Flowchart demonstrating the number of editorial board members per journal and the number of participants that completed a disclosure per meeting or index.

<p>NASS = North American Spine Society, SRS = Scoliosis Research Society, IMAST = International Meeting on Advanced Spine Techniques, AOSpine = Arbeitsgemeinschaft für Osteosynthesefragen Spine, AAOS = American Academy of Orthopaedic Surgeons.</p

Potential conflicts of interest of editorial board members.

<p>* Editorial board members who completed a disclosure for: (1) North American Spine Society national spine meeting 2013 [<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0127362#pone.0127362.ref029" target="_blank">29</a>]; (2) Scoliosis Research Society 48th annual meeting & course 2013 [<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0127362#pone.0127362.ref031" target="_blank">31</a>]; (3) Scoliosis Research Society 20th International Meeting on Advanced Spine Techniques 2013 [<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0127362#pone.0127362.ref030" target="_blank">30</a>]; (4) AOSpine global spine congress 2013 [<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0127362#pone.0127362.ref033" target="_blank">33</a>]; (5) Eurospine 2013 Annual Meeting [<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0127362#pone.0127362.ref034" target="_blank">34</a>], and/or (6) the American Academy of Orthopaedic Surgeons 2012/2013 [<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0127362#pone.0127362.ref032" target="_blank">32</a>].</p><p>^† Editorial board members as published on websites of the journals, January 2013 [<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0127362#pone.0127362.ref023" target="_blank">23</a>–<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0127362#pone.0127362.ref027" target="_blank">27</a>].</p><p>^‡ Biomet, Zimmer, Stryker, Smith & Nephew, Medtronic, Johnson & Johnson (including the subsidiaries DePuy & Synthes) [<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0127362#pone.0127362.ref036" target="_blank">36</a>].</p><p>Potential conflicts of interest of editorial board members.</p

Baseline: editorial boards of the five leading spine journals.

<p>* Impact Factor for the year 2012 according to Journal Citation Reports, Thomson Reuters, 2013 [<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0127362#pone.0127362.ref028" target="_blank">28</a>].</p><p>^† Editorial board members as published on websites of the journals, January 2013 [<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0127362#pone.0127362.ref023" target="_blank">23</a>–<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0127362#pone.0127362.ref027" target="_blank">27</a>].</p><p>^‡ only the traceable editorial board members are mentioned and used to calculate percentage per category</p><p>Baseline: editorial boards of the five leading spine journals.</p

ALP expression by MSCs after short TNF-α or LPS treatment.

<p>Cells were exposed to TNF-α (50 ng/mL) or LPS (5 μg/mL) for 2 days, after which the mediators were withdrawn. At day 10, ALP activity levels were measured and normalized for DNA. Data represent the means ± SD (<i>n</i> = 4). *P<0.05 compared to untreated cells cultured in the same medium. See <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0132781#pone.0132781.s002" target="_blank">S2C Fig</a> for all experimental conditions.</p

Morphological characteristics of diffuse idiopathic skeletal hyperostosis in the cervical spine

<div><p>Objectives</p><p>Diffuse idiopathic skeletal hyperostosis (DISH) is characterized by anterior ossification of the spine and can lead to dysphagia and airway obstruction. The morphology of the newly formed bone in the cervical spine is different compared to the thoracic spine, possibly due to dissimilarities in local vascular anatomy. In this study the spatial relationship of the new bone with the arterial system, trachea and esophagus was analyzed and compared between subjects with and without DISH.</p><p>Methods</p><p>Cervical computed tomography (CT) scans were obtained from five patients with dysphagia and DISH and ten control subjects. The location of the vertebral and carotid arteries, surface area of the hyperostosis and distance between the vertebral body and the trachea and esophagus was assessed in the axial view.</p><p>Results</p><p>The surface area of the newly formed bone was located symmetrically anterior to the vertebral body. The ossifications were non-flowing in the sagittal view and no segmental vessels were observed. Substantial displacement of the trachea/esophagus was present in the group with DISH compared to the controls.</p><p>Conclusions</p><p>The hyperostosis at the cervical level was symmetrically distributed anterior to the vertebral bodies without a flowing pattern, in contrast to the asymmetrical flowing pattern typically found in the thoracic spine. The hypothesis that the vascular system acts as a natural barrier against new bone formation in DISH could be further supported with these findings. The significant ventral displacement of the trachea and esophagus may explain the mechanism of dysphagia and airway obstruction in DISH.</p></div

Graphical illustration of the measurements on the CT images.

<p>In (A) the CT scan is shown of a control subject with corresponding illustration (B). The parallel lateral lines are presented in light blue and carotid and vertebral arteries in red. CT scan (C) represents a male subject with DISH (72 years old) and matches illustrations (D and E). The parallel lateral lines (light blue) and the midsagittal anteroposterior (MAP) line (dark blue) were used to compare the different surface areas of newly formed bone (light/dark grey). CT scan (F) shows a male subject with DISH (61 years old) and corresponds to illustrations (G and H). The green lines demonstrate the distances between the center of the vertebral body and the trachea and esophagus, respectively.</p

Typical examples of newly formed bone due to DISH in the cervical and thoracic spine.

<p>(A) Plain lateral radiograph shows a 69 year old male with DISH in the cervical spine. A solid formation of new bone is extending over at least four vertebral bodies. (B) Computed tomography (CT) visualizes the thoracic spine of a 72 year old male in the sagittal view. The scan shows a flowing ossification of the anterolateral spine with bridging over more than four contiguous vertebral bodies. The intervertebral discs and apophyseal joints are relatively intact in both images. (C + D) The CT scans in axial view demonstrate the differences in position of the new bone formation depending on the region. (C) The CT scan of the cervical spine corresponds to the radiographic image (A) and demonstrates symmetrical hyperostosis (yellow) anterior to the vertebral body and possible displacement of the trachea. (D) The axial CT of the mid thoracic spine in a 58 year old male with DISH shows the newly formed bone on the right anterolateral side with the aorta clearly located on the left anterolateral side.</p

Results of the four different types of measurements.

<p>The location of the major arteries in the cervical spine was in all cases and at all levels lateral to the parallel lateral lines for the DISH and control group as shown in (A). The median total surface area of the newly formed bone per cervical level was significantly larger at the anterior location compared to the lateral location (B). There was no statistical difference between the left and right side of the MAP line (C). The distance between the center of the vertebral body and the trachea/esophagus was significantly larger in the group with DISH compared to the control group (D). The asterisk represents a p-value ≤ 0.05 and the triple asterisk represents a p-value ≤ 0.001. The error bars represent the standard error. VB–Vertebral body.</p

Graphical illustration of the planes used for the measurements.

<p>Measurements were performed at three levels in the C4, C5 and C6 vertebral bodies. The axial CT images were reconstructed to planes parallel to the endplate. (A) Sagittal CT image from a 69 year old male. The illustration (B) shows the three levels (C4, C5, C6) and three transverse locations at C5 (1, 2, 3) that were used for the measurements in the axial plane. The dashed line 1 shows the level adjacent to the cranial endplate, line 2 the mid-vertebral level and line 3 the level adjacent to the caudal endplate. The same approach (using the three lines for the transversal levels) was also used for the C4 and C6 vertebral body.</p

Late osteogenic differentiation in pre-osteoblasts.

<p>A. Pre-osteoblasts were exposed to TNF-α (50 ng/mL) or LPS (5 μg/mL). The ALP activity was measured after 8 days and normalized for DNA content. The total calcium deposition was quantified at day 14 after continuous (B) and short (C) stimulation with TNF-α (5 ng/mL) or LPS (0.5 μg/mL). D. Cells were exposed to LPS (0.5 μg/mL) or TNF-α (5 ng/mL) from days 12 to 26 of culture. Immunocytochemical staining for intracellular osteocalcin was performed as a marker of osteogenic differentiation. Osteocalcin and Hoechst are shown in green and blue, respectively (representative for 2 donors). Scale bar: 500 μm. See <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0132781#pone.0132781.s004" target="_blank">S4 Fig</a> for a dose response. Data represent the means ± SD (<i>n</i> = 4). *P<0.05/**P<0.005 compared to untreated cells cultured in the same medium.</p