Virtual Healthcare Simulation: Implementation, Distractions, and Preferences.

Introduction: Social distancing guidelines related to COVID-19 resulted in many simulation centers temporarily closing or adopting virtual simulation-based education (SBE). This mixed methods study aimed to evaluate our center's readiness to implement virtual SBE, the preferred method of delivery (virtual vs. nonvirtual), and any reported distractions.

Influence of Socioeconomic Bias on Emergency Medicine Resident Decision Making and Patient Care.

Introduction: Physician bias impacts clinical decision making, resulting in disparities in patient care. Most existing studies focus on sex and racial bias. This study aimed to investigate disparities in physician decision making among patients of varying socioeconomic status (SES).

Mucin 1, a signal transduction membrane-bound mucin, is present in human disc tissue and is downregulated in vitro by exposure to IL-1ß or TNF-α.

Background: Back pain and disc degeneration have a growing socioeconomic healthcare impact. Mucin 1 (MUC1) is a transmembrane glycoprotein whose extracellular and intracellular domains participate in cellular signaling. Little is currently known about the presence or role of MUC1 in human disc degeneration.

Human annulus progenitor cells: Analyses of this viable endogenous cell population.

Back pain and intervertebral disc degeneration have growing socioeconomic/health care impacts. Increasing research efforts address use of stem and progenitor cell-based replacement therapies to repopulate and regenerate the disc. Data presented here on the innate human annulus progenitor cells: (i) assessed osteogenic, chondrogenic and adipogenic potentials of cultured human annulus cells; and (ii) defined progenitor-cell related gene expression patterns.

Human annulus signaling cues for nerve outgrowth: In vitro studies.

The relationship between neurotrophins produced by human annulus cells, such as neurotrophin-4 (NT4) and brain-derived neurotrophic factor (BDNF) which function in neurite survival and outgrowth, and nerve ingrowth into the disc remains poorly understood. In this work, we tested F11 neurite growth during exposure to control media, media with added nerve growth factor (NGF), conditioned media (CM) harvested from previous human annulus culture, or co-culture with annulus cells. Co-culture of F11 cells with annulus cells significantly increased media levels of amphiregulin, BDNF, glial-derived neurotrophic factor, and vascular endothelial growth factor compared to levels from in culture of F11 cells alone (p ≤ 0.

Autophagy in the Degenerating Human Intervertebral Disc: In Vivo Molecular and Morphological Evidence, and Induction of Autophagy in Cultured Annulus Cells Exposed to Proinflammatory Cytokines-Implications for Disc Degeneration.

Study Design: Autophagy-related gene expression and ultrastructural features of autophagy were studied in human discs.

Objective: To obtain molecular/morphological data on autophagy in human disc degeneration and cultured human annulus cells exposed to proinflammatory cytokines.

Summary Of Background Data: Autophagy is an important process by which cytoplasm and organelles are degraded; this adaptive response to sublethal stresses (such as nutrient deprivation present in disc degeneration) supplies needed metabolites.

Mitochondrial Membrane Potential and Nuclear and Gene Expression Changes During Human Disc Cell Apoptosis: In Vitro and In Vivo Annulus Findings.

Study Design: A study using cultured human annulus cells and human annular tissue.

Objective: To further explore and define mitochondrial mechanisms related to disc cell apoptosis in vitro and in vivo.

Summary Of Background Data: Mitochondrial-dependent intrinsic signaling pathways are a well-recognized component of apoptosis (programmed cell death).

High-mobility group box-1 gene, a potent proinflammatory mediators, is upregulated in more degenerated human discs in vivo and its receptor upregulated by TNF-α exposure in vitro.

Mechanisms which control and enhance proinflammatory cytokine expression during human disc degeneration are still poorly understood. The high-mobility group box-1 gene (HMGB1) produces a protein which can itself act as a cytokine, or can function as a potent proinflammatory mediator. Little is known about expression of HMGB1 in the human disc.

Proinflammatory cytokines modulate the chemokine CCL2 (MCP-1) in human annulus cells in vitro: CCL2 expression and production.

Chemokines are important secondary inflammatory mediators released in response to stimuli which act as second-order cytokines with specialized functions in inflammation. The role of many of these specialized mediators is as yet poorly understood in the human intervertebral disc. Here we investigated CCL2 (chemokine (C-C motif) ligand 2, also known as monocyte chemotactic protein-1 (MCP-1)) in a study of its immunolocalization in disc tissue, and then hypothesized that exposure of cultured human annulus cells to proinflammatory cytokines might alter CCL2 gene expression and CCL2 production.

A novel catechol-O-methyltransferase variant associated with human disc degeneration.

Background: Disc degeneration and its associated low back pain are a major health care concern causing disability with a prominent role in this country's medical, social and economic structure. Low back pain is devastating and influences the quality of life for millions. Low back pain lifetime prevalence approximates 80% with an estimated direct cost burden of $86 billion per year.

Growth and differentiation factor-5 (GDF-5) in the human intervertebral annulus cells and its modulation by IL-1ß and TNF-α in vitro.

Growth and differentiation factor-5 (GDF-5) is a member of the TGF-ß superfamily which regulates cell division and differentiation. GDF-5 attracted high interest because of its role in skeletal development, especially in cartilaginous sites. Little is known, however, about the role of GFD-5 in disc cell biology.

Production and expression of RANTES (CCL5) by human disc cells and modulation by IL-1-β and TNF-α in 3D culture.

Chemokines act as important secondary inflammatory mediators which are released by cells in response to a variety of stimuli. Chemokines bind to cell surface receptors and act as second-order cytokines with specialized functions in inflammation. The role of RANTES (Regulated upon Activation, Normal T-cell Expressed, and Secreted) (also called CCL5 (chemokine (C-C motif) ligand 5)) has received little attention to date in disc tissue.

Human annulus cells regulate PAPP-A and IGFBP-4 expression, and thereby insulin-like growth factor bioavailability, in response to proinflammatory cytokine exposure in vitro.

Pregnancy-associated plasma protein-A (PAPP-A) is a metalloproteinase which cleaves IGF binding protein (BP)-4 in the extracellular matrix, making IGF available to nearby cells. We have shown that PAPP-A is present in the human intervertebral disc, and is significantly upregulated in more degenerated discs where increased proinflammatory cytokine levels are present. We hypothesized that increased proinflammatory cytokines present in the degenerating disc might be related to PAPP-A expression.

Genomewide molecular and biologic characterization of biomembrane formation adjacent to a methacrylate spacer in the rat femoral segmental defect model.

Objectives: This study focuses upon the morphologic and molecular features of the layer of cells, termed the "biomembrane," which forms around methacrylate spacers in bone segmental defects. The objective of this research was to assess the biomembrane formed in a novel rodent femoral segmental defect model at 4, 8, and 16 weeks with histologic and molecular studies.

Methods: Following Institutional Animal Care and Use Committee approval, a segmental defect was created in the rat femur and stabilized with the AO LockingRatNail and analyzed at 4, 8, and 16 weeks postsurgery using digital radiologic imaging, morphological and immunohistochemical studies, and genomewide gene expression studies employing microarray analysis.

Cell-based tissue engineering augments tendon-to-bone healing in a rat supraspinatus model.

Rotator cuff pathology causes substantial pain/disability and health care costs. Cell-based tissue engineering offers promise for improved outcomes in tendon to bone healing. Cells from the tendon-bone interface were used here to amplify surgical defect healing in a rat model.

Genome-wide analysis of pain-, nerve- and neurotrophin -related gene expression in the degenerating human annulus.

Background: In spite of its high clinical relevance, the relationship between disc degeneration and low back pain is still not well understood. Recent studies have shown that genome-wide gene expression studies utilizing ontology searches provide an efficient and valuable methodology for identification of clinically relevant genes. Here we use this approach in analysis of pain-, nerve-, and neurotrophin-related gene expression patterns in specimens of human disc tissue.

Deleterious effects of discography radiocontrast solution on human annulus cell in vitro: changes in cell viability, proliferation, and apoptosis in exposed cells.

Background Context: Carragee et al. have recently shown that modern discography injections are associated with subsequent acceleration of disc degeneration, herniation, and loss of disc height. Although needle puncture and pressurization are known trauma events that can create disc degeneration in animal models, another likely culprit in clinical discography-associated degeneration is a direct effect of the contrast agent itself on disc cells.

Osteogenic and chondrogenic potential of biomembrane cells from the PMMA-segmental defect rat model.

A layer of cells (the "biomembrane") has been identified in large segmental defects between bone and surgically placed methacrylate spacers or antibiotic-impregnated cement beads. We hypothesize that this contains a pluripotent stem cell population with potential valuable applications in orthopedic tissue engineering. Objectives using biomembranes harvested from rat segmental defects were to: (1) Culture biomembrane cells in specialized media to direct progenitor cells along bone or cartilage cell differentiation lineages; (2) evaluate harvested biomembranes for mesenchymal stem cell markers, and (3) define relevant gene expression patterns in harvested biomembranes using microarray analysis.

Matrix metalloproteinase-26, a novel MMP, is constitutively expressed in the human intervertebral disc in vivo and in vitro.

Matrix metalloproteinase (MMP) regulation and expression is important in the aging/degenerating human intervertebral disc. MMP-26 (also known as matrilysin-2 or endometase) is a newly discovered MMP which degrades type IV collagen, fibronectin, fibrinogen, vitronectin, denatured collagen types I-IV, insulin-like growth factor binding protein 1, and activated pro-MMP-9. Our objective here was to determine if it is present in human disc tissue and cultured disc cells.

Constitutive expression of cathepsin K in the human intervertebral disc: new insight into disc extracellular matrix remodeling via cathepsin K and receptor activator of nuclear factor-κB ligand.

Introduction: Cathepsin K is a recently discovered cysteine protease which cleaves the triple helical domains of type I to II collagen. It has been shown to be up-regulated in synovial tissue from osteoarthritic and rheumatoid patients, and is a component in normal and nonarthritic cartilage, where it increases with aging. Studies on heart valve development have recently shown that receptor activator of nuclear factor-κB ligand (RANKL) acts during valve remodeling to promote cathepsin K expression.

Mitochondrial gene expression in the human annulus: in vivo data from annulus cells and selectively harvested senescent annulus cells.

Background Context: Mitochondrial dysfunction is recognized during cell senescence and apoptosis, two important components of human disc aging/degeneration. We hypothesize that mitochondrial dysfunction is present in the degenerating and senescent annulus cells. The objective of the present study was to analyze gene expression profiles related to mitochondrial function in vivo.

Variations in aggrecan localization and gene expression patterns characterize increasing stages of human intervertebral disk degeneration.

During disk degeneration, annulus dehydration and matrix fraying culminate in the formation of tears through which nucleus and annulus disk material may rupture, causing radicular pain. Annular tears are present in more than half of the patients in early adulthood and are almost always present in the elderly. Aggrecan, which provides the disk with a shock absorber function under loading, is a key disk extracellular matrix (ECM) component.

Annulus cells from more degenerated human discs show modified gene expression in 3D culture compared with expression in cells from healthier discs.

Background Context: Understanding gene expression patterns of disc cells in culture is important as we develop biologic therapies for disc degeneration. The objective of the present study was to determine if cells from more degenerated discs expressed different genes, or differed in their expression patterns, compared with patterns of cells from healthier discs.

Purpose: To determine if annulus cells from more degenerated discs expressed different gene expression patterns compared with patterns of cells from healthier discs using genome-wide analysis.

Human adipose-derived mesenchymal stem cells: direction to a phenotype sharing similarities with the disc, gene expression profiling, and coculture with human annulus cells.

Biologic therapies for disc degeneration hold great promise as an emerging concept. Due to ease of harvest and abundance, adipose derived-mesenchymal stem cells (AD-MSC) are a readily available cell source for such therapies. Our objectives in this study were (1) to develop/validate methods to harvest AD-MSC and direct them to a disc-like phenotype by three-dimensional (3D) culture and transforming growth factor (TGF)-beta3 exposure, (2) to assess cell phenotypes with gene expression profiling for these human AD-MSC and annulus cells, and (3) to test whether disc cell-AD-MSC coculture could augment glycosaminoglycan (GAG) production.