ABSTRACT
Background The treatment of AOSpine A3 and A4 fractures is controversial with no consensus regarding their management in the absence of neurologic deficits. While conservative management with spinal orthosis is a reasonable treatment option, it is believed to run the risk of progressive segmental kyphosis. Methodology A retrospective chart review was conducted of all patients undergoing treatment for thoracolumbar burst fractures from T11 to L2. Patients treated with conservative management with lumbar orthosis were included. Upright radiographs at the time of presentation and the one-year follow-up were compared. Results In total, 112 patients were evaluated as being treated with thoracolumbar orthosis. Of these, 61 patients presented with A3 fractures compared with 51 who presented with A4 fractures. Of these, two patients in each group failed conservative management and required surgical intervention. At the one-year follow-up, A3 fractures demonstrated an average change in Cobb angle of 4.1 degrees compared with 6.1 degrees in A4 fractures (p = 0.021). In addition, A4 fractures demonstrated a significantly worse kyphotic angle and Gardner angle at the one-year follow-up (p = 0.05 and p = 0.026, respectively). Conclusions A3 and A4 fractures can be safely treated with orthosis with overall low rates for failure; however, A4 fractures result in significantly worse segmental kyphosis at the one-year follow-up.
ABSTRACT
Even though there are hundreds of reports in the published literature supporting the hypothesis that G protein-coupled receptors (GPCR) form and function as dimers this remains a highly controversial area of research and mechanisms governing homodimer formation are poorly understood. Crystal structures revealing homodimers have been reported for many different GPCR. For adrenergic receptors, a potential dimer interface involving transmembrane domain 1 (TMD1) and helix 8 (H8) was identified in crystal structures of the beta1-adrenergic (ß1-AR) and ß2-AR. The purpose of this study was to investigate a potential role for TMD1 and H8 in dimerization and plasma membrane expression of functional ß2-AR. Charged residues at the base of TMD1 and in the distal portion of H8 were replaced, singly and in combination, with non-polar residues or residues of opposite charge. Wild type and mutant ß2-AR, tagged with YFP and expressed in HEK293 cells, were evaluated for plasma membrane expression and function. Homodimer formation was evaluated using bioluminescence resonance energy transfer, bimolecular fluorescence complementation, and fluorescence correlation spectroscopy. Amino acid substitutions at the base of TMD1 and in the distal portion of H8 disrupted homodimer formation and caused receptors to be retained in the endoplasmic reticulum. Mutations in the proximal region of H8 did not disrupt dimerization but did interfere with plasma membrane expression. This study provides biophysical evidence linking a potential TMD1/H8 interface with ER export and the expression of functional ß2-AR on the plasma membrane. This article is part of a Special Issue entitled: Interactions between membrane receptors in cellular membranes edited by Kalina Hristova.
