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Background: Significant debate exists regarding optimal repair for unstable syndesmosis injuries. Techniques range from screw fixation, suture-button fixation, or a combination of the two. In this study, 3 common repairs were compared using a simulated weightbearing protocol with internal and external rotation of the foot., Methods: Twenty-four lower leg specimens with mean age 54 years (range, 38-68 years) were used for testing. Following creation of a complete syndesmotic injury (AITFL, ITFL, PITFL, interosseous membrane), specimens were repaired using 1 of 3 randomly assigned techniques: (1) one 3.5-mm syndesmotic screw, (2) 1 suture-button construct, and (3) 2 divergent suture-button constructs. Repairs were cycled for 500 cycles between 7.5 Nm of internal/external rotation torque under a constant 750 N axial compressive load in a neutral dorsiflexion position. At 0, 10, 100, and 500 cycles, torsional cyclic loading was interrupted to assess torsional resistance to rotation within a physiologic range of motion (15 degrees external rotation to 10 degrees internal rotation). Torque (Nm), rotational position (degrees), and 3-dimensional data were collected throughout the testing to characterize relative spatial relationships of the tibiofibular articulation., Results: There were no significant differences between repair techniques in resistance to internal and external rotation with respect to the intact syndesmosis. Three-dimensional analysis revealed significant differences between repair techniques for sagittal fibular translation with external rotation of the foot. Screw fixation had the smallest magnitude of posterior sagittal translation (2.5 mm), and a single suture-button construct demonstrated the largest magnitude of posterior sagittal translation (4.6 mm). Screw fixation also allowed for significantly less anterior sagittal translation with internal rotation of the foot (0.1 mm) when compared to both 1 (2.7 mm) and 2 (2.9 mm) suture-button constructs., Conclusion: All repairs provided comparable rotational stability to the syndesmosis; however, no repair technique completely restored rotational stability and tibiofibular anatomic relationships of the preinjury state., Clinical Relevance: Constructs were comparable across most conditions; however, when repairing injuries with a suture-button construct, a single suture-button construct may not provide sufficient resistance to sagittal translation of the fibula.

Background: Biomechanical data and contributions to ankle joint stability have been previously reported for the individual distal tibiofibular ligaments. These results have not yet been validated based on recent anatomic descriptions or using current biomechanical testing devices., Methods: Eight matched-pair, lower leg specimens were tested using a dynamic, biaxial testing machine. The proximal tibiofibular joint and the medial and lateral ankle ligaments were left intact. After fixation, specimens were preconditioned and then biomechanically tested following sequential cutting of the tibiofibular ligaments to assess the individual ligamentous contributions to syndesmotic stability. Matched paired specimens were randomly divided into 1 of 2 cutting sequences: (1) anterior-to-posterior: intact, anterior inferior tibiofibular ligament (AITFL), interosseous tibiofibular ligament (ITFL), deep posterior inferior tibiofibular ligament (PITFL), superficial PITFL, and complete interosseous membrane; (2) posterior-to-anterior: intact, superficial PITFL, deep PITFL, ITFL, AITFL, and complete interosseous membrane. While under a 750-N axial compressive load, the foot was rotated to 15 degrees of external rotation and 10 degrees of internal rotation for each sectioned state. Torque (Nm), rotational position (degrees), and 3-dimensional data were recorded continuously throughout testing., Results: Testing of the intact ankle syndesmosis under simulated physiologic conditions revealed 4.3 degrees of fibular rotation in the axial plane and 3.3 mm of fibular translation in the sagittal plane. Significant increases in fibular sagittal translation and axial rotation were observed after syndesmotic injury, particularly after sectioning of the AITFL and superficial PITFL. Sequential sectioning of the syndesmotic ligaments resulted in significant reductions in resistance to both internal and external rotation. Isolated injuries to the AITFL resulted in the most substantial reduction of resistance to external rotation (average of 24%). However, resistance to internal rotation was not significantly diminished until the majority of the syndesmotic structures had been sectioned., Conclusion: The ligaments of the syndesmosis provide significant contributions to rotary stability of the distal tibiofibular joint within the physiologic range of motion., Clinical Relevance: This study defined normal motion of the syndesmosis and the biomechanical consequences of injury. The degree of instability was increased with each additional injured structure; however, isolated injuries to the AITFL alone may lead to significant external rotary instability.

Background: Secondary surgical repair of ankle ligaments is often indicated in cases of chronic lateral ankle instability. Recently, arthroscopic Broström techniques have been described, but biomechanical information is limited. The purpose of the present study was to analyze the biomechanical properties of an arthroscopic Broström repair and augmented repair with a proximally placed suture anchor. It was hypothesized that the arthroscopic Broström repairs would compare favorably to open techniques and that augmentation would increase the mean repair strength at time zero., Methods: Twenty (10 matched pairs) fresh-frozen foot and ankle cadaveric specimens were obtained. After sectioning of the lateral ankle ligaments, an arthroscopic Broström procedure was performed on each ankle using two 3.0-mm suture anchors with #0 braided polyethylene/polyester multifilament sutures. One specimen from each pair was augmented with a 2.9-mm suture anchor placed 3 cm proximal to the inferior tip of the lateral malleolus. Repairs were isolated and positioned in 20 degrees of inversion and 10 degrees of plantarflexion and loaded to failure using a dynamic tensile testing machine. Maximum load (N), stiffness (N/mm), and displacement at maximum load (mm) were recorded., Results: There were no significant differences between standard arthroscopic repairs and the augmented repairs for mean maximum load and stiffness (154.4 ± 60.3 N, 9.8 ± 2.6 N/mm vs 194.2 ± 157.7 N, 10.5 ± 4.7 N/mm, P = .222, P = .685)., Conclusions: Repair augmentation did not confer a significantly higher mean strength or stiffness at time zero., Clinical Relevance: Mean strength and stiffness for the arthroscopic Broström repair compared favorably with previous similarly tested open repair and reconstruction methods, validating the clinical feasibility of an arthroscopic repair. However, augmentation with an additional proximal suture anchor did not significantly strengthen the repair., (© The Author(s) 2015.)

In mammalian cells, DNA double-strand breaks (DSBs) cause rapid phosphorylation of the H2AX core histone variant (to form gamma-H2AX) in megabase chromatin domains flanking sites of DNA damage. To investigate the role of H2AX in mammalian cells, we generated H2AX-deficient (H2AX(Delta)/Delta) mouse embryonic stem (ES) cells. H2AX(Delta)/Delta ES cells are viable. However, they are highly sensitive to ionizing radiation (IR) and exhibit elevated levels of spontaneous and IR-induced genomic instability. Notably, H2AX is not required for NHEJ per se because H2AX(Delta)/Delta ES cells support normal levels and fidelity of V(D)J recombination in transient assays and also support lymphocyte development in vivo. However, H2AX(Delta)/Delta ES cells exhibit altered IR-induced BRCA1 focus formation. Our findings indicate that H2AX function is essential for mammalian DNA repair and genomic stability.

The Kit receptor tyrosine kinase functions in hemato- poiesis, melanogenesis and gametogenesis. Kit receptor-mediated cellular responses include proliferation, survival, adhesion, secretion and differentiation. In mast cells, Kit-mediated recruitment and activation of phosphatidylinositol 3'-kinase (PI 3-kinase) produces phosphatidylinositol 3'-phosphates, plays a critical role in mediating cell adhesion and secretion and has contributory roles in mediating cell survival and proliferation. To investigate the consequences in vivo of blocking Kit-mediated PI 3-kinase activation we have mutated the binding site for the p85 subunit of PI 3-kinase in the Kit gene, using a knock-in strategy. Mutant mice have no pigment deficiency or impairment of steady-state hematopoiesis. However, gametogenesis is affected in several ways and tissue mast cell numbers are affected differentially. While primordial germ cells during embryonic development are not affected, Kit(Y719F)/Kit(Y719F) males are sterile due to a block at the premeiotic stages in spermatogenesis. Furthermore, adult males develop Leydig cell hyperplasia. The Leydig cell hyperplasia implies a role for Kit in Leydig cell differentiation and/or steroidogenesis. In mutant females follicle development is impaired at the cuboidal stages resulting in reduced fertility. Also, adult mutant females develop ovarian cysts and ovarian tubular hyperplasia. Therefore, a block in Kit receptor-mediated PI 3-kinase signaling may be compensated for in hematopoiesis, melanogenesis and primordial germ cell development, but is critical in spermatogenesis and oogenesis.