This trial supports the hypothesis that systemic administration of myostatin inhibitors provides an adequate safety margin for clinical studies. Further evaluation of more potent myostatin inhibitors for stimulating muscle growth in muscular dystrophy should be considered.

The cardiac conduction system is a network of cells responsible for the rhythmic and coordinated excitation of the heart. Components of the murine conduction system, including the peripheral Purkinje fibers, are morphologically indistinguishable from surrounding cardiomyocytes, and a paucity of molecular markers exists to identify these cells. The murine conduction system develops in close association with the endocardium. Using the recently identified CCS-lacZ line of reporter mice, in which lacZ expression delineates the embryonic and fully mature conduction system, we tested the ability of several endocardial-derived paracrine factors to convert contractile cardiomyocytes into conduction-system cells as measured by ectopic reporter gene expression in the heart. In this report we show that neuregulin-1, a growth and differentiation factor essential for ventricular trabeculation, is sufficient to induce ectopic expression of the lacZ conduction marker. This inductive effect of neuregulin-1 was restricted to a window of sensitivity between 8.5 and 10.5 days postcoitum. Using the whole mouse embryo culture system, neuregulin-1 was shown to regulate lacZ expression within the embryonic heart, whereas its expression in other tissues remained unaffected. We describe the electrical activation pattern of the 9.5-days postcoitum embryonic mouse heart and show that treatment with neuregulin-1 results in electrophysiological changes in the activation pattern consistent with a recruitment of cells to the conduction system. This study supports the hypothesis that endocardial-derived neuregulins may be the major endogenous ligands responsible for inducing murine embryonic cardiomyocytes to differentiate into cells of the conduction system.

Displaced midshaft clavicle fractures can be effectively managed with dual mini-fragment plating. This technique results in high union rates and excellent clinical outcomes. Compared to single plating, dual plating is biomechanically equivalent in axial loading and torsion, yet offers better multi-planar bending stiffness despite the use of smaller plates. This technique may decrease the need for secondary surgery due to implant prominence and may aid in fracture reduction by buttressing butterfly fragments in two planes.

Placing the plate anteroinferiorly on the clavicle provides a more stable construct in terms of bending rigidity with no detriment in axial and torsional stiffness compared with placing the plate superiorly. We believe that anteroinferior plating is preferred as a result of the increase in bending rigidity together with other advantages, including avoidance of neurovascular compromise, the use of longer screws, and decreased hardware prominence.

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Dorsal instability of the metatarsophalangeal joint (MTPJ) of the lesser toes is an important cause of forefoot pain. Both conservative and surgical treatment options have been proposed. However, the role of each static stabilizing structure has not been elucidated. We hypothesized that isolated sectioning of the plantar plate (PP) would result in greater dorsal translation compared to isolated sectioning of the medial collateral ligaments (MCL) or lateral (LCL) collateral ligaments, or the extensor hood (EH), and that combined injury to two or more structures would result in greater dorsal translation compared to isolated PP injury. Fifty‐four cadaveric lesser toe specimens were randomized into groups for individual and combined sectioning of the PP, EH, and LCL and MCL. A 30 N axial load was applied to each specimen in the plantar–dorsal direction and dorsal translation of the phalanx was measured for each condition. ANOVA was used to compare groups. A 19% change in MTP translation was found from intact after sectioning the PP. No significant difference in translation was seen after individual sectioning of the EH, MCL, or LCL. A significant increase in translation occurred from intact with the following sectioning combinations: MCL + LCL, 37%; EH + MCL + LCL, 45%; and PP + MCL + LCL, 63%. Thus, the PP is the main restraint for dorsal MTPJ translation. MCL and LCL have important partial contribution to MTPJ stability. Injury to the PP, individually, or combined injuries to the PP, EH, MCL, or LCL, appear to cause significant instability that may warrant more aggressive treatment. © 2012 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 30:1995–1998, 2012