Interfering with the connection between the nucleus and the cytoskeleton affects nuclear rotation, mechanotransduction and myogenesis

Mechanical stress controls a broad range of cellular functions. The cytoskeleton is physically connected to the extracellular matrix via integrin receptors, and to the nuclear lamina by the LINC complex that spans both nuclear membranes. We asked here how disruption of this direct link from the cytoskeleton to nuclear chromatin affects mechanotransduction. Fibroblasts grown on flexible silicone membranes reacted to cyclic stretch by nuclear rotation. This rotation was abolished by inhibition of actomyosin contraction as well as by overexpression of dominant-negative versions of nesprin or sun proteins that form the LINC complex. In an in vitro model of muscle differentiation, cyclic strain inhibits differentiation and induces proliferation of C2C12 myoblasts. Interference with the LINC complex in these cells abrogated their stretch-induced proliferation, while stretch increased p38 MAPK and NFkappaB phosphorylation and the transcript levels of myogenic transcription factors MyoD and myogenin. We found that the physical link from the cytoskeleton to the nuclear lamina is crucial for correct mechanotransduction, and that disruption of the LINC complex perturbs the mechanical control of cell differentiation.

The ischial spine sign: does pelvic tilt and rotation matter?

Although the ischial spine sign (ISS) has been advocated to detect acetabular retroversion, it is unknown whether the sign is valid on anteroposterior (AP) pelvic radiographs with tilted or rotated pelves. We therefore evaluated reliability of the ISS as a tool for diagnosing acetabular retroversion in the presence of considerable pelvic tilt and/or malrotation. We obtained radiographs of 20 cadaver pelves in 19 different malorientations resulting in 380 pelvis images (760 hips) for evaluation. In addition, 129 clinical radiographs of patients' hips that had varying pelvis orientations were reviewed. We found an overall sensitivity of 81% (90%), specificity of 70% (71%), positive predictive value of 77% (80.7%), and negative predictive value of 75% (85%) in the cadaver (patient) hips. Our data suggest the ISS is a valid tool for diagnosing acetabular retroversion on plain radiographs taken using a standardized technique regardless of the degree of pelvic tilt and rotation.

The use of weightbearing radiographs to assess the stability of supination-external rotation fractures of the ankle

Isolated lateral malleolar fractures usually result from a supination-external rotation (SER) injury and may include a deltoid ligament rupture. The necessity of operative treatment is based on the recognition of a relevant medial soft-tissue disruption. Currently used tests to assess ankle stability include manual stress radiographs and gravity stress radiographs, but seem to overestimate the need for fracture fixation.

Reversed shoulder arthroplasty with modified L'Episcopo for combined loss of active elevation and external rotation

In patients with a rotator cuff-deficient shoulder, a combined loss of active elevation and external rotation (CLEER) can occur when both the infraspinatus and teres minor muscles are absent. A reverse shoulder arthroplasty (RSA) can restore active elevation in these patients but cannot restore active external rotation because there are no other external rotator cuff muscles. We hypothesized that a modified L'Episcopo procedure (latissimus dorsi [LD] and teres major [TM] transfer) with a simultaneous RSA would restore shoulder function and activities of daily living (ADLs).

The role of rotation thromboelastometry in early prediction of massive transfusion

Early prediction of massive transfusion (MT) is critical in the management of severely injured trauma patients. Variables available early after injury including physiologic, laboratory, and rotation thromboelastometric (ROTEM) parameters were evaluated as predictors for the need of MT.

Left ventricular rotation: a neglected aspect of the cardiac cycle

To describe the mechanics and possible clinical importance of left ventricular (LV) rotation, exemplify techniques to quantify LV rotation and illustrate the temporal relationship of cardiac pressures, electrocardiogram and LV rotation.