantly higher MVIC percentage while using the HFSC ( P = .076). Conclusion: The HFSC subjects demonstrated increased muscle recruitment and intensity while maintaining cyclic contractions consistent with bipedal gait pattern. SAC demonstrated less recruitment and intensity with an isometric pattern regardless of the phase of gait. Clinical Relevance: Muscle atrophy following lower extremity immobilization.

Level III, comparative study.

Purpose: Treatment approaches using Hsp90 inhibitors at their maximum tolerated doses (MTDs) have not produced selective tumor toxicity. Inhibition of Hsp90 activity causes degradation of client proteins including those involved in recognizing and repairing DNA lesions. We hypothesized that if DNA repair proteins were degraded by concentrations of an Hsp90 inhibitor below those required to cause nonspecific cytotoxicity, significant tumor-selective radiosensitization might be achieved.Experimental Design: Tandem mass tagged-mass spectrometry was performed to determine the effect of a subcytotoxic concentration of the Hsp90 inhibitor, AT13387 (onalespib), on global protein abundance. The effect of AT13387 on in vitro radiosensitization was assessed using a clonogenic assay. Pharmacokinetics profiling was performed in mice bearing xenografts. Finally, the effect of low-dose AT13387 on the radiosensitization of three tumor models was assessed.Results: A subcytotoxic concentration of AT13387 reduced levels of DNA repair proteins, without affecting the majority of Hsp90 clients. The pharmacokinetics study using one-third of the MTD showed 40-fold higher levels of AT13387 in tumors compared with plasma. This low dose enhanced Hsp70 expression in peripheral blood mononuclear cells (PBMCs), which is a biomarker of Hsp90 inhibition. Low dose monotherapy was ineffective, but when combined with radiotherapy, produced significant tumor growth inhibition.Conclusions: This study shows that a significant therapeutic ratio can be achieved by a low dose of Hsp90 inhibitor in combination with radiotherapy. Hsp90 inhibition, even at a low dose, can be monitored by measuring Hsp70 expression in PBMCs in human studies.

Background: Foot and ankle injuries frequently require a period of nonweightbearing, resulting in muscle atrophy. Our previous study compared a hands-free single crutch (HFSC) to standard axillary crutches and found increased muscle recruitment and intensity while using the HFSC. Knee scooters are another commonly prescribed nonweightbearing device. The purpose of this study is to examine the electromyographic (EMG) differences between an HFSC and knee scooter, in conjunction with device preference and perceived exertion. Methods: A randomized crossover study was performed using 30 noninjured young adults. Wireless surface EMG electrodes were placed on the belly of the rectus femoris (RF), vastus lateralis (VL), lateral gastrocnemius (LG), and gluteus maximus (GM). Participants then ambulated along a 20-m walking area while 15 seconds of the gait cycle was recorded across 3 conditions: walking with a knee scooter, an HFSC, and with no assistive device. Mean muscle activity and peak EMG activity were recorded for each ambulatory modality. Immediately following testing, patient exertion and device preference was recorded. Results: The RF, LG, and GM showed increased peak EMG activity percentage, and the LG showed increased mean muscle activity while using the HFSC compared with the knee scooter. When comparing the knee scooter and HFSC to walking, both showed increased muscle activity in the RF, VL, and LG but no difference in the GM. There was no statistical difference in participant preference, whereas the HFSC had a statistically significant higher perceived exertion than the knee scooter ( P < .001). Conclusion: In this group of young, healthy noninjured volunteers, the HFSC demonstrated increased peak EMG activity in most muscle groups tested compared with the knee scooter. Level of Evidence: Level II, prospective comparative study.

<p>List of proteins identified in TMT-LC/MS assay and list of enriched pathways</p>