Comparison of Maxillofacial Morphology Between Modified Furlow's and Modified two-Flap Palatoplasty in Orofacial Clefts During the Primary Dentition Period.

OBJECTIVE: To assess the effect of two palatoplasty procedures, modified Furlow's palatoplasty (F procedure) and modified two-flap palatoplasty (T procedure), on the maxillofacial morphology of unilateral cleft lip and palate (UCLP) and bilateral cleft lip and palate (BCLP) during the primary dentition period. DESIGN: Retrospective cohort study. SETTING: Department of Orthodontics, School of Dentistry, Showa University. PARTICIPANTS: We enrolled 106 pediatric patients (63 boys, 43 girls; aged 4.43 ± 0.34 years) with non-syndromic orofacial clefts who underwent cheiloplasty and palatoplasty. INTERVENTIONS: Patients were divided into four groups according to cleft type (BCLP or UCLP) and palatoplasty procedure type (F or T procedure). MAIN OUTCOME MEASURES: Maxillofacial morphology was assessed by examining parameters on lateral cephalograms. RESULTS: Multiple comparisons revealed significant differences among N-A, N-ANS, and ANS-PNS distances and SNA and ANB angles among the groups. There were significant differences in N-A, N-ANS, ANS-PNS, SNA, and SNB among the UCLP and BCLP groups. The calculated effect sizes were all within 0.3-0.5. The statistical power was as follows: N-A, 86.41%; N-ANS, 79.77%; ANS-PNS, 97.49%; SNA, 96.88%; and ANB, 99.25%. CONCLUSIONS: Although UCLP and BCLP both exhibited differences in craniofacial distances and angles, the procedure type (either F or T procedure) had no significant effect on the maxillofacial morphology (as determined by lateral cephalograms). However, to rule out additional bias, patient-specific factors should be considered that may be affected by maxillofacial development when deciding surgical approaches.

Prevalence of saliva immunoglobulin A antibodies reactive with severe acute respiratory syndrome coronavirus 2 among Japanese people unexposed to the virus.

While the COVID-19 pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) poses a threat to public health as the number of cases and COVID-19-related deaths are increasing worldwide, the incidence of the virus infection is extremely low in Japan compared with many other countries. To explain this uncommon phenomenon, we investigated the prevalence of naturally occurring ("natural") antibodies, focusing on those of the secretory immunoglobulin A (sIgA) form, reactive with SARS-CoV-2 among Japanese people. One hundred and eighty healthy Japanese volunteers of a wide range of age who had been considered to be unexposed to SARS-CoV-2 participated in this study. Saliva samples and blood samples were collected from all of the 180 participants and 139 adults (aged ≥ 20 years) included therein, respectively. The determination of saliva IgA antibodies, mostly comprising sIgA antibodies, as well as serum IgA and immunoglobulin G antibodies, reactive with the receptor binding domain of the SARS-CoV-2 spike-1 subunit proteins was conducted using an enzyme-linked immunosorbent assay. The major findings were that 52.78% (95% confidence interval, 45.21%-60.25%) of the individuals who had not been exposed to SARS-CoV-2 were positive for saliva IgA antibodies with a wide range of levels between 0.002 and 3.272 ng/mL, and that there may be a negative trend in positivity for the antibodies according to age. As we had expected, a frequent occurrence of assumable "natural" sIgA antibodies reactive with SARS-CoV-2 among the studied Japanese participant population was observed.

Autocrine regulation of mesenchymal progenitor cell fates orchestrates tooth eruption.

Formation of functional skeletal tissues requires highly organized steps of mesenchymal progenitor cell differentiation. The dental follicle (DF) surrounding the developing tooth harbors mesenchymal progenitor cells for various differentiated cells constituting the tooth root-bone interface and coordinates tooth eruption in a manner dependent on signaling by parathyroid hormone-related peptide (PTHrP) and the PTH/PTHrP receptor (PPR). However, the identity of mesenchymal progenitor cells in the DF and how they are regulated by PTHrP-PPR signaling remain unknown. Here, we show that the PTHrP-PPR autocrine signal maintains physiological cell fates of DF mesenchymal progenitor cells to establish the functional periodontal attachment apparatus and orchestrates tooth eruption. A single-cell RNA-seq analysis revealed cellular heterogeneity of PTHrP+ cells, wherein PTHrP+ DF subpopulations abundantly express PPR. Cell lineage analysis using tamoxifen-inducible PTHrP-creER mice revealed that PTHrP+ DF cells differentiate into cementoblasts on the acellular cementum, periodontal ligament cells, and alveolar cryptal bone osteoblasts during tooth root formation. PPR deficiency induced a cell fate shift of PTHrP+ DF mesenchymal progenitor cells to nonphysiological cementoblast-like cells precociously forming the cellular cementum on the root surface associated with up-regulation of Mef2c and matrix proteins, resulting in loss of the proper periodontal attachment apparatus and primary failure of tooth eruption, closely resembling human genetic conditions caused by PPR mutations. These findings reveal a unique mechanism whereby proper cell fates of mesenchymal progenitor cells are tightly maintained by an autocrine system mediated by PTHrP-PPR signaling to achieve functional formation of skeletal tissues.

Methods in Genetic Analysis for Evaluation Mandibular Shape and Size Variations in Human Mandible.

ABSTRACT: The human mandible has been investigated from both clinical and evolutionary perspectives. Recent advances in genome science have identified the genetic regulation of human mandibular shape and size. Identification of genes that regulate mandibular shape and size would not only enhance our understanding of the mechanisms of mandibular growth and development but also help define a strategy to prevent mandibular dysplasia. This review provides a comprehensive summary of why and how the mandible was evaluated in the human mandible genome study. The variation in human mandibular shape and size has been progressively clarified, not only by focusing on the mandible alone but also by using extremely diverse approaches. The methods of data acquisition for evaluating human mandibular shape and size variation are well established. Furthermore, this review explains how to proceed with future research.

A three-dimensional analysis of primary failure of eruption in humans and mice.

OBJECTIVES: Primary failure of eruption (PFE) is a genetic disorder exhibiting the cessation of tooth eruption. Loss-of-function mutations in parathyroid hormone (PTH)/parathyroid hormone-related peptide (PTHrP) receptor (PTH/PTHrP receptor, PPR) were reported as the underlying cause of this disorder in humans. We showed in a PFE mouse model that PTHrP-PPR signaling is responsible for normal dental follicle cell differentiation and tooth eruption. However, the mechanism underlying the eruption defect in PFE remains undefined. In this descriptive study, we aim to chronologically observe tooth eruption and root formation of mouse PFE molars through 3D microCT analyses. SETTING AND SAMPLE POPULATION: Two individuals with PFE were recruited at Showa University. A mouse PFE model was generated by deleting PPR specifically in PTHrP-expressing dental follicle and divided into three groups, PPRfl/fl ;R26RtdTomato/+ (Control), PTHrP-creER;PPRfl/+ ;R26RtdTomato/+ (cHet), and PTHrP-creER;PRRfl/fl ;R26RtdTomato/+ (cKO). MATERIALS AND METHODS: Images from human PFE subjects were acquired by CBCT. All groups of mouse samples were studied at postnatal days 14, 25, 91, and 182 after a tamoxifen pulse at P3, and superimposition of 3D microCT images among three groups was rendered. RESULTS: Mouse and human PFE molars exhibited a similar presentation in the 3D CT analyses. The quantitative analysis in mice demonstrated a statistically significant decrease in the eruption height of cKO first and second molars compared to other groups after postnatal day 25. Additionally, cKO molars demonstrated significantly shortened roots with dilacerations associated with the reduced interradicular bone height. CONCLUSIONS: Mouse PFE molars erupt at a much slower rate compared to normal molars, associated with shortened and dilacerated roots and defective interradicular bones.

Orthognathic surgery induces genomewide changes longitudinally in DNA methylation in saliva.

OBJECTIVE: Orthognathic surgery dramatically changes morphology of the maxillofacial deformity and improves the malocclusion morphologically and functionally. We investigated the influence of orthognathic surgery on genomewide DNA methylation in saliva. METHODS: Saliva was obtained from nine patients undergoing orthognathic surgery and two healthy reference individuals before and 3 months after orthognathic surgery. Genomewide DNA methylation profiling of saliva (341,482 CpG dinucleotides) was conducted using Infinium HumanMethylation450 BeadChips. RESULTS: Comparison between pre- and postsurgery saliva samples revealed significant changes in DNA methylation patterns at 2,381 CpG sites (p < 0.01) with suggestive significance. The differentially methylated probe sets were significantly associated with the cancer pathway (p = 2.8 × 10-7 ; a false discovery rate q-value = 3.7 × 10-4 ) and PI3K-Akt signalling pathway (p = 2.4 × 10-5 ; a false discovery rate q-value = 3.1 × 10-2 ). CONCLUSION: Pathway enrichment analysis of genes with suggestive significance demonstrated that altered DNA methylation in saliva of patients undergoing orthognathic surgery, possibly as a response to surgical stress or bone injury. Further studies with a large sample size and long-term observation are needed to validate the phenomena identified in this study.

Analysis of the relationship between the morphology of the palate and facial skeletal patterns in Class III malocclusion using structural equation modelling.

INTRODUCTION: The present study investigated the relationship between facial skeletal patterns and morphology of the palate in adult patients with Class III malocclusion using structural equation modelling (SEM). SETTING AND SAMPLE POPULATION: One hundred cone beam computed tomography images of Class III adults were evaluated for skeletal measurements. MATERIALS AND METHODS: The skeletal measurements were classified into the vertical, anteroposterior and transverse group based on factor analysis. 3D scanning model of the maxilla was analysed by Generalized procrustes analysis (GPA) and principal component analysis (PCA). Structural equation modelling was used to analyse relationship among the skeletal and morphometric factors. RESULTS: According to the factor analysis, latent variables were extracted by each skeletal variable. First principal component (PC1) and PC2 of palatal morphology were used to analyse relationship with skeletal variables. As results of the structural equation model, the transverse latent variable had the most influence on PC1, followed by vertical and anteroposterior variables. This result means that as the facial width increases, the palate becomes narrower, deeper and longer. CONCLUSIONS: The relationship between the skeletal pattern with Class III malocclusion and palatal morphology was analysed through SEM. The transverse facial skeletal pattern showed the highest correlation with PC1 of palatal morphology.

Association between the FGFR1 rs13317 single nucleotide polymorphism and orbitale-nasion depth based on cephalometric images.

The fibroblast growth factor receptor 1 (FGFR1) gene plays an important role in craniofacial morphogenesis. In our previous study, an association between FGFR1 single nucleotide polymorphisms (SNPs) and craniofacial morphology was demonstrated in Japanese and Korean subjects. The present study aimed to evaluate the relationship between a common FGFR1 SNP (rs13317) with craniofacial morphology, increasing the number of measurements and examining Egyptian subjects (n = 191) in addition to the Japanese (n = 211) and Korean (n = 226) subjects. Genotyping for rs13317 was performed using the TaqMan assay, and its associations with 81 craniofacial measurements derived from lateral and posteroanterior cephalograms were analyzed by multiple regression analysis controlling sex and facial size. The results from each of the populations were then statistically combined. In the Egyptian subjects, rs13317 was significantly associated with the nasion-orbitale depth (P = 0.00040), and a suggestive association was also observed in the Japanese (P = 0.037) and Korean subjects (P = 0.045). The combined analysis revealed that only the nasion-orbitale depth showed a significant association (P = 0.000062) and that several measurements showed a suggestive association. Our results strongly indicate that rs13317 is associated with a smaller depth between the nasion and orbitale, representing a relative protrusion of the cheekbones and retrusion of the nasal root. A similar characteristic is also observed in individuals with Pfeiffer syndrome, which is caused by a dysfunctional FGFR1 mutation.

Whole-genome sequencing in a pair of monozygotic twins with discordant cleft lip and palate subtypes.

OBJECTIVE: Orofacial clefts (OFCs) are common and etiologically complex birth defects. This study explored potential genetic differences in a pair of Japanese monozygotic (MZ) twins with different forms of OFC using whole-genome sequencing. SUBJECTS AND METHODS: One co-twin (MZ-1) presented with nonsyndromic bilateral cleft lip and palate; the other co-twin (MZ-2) had nonsyndromic bilateral cleft lip and unilateral left-sided cleft alveolus. Neither parent had an OFC. Craniofacial morphologic features and potential genetic differences were compared using standard cephalometry and whole-genome sequencing, respectively. RESULTS: Morphologically, MZ-1 had a smaller vertical mandibular height, compared to MZ-2. However, no discordant genetic differences were detected. Moreover, both twins and their parents harbored rare candidate gene variants (GRHL3; TPM1) considered to be associated with OFCs. CONCLUSION: The observed differences between MZ-1 and MZ-2 in craniofacial morphology assessed by cephalograms might be directly attributable to the effects of the OFC on growth and/or differences in surgical history, given the lack of any differences in genetic background. However, comparisons of discordant MZ twins should continue to identify novel candidates that might control OFC or that might partly explain the missing heritability for this common birth defect, in addition to understanding craniofacial growth and development.

Common polymorphisms in WNT10A affect tooth morphology as well as hair shape.

Hair and teeth are appendages of ectodermal origin, and there are common molecular backgrounds involved in their formation. To date, it has been revealed that a non-synonymous polymorphism in EDAR has effects on the morphological variation in both hair and teeth. Previous association studies have confirmed that single-nucleotide polymorphisms (SNPs) in/near THADA, FRAS1, WNT10A, NAF1 and FGFR2 are associated with hair morphology. In this study, we thus examined whether these SNPs are also associated with dental characteristics. We measured metric dental traits including crown size and also evaluated non-metric dental traits using plaster casts obtained from subjects (272 Japanese and 226 Koreans). DNA samples were prepared from the subjects and genotyped for the hair morphology-associated SNPs. We observed a significant association of crown size with an SNP in WNT10A (rs7349332), but not with SNPs in other genes. Therefore, we further examined four SNPs within and around WNT10A, among which rs10177996 had the strongest association with dental traits. World distribution of the derived allele in rs10177996, which is associated with larger teeth, showed that Eurasians have a higher allele frequency than Africans. Together with previous studies on hair morphology, this study demonstrated that common variations in WNT10A have pleiotropic effects on the morphology of ectodermal appendages.

Assessment of the root apex position of impacted maxillary canines on panoramic films.

INTRODUCTION: In this study, we aimed to analyze the root apex positions of impacted maxillary canines on panoramic radiographs according to their labiopalatal positions and to propose a new panoramic radiographic predictor of impacted maxillary canines. METHODS: Paired panoramic films and cone-beam computed tomography images of 104 patients with unilateral impacted maxillary canines were selected. The sector locations of the impacted canine root apices on the panoramic radiographs were compared with the labiopalatal positions of impacted maxillary canines on cone-beam computed tomography. Statistical correlations between panoramic and cone-beam computed tomography findings were examined with the chi-square test. RESULTS: A statistically significant association was observed between the sector locations of impacted canine root apices and the labiopalatal positions of the canines (P <0.001). The root apices of labially impacted canines were more frequently located in sector 2 (corresponding to the lateral incisor position), those of palatally impacted canines were more frequently located in sector 4 (corresponding to the first premolar), and those of midalveolus impacted canines were more frequently located in sector 3 (corresponding to the canine). CONCLUSIONS: On panoramic films, the root apices of palatally impacted canines tended toward the root apices of the maxillary first premolars, whereas those of labially impacted canines tended toward the root apices of the maxillary lateral incisors. Therefore, the sector locations of impacted canine root apices on panoramic radiographs could be used for the early prediction of maxillary canine impactions and determination of the labiopalatal positions of impacted canines.

Model-based verification of hypotheses on the origin of modern Japanese revisited by Bayesian inference based on genome-wide SNP data.

Various hypotheses for the peopling of the Japanese archipelago have been proposed, which can be classified into three models: transformation, replacement, and hybridization. In recent years, one of the hybridization models ("dual-structure model") has been widely accepted. According to this model, Neolithic hunter-gatherers known as Jomon, who are assumed to have originated in southeast Asia and lived in the Japanese archipelago greater than 10,000 years ago, admixed with an agricultural people known as Yayoi, whom were migrants from the East Asian continent 2,000-3,000 years ago. Meanwhile, some anthropologists propose that rather, morphological differences between the Jomon and Yayoi people can be explained by microevolution following the lifestyle change. To resolve this controversy, we compared three demographic models by approximate Bayesian computation using genome-wide single nucleotide polymorphism (gwSNP) data from the Ainu people who are thought to be direct descendants of indigenous Jomon. If we assume Chinese people sampled in Beijing from HapMap have the same ancestry as Yayoi, then the hybridization model is predicted to be between 29 and 63 times more likely than the replacement and transformation models, respectively. Furthermore, our data provide strong support for a model in which the Jomon lineages had population structure diversified in local areas before the admixture event. Initial divergence between the Jomon and Yayoi ancestries was dated to late Pleistocene, followed by the divergence of Jomon lineages at early Holocene. These results suggest gwSNP data provides a detailed picture of the complex hybridization model for Japanese population history.

Genome-wide SNP analysis reveals population structure and demographic history of the ryukyu islanders in the southern part of the Japanese archipelago.

The Ryukyu Islands are located to the southwest of the Japanese archipelago. Archaeological evidence has revealed the existence of prehistoric cultural differentiation between the northern Ryukyu islands of Amami and Okinawa, and the southern Ryukyu islands of Miyako and Yaeyama. To examine a genetic subdivision in the Ryukyu Islands, we conducted genome-wide single nucleotide polymorphism typing of inhabitants from the Okinawa Islands, the Miyako Islands, and the Yaeyama Islands. Principal component and cluster analyses revealed genetic differentiation among the island groups, especially between Okinawa and Miyako. No genetic affinity was observed between aboriginal Taiwanese and any of the Ryukyu populations. The genetic differentiation observed between the inhabitants of the Okinawa Islands and the Miyako Islands is likely to have arisen due to genetic drift rather than admixture with people from neighboring regions. Based on the observed genetic differences, the divergence time between the inhabitants of Okinawa and Miyako islands was dated to the Holocene. These findings suggest that the Pleistocene inhabitants, whose bones have been found on the southern Ryukyu Islands, did not make a major genetic contribution, if any, to the present-day inhabitants of the southern Ryukyu Islands.

Quantitative skeletal maturation estimation using cone-beam computed tomography-generated cervical vertebral images: a pilot study in 5- to 18-year-old Japanese children.

OBJECTIVES: The purpose of this study was to establish multivariable regression models for the estimation of skeletal maturation status in Japanese boys and girls using the cone-beam computed tomography (CBCT)-based cervical vertebral maturation (CVM) assessment method and hand-wrist radiography. MATERIALS AND METHODS: The analyzed sample consisted of hand-wrist radiographs and CBCT images from 47 boys and 57 girls. To quantitatively evaluate the correlation between the skeletal maturation status and measurement ratios, a CBCT-based CVM assessment method was applied to the second, third, and fourth cervical vertebrae. Pearson's correlation coefficient analysis and multivariable regression analysis were used to determine the ratios for each of the cervical vertebrae (p < 0.05). RESULTS: Four characteristic parameters ((OH2 + PH2)/W2, (OH2 + AH2)/W2, D2, AH3/W3), as independent variables, were used to build the multivariable regression models: for the Japanese boys, the skeletal maturation status according to the CBCT-based quantitative cervical vertebral maturation (QCVM) assessment was 5.90 + 99.11 × AH3/W3 - 14.88 × (OH2 + AH2)/W2 + 13.24 × D2; for the Japanese girls, it was 41.39 + 59.52 × AH3/W3 - 15.88 × (OH2 + PH2)/W2 + 10.93 × D2. CONCLUSIONS: The CBCT-generated CVM images proved very useful to the definition of the cervical vertebral body and the odontoid process. The newly developed CBCT-based QCVM assessment method showed a high correlation between the derived ratios from the second cervical vertebral body and odontoid process. CLINICAL RELEVANCE: There are high correlations between the skeletal maturation status and the ratios of the second cervical vertebra based on the remnant of dentocentral synchondrosis.

Identification of gene expression profile of neural crest-derived cells isolated from submandibular glands of adult mice.

Neural crest cells in the embryo migrate to reach target sites as neural crest-derived cells (NCDCs) where they differentiate into a variety of derivatives. Some NCDCs are maintained in an undifferentiated state throughout the life of the animal and are considered to be a useful cell source for regenerative medicine. However, no established method to obtain NCDCs sufficient for regenerative medicine from adults with high purity has been presented, since their distribution in adult tissues is not fully understood. It is critical to identify reliable markers for NCDCs in adults, as the expressions of P0 and Wnt1, the most reliable NCDC markers, are shut off in the embryonic stage. To analyze the characteristics of NCDCs in adult tissues, we utilized a double transgenic mouse strain, P0-Cre/CAG-CAT-EGFP transgenic mice (P0 mice), in which NCDCs were shown to express EGFP and we were able to recognize GFP-positive cells in those. We focused on the submandibular glands (SMGs), which are known to be derived from the neural crest. GFP-positive cells were shown to be scattered like islands in the SMGs of adult P0 mice. We surgically removed SMGs from adult mice and digested samples into single cell suspensions. GFP-positive cells separated using flow cytometry expressed a high level of Sox10, a marker of embryonic neural crest cells, suggesting successful isolation of NCDCs. To identify candidate marker genes in isolated NCDCs, we performed DNA microarray analyses and real-time PCR analysis of GFP-positive and -negative cells isolated from P0 mice, then selected genes showing differential gene expression patterns. As compared to GFP-negative cells, GFP-positive cells expressed Gpr4 and Ednrb at higher levels, whereas Pdgfra and Pdgfrb were expressed at lower levels. Furthermore, DNA microarray analysis showed that GFP-positive cells were positive for aquaporin 5, a marker for acinar cells. Together, our results indicate that NCDCs in adult SMGs have characteristic gene expression profiles specially their cell surface molecules. Cell sorting using a combination of these specific cell surface proteins would be a useful strategy for isolation of NCDCs from SMGs with high purity.

Characteristics of Craniofacial Morphology and Occlusion in Shwachman-Diamond Syndrome: A Case Report of a Japanese Sibling Pair.

Shwachman-Diamond syndrome (SDS) is a rare autosomal recessive disorder mainly caused by mutations in the Shwachman-Bodian-Diamond syndrome gene on chromosome 7q11. Although skeletal abnormalities are a feature of SDS, no reports have focused on the craniofacial morphology of patients with SDS. Moreover, the detailed dental characteristics of SDS remain unknown. In the present case report, we evaluated the craniofacial morphology and dental findings of two patients with SDS. A Japanese adolescent sibling pair with SDS had the chief complaint of excessive overjet. Cephalometric analysis revealed similar craniofacial morphology in both patients: skeletal class I malocclusion with a hypodivergent pattern and labial inclination of the maxillary and mandibular incisors. A panoramic photograph showed the tendency of delayed permanent tooth eruption and replacement in both patients. These cases suggest that malocclusion requiring orthodontic treatment might be a feature of patients with SDS.

Comparison of Bond Strength Between Two Resin Cement Types and Additive Manufacturing or Cast Cobalt-Chromium Alloys.

OBJECTIVE: To compare the bond strength of two types of resin cement to that of additive manufacturing (AM) or cast cobalt-chromium (Co-Cr) alloys. MATERIALS AND METHODS: Two types of resin luting cement, composite resin and methyl methacrylate (MMA), were bonded to AM or cast Co-Cr alloys, and shear bond tests were performed after seven days of storage in distilled water at 37°C. Co-Cr alloy adhesive elements AM to the enamel surface of the labial aspect of a bovine mandibular central incisor crown were bonded with two types of resin luting cement and subjected to 1,000 cycles of storage in water for one day and 28 days or thermal cycling, followed by shear bonding tests. Residual cement on the metal and enamel surfaces after the bonding tests was evaluated using an optical microscope. The normality of the results was evaluated using statistical software Statcel4, analysis of variance, or Kruskal-Wallis test, depending on normality, and multiple comparison tests were performed using the Tukey-Kramer or Steel-Dwass tests. RESULTS: After one day, the shear bond strength (SBS) was 25.9 MPa for Panavia V5 (PV; Kuraray Noritake Dental Corporation, Niigata, Japan) and 23.5 MPa for Super-Bond (SB; Sun Medical Corporation, Shiga, Japan), with no significant difference between the two cement types (P > 0.05). After 28 days, the SBS decreased to 4.1 MPa for PV and 6.7 MPa for SB, showing a significant difference between the two cements (P < 0.05). Following 1,000 thermal cycles, the SBS was 2.0 MPa for PV and 5.6 MPa for SB, with SB exhibiting a significantly higher value (P < 0.05). The adhesive strength was significantly lower after 28 days of storage and thermal cycling compared to after one day of storage (P < 0.05). The Co-Cr alloy exhibited more residual cement on the enamel surface due to interfacial fracture with the resin cement. The Co-Cr alloy showed more residual cement on the enamel surface due to interfacial fracture with the resin cement. CONCLUSION: MMA-based resin cement showed optimal bond strength and may be suitable for clinical use in computer-aided design (CAD)/computer-aided manufacturing (CAM) orthodontic appliances.

3D Printer-Assisted Layered Fabrication of a Novel Appliance for Oral Myofunctional Therapy and Functional Evaluation of Its Effects on Orofacial Muscles During Wear.

Aim Balanced function of the orofacial muscles is important for normal occlusion and dentition; however, patients with malocclusion often present with myofunctional disorder (MFD). Myofunctional therapy (MFT) has received much attention as a method for reducing MFD. Moreover, prefabricated functional appliances (PFAs) have been developed as a method to eliminate abnormal muscle pressure and guide the tongue into the correct position. However, PFAs have disadvantages, such as poor intraoral retention, limited usage time due to discomfort and poor patient compliance, and changes in the axis of the mandibular anterior teeth. Therefore, this study aimed to develop a new custom-made splint-type orthodontic appliance with CAD/CAM technology. Moreover, we evaluated the characteristics of the appliance and conducted functional tests to determine the effects of the appliance on the orofacial muscles and the discomfort associated with its use. Materials and methods Twenty-five volunteers (nine females and 16 males; mean age 28.4 ± 3.4 years) with normal swallowing function were included in the study. Lip-closing strength (LCS), electromyogram during swallowing, oxygen saturation, and pulse rate were measured and compared when the appliance was not worn and when it was worn. In addition, tongue habits were evaluated, and the maximum tongue pressure was measured when the appliance was not worn. The subjects were asked to answer a questionnaire using a numerical rating scale (NRS) regarding discomfort when wearing the appliance. The evaluation items were swallowing difficulty, speaking difficulty, and breathlessness, which were rated on an 11-point scale ranging from 0 to 10. Statistical tests were conducted using IBM SPSS version 28.0.1 (IBM, Armonk, NY, USA) with the Shapiro-Wilk and Levene's test, followed by the Wilcoxon signed rank sum test. The significance level was set at α = 0.05. The measurement error for each measurement item was evaluated using an intraclass correlation coefficient. Results A new custom-made splint-type orthodontic appliance was fabricated for each subject. The fit and retention of the appliance in the mouth were good when fitted, and a comparison of the functional test measurements of 25 subjects with and without the appliance showed that the LCS decreased significantly (p<0.05) before and after wearing the appliance. However, no statistically significant differences were found for the other items. The Mann-Whitney U test regarding the effects of sex, previous orthodontic treatment, or MFT, and oral habits did not statistically significantly influence the effects of wearing the device. In the NRS results, "difficulty swallowing" was observed in half of the subjects, "difficulty breathing" was rarely observed, and "difficulty speaking" was observed in all subjects. Conclusions A novel custom-made splint-type orthodontic appliance was designed and fabricated using digital workflow and 3D printing technology. This appliance was designed to correct oral habits and was made from a new material classified as a class II medical appliance according to the international harmonized classification.

A genome-wide association study of third molar agenesis in Japanese and Korean populations.

Tooth agenesis is the most common developmental anomaly of human dentition, occurring most often in the third molar (wisdom tooth). It is affected by genetic variation, so this study aimed to identify susceptibility genes associated with third molar agenesis. Examination of panoramic radiographs and medical history about third molar extraction were used to diagnose third molar agenesis. We then conducted a genome-wide association study of 149 cases with at least one-third molar agenesis and 338 controls from Japan and Korea using the Illumina HumanOmniExpress BeadChip. After rigorous quality-control filtering, approximately 550 000 single-nucleotide polymorphisms (SNPs) were analyzed in association tests with the status. We identified three SNPs showing evidence of association at P<1 × 10(-5) and 69 SNPs showing evidence of association at P<1 × 10(-4). SNP rs1469622, which maps to an intron of THSD7B (thrombospondin, type I, domain containing 7B) on chromosome 2, showed the strongest association (combined odds ratio=1.88, 95% confidence interval=1.43-2.47, P=7.5 × 10(-6)). The identified SNPs may be considered candidates for future replication studies in independent samples.

Validation of Machine Learning Models for Craniofacial Growth Prediction.

This study identified the most accurate model for predicting longitudinal craniofacial growth in a Japanese population using statistical methods and machine learning. Longitudinal lateral cephalometric radiographs were collected from 59 children (27 boys and 32 girls) with no history of orthodontic treatment. Multiple regression analysis, least absolute shrinkage and selection operator, radial basis function network, multilayer perceptron, and gradient-boosted decision tree were used. The independent variables included 26 coordinated values of skeletal landmarks, 13 linear skeletal parameters, and 17 angular skeletal parameters in children ages 6 to 12 years. The dependent variables were the values of the 26 coordinated skeletal landmarks, 13 skeletal linear parameters, and 17 skeletal angular parameters at 13 years of age. The difference between the predicted and actual measured values was calculated using the root-mean-square error. The prediction model for craniofacial growth using the least absolute shrinkage and selection operator had the smallest average error for all values of skeletal landmarks, linear parameters, and angular parameters. The highest prediction accuracies when predicting skeletal linear and angular parameters for 13-year-olds were 97.87% and 94.45%, respectively. This model incorporates several independent variables and is useful for future orthodontic treatment because it can predict individual growth.