BACKGROUND: Although oral appliances are effective in some patients with obstructive sleep apnoea (OSA), they are not universally effective. A novel anterior mandibular positioner (AMP) has been developed with an adjustable hinge that allows progressive advancement of the mandible. The objective of this prospective crossover study was to compare efficacy, side effects, patient compliance, and preference between AMP and nasal continuous positive airway pressure (nCPAP) in patients with symptomatic mild to moderate OSA. METHODS: Twenty four patients of mean (SD) age 44.0 (10.6) years were recruited with a mean (SD) body mass index of 32.0 (8.2) kg/m2, Epworth sleepiness score 10.7 (3.4), and apnoea/hypopnoea index 26.8 (11.9)/hour. There was a two week wash-in and a two week wash-out period and two treatment periods (AMP and nCPAP) each of four months. Efficacy, side effects, compliance, and preference were evaluated by a questionnaire and home sleep monitoring. RESULTS: One patient dropped out early in the study and three refused to cross over so treatment results are presented on the remaining 20 patients. The apnoea/hypopnoea index (AHI) was lower with nasal CPAP 4.2 (2.2)/hour than with the AMP 13.6 (14.5)/hour (p < 0.01). Eleven of the 20 patients (55%) who used the AMP were treatment successes (reduction of AHI to < 10/hour and relief of symptoms), one (5%) was a compliance failure (unable or unwilling to use the treatment), and eight (40%) were treatment failures (failure to reduce AHI to < 10/hour and/or failure to relieve symptoms). Fourteen of the 20 patients (70%) who used nCPAP were treatment successes, six (30%) were compliance failures, and there were no treatment failures. There was greater patient satisfaction with the AMP (p < 0.01) than with nCPAP but no difference in reported side effects or compliance. CONCLUSIONS: AMP is an effective treatment in some patients with mild to moderate OSA and is associated with greater patient satisfaction than nCPAP.

Bone is one of the preferred sites for the metastasis of malignant tumours, such as breast cancer, lung cancer and malignant melanoma. Tumour cells colonizing bone have the capacity to induce the expression of receptor activator of nuclear factor-κB ligand (RANKL), which promotes osteoclast differentiation and activation. Tumour-induced osteoclastic bone resorption leads to a vicious cycle between tumours and bone cells that fuels osteolytic tumour growth, causing bone pain and hypercalcaemia. Furthermore, RANKL contributes to bone metastasis by acting as a chemoattractant to bone for tumour cells that express its receptor, RANK. Thus inhibition of the RANKL–RANK pathway is a promising treatment for bone metastasis, and a human monoclonal anti-RANKL antibody, denosumab, has been used in the clinic. However, orally available drugs targeting RANKL must be developed to increase the therapeutic benefits to patients. Here we report the efficacy of the small-molecule RANKL inhibitor AS2676293 in treating bone metastasis using mouse models. Oral administration of AS2676293 markedly inhibited bone metastasis of human breast cancer cells MDA-MB-231-5a-D-Luc2 as well as tumour-induced osteolysis. AS2676293 suppressed RANKL-mediated tumour migration in the transwell assay and inhibited bone metastasis of the murine cell line B16F10, which is known not to trigger osteoclast activation. Based on the results from this study, RANKL inhibition with a small-molecule compound constitutes a promising therapeutic strategy for treating bone metastasis by inhibiting both osteoclastic bone resorption and tumour migration to bone.

Mastication is an indispensable oral function related to physical, mental, and social health throughout life. The elderly tend to have a masticatory dysfunction due to tooth loss and fragility in the masticatory muscles with aging, potentially resulting in impaired cognitive function. Masticatory stimulation has influence on the development of the central nervous system (CNS) as well as the growth of maxillofacial tissue in children. Although the relationship between mastication and cognitive function is potentially important in the growth period, the cellular and molecular mechanisms have not been sufficiently elucidated. Here, we show that the reduced mastication resulted in impaired spatial memory and learning function owing to the morphological change and decreased activity in the hippocampus. We used an in vivo model for reduced masticatory stimuli, in which juvenile mice were fed with powder diet and found that masticatory stimulation during the growth period positively regulated long-term spatial memory to promote cognitive function. The functional linkage between mastication and brain was validated by the decrease in neurons, neurogenesis, neuronal activity, and brain-derived neurotrophic factor (BDNF) expression in the hippocampus. These findings taken together provide in vivo evidence for a functional linkage between mastication and cognitive function in the growth period, suggesting a need for novel therapeutic strategies in masticatory function–related cognitive dysfunction.

The tactile sensation of the teeth is involved in various oral functions, such as mastication and speech. Using functional magnetic resonance imaging, we investigated the cortical sensory representation of the oral area, including the teeth. First, we identified the somatotopic representation of the lips, teeth and tongue in the postcentral gyrus (GpoC). Tactile stimuli were applied to the lower lip, tongue and teeth. The foci activated by each stimulus were characterized by the center of gravity (COG) of activated areas. Secondly, we examined the rostro-caudal changes in the somatotopic organization in the GPoC in terms of the overlap between each sensory representation. In the rostral portion of the GPoC, the COG of the representation of teeth was located significantly superior to that of the tongue and inferior to that of the lip, consistent with the classical ‘sensory homunculus’ proposed by Penfield; however, this somatotopic representation became unclear in the middle and caudal portions of the GPoC. The overlap between each representation in the middle and caudal portions of the GPoC was significantly greater than that in the rostral portion of the GPoC. These findings support the theory that the input from oral structures converges hierarchically across the primary somatosensory cortex.

This study was carried out to test the hypothesis that changes in head/body position induce changes in upper-airway dimensions. Contiguous images were obtained by means of magnetic resonance imaging in normal awake subjects during nasal breathing. A statistical analysis was made on 5 consecutive slices, including the most constricted sites in both the retropalatal and retroglossal regions. Dimensional changes in the upper airway in association with changes in head/body position were evaluated. In the retropalatal region, there was a significant decrease in the lateral dimension in the lateral recumbent position compared with that in the supine position. The cross-sectional area in the retroglossal region was significantly increased in both the "supine with the head rotated" and "lateral recumbent" positions. This change was accompanied by significant volumetric changes in the retroglossal region. Thus, sleeping with the head rotated may be effective for improving upper-airway obstruction.

To define morphological changes in the upper airway and its surrounding structures after the insertion of a titratable mandibular repositioner. Ten non-apneic adult males participated in this study. A set of supine lateral cephalograms was taken for each subject at the end of expiration with a titratable oral appliance in place in four mandibular positions: most retruded (RP), maximum protrusion (MAX), 33% of MAX (MAX₃₃), and 67% of MAX (MAX₆₇). Changes in the anteroposterior width of the upper airway, positions of the hyoid bone and the third cervical vertebra were compared between the four mandibular positions. An ANOVA was used to test for statistical significance. N/A N/A N/A The anteroposterior width of the velopharynx significantly increased when the mandible was advanced from RP to MAX₆₇ and MAX. However, there were no significant changes in the anteroposterior width of the oropharynx. Significant forward displacement of the hyoid bone and third cervical vertebra together with the mandible was found in MAX₆₇ and MAX compared to RP. Especially in MAX₆₇ and MAX, the titratable oral appliance significantly enlarges upper airway size in the velopharynx and results in a forward displacement of the hyoid bone and the third cervical vertebra.