BackgroundIntervertebral disc degeneration (IVDD) is considered a multifactorial disease that is influenced by both environmental and genetic factors. The last two decades of research strongly demonstrate that genetic factors contribute about 75% of the IVDD etiology. Recent total genome sequencing studies have shed light on the various single-nucleotide polymorphisms (SNPs) that are associated with IVDD.AimThis review presents comprehensive and updated information about the diversity of genetic factors in the inflammatory, degradative, homeostatic, and structural systems involved in the IVDD. An organized collection of information is provided regarding genetic polymorphisms that have been identified to influence the risk of developing IVDD. Understanding the proteins and signaling systems involved in IVDD can lead to improved understanding and targeting of therapeutics.Materials and methodsAn electronic literature search was performed using the National Library of Medicine for publications using the keywords genetics of IVDD, lumbar disc degeneration, degenerative disc disease, polymorphisms, SNPs, and disc disease. The articles were then screened based on inclusion criteria that included topics that covered the correlation of SNPs with developing IVDD. Sixty-five articles were identified as containing relevant information. Articles were excluded if they investigated lower back pain or just disc herniation without an analysis of disc degeneration. This study focuses on the chronic degeneration of IVDs.ResultsVarious genes were identified to contain SNPs that influenced the risk of developing IVDD. Among these are genes contributing to structural proteins, such as COL1A1, COL9A3, COL9A3, COL11A1, and COL11A2, ACAN, and CHST3. Furthermore, various SNPs found in the vitamin-D receptor gene are also associated with IVDD. SNPs related to inflammatory cytokine imbalance are associated with IVDD, although some effects are limited by sex and certain populations. SNPs in genes that code for extracellular matrix-degrading enzymes, such as MMP-1, MMP-2, MMP-3, MMP-9, MMP-14, ADAMTS-4, and ADAMTS-5 are also associated with IVDD. Apoptosis-mediating genes, such as caspase 9 gene (CASP9), TRAIL, and death receptor 4 (DR4), as well as those for growth factors, such as growth differentiation factor 5 and VEGF, are identified to have polymorphisms that influence the risk of developing IVDD.ConclusionWithin the last 10 years, countless new SNPs have been identified in genes previously unknown to be associated with IVDD. Furthermore, the last decade has also revealed new SNPs identified in genes already known to be involved with increased risk of developing IVDD. Improved understanding of the numerous genetic variants behind various pathophysiological elements of IVDD could help advance personalized care and pharmacotherapeutic strategies for patients suffering from IVDD in the future.

Background: Previous studies showed that confocal laser endomicroscopy (CLE) images of brain tumors acquired by a first-generation (Gen1) CLE system using fluorescein sodium (FNa) contrast yielded a diagnostic accuracy similar to frozen surgical sections and histologic analysis. We investigated performance improvements of a second-generation (Gen2) CLE system designed specifically for neurosurgical use. Methods: Rodent glioma models were used for in vivo and rapid ex vivo CLE imaging. FNa and 5-aminolevulinic acid were used as contrast agents. Gen1 and Gen2 CLE images were compared to distinguish cytoarchitectural features of tumor mass and margin and surrounding and normal brain regions. We assessed imaging parameters (gain, laser power, brightness, scanning speed, imaging depth, and Z-stack [3D image acquisition]) and evaluated optimal values for better neurosurgical imaging performance with Gen2. Results: Efficacy of Gen1 and Gen2 was similar in identifying normal brain tissue, vasculature, and tumor cells in masses or at margins. Gen2 had smaller field of view, but higher image resolution, and sharper, clearer images. Other advantages of the Gen2 were auto-brightness correction, user interface, image metadata handling, and image transfer. CLE imaging with FNa allowed identification of nuclear and cytoplasmic contours in tumor cells. Injection of higher dosages of FNa (20 and 40 mg/kg vs. 0.1–8 mg/kg) resulted in better image clarity and structural identification. When used with 5-aminolevulinic acid, CLE was not able to detect individual glioma cells labeled with protoporphyrin IX, but overall fluorescence intensity was higher ( p < 0.01) than in the normal hemisphere. Gen2 Z-stack imaging allowed a unique 3D image volume presentation through the focal depth. Conclusion: Compared with Gen1, advantages of Gen2 CLE included a more responsive and intuitive user interface, collection of metadata with each image, automatic Z-stack imaging, sharper images, and a sterile sheath. Shortcomings of Gen2 were a slightly slower maximal imaging speed and smaller field of view. Optimal Gen2 imaging parameters to visualize brain tumor cytoarchitecture with FNa as a fluorescent contrast were defined to aid further neurosurgical clinical in vivo and rapid ex vivo use. Further validation of the Gen2 CLE for microscopic visualization and diagnosis of brain tumors is ongoing.

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Spinal cord injury (SCI) is a devastating condition that affects many people worldwide. Treatment focuses on controlling secondary injury cascade and improving regeneration. It has recently been suggested that both the secondary injury cascade and the regenerative process are heavily regulated by microRNAs (miRNAs). The measurement of specific biomarkers could improve our understanding of the disease processes, and thereby provide clinicians with the opportunity to guide treatment and predict clinical outcomes after SCI. A variety of miRNAs exhibit important roles in processes of inflammation, cell death, and regeneration. These miRNAs can be used as diagnostic tools for predicting outcome after SCI. In addition, miRNAs can be used in the treatment of SCI and its symptoms. Significant laboratory and clinical evidence exist to show that miRNAs could be used as robust diagnostic and therapeutic tools for the treatment of patients with SCI. Further clinical studies are warranted to clarify the importance of each subtype of miRNA in SCI management.

Background:Extracranial–intracranial bypass is a challenging procedure that requires special microsurgical skills and an operative microscope. The exoscope is a tool for neurosurgical visualization that provides view on a heads-up display similar to an endoscope, but positioned external to the operating field, like a microscope. The authors carried out a proof-of-concept study evaluating the feasibility and effectiveness of performing microvascular bypass using various new exoscopic tools.Methods:We evaluated microsurgical procedures using a three-dimensional (3D) endoscope, hands-free robotic automated positioning two-dimensional (2D) exoscope, and an ocular-free 3D exoscope, including surgical gauze knot tying, surgical glove cutting, placental vessel anastomoses, and rat vessel anastomoses. Image quality, effectiveness, and feasibility of each technique were compared among different visualization tools and to a standard operative microscope.Results:3D endoscopy produced relatively unsatisfactory resolution imaging. It was shown to be sufficient for knot tying and anastomosis of a placental artery, but was not suitable for anastomosis in rats. The 2D exoscope provided higher resolution imaging, but was not adequate for all maneuvers because of lack of depth perception. The 3D exoscope was shown to be functional to complete all maneuvers because of its depth perception and higher resolution.Conclusion:Depth perception and high resolution at highest magnification are required for microvascular bypass procedures. Execution of standard microanastomosis techniques was unsuccessful using 2D imaging modalities because of depth-perception-related constraints. Microvascular anastomosis is feasible under 3D exoscopic visualization; however, at highest magnification, the depth perception is inferior to that provided by a standard operative microscope, which impedes the procedure.

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