Reduction of sleep bruxism events according to contingent electrical stimulus intensity.

BACKGROUND: Although biofeedback with contingent electrical stimulation (CES) has demonstrated the reduction effect on sleep bruxism (SB), the relationship between the actual applied CES intensity and efficacy remains uncertain. OBJECTIVE: This study aimed to investigate whether the reduction of bruxism events and jaw muscle symptoms could vary according to the intensity of CES and in probable sleep bruxers. METHODS: Twenty probable sleep bruxers were initially screened for bruxer confirmation based on a 2-week recording of SB events with a portable electromyography recorder (BUTLER®GrindCare®, GC4). A 3-week recording was conducted without CES using a GC4, followed by another 3-week recording with CES. At baseline and before and after the CES (+) session, clinical muscle symptoms were assessed using a 0-10 numerical rating scale (NRS). The relationships between the actual applied CES intensity and the number of SB events/hour, as well as the NRS of clinical muscle symptoms, were analysed. RESULTS: The actual applied CES intensity was positively correlated with the reduction rate of the number of SB events/hour (R = .643, p = .002), as well as with the reduction rate of NRS for pain, unpleasantness, fatigue, tension and stiffness (R > .500, p < .011). CONCLUSION: Higher CES elicited a more robust reduction in SB events and clinical muscle symptoms, in probable bruxers. Prior to selecting CES biofeedback as a management option for SB, it would be beneficial to assess the tolerance threshold of CES in each bruxer in order to predict the effectiveness of CES in probable sleep bruxers.

Exploration of reference genes for the development of a diagnostic kit on vascular aging in human saliva.

Identifying reliable biomarkers in saliva can be a promising approach to developing a rapid diagnostic kit for detecting vascular aging. This study investigated the most suitable reference gene for polymerase chain reaction (PCR) in saliva that is not affected by vascular aging variables. Whole saliva samples were collected to assess the expression of reference genes: actin beta (ACTB), 18S ribosomal RNA (18S rRNA), beta-2-microglobulin, and glyceraldehyde-3-phosphate dehydrogenase (GAPDH). The most abundantly expressed gene was 18S rRNA, and the least expressed gene was GAPDH. Four genes were ranked according to their relative stability, as determined by mathematical algorithms, indicating that ACTB and 18S rRNA were stably expressed as reference genes. 18S rRNA was identified as the most promising reference gene for detecting systemic diseases using saliva from patients with vascular aging in these limited experimental conditions.

Effect of ageing and tooth loss on sensory function of alveolar mucosa.

BACKGROUND: Maintaining quality of life of elderly denture wearers is one of the most crucial tasks for dentists in the super-aged society. Although external mechanical load on removable dentures has been investigated to minimise a risk of soreness caused by dentures, sensory perception of the alveolar mucosa remains obscure. OBJECTIVES: This study aimed to investigate effect of ageing and tooth loss in sensory function on the alveolar mucosa for deep understanding of the characteristics of pain sensitivity in edentulous individuals. METHODS: Eighteen edentulous participants (ED), as well as 18 age-matched dentate participants (EC) and 18 young dentate participants (YC), participated in this study. Tactile detection threshold (TDT) and pain threshold (PT) were measured with von Frey filaments (0.125-512 mN). Mechanical pain sensitivity (MPS) after a 2-sec application of 1 kg palpation was assessed with a 0-50-100 Numerical Rating Scale (NRS) (0: no pain, 50: slight pain and 100: the worst pain imaginable). Furthermore, entropy scores of TDT, PT and NRS on MPS were calculated. RESULTS: In both maxilla and mandible, EC showed significantly higher TDT and PT, compared with YC, whereas ED showed significantly lower TDT and PT, compared with EC. NRS on MPS in ED was significantly higher than that in EC. The entropy scores of all the outcome parameters showed no significant difference between groups. CONCLUSION: Both ageing and tooth loss can alter tactile and pain perception in the oral mucosa. This suggests that it might be beneficial to assess sensory function of the alveolar mucosa in edentulous patients clinically in prior to denture fabrication.

Transcription Factor MafB Coordinates Epidermal Keratinocyte Differentiation.

Mammalian epidermis is a stratified epithelium composed of distinct layers of keratinocytes. The outermost cornified layer is a primary barrier that consists of a cornified envelope, an insoluble structure assembled by cross-linked scaffold proteins, and a surrounding mixture of lipids. Skin keratinocytes undergo a multistep differentiation process, but the mechanism underlying this process is not fully understood. We demonstrate that the transcription factor MafB is expressed in differentiating keratinocytes in mice and is transcriptionally upregulated upon human keratinocyte differentiation in vitro. In MafB-deficient mice, epidermal differentiation was partially impaired and the cornified layer was thinner than in wild-type mice. On the basis of transcriptional profiling, we detected reduced expression levels of a subset of cornified envelope genes, for example, filaggrin and repetin, in the MafB(-/-) epidermis. By contrast, the expression levels of lipid metabolism-related genes, such as Alox12e and Smpd3, increased. The upregulated genes in the MafB(-/-) epidermis were enriched for putative target genes of the transcription factors Gata3, Grhl3, and Klf4. Immunohistochemical analysis of skin biopsy samples revealed that the expression levels of filaggrin and MafB were significantly reduced in patients with human atopic dermatitis and psoriasis vulgaris. Our results indicate that MafB is a component of the gene expression program that regulates epidermal keratinocyte differentiation.

RNA interference-mediated knockdown of Smad1 inhibits receptor activator of nuclear factor κB ligand expression induced by BMP-2 in primary osteoblasts.

OBJECTIVE: BMP-2 induces osteoblast differentiation and activates osteoclast formation. Here, we investigated the role of Smad1, a molecule that signals downstream of BMP-2, in mediating the effects of BMP-2 on osteoclast differentiation induced by 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) in osteoblasts. DESIGN: The effects of 1,25(OH)2D3 and BMP-2 in osteoclasts were examined using polymerase chain reaction and Western blotting to measure changes in target gene and protein expression. Immunostaining was carried out to investigate the localization of the vitamin D receptor (VDR) in the nucleus in response to BMP-2. RESULTS: Stimulation with both 1,25(OH)2D3 and BMP-2 resulted in significantly greater osteoclast formation and receptor activator of nuclear factor κB ligand (RANKL) mRNA expression compared to stimulation with 1,25(OH)2D3 alone. In addition, expression of the VDR protein was increased, enhancing the activity of 1,25(OH)2D3. Interestingly, knockdown of Smad1 resulted in reduced osteoclast formation, RANKL mRNA expression, and VDR protein expression compared with control cells. Costimulation with 1,25(OH)2D3 and BMP-2 enhanced VDR localization in the nucleus. CONCLUSIONS: We found that BMP-2 induced Smad1 activation, thereby influencing the localization of VDR in the nucleus in the presence of 1,25(OH)2D3 and resulting in increased RANKL mRNA expression. These effects ultimately resulted in enhanced osteoclast differentiation.

MafB interacts with Gcm2 and regulates parathyroid hormone expression and parathyroid development.

Serum calcium and phosphate homeostasis is critically regulated by parathyroid hormone (PTH) secreted by the parathyroid glands. Parathyroid glands develop from the bilateral parathyroid-thymus common primordia. In mice, the expression of transcription factor Glial cell missing 2 (Gcm2) begins in the dorsal/anterior part of the primordium on embryonic day 9.5 (E9.5), specifying the parathyroid domain. The parathyroid primordium then separates from the thymus primordium and migrates to its adult location beside the thyroid gland by E15.5. Genetic ablation of gcm2 results in parathyroid agenesis in mice, indicating that Gcm2 is essential for early parathyroid organogenesis. However, the regulation of parathyroid development at later stages is not well understood. Here we show that transcriptional activator v-maf musculoaponeurotic fibrosarcoma oncogene homologue B (MafB) is developmentally expressed in parathyroid cells after E11.5. MafB expression was lost in the parathyroid primordium of gcm2 null mice. The parathyroid glands of mafB(+/-) mice were mislocalized between the thymus and thyroid. In mafB(-/-) mice, the parathyroid did not separate from the thymus. Furthermore, in mafB(-/-) mice, PTH expression and secretion were impaired; expression levels of renal cyp27b1, one of the target genes of PTH, was decreased; and bone mineralization was reduced. We also demonstrate that although Gcm2 alone does not stimulate the PTH gene promoter, it associates with MafB to synergistically activate PTH expression. Taken together, our results suggest that MafB regulates later steps of parathyroid development, that is, separation from the thymus and migration toward the thyroid. MafB also regulates the expression of PTH in cooperation with Gcm2.