Night-time autonomic nervous system ultradian cycling and masticatory muscle activity.

OBJECTIVES: To test if there was a correlation between night-time masticatory muscle activity, as measured by duty factors, and ultradian cycling of autonomic nervous system (ANS) spectral powers in subjects without temporomandibular disorder (TMD)-related pain. SETTING AND SAMPLE POPULATION: The University of Missouri-Kansas City School of Dentistry. Three women and four men of average ages 38 ±8 and 56 ± 17 years, respectively, gave informed consent to participate. MATERIAL AND METHODS: Investigators taught subjects to record heart (electrocardiography, ECG) and masticatory muscle activities (electromyography, EMG). ECG recordings were analysed for ANS ultradian cycling by a polynomial fit to the ratio of sympathetic and parasympathetic spectral powers (ms2 ). Masseter and temporalis EMG recordings were analysed over 20-minute epochs around peaks and valleys in the ANS ultradian cycles. Duty factors (% time of masticatory muscle activity/20-minute epoch) were determined relative to average threshold EMG (TEMG ) required to produce a given bite force (N). Regression analyses quantified relationships between normalized muscle duty factors and ANS spectral powers. RESULTS: Subjects made a total of 27 sets of night-time ECG and EMG recordings that averaged 6.6 ± 1.1 hours per recording. Highest average duty factors were associated with TEMG of 1-2 N and showed cumulative masseter and temporalis activities of 9.2 and 8.8 seconds/20-minute epoch, respectively. Normalized masticatory muscle duty factors showed non-linear relationships with normalized sympathetic (R2  = +0.82), parasympathetic (R2  = -0.70) and sympathetic/parasympathetic spectral powers (R2  = +0.75). CONCLUSIONS: Night-time ANS spectral powers showed ultradian cycling and were correlated with masseter and temporalis muscle activities in adult subjects without TMD.

Preface to COAST 2018 Innovators' Workshop: Bridging the biology and technology gap in orthodontics and craniofacial care.

OBJECTIVE: A third focused workshop explored how to transfer novel findings into clinical orthodontic practice. SETTING AND SAMPLE POPULATION: Participants met at the Scottsdale Plaza Resort, 12-16 September 2018 for the Consortium for Orthodontic Advances in Science and Technology 2018 Innovators' Workshop. Thirty speakers and four lunch-hour focus group leaders shared and exchanged information with approximately 45 registered attendees. MATERIAL AND METHODS: This Innovators' Workshop was organized according to five themed sessions which covered: (a) The relevance of genetics, biology and environment to therapeutic outcomes; (b) Application of bioinformatics in craniofacial research; (c) Regeneration with and for orthodontic treatment; (d) Technology in precision orthodontics; and (e) Muscle, joint, and airway: Growth, function and pain. RESULTS: The papers that comprise this supplemental issue exemplify the important outcomes of the 2018 COAST Workshop. In addition, matters identified as important needs include improved understanding of neural, skeletal and muscle tissue crosstalk in early craniofacial growth; standardized methods for three-dimensional radiographic and surface landmark and reference plane identification, measurements and serial superimpositioning techniques for use in the clinic; sharing and making available existing data sets (eg, cone beam computed tomography images, genotype-phenotype data); evidence of the usefulness and effectiveness of new devices; guidelines of what to measure to characterize the airway; more information about the influences of the soft tissues on craniofacial morphology; and information about effective digital work flows applied to clinical and educational settings. CONCLUSIONS: Progress in bridging the biology-technology gap has identified new needs for improvements in orthodontics and craniofacial care.

Targeting of humanized antibody D93 to sites of angiogenesis and tumor growth by binding to multiple epitopes on denatured collagens.

A humanized, affinity-matured IgG1 antibody, called D93, and its parental murine IgM HUI77 have been shown to specifically bind denatured collagens and thereby inhibit angiogenesis and tumor growth in various animal models. In this study, we have identified epitopes for both HUI77 and D93 on human collagen type IV. Several tryptic D93-binding peptides were identified by Western blot analysis and protein sequencing. Epitopes for D93 were ultimately identified by screening a synthetic 16-mer peptide array spanning immunoreactive tryptic peptides. D93 reacted with a peptide corresponding to alpha1(IV) P(1337)-Y(1352) that could inhibit binding of both D93 and HUI77 to denatured collagen IV in a concentration-dependent manner. A 9-mer peptide corresponding to alpha1(IV) G(1344)-Y(1352) showed maximum inhibition of D93 and HUI77 antibody binding to denatured collagen IV, and was critically dependent on the presence of hydroxyproline. D93 bound with similar affinity to denatured collagen IV and synthetic peptides with a K(D) of 1-10 microM for monovalent and of 30-63 nM for bivalent binding. Potential epitopes for D93 are highly repeated in multiple collagen types of diverse vertebrate species explaining reactivity of D93 with denatured collagens types I-V from chicken to man. Our data suggest that D93 inhibits angiogenesis and tumor growth by blockade of cryptic bioactive signals on proteolyzed collagens with importance for growth of tumors and new blood vessels.