Preface to COAST 2016 innovators' workshop on personalized and precision orthodontic therapy.

OBJECTIVE: A second focused workshop explored how to transfer novel findings into clinical orthodontic practice. SETTING AND SAMPLE POPULATION: Participants met in West Palm Beach (Florida, USA), on 9-11 September 2016 for the Consortium for Orthodontic Advances in Science and Technology 2016 Innovators' Workshop (COAST). Approximately 65 registered attendees considered and discussed information from 27 to 34 speakers, 8 to 15 poster presenters and four lunch-hour focus group leaders. MATERIAL AND METHODS: The innovators' workshops were organized according to five themed sessions. The aims of the discussion sessions were to identify the following: i) the strength and impact of the evidenced-based discoveries, ii) required steps to enable further development and iii) required steps to translate these new discoveries into orthodontic practice. RESULTS: The role of gene-environment interactions that underlie complex craniofacial traits was the focus of several sessions. It was agreed that diverse approaches are called for, such as (i) large-scale collaborative efforts for future genetic studies of complex traits; (ii) deep genome sequencing to address the issues of isolated mutations; (iii) quantifying epigenetic-environmental variables in diverse areas myofascial pain, alveolar remodelling and mandibular growth. Common needs identified from the themed sessions were multiscale/multispecies modelling and experimentation using controlled and quantified mechanics and translation of the findings in bone biology between species. Panel discussions led to the consensus that a consortium approach to establish standards for intra-oral scanning and 3D imaging should be initiated. CONCLUSIONS: Current and emerging technologies still require supported research to translate new findings from the laboratory to orthodontic practice.

Personalized and precision orthodontic therapy.

OBJECTIVE: To bring together orthodontic stakeholders from academics, industry, and private practice for a series of thematically focused workshops to explore and develop the transfer of novel approaches into clinical orthodontic practice. SETTING AND SAMPLE POPULATION: Twenty-seven invited speakers, eight poster presenters, and participants of the Consortium for Orthodontic Advances in Science and Technology (COAST) 2014 Innovators' Workshop at the Eaglewood Resort and Spa, Itasca, Illinois, September 11-14, 2014. MATERIAL AND METHODS: Five themed sessions involving between 4-7 presentations followed by panel discussions were organized. The aims of the discussion sessions were to highlight important findings and consider the strength of evidence for these, indicate next steps and needed research or technological developments to move forward, and to weigh the expected benefits from these findings and steps to implement in clinical practice. RESULTS: Among important areas for attention identified were need for multiscale and multispecies modeling and experimentation for interspecies translation of results; large-scale collaborative efforts within the profession to address the need for adequate sample sizes for future genetic studies of complex traits such as malocclusion; a consortium approach to improve new technologies such as intra-oral scanning and 3D imaging by establishing standards; and harnessing the growing body of knowledge about bone biology for application in orthodontics. CONCLUSIONS: With increased awareness of the potential of current and emerging technologies, translation of personalized and precision approaches in the field of orthodontics holds ever-increasing promise.

Accuracy of alveolar bone measurements from cone beam computed tomography acquired using varying settings.

OBJECTIVES: To investigate the accuracy and reliability of cone beam computed tomography (CBCT) measurements of buccal alveolar bone height (BBH) and thickness (BBT) using custom acquisition settings. SETTINGS AND SAMPLE POPULATION: School of Dentistry, Oregon Health & Science University. Twelve embalmed cadavers. MATERIALS AND METHODS: Cadaver heads were imaged by CBCT (i-CAT® 17-19, Imaging Sciences International, Hatfield, PA) using a 'long scan' (LS) setting with 619 projection images, 360° revolution, 26.9 s duration, and 0.2 mm voxel size, and using a 'short scan' (SS) setting with 169 projection images, 180° rotation, 4.8 s duration, and 0.3 mm voxel size. BBH and BBT were measured with 65 teeth, indirectly from CBCT images and directly through dissection. Comparisons were assessed using paired t-tests (p≤0.05). Level of agreement was assessed by concordance correlation coefficients, Pearson's correlation coefficients, and Bland-Altman plots. RESULTS: Mean differences in measurements compared to direct measurements were as follows, LS 0.17±0.12 (BBH) and 0.10±0.07 mm (BBT), and SS 0.41±0.32 (BBH) and 0.12±0.11 mm (BBT). No statistical differences were found with any of BBH or BBT measurements. Correlation coefficients and Bland-Altman plots showed agreement was high between direct and indirect measurement methods, although agreement was stronger for measurements of BBH than BBT. CONCLUSIONS: Compared to the LS, the similarity in results with the reduced scan times and hence reduced effective radiation dose, favors use of shorter scans, unless other purposes for higher resolution imaging can be defined.

A cephalometric study of class II Division 1 malocclusions treated with the Jasper Jumper appliance.

This lateral cephalometric study investigated the dental and skeletal effects of the Jasper Jumper appliance used in the correction of Class II Division 1 malocclusions. A sample of 36 growing patients treated with the Jasper Jumper appliance was divided into two groups: (1) 24 patients with records obtained at the start and completion of orthodontic treatment, and (2) 12 patients with records available at the beginning and end of the Jumper phase of treatment. Treatment effects were determined by statistical comparisons of cephalometric changes in the patients relative to age-adjusted cephalometric standards, and from structural superimpositions. While the Jumpers were in place, maxillary incisors were retroclined and the molars were moved distally, tipped back, and intruded. The mandibular incisors were proclined and intruded, while the molars were translated mesially, tipped forward, and extruded. Skeletal measures showed reduced forward maxillary displacement and no significant alteration of horizontal mandibular growth. During orthodontic finishing, molar tipping and maxillary incisor retroclination were corrected, although the mandibular incisors remained proclined. In summary, this study found that the Jasper Jumper appliance corrected Class II discrepancies largely through maxillary and mandibular dentoalveolar effects and, to a limited extent, by restraint of forward maxillary growth.

Wheat germ agglutinin conjugated to TRITC: a novel approach for labeling primary projection neurons of peripheral afferent nerves.

Wheat germ agglutinin conjugated to tetramethylrhodamine isothiocyanate-dextran (WGA-TRITC) was studied as a novel tracer of primary projection neurons of pharyngeal (PhN) and superior laryngeal (SLN) branches of the vagus nerve. The SLN and PhN were dissected from rat cervical tissues and the proximal end of the nerves were bathed in tracer for 60-90 min. The animals were sacrificed 42-72 h later. The tissue was fixed, sliced, mounted on slides and viewed under epifluorescence. The clarity of the fluorescent label in projection neurons was confounded in some regions of the brainstem by autofluorescence. A computer image analysis method was developed to quantify fluorescence intensity for definitive identification of labeled neurons. Brainstem neurons labeled by afferent projections of the SLN and PhN were localized to the nucleus tractus solitarius. Efferents were identified in the nucleus ambiguus. WGA-TRITC labeled cells were observed in the ipsilateral brainstem at intensities significantly different from the fluorescence observed in controls (P<0.01). The distribution and density of labeling is in agreement with results of previous investigations, suggesting that WGA-TRITC is a useful alternative for tracing SLN and PhN projections to brainstem nuclei.

Comparison of occlusal contacts with use of Hawley and clear overlay retainers.

Following orthodontic treatment, an increase in the number of occlusal contacts is usually desired during retention. In this study, Hawley and clear overlay orthodontic retainers were compared relative to changes in the number of occlusal contacts. Occlusal contacts were quantified in 30 orthodontic patients at debonding, at retainer delivery, and after 3 months of retention. The paired t-test was applied to evaluate longitudinal changes in the number of and intensity of contacts. Results show that with the Hawley retainer there was a significant increase in occlusal contacts on posterior teeth and no change on anterior teeth. With the clear overlay retainer there was no significant change in either posterior or anterior contacts during retention. The retentive capacities of the two retainers differ: the Hawley retainer allows relative vertical movement (settling) of the posterior teeth while the clear overlay retainer holds teeth in their debanding position.

A comparison of a computer-based orthognathic surgery prediction system to postsurgical results.

This retrospective study analyzes the accuracy of a prediction algorithm from Quick Ceph Image. Pre- and postsurgical lateral cephalograms of 35 adult patients were computer imaged and specific landmarks digitized. Digitization error was assessed from duplicate digitizations. Sixteen measurements of the predicted and actual postsurgical hard and soft tissue landmarks were compared using Student's t test, one- and two-way analysis of variance, and a modified Bradley-Blackwood test. Results showed a good correlation between repeated digitization of all variables except soft tissue point B and E-plane. Comparison of the predicted and actual changes found that all differences were less than 1.8 mm or 3.1 degrees. Student's t test showed 10 of the 16 measurements did not differ significantly, and interclass correlation demonstrated moderate to good correlations for 13 of 16 variables. Overall the results of this study suggest that the magnitude of the differences were within clinically acceptable limits.

Periosteal migration in the growing mandible: an animal model.

Migration of mandibular periosteum and attached musculature was tracked along the inferior border of the ramus in growing and nongrowing guinea pigs (Cavia porcellus) over a 6-week period. Particulate metallic growth-tracing implants were placed through the bony mandible and adjacent musculature at two anteroposterior locations and two bony reference markers were placed anteriorly. Quantification from weekly radiographs of growing animals showed marked posterior migration of the periosteum, whereas in nongrowing animals there was negligible periosteum movement. Significantly greater migration occurred in posterior (6.37 +/- 0.76 mm) implants relative to the anterior implants (3.45 +/- 0.86 mm, p < 0.001). The neutral zone, where little periosteal migration occurs, was calculated to be approximately at the anteroposterior center of the molar tooth row. Analysis of the orientation of the medial pterygoid muscle relative to the mandible showed that muscle fibers on average become more horizontal. Thus, the study found differential anteroposterior migration of the mandibular periosteum in growing animals and correlative changes in orientation of the medial pterygoid muscle.

Embryonic development of the chick primary trigeminal sensory-motor complex.

The objective of this study is to define the development of all components in the chick embryonic trigeminal primary sensory-motor complex, from their first appearance through the formation of central and peripheral axonal projections up to stage 34 (8 days of incubation). This was accomplished by two labeling procedures: application of the monoclonal antibody HNK-1, which binds to the precursors of all these components except the placode-derived neurons, and application of HRP to axons cut immediately distal to the trigeminal ganglion. Single immunopositive motor neuron precursors are present at stage 12. These accumulate in the transient medial motor column, whose neurons initiate axon outgrowth by stage 13-14, concomitant with the onset of translocation of their somata to form the definitive trigeminal lateral motor column (LMC). Initially these translocating somata accumulate on the medial margin of the LMC. Beginning on incubation day 5, axons growing from newly formed motor neurons pass beside the lateral margin of the LMC, and the nuclei of these cells subsequently follow this pathway. These events follow a rostral-to-caudal sequence, and this phase of motor nucleus formation is complete by day 8. The lateral translocation of some caudally located nuclei is arrested beginning on day 5. This cessation, which proceeds rostrally, demarcates neurons that form the dorsal motor nucleus of the trigeminal complex. Sensory neurite formation is initiated in ophthalmic placode-derived cells at stage 14.5, one stage later by maxillomandibular neurons, and from mesencephalic V cells at stage 15. Neural crest cells do not initiate axon formation until at least day 4 to 5. Following application of HRP distal to the condensing ganglion at stage 16, labeled ophthalmic nerve projections appear in contact with the wall of the hindbrain centrally and overlying the optic vesicle peripherally. Fibers forming the descending tract elongate rapidly, reaching the level of the VIIth nerve root (200 microns caudal to the trigeminal root) by stage 18 and the cervical cord by stage 22. Labeled terminal arborizations of descending trigeminal afferents are first visible at stage 22 and are evident along the entire descending and proximal ascending tracts by stage 27. Later-developing descending axons grow in close association with existing trigeminal fibers, though a few growth cones are consistently evident superficial to the other fibers. No projections different from those reported in adult birds are seen, nor are there any contralateral afferent projections.(ABSTRACT TRUNCATED AT 400 WORDS)

Regenerating afferent fibers stimulate the recovery of mauthner cell dendritic branching in the axolotl.

In the medulla of the axolotl (Ambystoma mexicanum), Mauthner cells (M-cells) occur as a pair of large identifiable neurons at the level of entry of the vestibular nerve (nVIII). Each receives synapses from the ipsilateral nVIII; the terminals can be identified as club endings and are restricted to a specific set of M-cell dendritic branches. We have examined these branches for morphologic changes following long-term deafferentation in the presence and absence of nerve regeneration. Deafferentation was brought about in a group of young larvae by unilaterally severing nVIII. The nerve was allowed to regenerate in half of the larvae. In those remaining, the nVIII ganglion was damaged to preclude or limit nerve regeneration. The contralateral side served as control. After 3 months survival, the larvae were killed and the medullae prepared for microscopy. To estimate the extent of nerve regeneration, axons in the experimental nVIII tract were counted and compared with the number in the control. The mean number of axons in the nVIII tract ipsilateral to intact ganglia indicated that 69% of the fibers had regenerated. In contrast, only 31% regenerated in larvae with damaged ganglia. Electron microscopic analysis of selected sections revealed that the mean number of nVIII terminals per section through M-cells ipsilateral to destroyed ganglia was significantly less than the mean number in analogous sections through either control cells or cells ipsilateral to intact ganglia. Control and experimental M-cells were reconstructed from serial sections. Deprived M-cells had significantly reduced dendritic branching patterns in the region that normally receives nVIII input. On the other hand, the extent of branching on cells receiving regenerated afferents from intact ganglia was like that of their contralateral controls. The distribution of dendritic branches on many reinnervated M-cells, however, was broader than that on control cells. Electron microscopic examination of the displaced dendritic branches (those extending into adjacent tracts) revealed that they received vestibular synapses. Thus, in some animals, regenerated vestibular fibers were not restricted to the nVIII tract. Deafferentation of the M-cells results in a reduction of dendritic branches in the region deprived of vestibular contacts.(ABSTRACT TRUNCATED AT 400 WORDS)