Purpose:In patients with adolescent idiopathic scoliosis (AIS), radiographic surveillance is the gold standard of assessing spinal deformity, but has negative long-term effects. The Formetric 4D surface topography system was compared to standard radiography as a safer option for evaluating patients with AIS.Methods:Fourteen volunteers with typical AIS patient stature had 30 repeated Formetric 4D measurements taken, and reproducibility was assessed. Sixty-four patients with AIS were then enrolled during routine clinic visits. Evaluation included standard radiographs and surface topography measurements. A comparison analysis was performed.Results:When assessing same-day repeated scans, a standard deviation of +/- 3.4 degrees for scoliosis curve measurements was determined, and the Reliability Coefficient (Cronbach) was very high (0.996). Cobb angles measured with the Formetric 4D differed from radiographic measurements by an average of 9.42 (lumbar) and 6.98 (thoracic) degrees, while the correlation between the two measurements was strong (95% confidence interval [CI]), 0.758 (lumbar) and 0.872 (thoracic) respectively.Conclusions:The Formetric 4D is comparable to radiography in terms of its test-retest reproducibility. Although this device does not predict curve magnitude exactly, the predictions correlate strongly with the Cobb angles determined from radiographs. It can be reliably used in the surveillance of patients with AIS.

Acute traumatic brain injury (TBI) is associated with long-term cognitive and behavioral dysfunction. In vivo studies have shown histone deacetylase inhibitors (HDACis) to be neuroprotective following TBI in rodent models. HDACis are intriguing candidates because they are capable of provoking widespread genetic changes and modulation of protein function. By using known HDACis and a unique small-molecule pan-HDACi (LB-205), we investigated the effects and mechanisms associated with HDACi-induced neuroprotection following CNS injury in an astrocyte scratch assay in vitro and a rat TBI model in vivo. We demonstrate the preservation of sufficient expression of nerve growth factor (NGF) and activation of the neurotrophic tyrosine kinase receptor type 1 (TrkA) pathway following HDACi treatment to be crucial in stimulating the survival of CNS cells after TBI. HDACi treatment up-regulated the expression of NGF, phospho-TrkA, phospho-protein kinase B (p-AKT), NF-κB, and B-cell lymphoma 2 (Bcl-2) cell survival factors while down-regulating the expression of p75 neurotrophin receptor (NTR), phospho-JNK, and Bcl-2-associated X protein apoptosis factors. HDACi treatment also increased the expression of the stem cell biomarker nestin, and decreased the expression of reactive astrocyte biomarker GFAP within damaged tissue following TBI. These findings provide further insight into the mechanisms by which HDACi treatment after TBI is neuroprotective and support the continued study of HDACis following acute TBI.A cute traumatic brain injury (TBI) is a leading cause of disability and death, and results in reduced quality of life for surviving patients and prolonged economic effects on society (1). Primary injury occurs at the moment of trauma and is the direct result of shearing, tearing, and stretching of the brain parenchyma affecting neural tissue and blood vessels, and causing immediate contusion, hemorrhage, diffuse axonal injury, and ischemia (2, 3). TBI brings about cognitive and behavioral dysfunction through a complex sequence of secondary pathologic changes following injury. The mechanisms evolve over time and include excessive neurotransmitter release, mitochondrial dysfunction, increased bloodbrain barrier (BBB) permeability, cerebral edema, inflammation, and seizures, causing cell death and clinical morbidity (4).Clinical trials designed to test therapeutic agents aimed at improving residual cerebral function after TBI have not been successful because of the multifactorial nature of the disorder (2, 5-7). No pharmacological agent is currently approved for the treatment of acute TBI. The present standard of care consists of maintaining physiologic function by preserving adequate cerebral perfusion and normal intracranial pressure. Histone deacetylase inhibitors (HDACis) are potential candidates for the treatment of TBI. They are capable of inducing widespread alterations in cellular function and protein expression through posttranslational modification of histones, transcriptional factors, and heat shock chaperones (8-...

Protein Phosphatase 2A (PP2A) is a tumor suppressor whose function is lost in many cancers. An emerging, though counterintuitive, therapeutic approach is inhibition of PP2A to drive damaged cells through the cell cycle, sensitizing them to radiation therapy. We investigated the effects of PP2A inhibition on U251 glioblastoma cells following radiation treatment in vitro and in a xenograft mouse model in vivo. Radiation therapy alone augmented PP2A activity, though this was significantly attenuated with combination LB100 treatment. LB100 treatment yielded a radiation dose enhancement factor of 1.45 and increased the rate of post-radiation mitotic catastrophe at 72 and 96 hours. Glioblastoma cells treated with combination LB100 and radiation therapy maintained increased γ-H2AX expression at 24 hours, diminishing cellular repair of radiation-induced DNA double-strand breaks. Combination therapy significantly enhanced tumor growth delay and mouse survival and decreased p53 expression 3.68-fold, compared to radiation therapy alone. LB100 treatment effectively inhibited PP2A activity and enhanced U251 glioblastoma radiosensitivity in vitro and in vivo. Combination treatment with LB100 and radiation significantly delayed tumor growth, prolonging survival. The mechanism of radiosensitization appears to be related to increased mitotic catastrophe, decreased capacity for repair of DNA double-strand breaks, and diminished p53 DNA damage response pathway activity.

von Hippel-Lindau disease (VHL) patients develop highly vascular tumors, including central nervous system hemangioblastomas. It has been hypothesized that the vascular nature of these tumors is the product of reactive angiogenesis. However, recent data indicate that VHL-associated hemangioblastoma neoplastic cells originate from embryologically-arrested hemangioblasts capable of blood and endothelial cell differentiation. To determine the origin of tumor vasculature in VHL-associated hemangioblastomas, we analyzed the vascular elements in tumors from VHL patients. We demonstrate that isolated vascular structures and blood vessels within VHL-associated hemangioblastomas are a result of tumor-derived vasculogenesis. Further, similar to hemangioblastomas, we demonstrate that other VHL-associated lesions possess vascular tissue of tumor origin and that tumor-derived endothelial cells emerge within implanted VHL deficient UMRC6 RCC murine xenografts. These findings further establish the embryologic, developmentally arrested, hemangioblast as the tumor cell of origin for VHL-associated hemangioblastomas and indicate that it is also the progenitor cell for other VHL-associated tumors.