subpial-adeno-associated-virus-9-aav9-vector-delivery-in-adult-mice

Subpial Adeno-associated Virus 9 (AAV9) Vector Delivery in Adult Mice

The successful development of a subpial adeno-associated virus 9 (AAV9) vector delivery technique in adult rats and pigs has been reported on previously. ...

University of California, San Diego

Fracture of acrylic resin prosthetic teeth from acrylic resin denture bases can be a problem for some patients. The optimal combination of acrylic resin denture tooth, denture base material, and processing method is not known. Purpose. The objective of this study was to compare the tensile bond strengths of heat- and microwave-polymerized acrylic resins among 4 types of acrylic resin denture teeth.

Tensile bond strength of acrylic resin denture teeth to a microwave- or heat-processed denture base.

The multidisciplinary treatment of a patient with a Class II malocclusion and an impacted maxillary central incisor is presented. Nonextraction correction of the distoclusion was achieved through mandibular growth and protraction of the mandibular first molars. Closed-eruption surgical exposure of the incisor, combined with soft-tissue revision posteruption, resulted in significantly improved facial esthetics.

Nonextraction treatment of a Class II malocclusion and impacted maxillary central incisor.

Traumatic retrolisthesis of the lumbar spine is a rare clinical entity. Only a few case reports have shown retrolisthesis of the fractured fragment over the inferior vertebral body. Fracture dislocations of the spine are unstable injuries that require operative fixation to restore alignment and prevent progressive deformity. We present the case of a traumatic L5-S1 fracture dislocation with retrolisthesis of the L5 vertebral body over the superior aspect of S1 managed with anterior, middle, and posterior column reconstruction. The patient presented with paraplegia and bowel and bladder incontinence. Retrolisthesis fracture dislocations injuries are rare, and as such, there are no guidelines regarding their management. In our case, we performed an L5 vertebrectomy with anterior, middle, and posterior column reconstruction via a posterior approach using a lumbosacral-pelvic construct. The patient did not regain function in his distal lower extremities postoperatively.

Traumatic L5 Posterolateral Spondyloptosis: A Case Report and Review of the Literature.

Spinal cord injury (SCI) resulting in paraplegia or quadriplegia is a significant burden in the world. It is estimated that there are approximately 250 000 people living with SCI in the United States alone. Our study offered the direct implantation of human-derived stem cells into the spinal cord of subjects who have chronic SCI. The primary objective of the study is to determine the safety and toxicity of human spinal stem cell transplantation for the treatment of paralysis. The secondary objectives of the study are to evaluate (1) graft survival in the transplant site, (2) effectiveness of transient immunosuppression as determined by absence of donor-specific HLA antibodies, and (3) potential therapeutic role of implantation on motor and sensory function in SCI.

172 A Phase I, Open-Label, Single-Site, Safety Study of Human Spinal Cord-Derived Neural Stem Cell Transplantation for the Treatment of Chronic Spinal Cord Injury.

We conducted a retrospective cohort analysis of early outcomes after elective anterior cervical discectomy and fusion (ACDF) vs cervical artificial disc replacement (C-ADR) using the National Surgical Quality Improvement Program database. Risk factors associated with operation time, hospital length of stay, early complications, and discharge destination were studied.

345 Elective Anterior Cervical Discectomy and Fusion vs Cervical Artificial Disc Replacement: A Comparison of Perioperative Morbidity and Early Outcomes.

Effective in vivo use of adeno-associated virus (AAV)-based vectors to achieve gene-specific silencing or upregulation in the central nervous system has been limited by the inability to provide more than limited deep parenchymal expression in adult animals using delivery routes with the most clinical relevance (intravenous or intrathecal). Here, we demonstrate that the spinal pia membrane represents the primary barrier limiting effective AAV9 penetration into the spinal parenchyma after intrathecal AAV9 delivery. We develop a novel subpial AAV9 delivery technique and AAV9-dextran formulation. We use these in adult rats and pigs to show (i) potent spinal parenchymal transgene expression in white and gray matter including neurons, glial and endothelial cells after single bolus subpial AAV9 delivery; (ii) delivery to almost all apparent descending motor axons throughout the length of the spinal cord after cervical or thoracic subpial AAV9 injection; (iii) potent retrograde transgene expression in brain motor centers (motor cortex and brain stem); and (iv) the relative safety of this approach by defining normal neurological function for up to 6 months after AAV9 delivery. Thus, subpial delivery of AAV9 enables gene-based therapies with a wide range of potential experimental and clinical utilizations in adult animals and human patients.

Potent spinal parenchymal AAV9-mediated gene delivery by subpial injection in adult rats and pigs.

To review the literature of spinal cord injury and stem cell therapy for large animal models and incorporate those results into an understanding of stem cell therapy for human cord injury.

A Review of Stem Cell Therapy for Spinal Cord Injury: Large Animal Models and the Frontier in Humans.

Laminectomy plus excision of spinal neoplasms is commonly performed. The current study examines risk profiles associated with elective laminectomies of benign, malignant primary, and secondary/metastatic neoplasms of the thoracic spine.

Elective laminectomy and excision of the thoracic spine neoplasm: an evaluation of early outcomes.

OBJECTIVE Normative data exists for stimulus-evoked pedicle screw electromyography (EMG) current thresholds in the lumbar spine, and is routinely referenced during spine surgeries to detect a screw breach, prevent injury of neural elements, and ensure the most biomechanically sound instrumentation construct. To date, similar normative data for cervical lateral mass screws is limited, thus the utility of lateral mass screw testing remains unclear. To address this disparity, in this study the authors describe cumulative lateral mass screw stimulation threshold data in patients undergoing posterior cervical instrumentation with lateral mass screws. These data are correlated with screw placement on postoperative imaging, and a novel correlation is discovered with direct clinical implications. METHODS Using a ball-tip probe, 154 lateral mass screws in 21 patients were electrically tested intraoperatively. In each case, for each screw, the lowest (or threshold) current at which the first polyphasic stimulus-evoked EMG response was reproducibly observed by a neurophysiologist was recorded. All patients underwent postoperative CT. Screw position within the lateral mass was first measured in the axial and sagittal planes for each lateral mass screw using the CT images. Screw placement was also evaluated by 2 independent physicians, blinded to current threshold data, on a binary scale of acceptability. The predictive capacity of screw EMG threshold data was evaluated via multivariable regression analyses and receiver operating characteristic (ROC) analyses. Predictive capacity was examined with respect to screw position within the lateral mass, as well as screw acceptability. RESULTS Lateral mass screw EMG thresholds did not appear to differ significantly for screws considered "acceptable" versus "unacceptable" according to the radiographic criteria. Accordingly, ROC analysis confirmed that EMG current threshold data were of minimal utility in predicting screw radiographic acceptability. However, EMG threshold was significantly predictive of screw medial distance from the spinal canal. A screw stimulating below 7.5 mA correctly identified a screw as being within 2 mm of the spinal canal with 75% sensitivity and 92% specificity (positive predictive value 20%, negative predictive value 99.3%), independent of its distance relative to other lateral mass landmarks. EMG current threshold was not significantly predictive of screw deviation in the superior or inferior directions, and was inversely predictive of screw deviations in the lateral direction. CONCLUSIONS In the context of uncertainty regarding the utility of cervical lateral mass EMG current threshold data, this study found that EMG current thresholds correspond significantly, and exclusively, with screw distance from the spinal canal. This association appears independent of other criteria for screw misplacement. As such, the authors recommend that EMG current thresholds be referenced in the case of a suspected medial breach as an effective means to rule out screw placement too medial to the spinal canal.

Lateral mass screw stimulation thresholds in posterior cervical instrumentation surgery: a predictor of medial deviation.

Cervical disc arthroplasty (CDA) is a recent alternative to anterior cervical discectomy and fusion (ACDF) in patients suffering cervical disc herniation and degeneration. To date, a systematic analysis of their comparative advantages and risks following elective surgery remains elusive.

Article	Year
Tensile bond strength of acrylic resin denture teeth to a microwave- or heat-processed denture base. The Journal of prosthetic dentistry\| PubMed ID: 12397241	2002
Nonextraction treatment of a Class II malocclusion and impacted maxillary central incisor. American journal of orthodontics and dentofacial orthopedics : official publication of the American Association of Orthodontists, its constituent societies, and the American Board of Orthodontics\| PubMed ID: 14718887	2004
Traumatic L5 Posterolateral Spondyloptosis: A Case Report and Review of the Literature. Cureus\| PubMed ID: 26180701	2015
172 A Phase I, Open-Label, Single-Site, Safety Study of Human Spinal Cord-Derived Neural Stem Cell Transplantation for the Treatment of Chronic Spinal Cord Injury. Neurosurgery\| PubMed ID: 27399451	2016
345 Elective Anterior Cervical Discectomy and Fusion vs Cervical Artificial Disc Replacement: A Comparison of Perioperative Morbidity and Early Outcomes. Neurosurgery\| PubMed ID: 27399543	2016
Potent spinal parenchymal AAV9-mediated gene delivery by subpial injection in adult rats and pigs. Molecular therapy. Methods & clinical development\| PubMed ID: 27462649	2016
A Review of Stem Cell Therapy for Spinal Cord Injury: Large Animal Models and the Frontier in Humans. World neurosurgery\| PubMed ID: 27876663	2017
Elective laminectomy and excision of the thoracic spine neoplasm: an evaluation of early outcomes. Journal of neurosurgical sciences\| PubMed ID: 27879953	2016
Lateral mass screw stimulation thresholds in posterior cervical instrumentation surgery: a predictor of medial deviation. Journal of neurosurgery. Spine\| PubMed ID: 27935447	2017
A matched cohort comparison of cervical disc arthroplasty versus anterior cervical discectomy and fusion: Evaluating perioperative outcomes. Journal of clinical neuroscience : official journal of the Neurosurgical Society of Australasia\| PubMed ID: 28511972	2017

Erik Curtis

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