Orthodontic Management of Severe Hypodontia and Impacted Maxillary Second Molars in a Patient with Sotos Syndrome.

Sotos syndrome is a genetic disorder characterized by distinct craniofacial features, overgrowth in childhood, and impaired intellectual development. We herein report the successful orthodontic treatment of a 14-year-old boy with Sotos syndrome caused by a heterozygous mutation in the NSD1 gene. He showed severe hypodontia, impaction of the maxillary second molars and a skeletal Class III jaw-base relationship. Orthodontic management, including space control by protraction of the maxillary first molars and traction of the impacted molars, was performed using fixed appliances and miniscrews. As a result, acceptable occlusion was obtained without any discernible relapse 18 months postretention.

Sex differences in airway volume and 3-dimensional shape in Japanese adults.

(1) To establish normative data for three-dimensional (3D) measurements of the upper airway in young Japanese adults, and (2) to investigate sex-related differences in linear and volumetric measurements, as well as shape. This study employed cone-beam computed tomography (CBCT) images of 56 Japanese young adults preselected from among 1000 patients, so that samples matched a historic 2D cephalometric cohort with normal occlusion using propensity score matching. Three-dimensional models of the oropharynx and hypopharynx were reconstructed from CBCT images and their volumes were calculated. We defined 20 landmarks on the surface of the 3D model and performed seven linear measurements between them. The mean and standard deviation of the linear measurements were calculated as the normative data for each sex as well as the volumes. Sex-related differences were analyzed using t-test (p < 0.05). Principal component discriminant analysis of the coordinate values of the landmarks was also performed to examine sex differences in shape. The normative ranges of the 3D measurements of the oropharynx and hypopharynx were determined according to sex. Sex-related differences in the measurement results were observed in hypopharyngeal length but not in volume. The hypopharynx length in males was significantly longer than that in females. The discriminant analysis showed that males tended to show longer and straight shapes, while females showed inversed triangular shapes from the frontal view. This result will allow clinicians to evaluate how patient airway characteristics differ from the normative 3D morphology of the upper airway.

Relationship Between Stigma Experience and Self-Perception Related to Facial Appearance in Young Japanese Patients with Cleft lip and/or Palate.

OBJECTIVE: To examine the relationship between stigma experience related to facial appearance in Japanese youths with cleft lip and/or palate (CL/P) and their self-perception. DESIGN: A cross-sectional study. PARTICIPANTS: Sixty-nine Japanese youths with CL/P (11-18 years old). OUTCOME MEASURES: The participants' stigma experience in relation to facial appearance (measured with 7 single contextual scale items) and their self-perception (measured with 5 domain scores based on 30 perceptual items) were assessed using the Japanese version of the Youth Quality of Life Instrument-Facial Differences Module. Participants were categorized into high and low self-perception subgroups with a threshold of 1 standard deviation for each domain. The frequency of stigma experiences was compared between the following 2 subgroups: age, sex, cleft palate only versus other cleft, and high versus low self-perception. Correlations between the responses regarding stigma and all domain scores were examined. RESULTS: Sixteen percent of the participants reported experiencing stigma. Hearing others say something about their face occurred significantly more frequently in youths 15 to 18 years of age than in youths 11 to 14 years of age. Stigma frequency was not found to differ by sex or cleft type. Stigma experiences were significantly more frequent for youth with higher scores across negative self-perception domains as well as higher coping skills. Significant correlations were identified between responses regarding stigma items and all domain scores (r = 0.27-0.63, p < .05). CONCLUSIONS: It was found that stigma experiences related to facial appearance may influence negative self-perceptions of facial differences as well as higher coping skills among Japanese youths with CL/P.

Evaluation of Facial Appearance-Related Quality of Life in Young Japanese Patients With Cleft Lip and/or Palate.

OBJECTIVE: (1) To confirm the reliability of a Japanese version of the Youth Quality of Life Instrument-Facial Differences Module (YQOL-FD); (2) to assess the quality of life (QoL) related to facial difference in Japanese youths with cleft lip and/or palate (CL/P) using this instrument; and (3) to examine the QoL differences according to age, sex, and cleft type. DESIGN: A cross-sectional study. SETTING: Japanese youths with CL/P were recruited through our hospital and asked to complete the YQOL-FD. PARTICIPANTS: Sixty-nine Japanese youths (age, 11-18 years) with CL/P. OUTCOME MEASURES: The domain scores of stigma, negative consequences, negative self-image, positive consequences, and coping in the YQOL-FD, and the reliability of such scores were evaluated. RESULTS: The instrument showed an acceptable internal consistency (Cronbach α = 0.74-0.92) and test-retest reliability (intraclass correlation coefficient = 0.94-0.98), except for the coping domain. The individual's domain scores were spread out from the lowest score to the high scores among all domains, thus indicating the negative and positive impacts of living with facial differences regarding their QoL may vary among individuals with CL/P. All domain scores in the 15- to 18-year-old group were significantly higher than those in 11- to 14-year-old group; there were no significant differences according to sex or cleft type. CONCLUSIONS: The instrument showed acceptable reliability, except for the coping domain. There were individual variations in QoL concerning the facial difference among Japanese youths with CL/P as measured by the YQOL-FD, suggesting the importance of individual evaluations. Perceptions were influenced by age, but not sex or cleft type.

Clinical applicability of automated cephalometric landmark identification: Part II - Number of images needed to re-learn various quality of images.

AIM: To estimate the number of cephalograms needed to re-learn for different quality images, when artificial intelligence (AI) systems are introduced in a clinic. SETTINGS AND SAMPLE POPULATION: A total of 2385 digital lateral cephalograms (University data [1785]; Clinic F [300]; Clinic N [300]) were used. Using data from the university and clinics F and N, and combined data from clinics F and N, 50 cephalograms were randomly selected to test the system's performance (Test-data O, F, N, FN). MATERIALS AND METHODS: To examine the recognition ability of landmark positions of the AI system developed in Part I (Original System) for other clinical data, test data F, N and FN were applied to the original system, and success rates were calculated. Then, to determine the approximate number of cephalograms needed to re-learn for different quality images, 85 and 170 cephalograms were randomly selected from each group and used for the re-learning (F85, F170, N85, N170, FN85 and FN170) of the original system. To estimate the number of cephalograms needed for re-learning, we examined the changes in the success rate of the re-trained systems and compared them with the original system. Re-trained systems F85 and F170 were evaluated with test data F, N85 and N170 from test data N, and FN85 and FN170 from test data FN. RESULTS: For systems using F, N and FN, it was determined that 85, 170 and 85 cephalograms, respectively, were required for re-learning. CONCLUSIONS: The number of cephalograms needed to re-learn for images of different quality was estimated.

Clinical applicability of automated cephalometric landmark identification: Part I-Patient-related identification errors.

OBJECTIVES: To determine whether AI systems that recognize cephalometric landmarks can apply to various patient groups and to examine the patient-related factors associated with identification errors. SETTING AND SAMPLE POPULATION: The present retrospective cohort study analysed digital lateral cephalograms obtained from 1785 Japanese orthodontic patients. Patients were categorized into eight subgroups according to dental age, cleft lip and/or palate, orthodontic appliance use and overjet. MATERIALS AND METHODS: An AI system that automatically recognizes anatomic landmarks on lateral cephalograms was used. Thirty cephalograms in each subgroup were randomly selected and used to test the system's performance. The remaining cephalograms were used for system learning. The success rates in landmark recognition were evaluated using confidence ellipses with α = 0.99 for each landmark. The selection of test samples, learning of the system and evaluation of the system were repeated five times for each subgroup. The mean success rate and identification error were calculated. Factors associated with identification errors were examined using a multiple linear regression model. RESULTS: The success rate and error varied among subgroups, ranging from 85% to 91% and 1.32 mm to 1.50 mm, respectively. Cleft lip and/or palate was found to be a factor associated with greater identification errors, whereas dental age, orthodontic appliances and overjet were not significant factors (all, P < .05). CONCLUSION: Artificial intelligence systems that recognize cephalometric landmarks could be applied to various patient groups. Patient-oriented errors were found in patients with cleft lip and/or palate.

Widespread corticopetal projections from the oval paracentral nucleus of the intralaminar thalamic nuclei conveying orofacial proprioception in rats.

The oval paracentral nucleus (OPC) was initially isolated from the paracentral nucleus (PC) within the intralaminar thalamic nuclei in rats. We have recently shown that the rat OPC receives proprioceptive inputs from jaw-closing muscle spindles (JCMSs). However, it remains unknown which cortical areas receive thalamic inputs from the OPC, and whether the cortical areas receiving the OPC inputs are distinct from those receiving inputs from the other intralaminar nuclei and sensory thalamic nuclei. To address this issue, we injected an anterograde tracer, biotinylated dextranamine (BDA), into the OPC, which was electrophysiologically identified by recording of proprioceptive inputs from the JCMSs. Many BDA-labeled axonal fibers and terminals from the OPC were ipsilaterally observed in the rostral and rostroventral regions of the primary somatosensory cortex (S1), the rostral region of the secondary somatosensory cortex (S2), and the most rostrocaudal levels of the granular insular cortex (GI). In contrast, a BDA injection into the caudal PC, which was located slightly rostral to the OPC, resulted in ipsilateral labeling of axonal fibers and terminals in the rostrolateral region of the medial agranular cortex and the rostromedial region of the lateral agranular cortex. Furthermore, injections of a retrograde tracer, Fluorogold, into these S1, S2, and GI regions, resulted in preferential labeling of neurons in the ipsilateral OPC among the intralaminar and sensory thalamic nuclei. These findings reveal that the rat OPC has widespread, but strong corticopetal projections, indicating that there exist divergent corticopetal pathways from the intralaminar thalamic nucleus, which process JCMS proprioceptive sensation.

Comprehensive Orthodontic Treatment of a Patient With Prader-Willi Syndrome.

Prader-Willi syndrome (PWS) is a rare genetic disorder caused by a defect in paternally expressed genes in the 15q11-q13 region. Prader-Willi syndrome affects many parts of the body and involves craniofacial and dentofacial abnormalities. We herein report the successful 2-stage orthodontic treatment of an 8-year-old girl with PWS caused by paternal 15q11-q13 deletion. She presented with a skeletal class II relationship with mandibular deviation, a deep overbite, and severe crowding of the lower dental arch. Functional appliance therapy was utilized to improve her skeletal discrepancy. The second phase of orthodontic treatment using fixed appliances was started at 14.5 years old, which improved her remained crowding and large overbite. As a result, her facial appearance and occlusion were improved without any discernible relapse after 2 years of retention. We describe the outcomes of orthodontic treatment for a patient with PWS and discuss the specific attention during orthodontic treatment.

Observation of the Epithelial Cell Behavior in the Nasal Septum During Primary Palate Closure in Mice.

Epithelial fusion is critical in palatogenesis, and incomplete fusion results in various type of facial cleft, depending on the region that fails to fuse. In mammalian palatogenesis, the bilateral secondary palatal processes fuse in the middle of the face to form the secondary palate. Later, the dorsal side of the secondary palatal shelves fuses with the nasal septum to complete palatogenesis. Importantly, the anterior border of the secondary palatal shelf fuses with the primary palate, which is located at the anterior and ventral border of the nasal septum. While numerous studies have investigated the mechanism of fusion between secondary palatal shelves, very little is known about how the primary palate touches and fuses with the secondary palatal shelves. In this study, we investigate the possible epithelial cell behaviors on the surface of the primary palate using palatal explant cultures of K14-GFP mice. A time-lapse observation of the GFP-labeled epithelium and an SEM analysis revealed that the extrusion epithelium appeared at the region corresponding to the fusing area and expanded rostrally on the nasal septum surface in the absence of the secondary palatal processes. Unlike on the secondary palate surface, cellular migration and subsequent autonomous mesenchymal exposure were not evident on the nasal septum or the primary palate. TUNEL staining revealed that these extrusion epithelia were undergoing apoptosis. These findings indicated that extrusion with apoptosis was autonomously initiated at the presumptive region of the fusion without contact with the opposing secondary palate.

Proprioceptive thalamus receiving forelimb and neck muscle spindle inputs via the external cuneate nucleus in the rat.

Proprioceptive signals from body muscles have historically been considered to project to the rostrodorsal shell of the ventrobasal thalamic complex [the ventral posterolateral nucleus (VPL) and ventral posteromedial nucleus (VPM)]. However, we have recently found that proprioception from rat jaw-closing muscle spindles (JCMSs) is conveyed via the supratrigeminal nucleus to the caudo-ventromedial edge of the VPM, but not to the rostrodorsal shell of the VPM. Therefore, proprioception from other body muscles may also project to thalamic regions other than the rostrodorsal shell of the VPL. We thus examined the thalamic projection from the rat external cuneate nucleus (ECu), which receives proprioceptive inputs from forelimb and neck muscles. After injection of anterograde tracer into the ECu, axon terminals were contralaterally labeled in the ventromedial part (VPLvm) of the VPL, but not in the rostrodorsal shell of the VPL. After anterograde tracer injection into the cuneate nucleus (Cu), axon terminals were widely labeled in the contralateral VPL including the VPLvm. In the VPLvm, we electrophysiologically confirmed the proprioceptive inputs responsive to electrical stimulation of the ECu or median nerve and to the pressure of forelimb/neck muscles or wrist flexion. After retrograde tracer injection into the VPLvm, neurons were contralaterally labeled in the ECu and Cu. After retrograde tracer injection into the VPL where no such proprioceptive inputs were recorded, no ECu neurons were labeled. These findings indicate that proprioception from forelimb/neck muscle spindles and JCMSs is somatotopically transmitted to the ventromedial floor of the ventrobasal thalamic complex, but not to its rostrodorsal shell.

Observation of Dynamic Cellular Migration of the Medial Edge Epithelium of the Palatal Shelf in vitro.

Palatal fusion is a critical step during palatogenesis. In this fusing interface, the epithelial sheets need to be removed in order to achieve mesenchymal continuity. Epithelial cellular migration is one of the possible mechanisms, and live imaging of the labeled epithelium could provide direct evidence for it. However, the removal of medial edge epithelium (MEE) between the bilateral processes takes place in the middle of the dorso-ventral axis of the palatal shelf, and thus it is challenging to capture the cellular behavior directly. Here, we evaluate cellular behavior of MEE cells using a live imaging technique with a mouse model which expresses GFP under the promoter of Keratin14 (K14-GFP) and unpaired palatal shelf culture. Using this approach, we successfully obtained live images of epithelial behavior and detected epithelial cell migration on the surface of the secondary palatal shelf without touching of the opposing shelf. Additionally, the pattern of epithelial elimination resulted in oval-shaped exposed mesenchyme, which recapitulated the situation during secondary palate fusion in vivo. Detailed image processing revealed that most of the MEE migrated in an outward direction at the boundary regions as the oval shape of the exposed mesenchyme expanded. The migration was preceded by the bulging of MEE, and disappearance of GFP signals was not evident in bulging or migrating MEE at the boundary regions. Furthermore, the MEE migration and the subsequent mesenchymal exposure were disturbed by application of ROCK inhibitor. Together, these findings indicated that epithelial cell migration contributed importantly to the MEE removal and the subsequent exposure of the underlying mesenchyme. Furthermore, they indicated that the migration of epithelial cells was regulated in a time- and space-specific manner, since unpaired palatal shelf culture exhibited these cellular behaviors even in the absence of the opposing shelf. Altogether, present data indicated that this new experimental system combining live imaging with GFP-labeled epithelium mice and unpaired palatal shelf culture enabled direct visualization of cellular migration of MEE in vitro and could be a powerful tool to investigate its cellular and molecular mechanisms.

Thalamo-insular pathway conveying orofacial muscle proprioception in the rat.

Little is known about how proprioceptive signals arising from muscles reach to higher brain regions such as the cerebral cortex. We have recently shown that a particular thalamic region, the caudo-ventromedial edge (VPMcvm) of ventral posteromedial thalamic nucleus (VPM), receives the proprioceptive signals from jaw-closing muscle spindles (JCMSs) in rats. In this study, we further addressed how the orofacial thalamic inputs from the JCMSs were transmitted from the thalamus (VPMcvm) to the cerebral cortex in rats. Injections of a retrograde and anterograde neuronal tracer, wheat-germ agglutinin-conjugated horseradish peroxidase (WGA-HRP), into the VPMcvm demonstrated that the thalamic pathway terminated mainly in a rostrocaudally narrow area in the dorsal part of granular insular cortex rostroventrally adjacent to the rostralmost part of the secondary somatosensory cortex (dGIrvs2). We also electrophysiologically confirmed that the dGIrvs2 received the proprioceptive inputs from JCMSs. To support the anatomical evidence of the VPMcvm-dGIrvs2 pathway, injections of a retrograde neuronal tracer Fluorogold into the dGIrvs2 demonstrated that the thalamic neurons projecting to the dGIrvs2 were confined in the VPMcvm and the parvicellular part of ventral posterior nucleus. In contrast, WGA-HRP injections into the lingual nerve area of core VPM demonstrated that axon terminals were mainly labeled in the core regions of the primary and secondary somatosensory cortices, which were far from the dGIrvs2. These results suggest that the dGIrvs2 is a specialized cortical region receiving the orofacial proprioceptive inputs. Functional contribution of the revealed JCMSs-VPMcvm-dGIrvs2 pathway to Tourette syndrome is also discussed.

Direct projection from the lateral habenula to the trigeminal mesencephalic nucleus in rats.

Trigeminal mesencephalic nucleus (Vmes) neurons are primary afferents conveying deep sensation from the masticatory muscle spindles or the periodontal mechanoreceptors, and are crucial for controlling jaw movements. Their cell bodies exist in the brain and receive descending commands from a variety of cortical and subcortical structures involved in limbic (emotional) systems. However, it remains unclear how the lateral habenula (LHb), a center of negative emotions (e.g., pain, stress and anxiety), can influence the control of jaw movements. To address this issue, we examined whether and how the LHb directly projects to the Vmes by means of neuronal tract tracing techniques in rats. After injections of a retrograde tracer Fluorogold in the rostral and caudal Vmes, a number of neurons were labeled in the lateral division of LHb (LHbl) bilaterally, whereas a few neurons were labeled in the medial division of LHb (LHbm) bilaterally. After injections of an anterograde tracer, biotinylated dextranamine (BDA) in the LHbl, a small number of labeled axons were distributed bilaterally in the rostral and caudal levels of Vmes, where some labeled axonal boutons contacted the cell body of rostral and caudal levels of Vmes neurons bilaterally. After the BDA injection into the LHbm, however, no axons were labeled bilaterally in the rostral and caudal levels of Vmes. Therefore, the present study for the first time demonstrated the direct projection from the LHbl to the Vmes and the detailed projection patterns, suggesting that jaw movements are modulated by negative emotions that are signaled by LHbl neurons.

Jaw-opening and -closing premotoneurons in the nucleus of the solitary tract making contacts with laryngeal and pharyngeal afferent terminals in rats.

This study clarified the neural mechanisms underlying jaw movements in pharyngolaryngeal reflexes such as swallowing in rats. After retrograde tracer injections into the ventromedial division (Vmovm) of the trigeminal motor nucleus (Vmo) containing jaw-opening (JO) motoneurons or into the dorsolateral division (Vmodl) of Vmo containing jaw-closing (JC) motoneurons, JO and JC premotoneurons were labeled with an ipsilateral predominance in the medial and intermediate subnuclei of the rostrocaudal middle two-thirds of the nucleus of the solitary tract (Sol); JC premotoneurons were also in the lateral subnucleus of Sol. After anterograde tracer injections into the Sol, axons were labeled with an ipsilateral predominance in the Vmovm and Vmodl, prominently in the ipsilateral Vmovm. After transganglionic tracer applications to the superior laryngeal nerve (SLN) or the cervical trunk of the glossopharyngeal nerve (GpN-ct), labeled afferents were seen in the medial, intermediate, lateral and interstitial subnuclei of Sol at the rostral three-fourths of Sol, indicating considerable overlap with the JO and JC premotoneurons in the Sol. Double labeling experiments demonstrated contacts between the afferent terminals and the JO and JC premotoneurons. The present study has for the first time revealed the differential distribution of JO and JC premotoneurons in the Sol and features of their projections from the Sol, as well as their connections with SLN and GpN-ct afferent inputs. The JO and JC premotoneurons in the Sol may play an important role in generation and organization of jaw movements in pharyngolaryngeal reflexes evoked by SLN and GpN-ct inputs, such as swallowing.

Cortical area inducing chewing-like rhythmical jaw movements and its connections with thalamic nuclei in guinea pigs.

Repetitive electrical stimulation to the cortical masticatory areas (CMA) evokes rhythmical jaw movements (RJM), whose patterns vary depending on the stimulation site, in various species. In guinea pigs, although alternating bilateral jaw movements are usually seen during natural chewing, it is still unclear which cortical areas are responsible for chewing-like RJM. To address this issue, we first defined the cortical areas inducing chewing-like RJM by intracortical microstimulation. Stimulation of the most lateral area of the CMA, the granular cortex, induced chewing-like RJM, but from the region medial to this area, simple vertical RJM were induced. Subsequently, to reveal the properties of these two areas in the CMA, the connections between the CMA and the dorsal thalamus were examined by neuronal tract-tracing techniques. The area inducing chewing-like RJM possessed strong reciprocal connections, mainly with the medial part of the ventral posteromedial nucleus, which is the sensory-relay thalamus. On the other hand, the simple vertical RJM-inducing area had reciprocal connections with the motor thalamus. The present study suggests that the CMA inducing chewing-like RJM is different from the CMA inducing simple vertical RJM, and plays a role in cortically induced chewing-like RJM under the influence of the sensory thalamus in guinea pigs.

Thalamic afferent and efferent connectivity to cerebral cortical areas with direct projections to identified subgroups of trigeminal premotoneurons in the rat.

The roles of supramedullary brain mechanisms involved in the control of jaw movements are not fully understood. To address this issue, a series of retrograde (Fluorogold, FG) and anterograde (biotinylated dextran amine, BDA) tract-tracing studies were done in rats. At first, we identified projection patterns from defined sensorimotor cortical areas to subgroups of trigeminal premotoneurons that are located in defined brainstem areas. Focal injections of FG into these brainstem areas revealed that the rostralmost part of lateral agranular cortex (rmost-Agl), the rostralmost part of medial agranular cortex (rmost-Agm), and the rostralmost part of primary somatosensory cortex (rmost-S1) preferentially project to brainstem areas containing jaw-closing premotoneurons, jaw-opening premotoneurons and a mixture of both types of premotoneurons, respectively. The thalamic reciprocal connectivities to rmost-Agl, rmost-Agm, and rmost-S1 were then investigated following cortical injections of FG or BDA. We found many retrogradely FG-labeled neurons and large numbers of axons and terminals labeled anterogradely with BDA in the dorsal thalamus mainly on the side ipsilateral to the injection sites. The rmost-Agl had strong connections with the ventral lateral nucleus (VL), ventromedial nucleus (VM), parafascicular nucleus, and posterior nucleus (Po); the rmost-Agm with the ventral anterior nucleus, VL, VM, central lateral nucleus, paracentral nucleus, central medial nucleus, mediodorsal nucleus and Po; and the rmost-S1 with the ventral posteromedial nucleus and Po. The present results suggest that the descending multiple pathways from the cerebral cortex to jaw-closing and jaw-opening premotoneurons have unique functional roles in jaw movement motor control.