Effects of gum chewing training on occlusal force, masseter muscle thickness and mandibular shape: A randomised controlled clinical trial.

BACKGROUND: Masticatory muscle training by chewing gum can be performed easily and improve masticatory muscle function and strength. However, increased masticatory muscle activity and function may alter the mandibular shape. OBJECTIVE: We aimed to investigate the effects of gum chewing training on the occlusal force, masseter muscle thickness (MMT) and mandibular shape in healthy adults. METHODS: We conducted a prospective randomised controlled trial from January 2020 to September 2020 at the Yonsei University College of Dentistry. Fifty-eight participants were randomly assigned to the training and control groups. The training group chewed gum three times a day for 6 months, while the control group received no training. Changes in the maximum occlusal force and MMT were evaluated at baseline and after 1, 3 and 6 months. Changes in the mandibular shape were evaluated at baseline and after 6 months. RESULTS: The mean maximum occlusal force of the training group at 3 months was significantly higher than that at baseline, which was also significantly different from that in the control group (p < .001). As the maximum occlusal force increased, the occlusal contact area also increased (p = .020). There was no statistically significant difference in MMT or mandibular shape compared to the baseline. CONCLUSION: Mastication training using gum increases maximum occlusal force due to an increase in occlusal contact area but has no effect on MMT or mandibular shape.

Changes in condylar position during orthodontic treatment depending on the amount of incisor retraction: a cone-beam computed tomography study.

OBJECTIVES: Orthodontic treatment may be associated with temporomandibular disorders through changes in the condylar position. This study aimed to evaluate changes in the condylar position among different amounts of maxillary incisor retraction during orthodontic treatment using cone-beam computed tomography images. MATERIALS AND METHODS: Fifty-four participants were enrolled and divided into minimal (n = 14), moderate (n = 20), and maximal (n = 20) retraction groups based on the amount of incisor retraction (< 1, 1-6, and > 6 mm, respectively). Changes in condylar position before (T0) and after (T1) orthodontic treatment were assessed for the superior, anterior, posterior, and medial joint spaces (SJS, AJS, PJS, and MJS, respectively). Changes in joint spaces were compared between T0 and T1 in each group using paired t-tests and among the three groups using analysis of variance. RESULTS: Anterior movement of the condyle was observed in the maximal retraction group with a 0.2 mm decrease in ΔAJS and a 0.2 mm increase in ΔPJS, significantly greater than those in the minimal retraction group. The AJS and PJS showed statistically significant differences between T0 and T1 (P < 0.05) in the maximal retraction group. CONCLUSIONS: The condyle may show a statistically significant but clinically insignificant forward movement in the maximal incisor retraction group, whereas it was relatively stable in the minimal and moderate incisor retraction groups. CLINICAL RELEVANCE: More attention should be paid to the signs and symptoms of the condyle in patients with excessive incisor retraction during orthodontic treatment.

Effectiveness of remote monitoring and feedback on objective compliance with a mandibular advancement device for treatment of obstructive sleep apnea.

Compliance with a mandibular advancement device is important for the optimal treatment of obstructive sleep apnea. Recent advances in information and communication technology-based monitoring and intervention for chronic diseases have enabled continuous monitoring and personalized management. Self-evaluation and self-regulation through objective monitoring and feedback may improve compliance. The aim of this study was to evaluate the effects of information and communication technology-based remote monitoring and feedback services, using a smartphone application, on the objective compliance with a mandibular advancement device in patients with obstructive sleep apnea. Forty individuals who were diagnosed with obstructive sleep apnea by polysomnography were randomly assigned to groups A and B. During an initial 6-week evaluation period, the mandibular advancement device-wearing time was monitored with the smartphone application in group B, but not in group A. The two groups then switched the monitoring procedures during the second 6-week period (the smartphone application was then used by group B, but not by group A). If no input data were indicated on the cloud server of the smartphone application during the monitored period, push notifications were provided twice daily. Objective compliance, monitored by a micro-recorder within the mandibular advancement device, was noted and compared based on whether the monitoring service was provided. The number of mandibular advancement device-wearing days was significantly higher in the monitored period than in the unmonitored period. The mandibular advancement device-wearing time did not differ significantly between the two groups. In conclusion, information and communication technology-based remote monitoring and feedback services demonstrated a potential to increase the objective measures of compliance with mandibular advancement devices.

UBE3A Suppresses Overnutrition-Induced Expression of the Steatosis Target Genes of MLL4 by Degrading MLL4.

Regulation of the protein stability of epigenetic regulators remains ill-defined despite its potential applicability in epigenetic therapies. The histone H3-lysine 4-methyltransferase MLL4 is an epigenetic transcriptional coactivator that directs overnutrition-induced obesity and fatty liver formation, and Mll4+/- mice are resistant to both. Here we show that the E3 ubiquitin ligase UBE3A targets MLL4 for degradation, thereby suppressing high-fat diet (HFD)-induced expression of the hepatic steatosis target genes of MLL4. In contrast to Mll4+/- mice, Ube3a+/- mice are hypersensitive to HFD-induced obesity and fatty liver development. Ube3a+/-;Mll4+/- mice lose this hypersensitivity, supporting roles of increased MLL4 levels in both phenotypes of Ube3a+/- mice. Correspondingly, our comparative studies with wild-type, Ube3a+/- and Ube3a-/- and UBE3A-overexpressing transgenic mouse livers demonstrate an inverse correlation of UBE3A protein levels with MLL4 protein levels, expression of the steatosis target genes of MLL4, and their decoration by H3-lysine 4-monomethylation, a surrogate marker for the epigenetic action of MLL4. Conclusion: UBE3A indirectly exerts an epigenetic regulation of obesity and steatosis by degrading MLL4. This UBE3A-MLL4 regulatory axis provides a potential therapeutic venue for treating various MLL4-directed pathogeneses, including obesity and hepatic steatosis.

Effect of a looming visual cue on situation awareness and perceived urgency in response to a takeover request.

This study aimed to investigate the effect of a looming visual cue on situation awareness and perceived urgency in response to a takeover request (TOR), and to explore the underlying mechanisms of this effect through three experiments. In Experiment 1, the optimal size and speed of a red disk were determined, which were effective in capturing looming motion and conveying the urgency of the situation. The results indicated that both looming speed and size ratio had significant effects on situation awareness and perceived urgency. In Experiment 2, the effects of looming stimuli were compared with dimming stimuli, and the results showed that the looming visual cue was more effective in promoting perceived urgency and situation awareness. The results also indicated that the looming visual cue attracted more visual attention than the dimming visual cue, in line with previous studies. Experiment 3 utilized a driving simulator to test the effectiveness of the looming visual cue in promoting fast and appropriate responses to TORs in complex driving scenarios. The results showed that the looming visual cue was more effective in promoting perceived urgency and enhancing situation awareness, especially in highly complex driving situations. Overall, the findings suggest that the looming visual cue is a powerful tool for promoting fast and appropriate responses to TORs and enhancing situation awareness, particularly in complex driving scenarios. These results have important implications for designing effective TOR systems and improving driver safety on the road.

Parotid gland evaluation of menopausal women with xerostomia using the iterative decomposition of water and fat with echo asymmetry and least-squares estimation (IDEAL-IQ) method of MRI: a pilot study.

OBJECTIVES: This study aimed to analyze the quantitative fat fraction (FF) of the parotid gland in menopausal females with xerostomia using the iterative decomposition of water and fat with echo asymmetry and least-squares estimation (IDEAL-IQ) method. METHODS: A total 138 parotid glands of 69 menopausal females were enrolled in our study and participants were divided into normal group and xerostomia group. The xerostomia group was divided into those with or without Sjögren's syndrome. Participants underwent IDEAL-IQ sequences of MRI and the stimulated salivary flow test (s-SFR). The unpaired t-test was used to compare the FFs between the normal and xerostomia groups and between the subgroups with and without Sjögren's syndrome. The correlation between FF and s-SFR was analyzed by Pearson's correlation. RESULTS: Excellent intra- and interobserver agreement during the measurement of FFs by IDEAL-IQ method (ICC>0.99, respectively). FF value in the xerostomia group was statistically significantly higher than the value in the normal group (p < 0.05). Within the xerostomia group, the average FF value of females with Sjögren's syndrome was higher than that of females without Sjögren's syndrome. However, the difference was not statistically significant (p > 0.05). Within the xerostomia group, FF value correlated negatively with s-SFR (p < 0.05). CONCLUSIONS: The FF of the parotid gland was higher in the xerostomia group than in the normal group and FF value and s-SFR showed a negative correlation. Analyses of the FF using IDEAL-IQ in menopausal females can be helpful for the quantitative diagnosis of xerostomia.

Combined Effects of Botulinum Toxin Injection and Oral Appliance Therapy on Lower Facial Contouring: A Randomized Controlled Trial.

(1) Background: Botulinum toxin (BoNT) injection is an esthetically effective and safe treatment for contouring the lower face. This study aimed to evaluate the combined effects of BoNT and supplementary oral appliance (OA) therapy on lower facial contouring. (2) Methods: We conducted a prospective randomized controlled trial from January 2015 to June 2016 at the Yonsei University Dental Hospital. Volunteers aged 20−45 years with masseter hypertrophy were randomly assigned to one of two groups: the non-OA group and the OA group. The non-OA group received BoNT injections alone, whereas the OA group received an OA in addition to BoNT injections. Changes in the bulkiest height of the lower face were evaluated by three-dimensional laser scanning before and 4, 8, 12, and 24 weeks after injections in both groups. (3) Results: In both groups, the bulkiest height reductions decreased, with a significant interaction between group (p = 0.046) and time (p < 0.001), although the overall reduction was at a similar level at 24 weeks. (4) Conclusions: The pattern of the bulkiest height reduction of the lower face after BoNT injection differed between standalone treatment and OA therapy, implying a normalizing effect of OA on masseter muscle activity.

What Makes Consumers' Intention to Purchase Paid Stickers in Personal Messenger? The Role of Personality and Motivational Factors.

Many messengers and social networking services (SNSs) use emojis and stickers as a means of communication. Stickers express individual emotions well, allowing long texts to be replaced with small pictures. As the use of stickers increased, stickers were commercialized on a few platforms and showed remarkable growth as people bought and used stickers with their favorite characters, products, or entertainers online. Depending on their personality, individuals have different motivations for using stickers that determine the usefulness and enjoyment of stickers, affecting their purchase decisions. In the present study, participants (n = 302) who were randomly recruited from a university completed an online questionnaire assessing the Big Five personality characteristics, motivations for using stickers, and the technology acceptance model (TAM). Results using partial least squares structural equation modeling (PLS-SEM) revealed that each personality trait affected different motivations for using stickers. Moreover, motivations for using stickers also influenced different technology acceptance variables. Finally, perceived usefulness, enjoyment, and ease of use had a positive effect on the intention to purchase stickers. This study has implications in that it is an exploratory approach to the intention to purchase stickers, which has been investigated by few prior studies, and it sheds light on the relationship between personality, motivation, and TAM in purchasing stickers. It also suggests that personality and motivation factors can be considered in personalized recommendation services.

An Analysis of the Temporomandibular Joint Range of Motion and Related Factors in Children and Adolescents.

This study was designed to establish safe guidelines for pediatric dental practice regarding temporomandibular joint (TMJ) range of motion (ROM) and mouth area (MA). A total of 438 children aged 3-15 years old of homogenous ethnicity participated in the study; the distribution of participants was approximately equal (sex; n = 15; age, n = 30). Maximum mouth opening (MMO), body height, weight, and age of each participant were recorded, and the TMJ ROM including anterior and lateral movements, MA, and mouth width were documented. Males showed higher mouth width, MMO, and MA values than females. MMO and MA increased with age, height, and weight in a statistically significant manner. MMO of 40 mm is reached by the age of 5.2 years, at a height of 105.9 cm and a weight of 18.6 kg. MMO showed a moderate correlation with age, height, weight, and mouth width, and MA moderately correlated with mouth width. Anterior and lateral movements did not show any close relation to these aforementioned factors. The findings of this study suggest that forcible mouth opening over 40 mm should be more cautiously considered, especially in children shorter than 105 cm, lighter than 18 kg and in children under 5 years old.

Clinical Characteristics and Relevance of Oral Candida Biofilm in Tongue Smears.

Dimorphic Candida exist as commensal yeast carriages or infiltrate hyphae in the oral cavity. Here, we investigated the clinical relevance of Candida hyphae in non-pseudomembranous oral candidiasis (OC) by smears of tongue biofilms. We conducted a retrospective study of 2829 patients who had had tongue smears regardless of OC suspicion. Clinical characteristics were evaluated using a novel method of assessing hyphae. Clinical factors (moderate/severe stimulated pain, pain aggravated by stimulation, tongue dorsum appearance and initial topical antifungal use) were highly significant in the high-grade hyphae group but were statistically similar in the low-grade hyphae and non-observed hyphae group, suggesting low-grade hyphae infection as a subclinical OC state. In addition to erythematous candidiasis (EC), a new subtype named "morphologically normal symptomatic candidiasis" (MNSC) with specific pain patterns and normal tongue morphology was identified. MNSC had a significantly higher proportion of moderate and severe stimulated pain cases than EC. Low unstimulated salivary flow rate (<0.1 mL/min) was found to be a common risk factor in MNSC and EC. In non-pseudomembranous OC, pain patterns were dependent on Candida hyphae degree regardless of tongue dorsum morphology. Morphologic differences seen in high-grade hyphae infection were not associated with systemic diseases or nutritional deficiencies.

The histone H3-lysine 4-methyltransferase Mll4 regulates the development of growth hormone-releasing hormone-producing neurons in the mouse hypothalamus.

In humans, inactivating mutations in MLL4, which encodes a histone H3-lysine 4-methyltransferase, lead to Kabuki syndrome (KS). While dwarfism is a cardinal feature of KS, the underlying etiology remains unclear. Here we report that Mll4 regulates the development of growth hormone-releasing hormone (GHRH)-producing neurons in the mouse hypothalamus. Our two Mll4 mutant mouse models exhibit dwarfism phenotype and impairment of the developmental programs for GHRH-neurons. Our ChIP-seq analysis reveals that, in the developing mouse hypothalamus, Mll4 interacts with the transcription factor Nrf1 to trigger the expression of GHRH-neuronal genes. Interestingly, the deficiency of Mll4 results in a marked reduction of histone marks of active transcription, while treatment with the histone deacetylase inhibitor AR-42 rescues the histone mark signature and restores GHRH-neuronal production in Mll4 mutant mice. Our results suggest that the developmental dysregulation of Mll4-directed epigenetic control of transcription plays a role in the development of GHRH-neurons and dwarfism phenotype in mice.

Author Correction: Single cell transcriptome analysis of developing arcuate nucleus neurons uncovers their key developmental regulators.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

PRC2 Acts as a Critical Timer That Drives Oligodendrocyte Fate over Astrocyte Identity by Repressing the Notch Pathway.

PRC2 creates the repressive mark histone H3 Lys27 trimethylation. Although PRC2 is involved in various biological processes, its role in glial development remains ambiguous. Here, we show that PRC2 is required for oligodendrocyte (OL) differentiation and myelination, but not for OL precursor formation. PRC2-deficient OL lineage cells differentiate into OL precursors, but they fail to trigger the molecular program for myelination, highlighting that PRC2 is essential for directing the differentiation timing of OL precursors. PRC2 null OL lineage cells aberrantly induce Notch pathway genes and acquire astrocytic features. The repression of the Notch pathway restores the myelination program and inhibits abnormal astrocytic differentiation in the PRC2-deficient OL lineage, indicating that Notch is a major target of PRC2. Altogether, our studies propose a specific action of PRC2 as a novel gatekeeper that determines the glial fate choice and the timing of OL lineage progression and myelination by impinging on the Notch pathway.

Single cell transcriptome analysis of developing arcuate nucleus neurons uncovers their key developmental regulators.

Despite the crucial physiological processes governed by neurons in the hypothalamic arcuate nucleus (ARC), such as growth, reproduction and energy homeostasis, the developmental pathways and regulators for ARC neurons remain understudied. Our single cell RNA-seq analyses of mouse embryonic ARC revealed many cell type-specific markers for developing ARC neurons. These markers include transcription factors whose expression is enriched in specific neuronal types and often depleted in other closely-related neuronal types, raising the possibility that these transcription factors play important roles in the fate commitment or differentiation of specific ARC neuronal types. We validated this idea with the two transcription factors, Foxp2 enriched for Ghrh-neurons and Sox14 enriched for Kisspeptin-neurons, using Foxp2- and Sox14-deficient mouse models. Taken together, our single cell transcriptome analyses for the developing ARC uncovered a panel of transcription factors that are likely to form a gene regulatory network to orchestrate fate specification and differentiation of ARC neurons.

Germline and somatic mtDNA mutations in mouse aging.

The accumulation of acquired mitochondrial genome (mtDNA) mutations with aging in somatic cells has been implicated in mitochondrial dysfunction and linked to age-onset diseases in humans. Here, we asked if somatic mtDNA mutations are also associated with aging in the mouse. MtDNA integrity in multiple organs and tissues in young and old (2-34 months) wild type (wt) mice was investigated by whole genome sequencing. Remarkably, no acquired somatic mutations were detected in tested tissues. However, we identified several non-synonymous germline mtDNA variants whose heteroplasmy levels (ratio of normal to mutant mtDNA) increased significantly with aging suggesting clonal expansion of inherited mtDNA mutations. Polg mutator mice, a model for premature aging, exhibited both germline and somatic mtDNA mutations whose numbers and heteroplasmy levels increased significantly with age implicating involvement in premature aging. Our results suggest that, in contrast to humans, acquired somatic mtDNA mutations do not accompany the aging process in wt mice.

Evaluation of the Relationship between Circadian Blood Pressure Variation and Left Atrial Function Using Strain Imaging.

BACKGROUND: Non-dippers were reported as showing different left atrial function, compared to dippers, but no study to date investigated the changes in the left atrial function according to the diurnal blood pressure pattern, using tissue Doppler and strain imaging. METHODS: Forty never treated hypertensive patients between 30 and 80 years of age were enrolled in this study. Patients were classified as non-dippers when, during night time, they had a blood pressure decrease of less than 10%. Strain of the left atrium was measured during late systole, and peak strain rates of the left atrium were measured during systole, early and late diastolic periods. RESULTS: The left atrial expansion index, left atrial active emptying volume and left atrial active emptying fraction were all significantly increased in non-dippers. They also had increased values of mean peak left atrial strain (dippers = 21.26 ± 4.23% vs. non-dippers = 24.91 ± 5.20%, p = 0.02), strain rate during reservoir (dippers = 1.29 ± 0.23 s(-1) vs. non-dippers =1.52 ± 0.27 s(-1), p = 0.01) and contractile period (dippers = -1.38 ± 0.24 s(-1) vs. non-dippers = -1.68 ± 0.32 s(-1), p < 0.01). CONCLUSION: Strain and strain rate acquired from color Doppler tissue imaging demonstrate exaggerated reservoir and booster pump function in never-treated, non-dipper hypertensive patients. These methods are simple and sensitive for the early detection of subtle changes in the left atrial function.