Tungsten has been increasing in demand for use in manufacturing and recently, medical devices, as it imparts flexibility, strength, and conductance of metal alloys. Given the surge in tungsten use, our population may be subjected to elevated exposures. For instance, embolism coils made of tungsten have been shown to degrade in some patients. In a cohort of breast cancer patients who received tungsten-based shielding for intraoperative radiotherapy, urinary tungsten levels remained over tenfold higher 20 months post-surgery. In vivo models have demonstrated that tungsten exposure increases tumor metastasis and enhances the adipogenesis of bone marrow-derived mesenchymal stem cells while inhibiting osteogenesis. We recently determined that when mice are exposed to tungsten [15 ppm] in their drinking water, it bioaccumulates in the intervertebral disc tissue and vertebrae. This study was performed to determine the toxicity of tungsten on intervertebral disc. Bovine nucleus pulposus (bNP) and annulus fibrosus (bAF) cells were isolated from bovine caudal tails. Cells were expanded in flasks then prepared for 3D culturing in alginate beads at a density of 1×10∧6 cells/mL. Beads were cultured in medium supplemented with increasing tungsten concentrations in the form of sodium tungstate [0, 0.5, 5, 15 ug/mL] for 12 days. A modified GAG assay was performed on the beads to determine proteoglycan content and Western blotting for type II collagen (Col II) synthesis. Cell viability was determined by counting live and dead cells in the beads following incubation with the Live/Dead Viability Assay kit (Thermo Fisher Scientific). Cell numbers in beads at the end of the incubation period was determined using Quant-iT dsDNA Assay Kit (Thermo Fisher Scientific) Tungsten dose-dependently decreased the synthesis of proteoglycan in IVD cells, however, the effect was significant at the highest dose of 15 ug/mL. (n=3). Furthermore, although tungsten decreased the synthesis of Col II in IVD cells, it significantly increased the synthesis of Col I. Upregulation of catabolic enzymes ADAMTS4 and −5 were also observed in IVD cells treated with tungsten (n=3). Upon histological examination of spines from mice treated with tungsten [15 ug/mL] in their drinking water for 30 days, disc heights were diminished and Col I upregulation was observed (n=4). Cell viability was not markedly affected by tungsten in both bNP and bAF cells, but proliferation of bNP cells decreased at higher concentration. Surprisingly, histological examination of IVDs and gene expression analysis demonstrated upregulation of NGF expression in both NP and AF cells. In addition, endplate capillaries showed increases in CGRP and PGP9.5 expression as determined on histological sections of mouse IVDs, suggesting the development of sensory neuron invasion of the disc. We provide evidence that prolonged tungsten exposure can induce disc fibrosis and increase the expression of markers associated with pain. Tungsten toxicity may play a role in disc degeneration disease.
“Simulation”, “deliberate practice”, “rehearsal” have been used to describe safe acquisition and practice of skills before patient contact. Simulation resources are being introduced as a General Medical Council mandate. Individual simulators have shown multi-level evidence but there is no guidance to form a simulation curriculum. We devised a pilot arthroscopy course based on a 4-stage model. Stage 1: session covering anatomy, equipment, and skills required; Stage 2: practice on low fidelity simulators (Arthroscopic Skills Acquisition Tools (ASATs), ArthroBox, Synthetic Knee); Stage 3: practice on high fidelity simulators (Cadaveric Knee, Virtual Reality); Stage 4: assessment on performance intra-operatively. This study sought feedback on Stages 1–3 with the aim that the feedback will help identify how trainees wish to use simulators. Five arthroscopic simulators were used in this one-day pilot course. Prior to commencing, participants were asked which simulator they felt would help them the most. Feedback on each stage, and individual simulator (Likert scale), and how trainees would like to be trained was prospectively collected. Seven orthopaedic juniors took part. All felt the high-fidelity simulators will be the most useful. All stages were ranked with equal importance, whilst cadaveric, plastic, VR, Arthrobox and lastly ASATs ranked in order of realism respectively. For cadaveric arthroscopy trainees wished the trainers to be there all the time (6/7), whilst for VR all trainees wanted their trainers part of the time. We have shown that junior trainees value a structured method of skills acquisition and have identified that high fidelity simulation requires trainers to be present to provide relevant feedback. Such feedback mechanisms need to be incorporated in any curriculum so that simulation tools are not seen as a standalone training method.