IntroductionRecent three-dimensional (3D) kinematic research has revealed foot abduction is the strongest predictor of standing functional and forced turnout postures. However, it is still unknown how the internal foot joints enable a large degree of foot abduction in turnout. The primary purpose of this study was to use a dance specific multi-segment foot model to determine the lower leg and foot contributions to turnout that female university-level ballets use to accentuate their turnout.MethodsEighteen female dance students (mean age, 18.8 ± 1.6 years) volunteered for this study. Retro-reflective markers were attached to the dancers’ dominant foot. Each dancer performed three repetitions of functional turnout, forced turnout and ten consecutive sautés in first position. Repeated measures ANOVA with Bonferroni adjustments for the multiple comparisons were used to determine the kinematic adjustments, hindfoot eversion, midfoot and forefoot abduction, navicular drop (i.e. lowering of the medial longitudinal arch) and first metatarsophalangeal joint abduction between natural double leg up-right posture and the first position conditions.ResultsHindfoot eversion (4.6°, p < 0.001) and midfoot abduction (2.8°, p < 0.001) significantly increased in functional turnout compared to the natural double leg up-right posture. Thirteen dancers demonstrated increased first metatarsophalangeal joint (MTPJ) abduction in forced turnout, however no statistically significant increase was found. Navicular drop during sautés in first position significantly increased by 11 mm (p < 0.001) compared to the natural double leg up-right posture.ConclusionOur findings suggest dancers do pronate, via hindfoot eversion and midfoot abduction in both functional and forced turnout, however, no immediate association was found between forced turnout and first MTPJ abduction. Foot pronation does play a role in achieving turnout. Further prospective research on in situ measures of the lower limb in turnout and injury surveillance is required to improve our understanding of the normal and abnormal dance biomechanics.Electronic supplementary materialThe online version of this article (10.1186/s13047-019-0318-1) contains supplementary material, which is available to authorized users.

The purpose of this study was to determine the intra and inter-assessor repeatability of a modified Rizzoli Foot Model for analysing the foot kinematics of ballet dancers. Six university-level ballet dancers performed the movements; parallel stance, turnout plié, turnout stance, turnout rise and flex-point-flex. The three-dimensional (3D) position of individual reflective markers and marker triads was used to model the movement of the dancers' tibia, entire foot, hindfoot, midfoot, forefoot and hallux. Intra and inter-assessor reliability demonstrated excellent (ICC ≥ 0.75) repeatability for the first metatarsophalangeal joint in the sagittal plane. Intra-assessor reliability demonstrated excellent (ICC ≥ 0.75) repeatability during flex-point-flex across all inter-segmental angles except for the tibia-hindfoot and hindfoot-midfoot frontal planes. Inter-assessor repeatability ranged from poor to excellent (0.5 > ICC ≥ 0.75) for the 3D segment rotations. The most repeatable measure was the tibia-foot dorsiflexion/plantar flexion articulation whereas the least repeatable measure was the hindfoot-midfoot adduction/abduction articulation. The variation found in the inter-assessor results is likely due to inconsistencies in marker placement. This 3D dance specific multi-segment foot model provides insight into which kinematic measures can be reliably used to ascertain in vivo technical errors and/or biomechanical abnormalities in a dancer's foot motion.

Persistent androgen receptor (AR) signaling in castration resistant prostate cancer (CRPC) underpins the urgent need for therapeutic strategies that better target this pathway. Combining classes of agents that target different components of AR signaling has the potential to delay resistance and improve patient outcomes. Many oncoproteins, including the AR, rely on the molecular chaperone heat shock protein 90 (Hsp90) for functional maturation and stability. In this study, enhanced anti-proliferative activity of the Hsp90 inhibitors 17-allylamino-demethoxygeldanamycin (17-AAG) and AUY922 in androgen-sensitive and CRPC cells was achieved when the agents were used in combination with AR antagonists bicalutamide or enzalutamide. Moreover, significant caspasedependent cell death was achieved using sub-optimal agent doses that individually have no effect. Expression profiling demonstrated regulation of a broadened set of AR target genes with combined 17-AAG and bicalutamide compared with the respective single agent treatments. This enhanced inhibition of AR signaling was accompanied by impaired chromatin binding and nuclear localization of the AR. Importantly, expression of the AR variant AR-V7 that is implicated in resistance to AR antagonists was not induced by combination treatment. Likewise, the heat shock response that is typically elicited with therapeutic doses of Hsp90 inhibitors, and is a potential mediator of resistance to these agents, was significantly reduced by combination treatment. In summary, the co-targeting strategy in this study more effectively inhibits AR signaling than targeting AR or HSP90 alone and prevents induction of key resistance mechanisms in prostate cancer cells. These findings merit further evaluation of this therapeutic strategy to prevent CRPC growth.

Turnout is a central element of classical ballet which involves sustained external rotation of the lower limbs during dance movements. Lower leg and foot compensation mechanisms which are often used to increase turnout have been attributed to the high incidence of lower limb injury in dancers. Evaluation of dancers' leg posture is needed to provide insight into the lower limb kinematic strategies used to achieve turnout. The primary purpose of this study was to use 3D kinematic analyses to determine the lower leg and foot compensations that are incorporated by female university dancers to accentuate their turnout. Active and passive external tibiofemoral rotation (TFR) was also measured. A moderate-strong negative relationship was observed between hip external rotation (HER) and foot abduction in the three first position conditions. A moderate negative relationship was found between passive TFR and foot abduction in all first position conditions. Our findings suggest dancers are more likely to pronate, than rotate the knee to compensate for limited HER. Dancers with a limited capacity to pronate may force additional rotation via the knee. Ongoing research would benefit from more in-depth analyses of the foot/ankle complex using a multi-segment foot model.

These findings suggest that the lower leg does contribute to dancers' overall position of functional turnout. However, current methods are not useful in predicting a dancer's lower-leg contribution and alignment in functional turnout in first position.

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Background The total-contact cast (TCC) is the gold standard for off-loading diabetic foot ulcers (DFUs) given its nonremovable nature. However, this modality remains underused in clinical settings due to the time and experience required for appropriate application. The TCC-EZ is an alternative off-loading modality marketed as being nonremovable and having faster and easier application. This study aims to investigate the potential of the TCC-EZ to reduce foot plantar pressures. Methods Twelve healthy participants (six males, six females) were fitted with a removable cast walker, TCC, TCC-EZ, and TCC-EZ with accompanying brace removed. These off-loading modalities were tested against a control. Pedar-X technology measured peak plantar pressures in each condition. Statistical analysis of four regions of the foot (rearfoot, midfoot, forefoot, and hallux) was conducted with Friedman and Wilcoxon signed rank tests. Significance was set at P &lt; .05. Results All of the off-loading conditions significantly reduced pressure compared with the control, except the TCC-EZ without the brace in the hallux region. There was no statistically significant difference between TCC-EZ and TCC peak pressure in any foot region. The TCC-EZ without the brace obtained significantly higher peak pressures than with the brace. The removable cast walker produced similar peak pressure reduction in the midfoot and forefoot but significantly higher peak pressures in the rearfoot and hallux. Conclusions The TCC-EZ is a viable alternative to the TCC. However, removal of the TCC-EZ brace results in minimal plantar pressure reduction, which might limit clinical applications of the TCC-EZ.

The molecular chaperone heat shock protein 90 (Hsp90) is an important target for cancer therapy as it is required for the correct maturation and function of its various client proteins, many of which are known oncogenes. In prostate cancer, targeting Hsp90 is particularly attractive as the androgen receptor (AR), the key mediator of prostate cancer cell growth and survival, depends on Hsp90 for its ligand-binding capacity and stability. Despite promising results in pre-clinical studies, to date Hsp90 inhibitors including 17-allylamino-demethoxygeldanamycin (17-AAG) have demonstrated limited efficacy in clinical trials for advanced prostate cancer. While this is in part due to drug formulation issues, we propose that a treatment strategy that simultaneously targets multiple aspects of AR action will more effectively eliminate AR-dependent prostate cancer cells than single agent treatment strategies. In this study, we markedly enhanced the efficacy of 17-AAG by combining lower doses of this agent with either an antiandrogen (bicalutamide) or a histone deacetylase inhibitor (vorinostat), both of which are inhibitors of AR function and/or expression. Interestingly, comparison of gene expression profiles altered by each combination indicated that these treatments did not markedly enhance abrogation of androgen signaling compared with individual agents. Rather, the combination treatments regulated expression of unique gene sets that were enriched for cell cycle, apoptosis, MAPK and insulin signaling. To further enhance the efficacy of a combinatorial approach involving Hsp90 inhibitors, we investigated two new generation Hsp90 inhibitors, NVP-AUY922 and the orally available NVP-HSP990. We found that both agents were significantly more potent with regards to modulation of Hsp90 client proteins, inhibition of cell proliferation and induction of cell death than 17-AAG in prostate cancer cell lines. To assess the combinatorial approach in human disease, we have developed a unique approach to study human prostate cancer where tumors are cultured as explants for up to 7 days with maintenance of tissue integrity, cell proliferation and androgen signaling. Using this ex vivo strategy, we observed that human prostate tumor tissue responds to the novel synthetic Hsp90 inhibitors, but not 17-AAG, with a marked reduction in proliferation. Importantly, these studies revealed dissociation between client protein modulation and proliferative response to Hsp90 inhibition, which was not seen in prostate cancer cell lines in vitro. Collectively, these findings suggest that these novel Hsp90 inhibitors warrant further clinical investigation in prostate cancer. Moreover, ex vivo tumor culture may better predict efficacy of these agents on an individual patient basis, and improve identification of markers of clinical response. Citation Format: Margaret M. Centenera, Sarah L. Carter, Joanna L. Gillis, Luke A. Selth, Peter D. Sutherland, Wayne D. Tilley, Lisa M. Butler. Targeting Hsp90-dependent functional maturation of the androgen receptor in human prostate cancer [abstract]. In: Proceedings of the AACR Special Conference on Advances in Prostate Cancer Research; 2012 Feb 6-9; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2012;72(4 Suppl):Abstract nr C6.