Exploring the functional composition of the human microbiome using a hand-curated microbial trait database.

BACKGROUND: Even when microbial communities vary wildly in their taxonomic composition, their functional composition is often surprisingly stable. This suggests that a functional perspective could provide much deeper insight into the principles governing microbiome assembly. Much work to date analyzing the functional composition of microbial communities, however, relies heavily on inference from genomic features. Unfortunately, output from these methods can be hard to interpret and often suffers from relatively high error rates. RESULTS: We built and analyzed a domain-specific microbial trait database from known microbe-trait pairs recorded in the literature to better understand the functional composition of the human microbiome. Using a combination of phylogentically conscious machine learning tools and a network science approach, we were able to link particular traits to areas of the human body, discover traits that determine the range of body areas a microbe can inhabit, and uncover drivers of metabolic breadth. CONCLUSIONS: Domain-specific trait databases are an effective compromise between noisy methods to infer complex traits from genomic data and exhaustive, expensive attempts at database curation from the literature that do not focus on any one subset of taxa. They provide an accurate account of microbial traits and, by limiting the number of taxa considered, are feasible to build within a reasonable time-frame. We present a database specific for the human microbiome, in the hopes that this will prove useful for research into the functional composition of human-associated microbial communities.

Pulsed Electromagnetic Field Stimulators Efficacy for Noninvasive Bone Growth in Spine Surgery.

The growth of pulsed electromagnetic field (PEMF) therapy and its progress over the years for use in post-operative bone growth has been revolutionary in its effect on bone tissue proliferation and vascular flow. However, further progress in PEMF therapy has been difficult due to lack of more evidence-based understanding of its mechanism of action. Our objective was to review the current understanding of bone growth physiology, the mechanism of PEMF therapy action along with its application in spinal surgery and associated outcomes. The authors of this review examined multiple controlled, comparative, and cohort studies to compare fusion rates of patients undergoing PEMF stimulation. Examining spinal fusion rates, a rounded comparison of post-fusion outcomes with and without bone stimulator was performed. Results showed that postoperative spinal surgery PEMF stimulation had higher rates of fusion than control groups. Though PEMF therapy was proven more effective, multiple factors contributed to difficulty in patient compliance for use. Extended timeframe of treatment and cost of treatment were the main obstacles to full compliance. This review showed that PEMF therapy presented an increased rate of recovery in patients, supporting the use of these devices as an effective post-surgical aid. Given the recent advances in the development of PEMF devices, affordability and access will be much easier suited to the patient population, allowing for more readily available treatment options.

BIIB093 (intravenous glibenclamide) for the prevention of severe cerebral edema.

BACKGROUND: Vasogenic edema in the setting of acute ischemic stroke can be attributed to the opening of transient receptor potential 4 channels, which are expressed in the setting of injury and regulated by sulfonylurea receptor 1 (SUR1) proteins. Glibenclamide, also known as glyburide, RP-1127, Cirara, and BIIB093, is a second-generation sulfonylurea that binds SUR1 at potassium channels and may significantly reduce cerebral edema following stroke, as evidenced by recent clinical trials. This review provides a comprehensive analysis of clinical considerations of glibenclamide use and current patient outcomes when administered in the setting of acute ischemic stroke to reduce severe edema. METHODS: National databases (MEDLINE, EMBASE, Cochrane, and Google scholar databases) were searched to identify studies that reported on the clinical outcomes of glibenclamide administered immediately following acute ischemic stroke. RESULTS: The pharmacological mechanism of glibenclamide was reviewed in depth as well as the known indications and contraindications to receiving treatment. Eight studies were identified as having meaningful clinical outcome data, finding statistically significant differences in glibenclamide treatment groups ranging from matrix metalloproteinase-9 serum levels, midline shift, modified Rankin Scores, National Institute of Health Stroke Score, and mortality endpoints. CONCLUSION: Studies analyzing the GAMES-Pilot and GAMES-PR trials suggest that glibenclamide has a moderate, however, measurable effect on intermediate biomarkers and clinical endpoints. Meaningful conclusions are limited by the small sample size of patients studied.

Retro-Odontoid Pseudotumor Formation in the Context of Various Acquired and Congenital Pathologies of the Craniovertebral Junction and Surgical Techniques.

Retro-odontoid pseudotumor formation consists of an abnormal growth of granulation tissue typically posterior to the odontoid process, resulting as a manifestation of atlantoaxial instability. This instability can occur as a result of conditions ranging from severe mechanical trauma to metabolic disease or autoimmune conditions such as rheumatoid arthritis. A pseudotumor may impinge on the spinal nerves or even the spinal cord and brainstem, manifesting symptoms from severe neck pain to cervicomedullary compression or myelopathy, and in some cases even sudden death. The objective of this review is to consolidate the findings in published case reports and relevant prior literature reviews regarding the formation of retro-odontoid pseudotumor. We address the pathophysiology involved in acquired and congenital pseudotumor formation, including those associated with rheumatoid arthritis (panni). Additionally, we discuss past and current operative techniques designed to curtail and ultimately regress a retro-odontoid pseudotumor and pannus. Surgical techniques that are addressed include ventral decompression (both transoral and transnasal), dorsal decompression, and indications for posterior instrumentation in pannus formation, particularly in cases that may be sufficiently treated in lieu of an anterior approach. Finally, we will examine the role of external orthoses as both a method of conservative treatment as well as a potential adjunct to the aforementioned surgical procedures.

Enhanced Spinal Therapy: Extracorporeal Shock Wave Therapy for the Spine.

Extracorporeal shock wave therapy (ESWT) is a non-invasive therapeutic method used for pain management and muscle strength improvement through the use of shock waves. In vitro studies have demonstrated that shockwave therapy induces fluctuation in redox reaction regulation and increases in Mitogen-Activated Protein Kinase (MAPK) signal transduction pathways, stimulating increased gene expression in the nucleus. ESWT has also been shown to upregulate angiogenesis and growth factors through activation of endothelial nitric oxide synthase (eNOS) and vascular endothelial growth factor (VEGF). The use of ESWT in the treatment of various musculoskeletal disorders was widely adopted throughout Europe, South America, and Asia before being introduced in the United States in 2000. Within the past 20 years, the clinical application of ESWT in the treatment of musculoskeletal and bone disorders has grown. This paper provides a comprehensive narrative review of applications and outcomes of ESWT in clinical spinal pathology and assesses reported efficacy as it relates to the pathology. A review of the literature yielded studies describing the use of ESWT in degenerative osteoporotic neuro-spinal pathology, heterotopic ossification due to spinal cord injury, cervical spondylosis, scoliosis, sacroiliitis, and coccydynia. The efficacy of ESWT as an adjunct treatment in patients with spinal cord pathologies varied with the specific pathology, however, all pathologies discussed in this review provided evidence of potential benefits with minimal adverse effects. While the use of ESWT for pain management has widely been established, further literature should aim to identify the long-term benefits of ESWT.

Thoracic Endoscopic Spine Surgery: A Comprehensive Review.

BACKGROUND: From the 1990s, there has been growth in the literature demonstrating the feasibility of minimally invasive approaches for treating diverse spinal disorders. There is still much work to be done in circumnavigating the technical challenges and elucidating relative advantages of endoscopic techniques in spine surgery. In this comprehensive literature review, we discuss the history, advantages, disadvantages, approaches, and technology of, and critically examine peer-reviewed studies specifically addressing, endoscopic thoracic spinal surgery. METHODS: Literature review was conducted with the key words "endoscopic," "minimally invasive," and "thoracic spinal surgery," using PubMed, Web of Science, and Google Scholar. RESULTS: Review of 241 thorascopic procedures showed a success rate of 98% to 100%, low morbidity, and favorable complication profile. Review of 115 thoracic fixation procedures demonstrated high success rate, and 87% of screw positions were rated "good." Review of 55 full endoscopic uniportal decompressions showed sufficient decompression in most patients. Match pair analysis of 34 patients comparing video-assisted thoracoscopy surgery (VATS) or posterior spinal fusion reported the VATS group had increased operative duration but reduced blood loss. CONCLUSIONS: Based on our literature review, there is a high rate of positive outcomes with endoscopic thoracic spine surgery, which reduces tissue dissection, intraoperative blood loss, and epidural fibrosis. However, the technical challenge highlights the importance of further training and innovation in this rapidly evolving field. LEVEL OF EVIDENCE: 3. CLINICAL RELEVANCE: There is growing evidence demonstrating the success of endoscopic thoracic spinal surgery. Populations that could be helped include the elderly and immunocompromised, who would benefit from decreased hospital stay and enhanced recovery time.

Weight-Bearing Magnetic Resonance Imaging as a Diagnostic Tool That Generates Biomechanical Changes in Spine Anatomy.

Weight-bearing magnetic resonance imaging (MRI) is a unique modality in diagnostic imaging that allows for the assessment of spinal pathology in ways considered previously inaccessible or insufficient with the conventional MRI technique. Due to limitations in positioning within the MRI machine itself, difficulties would be posed in determining the underlying cause of a patient's pain or neurological symptoms, as the traditional supine position utilized can, in many cases, alleviate the severity of presented symptoms. Weight-bearing MRI addresses this concern by allowing a clinician to position a patient (to a certain degree) into flexion, extension, rotation, or side-bending with an axial load that can mimic physiologic conditions in order to replicate the conditions the patient experiences in order to give clinicians a clearer understanding of the anatomical relationship of the spine and surrounding tissues that may lead to a particular presentation of symptoms. These findings can then guide treatment approaches that are better tailored to a patient's needs in order to initiate treatment earlier and shorten the duration of treatment necessary for patient benefit. The goal of this review is to describe and differentiate weight-bearing MRI from conventional MRI as well as examine the advantages and disadvantages of either imaging modality. This will include assessing cost-effectiveness and improvements in clinical outcomes. Further, the advancements of weight-bearing MRI will be discussed, including potentially unique clinical applications in development.

Trait-based analysis of the human skin microbiome.

BACKGROUND: The past decade of microbiome research has concentrated on cataloging the diversity of taxa in different environments. The next decade is poised to focus on microbial traits and function. Most existing methods for doing this perform pathway analysis using reference databases. This has both benefits and drawbacks. Function can go undetected if reference databases are coarse-grained or incomplete. Likewise, detection of a pathway does not guarantee expression of the associated function. Finally, function cannot be connected to specific microbial constituents, making it difficult to ascertain the types of organisms exhibiting particular traits-something that is important for understanding microbial success in specific environments. A complementary approach to pathway analysis is to use the wealth of microbial trait information collected over years of lab-based, culture experiments. METHODS: Here, we use journal articles and Bergey's Manual of Systematic Bacteriology to develop a trait-based database for 971 human skin bacterial taxa. We then use this database to examine functional traits that are over/underrepresented among skin taxa. Specifically, we focus on three trait classes-binary, categorical, and quantitative-and compare trait values among skin taxa and microbial taxa more broadly. We compare binary traits using a Chi-square test, categorical traits using randomization trials, and quantitative traits using a nonparametric relative effects test based on global rankings using Tukey contrasts. RESULTS: We find a number of traits that are over/underrepresented within the human skin microbiome. For example, spore formation, acid phosphatase, alkaline phosphatase, pigment production, catalase, and oxidase are all less common among skin taxa. As well, skin bacteria are less likely to be aerobic, favoring, instead, a facultative strategy. They are also less likely to exhibit gliding motility, less likely to be spirillum or rod-shaped, and less likely to grow in chains. Finally, skin bacteria have more difficulty at high pH, prefer warmer temperatures, and are much less resilient to hypotonic conditions. CONCLUSIONS: Our analysis shows how an approach that relies on information from culture experiments can both support findings from pathway analysis, and also generate new insights into the structuring principles of microbial communities.