Tropism of engineered and evolved recombinant AAV serotypes in the rd1 mouse and ex vivo primate retina.

There is much debate on the adeno-associated virus (AAV) serotype that best targets specific retinal cell types and the route of surgical delivery-intravitreal or subretinal. This study compared three of the most efficacious AAV vectors known to date in a mouse model of retinal degeneration (rd1 mouse) and macaque and human retinal explants. Green fluorescent protein (GFP) driven by a ubiquitous promoter was packaged into three AAV capsids: AAV2/8(Y733F), AAV2/2(quad Y-F) and AAV2/2(7m8). Overall, AAV2/2(7m8) transduced the largest area of retina and resulted in the highest level of GFP expression, followed by AAV2/2(quad Y-F) and AAV2/8(Y733F). AAV2/2(7m8) and AAV2/2(quad Y-F) both resulted in similar patterns of transduction whether they were injected intravitreally or subretinally. AAV2/8(Y733F) transduced a significantly smaller area of retina when injected intravitreally compared with subretinally. Retinal ganglion cells, horizontal cells and retinal pigment epithelium expressed relatively high levels of GFP in the mouse retina, whereas amacrine cells expressed low levels of GFP and bipolar cells were infrequently transduced. Cone cells were the most frequently transduced cell type in macaque retina explants, whereas Müller cells were the predominant transduced cell type in human retinal explants. Of the AAV serotypes tested, AAV2/2(7m8) was the most effective at transducing a range of cell types in degenerate mouse retina and macaque and human retinal explants.

Vertical shear fractures of the femoral neck. A biomechanical study.

A biomechanical cadaver study was performed to compare the strength and stability of three cannulated cancellous lag screws with a sliding hip screw for fixation of a vertically oriented fracture of the femoral neck (Pauwels Type III). Using eight matched pairs of human cadaveric femurs, vertically oriented femoral neck osteotomies were created, reduced, and randomized to one of the two fixation methods. The constructs were tested with incremental axial loading from 100 N to 1200 N and cyclical loading at 1000 N for 10,000 cycles; fracture displacements and ultimate load to failure were determined. The specimens stabilized using a sliding hip screw showed less inferior femoral head displacement, less shearing displacement at the osteotomy site, and a much greater load to failure than did those stabilized with multiple cancellous lag screws. These results support the use of a sliding hip screw for treatment of vertically oriented fractures of the femoral neck.

The self-compressing tibial intramedullary nail.

Laboratory evaluation of a self-compressing tibial nail demonstrated that significant, initial compression of a simulated fracture or nonunion can be obtained and controlled. However, when this nail was tested in cyclic loading, loss of its initial static compression occurred.