Inclusions of TAR DNA-binding protein-43 (TDP-43), a nuclear protein that regulates transcription and RNA splicing, are the defining histopathological feature of frontotemporal lobar degeneration ...with ubiquitin-positive inclusions (FTLD-Us) and sporadic and familial forms of amyotrophic lateral sclerosis (ALS). In ALS and FTLD-U, aggregated, ubiquitinated, and N-terminally truncated TDP-43 can be isolated from brain tissue rich in neuronal and glial cytoplasmic inclusions. The loss of TDP-43 function resulting from inappropriate cleavage, translocation from the nucleus, or its sequestration into inclusions could play important roles in neurodegeneration. However, it is not known whether TDP-43 fragments directly mediate toxicity and, more specifically, whether their abnormal aggregation is a cause or consequence of pathogenesis. We report that the ectopic expression of a almost equal to25-kDa TDP-43 fragment corresponding to the C-terminal truncation product of caspase-cleaved TDP-43 leads to the formation of toxic, insoluble, and ubiquitin- and phospho-positive cytoplasmic inclusions within cells. The 25-kDa C-terminal fragment is more prone to phosphorylation at S409/S410 than full-length TDP-43, but phosphorylation at these sites is not required for inclusion formation or toxicity. Although this fragment shows no biological activity, its exogenous expression neither inhibits the function nor causes the sequestration of full-length nuclear TDP-43, suggesting that the 25-kDa fragment can induce cell death through a toxic gain-of-function. Finally, by generating a conformation-dependent antibody that detects C-terminal fragments, we show that this toxic cleavage product is specific for pathologic inclusions in human TDP-43 proteinopathies.
Pelvic positioning during total hip arthroplasty (THA) affects functional position of the acetabular component. We sought to evaluate whether preoperative pelvic tilt correlated with intraoperative ...pelvic tilt while positioned on a traction table for direct anterior THA and furthermore to evaluate whether there was a consistent and predictable effect on pelvic tilt while positioned for surgery.
We evaluated the sagittal spinopelvic preoperative standing and supine pelvic tilt radiographic measurements as compared with intraoperative measurements of 25 patients. Changes in pelvic tilt were analyzed for statistical significance and interobserver reliability.
The mean standing pelvic tilt was 13.5° ± 5.7°. The mean supine pelvic tilt was 13.3° ± 6.1°. There was no statistically significant difference between standing and supine pelvic tilt (P = .866). The mean intraoperative pelvic tilt was 3.0° ± 6.2°. There was a statistically significant decrease in pelvic tilt between both standing to intraoperative comparison and supine to intraoperative comparison (P < .0001 for both). Difference in mean between these comparisons was 10.5° ± 4.6° (95% confidence interval, 8.7°-12.3°) and 10.3° ± 6.3° (95% confidence interval, 7.8°-12.8°), respectively.
Patient positioning on a traction table for direct anterior THA has a reliable effect on pelvic tilt in the magnitude of approximately 10° decreased pelvic tilt. This effect on pelvic tilt correlates to approximately 7.4° and 3° altered anteversion and inclination, respectively. Taking into account this change in pelvic tilt at the time of surgery will allow the hip arthroplasty surgeon to more accurately place acetabular components in the desired functional position.
Background: Sparse documentation of Galeazzi fracture with associated nerve injury exists in the medical literature. The purpose of this report is to review the available literature in regard to ...incidence, nerve injury type, treatment strategies, and expected outcomes. Methods: We present a classic Galeazzi fracture dislocation with associated complete ulnar nerve transection injury at the level of the wrist. After rigid internal bony stabilization, allograft nerve repair was performed. The patient’s presentation, operative management, recovery, and a thorough literature review are discussed. Results: Fracture union was attained with near full wrist and elbow range of motion. Despite lack of ulnar nerve function return, the patient was able to resume manual labor occupation. Conclusions: Despite its close proximity to the dislocating distal radioulnar joint (DRUJ), thorough review reveals rare associated ulnar nerve palsy. If there is suspicion for nerve injury in the setting of open DRUJ dislocation, the nerve should be explored to identify possible entrapment or transection. Literature supports likely return of nerve function in cases of intact nerve; however, management of nerve transection remains debatable.
Hand gangrene following vascular cannula placement is uncommon and is usually the result of thrombotic occlusion of an artery. We describe a case of hand gangrene resulting in wrist disarticulation, ...following multiple unsuccessful attempts at internal jugular vein cannulation in a critically ill patient.
PDF
