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To visualize and characterize the unsteady properties of the wake trailing behind a wind turbine, we propose a novel numerical methodology in this study. Through a wind-tunnel experiment using a smoke generator, we succeeded in visualizing a compact-type small-scale wind turbine wake using continuous scalar plumes from a single point source. Next, to simulate the above wind-tunnel experiment, we proposed a method using the passive scalar advection–diffusion equation based on a high-fidelity large-eddy simulation (LES). The actuator-line method (ALM) was adopted for the wind turbine model. We succeeded in qualitatively reproducing the wake visualization experiment in the wind tunnel described above and verified the effectiveness of the proposed numerical visualization method. To evaluate the characteristics of wakes generated by wind turbines in more detail, we conducted a quantitative comparison using a disk-shaped volume source with the same size as the swept area, set behind the wind turbine model. The results indicated that the non-dimensional time-averaged passive scalar profile in the near- and far-wake regions qualitatively matched the shape of the stream-wise velocity profile, despite having opposite signs. In other words, it was shown that if a disk-shaped volume source with the same size as the swept area is placed just behind the wind turbine, it is possible to accurately predict the behavior of the wind turbine wake. Finally, to validate the proposed method for wind farm wake management, we performed a visualization of wake flows in a virtual offshore wind farm consisting of 12 wind turbines with short separation distances. Through detailed comparison of two types of numerical results with different wind directions, we showed that the proposed method can effectively demonstrate the range of spatial influence of the wakes formed by the wind turbine with special attention.

The purpose of this research was to compare insertion techniques and effects on mechanical and clinical parameters between 2 types of miniscrews.Forty-four consecutive patients whose orthodontic treatment involved the use of miniscrews (miniscrew A [MA] and miniscrew B [MB]) for anchorage were included in this study. Miniscrews were placed with predrilling or self-drilling; peak maximum insertion torque (MIT) and Periotest values were measured. Cone-beam computed tomography was performed after the insertion of miniscrews and root proximity determination; cortical bone thickness was also analyzed. Periotest values were measured after the application of orthodontic force.Self-drilling produced higher Periotest values (P 0.01) for MA and higher MIT (P 0.01) for MB with closer root proximity (P 0.05). MB had higher MIT and Periotest values with drilling compared with MA (P 0.05); MB also showed closer root proximity (P 0.05). Successful miniscrews had lower MIT (P 0.05) for MB and lower Periotest values (P 0.01) for both MA and MB, with significantly more distant root proximity (P 0.01). Self-drilling produced higher Periotest values at the time of placement (P 0.01) and after 4 weeks (P 0.05) in MA. Drilling produced higher Periotest values for MB at the time of placement (P 0.05). MIT had positive correlations with Periotest values for MB with self-drilling (P 0.01) and with root proximity for MA with drilling (P 0.01). Periotest values had negative correlations with root proximity for MA and the MB group with drilling (P 0.01).For miniscrews with larger diameters, higher MIT may result in more mobility (higher Periotest values). Drilling can avoid root contact and enhance primary stability, thus producing lower Periotest values.

Aim and objective: To present an Apert syndrome patient with midfacial growth deficiency treated with Le Fort III distraction osteogenesis and subsequent two-jaw surgery. Background: Apert syndrome is expressed as a severe and irregular craniosynostosis, midfacial hypoplasia, and symmetric syndactyly in the fingers and toes. For craniosynostosis syndromes, treatment planning is complex due to the disharmony between facial profile and occlusion. Case description: A 4-year-and-5-month-old boy, diagnosed with Apert syndrome, showed a concave profile accompanied with midfacial hypoplasia, moderate exorbitism, a reversed occlusion of −10.0 mm, an anterior open bite of −5.0 mm, and skeletal class III jaw-base relationship. The patient, aged 15 years and 4 months, underwent a Le Fort III osteotomy, and subsequent osteodistraction was performed via a rigid external distraction (RED) device. His midfacial bone was advanced by approximately 7.0 mm. One year after the distraction, preoperative treatment with 0.018-in preadjusted edgewise appliances was initiated. Two-jaw surgery with a Le Fort I osteotomy and bilateral sagittal split ramus osteotomy was performed after 42 months of preoperative orthodontic treatment. At the age of 20 years and 9 months, his facial profile dramatically changed to a straight profile, and an acceptable occlusion with an adequate interincisal relationship was obtained. A functional occlusion with an excellent facial profile was maintained throughout the 2-year retention period, although the upper dental arch width was slightly decreased, resulting in the recurrence of the left posterior crossbite. Conclusion: Our report indicates the necessity of long-term follow-up in patients with craniosynostosis because of syndrome-specific growth and methodologically induced relapse. Clinical significance: The two-stage operation combining early distraction osteogenesis and postgrowth orthognathic surgery proves to be an effective therapy for correcting midfacial hypoplasia and skeletal mandibular protrusion caused by Apert syndrome.

Objectives To determine the accuracy of three-dimensional (3D) printed models fabricated from cone-beam computed tomography (CBCT) scans of human mandibular dry skulls in comparison with models derived from intraoral scanner (IOS) data. Materials and Methods Six human mandibular dry skulls were scanned by IOS and CBCT. Digital models (DMs) constructed from the IOS and CBCT data were fabricated physically using a 3D printer. The width and thickness of individual teeth and intercanine and molar widths were measured using a digital caliper. The accuracy of the DMs was compared between IOS and CBCT. Paired t-tests were used for intergroup comparisons. Results All intraclass correlation coefficient values for the three measurements (mesial-distal, buccal-lingual, width) exceeded 0.9. For the mandibular teeth, there were significant discrepancies in model accuracy between the IOS (average discrepancies of 0.18 ± 0.08 mm and 0.16 ± 0.12 mm for width and thickness, respectively) and CBCT (0.28 ± 0.07 mm for width, 0.37 ± 0.2 mm for thickness; P < .01). Intercanine (P = .38) and molar widths (P = .41) showed no significant difference between groups. Conclusions There was a statistically significant difference in the accuracy of DMs obtained from CBCT and IOS; however, this did not seem to result in any important clinical difference. CBCT could be routinely used as an orthodontic diagnostic tool and for appliance construction.

Background/purpose: Primary stability of orthodontic miniscrew system is of great importance in maintaining stable anchorage during a treatment period. Thus, this study aimed to examine whether the thread shape of orthodontic miniscrew had an effect on its mechanical stability in bone. Materials and methods: Three different types of miniscrews (type A and B with a regular thread shape; type C with a novel thread shape) were placed in artificial bone block with different artificial cortical bone thickness of 1.5, 2.0 and 3.0 mm. Values of maximum insertion torque (MIT), removal torque (RT), torque ratio (TR), screw mobility, static stiffness (K), dynamic stiffness (K∗) and energy dissipation (tan δ) ability were assessed for each miniscrew system. Results: The MIT, RT, TR and K of type C miniscrew were significantly greater than those of type A and B miniscrews when the miniscrews were placed in the thinner artificial bone. Furthermore, the TR value of type C miniscrew was more than 1, indicating the MRT value was larger than the MIT value in the novel miniscrew. The values of K∗ and tan δ were almost similar among the three types of miniscrews. Conclusion: The miniscrew with a novel thread shape showed a higher initial stability compared to those with a regular thread shape. Thus, in order to obtain a sufficient initial stability, it is important to select the type of screw thread that is appropriate for the thickness of the cortical bone.

Mutations in PHEX cause X-linked hypophosphatemia (XLH), a form of hypophosphatemic rickets. Hyp ( Phex mutant) mice recapitulate the XLH phenotype. Dental disorders are prevalent in individuals with XLH; however, underlying dentoalveolar defects remain incompletely understood. We analyzed Hyp mouse dentoalveolar defects at 42 and 90 d postnatal to comparatively define effects of XLH on dental formation and function. Phex mRNA was expressed by odontoblasts (dentin), osteocytes (bone), and cementocytes (cellular cementum) in wild-type (WT) mice. Enamel density was unaffected, though enamel volume was significantly reduced in Hyp mice. Dentin defects in Hyp molars were indicated histologically by wide predentin, thin dentin, and extensive interglobular dentin, confirming micro–computed tomography (micro-CT) findings of reduced dentin volume and density. Acellular cementum was thin and showed periodontal ligament detachment. Mechanical testing indicated dramatically altered periodontal mechanical properties in Hyp versus WT mice. Hyp mandibles demonstrated expanded alveolar bone with accumulation of osteoid, and micro-CT confirmed decreased bone volume fraction and alveolar bone density. Cellular cementum area was significantly increased in Hyp versus WT molars owing to accumulation of hypomineralized cementoid. Histology, scanning electron microscopy, and nanoindentation revealed hypomineralized “halos” surrounding Hyp cementocyte and osteocyte lacunae. Three-dimensional micro-CT analyses confirmed larger cementocyte/osteocyte lacunae and significantly reduced perilacunar mineral density. While long bone and alveolar bone osteocytes in Hyp mice overexpressed fibroblast growth factor 23 ( Fgf23), its expression in molars was much lower, with cementocyte Fgf23 expression particularly low. Expression and distribution of other selected markers were disturbed in Hyp versus WT long bone, alveolar bone, and cementum, including osteocyte/cementocyte marker dentin matrix protein 1 ( Dmp1). This study reports for the first time a quantitative analysis of the Hyp mouse dentoalveolar phenotype, including all mineralized tissues. Novel insights into cellular cementum provide evidence for a role for cementocytes in perilacunar mineralization and cementum biology.

Atmospheric-pressure plasma chemical vaporization machining (AP-PCVM) using helium as a carrier gas to achieve uniform thickness of quartz crystal wafers has been practically applied to the mass production of high-performance crystal units. However, because of the high cost and limited supply of helium, the proposed use of argon instead of helium has garnered interest. Argon plasma at atmospheric pressure tends to become unstable, but it has been reported that the addition of a small amount of ethanol makes it possible to generate a stable and uniformly spread glow discharge atmospheric-pressure argon plasma. In this study, an AP-PCVM experiment was conducted on quartz crystal wafers using an argon-ethanol mixture gas as the carrier gas and CF4 and O2 as process gases. A uniform, stable glow discharge plasma was generated by applying the ethanol-containing process gas, and satisfactory removal characteristics for correcting the thickness deviation of a quartz crystal wafer were obtained.

One-third of postmenopausal women experience at least one osteoporotic bone fracture in their lifetime that occurs spontaneously or from low-impact events. However, osteoporosis-associated jaw bone fractures are extremely rare. It was also observed that jaw bone marrow stem cells (BMSCs) have a higher capacity to form mineralized tissues than limb BMSCs. At present, the underlying causes and mechanisms of variations between jaw bone and limb bone during postmenopause are largely unknown. Thus, the objective of the current study was to examine the site-specific effects of estrogen deficiency using comprehensive analysis of bone quantity and quality, and its association with characterization of cellular components of bone. Nine rats (female, 6 months old) for each bilateral sham and ovariectomy (OVX) surgery were obtained and maintained for 2 months after surgery. A hemi-mandible and a femur from each rat were characterized for parameters of volume, mineral density, cortical and trabecular morphology, and static and dynamic mechanical analysis. Another set of 5 rats (female, 9 months old) was obtained for assays of BMSCs. Following cytometry to identify BMSCs, bioassays for proliferation, and osteogenic, adipogenic, chondrogenic differentiation, and cell mitochondrial stress tests were performed. In addition, mRNA expression of BMSCs was analyzed. OVX decreased bone quantity and quality (mineral content, morphology, and energy dissipation) of femur while those of mandible were not influenced. Cellular assays demonstrated that mandible BMSCs showed greater differentiation than femur BMSCs. Gene ontology pathway analysis indicated that the mandibular BMSCs showed most significant differential expression of genes in the regulatory pathways of osteoblast differentiation, SMAD signaling, cartilage development, and glucose transmembrane transporter activity. These findings suggested that active mandibular BMSCs maintain bone formation and mineralization by balancing the rapid bone resorption caused by estrogen deficiency. These characteristics likely help reduce the risk of osteoporotic fracture in postmenopausal jawbone.

We aimed to elucidate stress distribution in miniscrews and the surrounding bone when miniscrews inserted at different depths were implanted vertically or obliquely. The distributions of the equivalent stress on the screw surface and the minimum principal stress in the surrounding bone were calculated using finite element models. When the miniscrews were inserted vertically and obliquely, screw head displacement, greatest equivalent stress on the miniscrew surface, and absolute value of minimum principal stresses in the surrounding bone decreased with increasing insertion depth. Stresses in the obliquely inserted miniscrew with upward traction were smaller than in other insertion conditions, irrespective of insertion depth. With the application of orthodontic force, stress distribution around the miniscrew and surrounding bone is closely related to the insertion depth and insertion angle, which mutually affect each other. In particular, the obliquely inserted miniscrew with upward traction might be the most secure against screw failure and fracture.

Aim and objective To present a growing patient with unilateral mandibular hypoplasia and microtia involved in the first and second branchial arch syndrome (FSBAS) treated with functional appliance. Background The FSBAS comprises several developmental facial hypoplasia in ear and maxillofacial bones, resulting in hemifacial microsomia. Treatment for hemifacial microsomia varies greatly depending on the grade of mandibular deformities. Functional appliance treatment during growth period is available for mild to moderate mandibular deformities. However, there are few reports of hemifacial microsomia treated with functional appliance. Case description The patient, an 8-year-and-5-month-old girl, had a chief complaint of mandibular deviation. She had been diagnosed with the FSBAS at birth. Her facial profile was straight and panoramic radiograph indicated that the mandibular ramal height of the affected side was about 60.4% compared to the unaffected side. The occlusal cant was 6°, and the right maxilla and mandible showed severe growth deficiency. At the age of 10 years, functional appliance with expander was used; for 2 years 6 months, the maxillomandibular growth was controlled and from panoramic radiograph, the ramus height of the affected side was increased to 65.0% compared to the unaffected left mandibular ramus. At the age of 12 years and 8 months, multibracket treatment was initiated. After 32 months of active treatment, proper occlusion with functional Class I canine and molar relationships was obtained, although facial asymmetry associated with the difference of ramus heights still existed. The resulting occlusion was stable during 1.5-year retention period. Conclusion Our results indicated the importance of orthopedic treatment during growth period in the patient with hemifacial microsomia involving the FSBAS. Clinical significance This report proposes an efficacy of conventional orthodontic treatment for growing patients with hemifacial microsomia involved in the FSBAS.

Objective: To understand the actual condition of orthodontic treatment in team care for patients with syndromic craniosynostosis (SCS) in Japan. Design: A nationwide collaborative survey. Setting: Twenty-four orthodontic clinics in Japan. Patients: A total of 246 patients with SCS. Main Outcome Measure: Treatment history was examined based on orthodontic records using common survey sheets. Results: Most patients first visited the orthodontic clinic in the deciduous or mixed dentition phase. Midface advancement was performed without visiting the orthodontic clinic in about a quarter of the patients, and more than a half of the patients underwent “surgery-first” midface advancement. First-phase orthodontic treatment was carried out in about a half of the patients, and maxillary expansion and protraction were performed. Tooth extraction was required in about two-thirds of patients, and the extraction of maxillary teeth was required in most patients. Tooth abnormalities were found in 37.8% of patients, and abnormalities of maxillary molars were frequently (58.3%) found in patients who had undergone midface surgery below the age of 6 years. Conclusions: Many patients underwent “surgery-first” midface advancement, and visiting the orthodontic clinic at least before advancement was considered desirable. First-phase orthodontic treatment should be performed considering the burden of care. Midface advancement below the age of 6 years had a high risk of injury to the maxillary molars. This survey is considered useful for improving orthodontic treatment in team care of patients with SCS.

Objectives: To evaluate the effectiveness of pre-surgical nasoalveolar molding (PNAM) in patients with unilateral cleft lip nasal deformities. Methods: This was a retrospective study involving 29 patients with unilateral cleft lip and palate defects, of whom 13 were treated with palatal devices with nasal stents (PNAM group) and 16 were treated with palatal devices without nasal stents or surgical tapes (control group). Submental oblique photographs and orthodontic models were longitudinally obtained at the initial visit (T1) and immediately before (T2) and after cheiloplasty (T3). Asymmetry of the external nose, degree of columellar shifting, nasal tip/ala nose ratio, nasal base angle, interalveolar gap, and the sagittal difference in the alveolar gap were measured. The study was conducted in the Orthodontic Clinic at Tokushima University Hospital, Tokushima, Japan between 1997 and 2012. Results: At T1, there were no significant intergroup differences in the first 4 asymmetry parameters. At T2, the PNAM group showed a significant improvement in all values compared to the control group. At T3, the PNAM group showed significant improvement in nasal asymmetry and columellar shifting. Model analysis showed significantly greater changes in the inter-alveolar gap and the sagittal difference of the alveolar cleft gap from T1 to T2 in the PNAM group. Conclusion: The use of PNAM is indispensable for pre-surgical orthodontic treatment at the early postnatal age. Saudi Med J 2018; Vol. 39 (2): 169-178 doi: 10.15537/smj.2018.2.21020 How to cite this article: Kinouchi N, Horiuchi S, Yasue A, Kuroda Y, Kawai N, Watanabe K,et al .Effectiveness of presurgical nasoalveolar molding therapy on unilateral cleft lip nasal deformity. Saudi Med J . 2018 Feb;39(2):169-178. doi: 10.15537/smj.2018.2.21020.

Temporary anchorage devices (TADs) have been widely used as one of the most efficient anchorage devices in orthodontic field in the last decade. TADs could be used to control anchorage in all anteroposterior (A-P), vertical, and transverse dimensions. In this chapter, we provide some information with regard to the effectiveness of TADs in controlling the anchorage in A-P dimension during distalization of the entire arch in nonextraction cases.

Summary Background/Objectives Primary stability is required for successful use of microscrew. This study investigated correlations among biomechanical, morphological, and clinical values in relationship to root contact and different placement locations. Materials/Methods Thirty-three microscrews were placed between the molars (n = 18) or in the body of the mandible (n = 15) in three pigs. Insertion torque, Periotest, resonance frequency analysis (RFA), and static and dynamic stiffness were measured. Cone beam computed tomography was performed before and after the insertion of microscrews. Interproximal microscrews were divided into root contacted microscrews (n = 9) and non-root contact microscrews (n = 9). Factorial analysis of variance was conducted, with significance set at P < 0.05. Results A significant difference was observed between bodily and root contacted microscrews in Periotest, RFA, static and dynamic stiffness, Tanδ, and bone density (RFA, P = 0.045; all others, P < 0.001). A significant difference was observed between bodily and non-root contact microscrews in Periotest, RFA, and bone density (RFA, P = 0.025; all others, P < 0.001). A significant difference was observed in static (P = 0.01) and dynamic (P = 0.038) stiffness between microscrews with and without contact. Dynamic stiffness (P = 0.02) and Tanδ (P = 0.03) showed significant correlations with Periotest results only in bodily microscrews. Limitations Since a pig bone was used, some differences in the quality and quantity of the bone might be observed between humans. Conclusions/Implications Stiffness values distinguished between microscrews with and without contact. Periotest and RFA results indicated that bodily microscrews were more stable than interproximal microscrews. Periotest and RFA may be useful with large, microscrews and/or in thick cortical bone, but further investigation is required to determine the stability of interproximal microscrews.

Background Miniscrew has been widely used as an absolute anchorage in orthodontic treatment. Types of miniscrew with different diameter, length, shape, and thread dimensions may have a substantial effect on mechanical stability of the miniscrew system. Thus, the objective of this study was to evaluate miniscrew type-dependent mechanical stability to assess mechanical properties of miniscrew systems in various thickness of artificial bone block using different measurement tools. Methods Two types of miniscrews (15 Tomas and 15 AbsoAnchor) were placed in artificial bone block with different thickness of 1.5, 2.0, 3.0 mm. Values of maximum insertion torque, removal torque, Periotest, implant stability quotient, static stiffness, dynamic stiffness, and energy dissipation ability were assessed for each miniscrew system. Findings The maximum insertion torque, removal torque, implant stability quotient, static and dynamic stiffness values significantly increased when the miniscrews were placed in thicker bone block while Periotest values decreased. The static stiffness, Periotest and implant stability quotient values were significantly correlated each other and also with other mechanical properties (p 0.35). However, the slopes of some correlations and absolute values of measurement were significantly different dependent on the miniscrew types (p Interpretation The current findings suggest that miniscrew type-dependent calibrations are required to estimate mechanical stability of the miniscrew systems despite the utilization of same measurement tool.

Aims.Public stigma alters attitudes towards people with mental illness, and is a particular concern for young people since most mental health problems occur in adolescence and young adulthood. However, little is known about the long-term effects of repeated filmed social contact (FSC) on reducing mental health-related stigma among young adults in the general population, compared with self-instructional Internet search (INS) and control interventions.Methods.This study is a parallel-group randomised controlled trial over 12 months conducted in Tokyo, Japan. A total of 259 university students (male n = 150, mean age = 20.0 years, s.d. = 1.2) were recruited from 20 colleges and universities between November 2013 and July 2014, without being provided information about the mental health-related survey or trial. Participants were assigned to one of three groups before completion of the baseline survey (FSC/INS/control = 89/83/87). The FSC group received a computer-based 30-min social contact film with general mental health education and five follow-up web-based FSCs at 2-month intervals. The INS group undertook a 30-min search for mental health-related information with five follow-up web-based reminders for self-instructional searches at 2-month intervals. The control group played PC games and had no follow-up intervention. The main outcome measures were the future (intended behaviour) domain of the Reported and Intended Behaviour Scale at 12 months after the intervention. Analysis was conducted in September 2015.Results.At the 12-month follow-up, 218 participants completed the survey (84.1%, 75:70:73). The FSC group showed the greatest change at the 12-month follow-up (FSC: mean change 2.11 [95% CI 1.49, 2.73], INS: 1.04 [0.29, 1.80], control: 0.71 [0.09, 1.33]; FSC v. INS p = 0.037, FSC v. controls p = 0.004). No adverse events were reported during the follow-up period.Conclusions.FSC was more successful in reducing stigma at 12 months after intervention than INS or control interventions. FSC could be used to reduce stigma in educational lectures and anti-stigma campaigns targeted at young people.Study registration.This study is registered at UMIN-CTR (No. UMIN000012239).

AIM Mental-health-related stigma affects help-seeking behavior and service utilization among young people. Whether mental-health-related stigma is different or correlated between parents and their children is unknown. It is also unknown whether the name change of schizophrenia in 2002 has had long-term effects on reducing stigma for adults in the general population. METHODS We recruited 143 parent-child pairs (mean ages [SD]: 51.5 [3.6] and 21.2 [1.2] years, respectively) to complete self-report questionnaires regarding mental-health-related stigma and experience. We also assessed negative stereotypes for three psychiatric disease names (old and new names of schizophrenia, and depression), and for diabetes mellitus as a physical illness comparison. The questionnaires also asked respondents to identify the old and new names of schizophrenia and dementia, respectively, among 10 names for mental and physical illnesses and conditions. RESULTS Parents showed lower stigma levels toward mental illness and diabetes mellitus, but similar or greater stigma levels toward schizophrenia, compared with their children. Stigma levels toward mental illness in parents and their children were significantly correlated. The rate of correct identification of the old and new names for schizophrenia was higher in parents than in their children (64.7% vs 41.4%, P < 0.001). Parents who responded correctly endorsed more negative stereotypes toward the new name of schizophrenia compared with those who responded incorrectly (P = 0.049). CONCLUSION The present findings suggest that stigma toward mental illness is shared between family members, and the name change of schizophrenia has effectively reduced stigma levels toward this disorder in adults of various ages.

Postmenopausal osteoporosis causes severe loss of bone quantity and quality in limb bone but has a lesser effect on jaw bone. Thus, the objective of this study was to examine whether ovariectomy (OVX) and mastication alter the regional variation of jaw bone characteristics. Sprague-Dawley female rats (6 months) were given a bilateral OVX or a sham operation (SHAM) (n=10 for each group). After 2 months post-OVX, the hemi-mandible from each rat was dissected. A micro-computed tomography based mean, standard deviation (SD), the lower and upper 5(th) percentile (Low(5) and High(5)) values of tissue mineral density (TMD) histograms were assessed for whole bone (WB), alveolar bone (AB), cortical bone (CB), and trabecular bone (TB) regions. Morphology of TB and periodontal ligament (PDL) was also obtained. Layers of AB were segmented up to 400 μm from the PDL. Mechanical properties at the tissue level were measured by nanoindentation at the same site by a single loading-unloading cycle of indentation in hydration. The AB and TB regions had significantly lower TMD Mean, Low(5), and High(5) but higher SD than the CB region for both sham and OVX groups (p0.06). Estrogen deficiency induced by OVX did not deteriorate bone characteristics including mineral density, morphology, and nanoindentation parameters in rat mandibles. Masticatory loading had an effect on the TMD parameters at the limited region of AB. These results provide insight into why osteoporosis-associated jaw bone fractures are extremely rare.

Background We successfully treated a 37-year-old male who had skeletal open bite with severe amelogenesis imperfecta (AI) with orthodontics, compression osteogenesis, and prosthodontics. Case presentation The patient was diagnosed with severe anterior open bite caused by severe AI. Corticotomy was performed on both buccal and palatal sides of the molar regions, and anchor plates were placed onto the bilateral zygomatic buttress and the center of the hard palate. After corticotomy, posterior maxillary segments were moved 3.5 mm superiorly to correct skeletal open bite with elastic chains. After 8-month, overbite had decreased by 2.0 mm. After further 5 months of prosthodontic preparation, orthodontic appliances were removed, and provisional crowns were set on all teeth. The anterior open bite was corrected, and ideal occlusion with a Class I molar relationship was achieved. The upper first molars were intruded 3.5 mm, resulting in 3.0o counter-clockwise rotation of the mandible. The total active treatment period was 16 months. Acceptable occlusion with a good facial profile was well maintained throughout the 8-year retention period. Conclusions Our results indicate long-term stability after interdisciplinary treatment combining orthodontics, oral surgery, and prosthodontics in a patient with severe anterior open bite and AI.

Osteoporotic fracture has become a major public health problem, and until today, the treatments available are not satisfactory. While there is growing evidence to support the individual treatment of parathyroid hormone (PTH) administration and low-intensity pulsed ultrasound (LIPUS) exposure as respectively systemic and local therapies during osteoporotic fracture healing, their effects have not yet been investigated when introduced concurrently. This study aimed to evaluate the effects of combined treatment with PTH (1-34) and LIPUS on fracture healing in ovariectomized (OVX) rats. Thirty-two, 12-week-old female Sprague-Dawley rats were OVX to induce osteoporosis. After 12 weeks, the rats underwent surgery to create bilateral mid-diaphyseal fractures of proximal tibiae. All animals were randomly divided into 4 groups (n = 8 for each): control group as placebo, PTH group, LIPUS group, and combined group. PTH group had PTH administration at a dose of 30 μg/kg/day for 3 days/week for 6 weeks. LIPUS group received ultrasound 5 days/week for 20 min/day for 6 weeks and combined group had both PTH administration and LIPUS exposure for 6 weeks. Fracture healing was observed weekly by anteroposterior radiography and micro-CT. Five weeks after the fracture, the tibia were harvested to permit histological assessments and at week 6, for mechanical property of the fracture callus. Micro-CT showed that the PTH and combined groups exhibited significantly higher BMD and trabecular bone integrity than control group at weeks 4-6. Radiography, fracture healing score and mean callus area indicated that the combined group revealed better healing processes than the individual groups. Mechanically, bending moment to failure was significantly higher in LIPUS, PTH and combined groups than in control group. These data suggest that the combined treatment of PTH and LIPUS have been shown to accelerate fracture bone healing and enhance bone properties rather than single agent therapy, and may be considered as a treatment remedy for fracture healing in postmenopausal osteoporosis.

Since there is no available serological methods to detect antibodies to ferret coronavirus (FRCoV), an enzyme-linked immunosorbent assay (ELISA) using recombinant partial nucleocapsid (N) proteins of the ferret coronavirus (FRCoV) Yamaguchi-1 strain was developed to establish a serological method for detection of FRCoV infection. Many serum samples collected from ferrets recognized both a.a. 1-179 and a.a. 180-374 of the N protein, but two serum samples did not a.a. 180-374 of the N protein. This different reactivity was also confirmed by immunoblot analysis using the serum from the ferret.Therefore, the a.a. 1-179 of the N protein was used as an ELISA antigen. Serological test was carried out using sera or plasma of ferrets in Japan. Surprisingly, 89% ferrets in Japan had been infected with FRCoV. These results indicated that our established ELISA using a.a. 1-179 of the N protein is useful for detection of antibody to FRCoV for diagnosis and seroepidemiology of FRCoV infection.

Tumor necrosis factor–related apoptosis-inducing ligand (TRAIL) agonists induce tumor-specific apoptosis indicating that they may be an attractive therapeutic strategy against cancers, including multiple myeloma (MM). Osteoclastogenesis is highly induced in MM, which in turn enhances MM growth, thereby forming a vicious cycle between MM tumor expansion and bone destruction. However, the effects of TRAIL on MM-enhanced osteoclastogenesis remain largely unknown. Here, we show that TRAIL induced apoptosis in MM cells, but not in osteoclasts (OCs), and that it rather facilitated receptor activator of NF-kB ligand–induced osteoclastogenesis along with upregulation of cellular FLICE inhibitory protein (c-FLIP). TRAIL did not induce death-inducing signaling complex formation in OCs, but formed secondary complex (complex II) with the phosphorylation of transforming growth factor b–activated kinase-1 (TAK1), and thus activated NF-kB signaling. c-FLIP knockdown abolished complex II formation, thus permitting TRAIL induction of OC cell death. The TAK1 inhibitor LLZ1640-2 abrogated the TRAIL-induced c-FLIP upregulation and NF-kB activation, and triggered TRAIL-induced caspase-8 activation and cell death in OCs. Interestingly, the TRAIL-induced caspase-8 activation caused enzymatic degradation of the transcription factor Sp1 to noticeably reduce c-FLIP expression, which further sensitized OCs to TRAIL-induced apoptosis. Furthermore, the TAK1 inhibition induced antiosteoclastogenic activity by TRAIL even in cocultures with MM cells while potentiating TRAIL’s anti-MM effects. These results demonstrated that osteoclastic lineage cells use TRAIL for their differentiation and activation through tilting caspase-8–dependent apoptosis toward NF-kB activation, and that TAK1 inhibition subverts TRAIL-mediated NF-kB activation to resume TRAIL-induced apoptosis in OCs while further enhancing MM cell death in combination with TRAIL.

Pim-2 kinase is overexpressed in multiple myeloma (MM) cells to enhance their growth and survival, and regarded as a novel therapeutic target in MM. However, the impact of Pim-2 inhibition on bone disease in MM remains unknown. We demonstrated here that Pim-2 expression was also upregulated in bone marrow stromal cells and MC3T3-E1 preosteoblastic cells in the presence of cytokines known as the inhibitors of osteoblastogenesis in MM, including interleukin-3 (IL-3), IL-7, tumor necrosis factor-α, transforming growth factor-β (TGF-β) and activin A, as well as MM cell conditioned media. The enforced expression of Pim-2 abrogated in vitro osteoblastogenesis by BMP-2, which suggested Pim-2 as a negative regulator for osteoblastogenesis. Treatment with Pim-2 short-interference RNA as well as the Pim inhibitor SMI-16a successfully restored osteoblastogenesis suppressed by all the above inhibitory factors and MM cells. The SMI-16a treatment potentiated BMP-2-mediated anabolic signaling while suppressing TGF-β signaling. Furthermore, treatment with the newly synthesized thiazolidine-2,4-dione congener, 12a-OH, as well as its prototypic SMI-16a effectively prevented bone destruction while suppressing MM tumor growth in MM animal models. Thus, Pim-2 may have a pivotal role in tumor progression and bone loss in MM, and Pim-2 inhibition may become an important therapeutic strategy to target the MM cell-bone marrow interaction.

Aim The Reported and Intended Behaviour Scale (RIBS) was developed in the UK to measure mental health-related behavior. The current study aimed to evaluate the applicability, and reliability of a Japanese version of the RIBS (RIBS-J) in a Japanese context, and further examine the construct validity of the RIBS-J. Methods The sample included 224 undergraduate and postgraduate students at a Japanese university. Cronbach's alpha was used to assess internal consistency. Pearson's correlation coefficient was used to examine the divergent validity between the RIBS-J and the Mental Health Knowledge Schedule and the convergent validity between the second subscale of the RIBS-J and Japanese version of the Social Distance Scale. Confirmatory factor analysis assessed the goodness of model fit of the RIBS-J. We also examined test–retest reliability with another undergraduate sample (n = 29). Results Most items exhibited no floor/ceiling effect. High internal consistency (α = 0.83) was reported. The second subscale of the RIBS-J, measuring intended behavior, correlated with the Mental Health Knowledge Schedule (r = 0.33, P

PAX9 is a transcription factor expressed in the tooth mesenchyme during tooth morphogenesis. In Pax9-null mice, tooth development is arrested at the bud stage. In humans, heterozygous mutations in PAX9 have been associated with non-syndromic tooth agenesis, predominantly in the molars. Here, we report 2 novel mutations in the paired domain of PAX9, a three-nucleotide deletion (73-75 delATC) and a missense mutation (C146T), in two unrelated Japanese patients with non-syndromic tooth agenesis. The individual with the 73-75del ATC mutation was missing all maxillary molars and mandibular second and third molars. The individual with the C146T mutation was missing the mandibular central incisors, maxillary second premolars, and first molars, along with all second and third molars. Both mutations affected amino acids that are highly conserved among different species and are critical for DNA binding. When both mutants were transfected to COS7 cells, nuclear localization of PAX9 proteins was not affected. However, reduced expression of the mutant proteins and almost no transcriptional activity of the target BMP4 gene were observed, suggesting haploinsufficiency of PAX9 as the cause of non-syndromic tooth agenesis.

Endoplasmic reticulum (ER) stress is induced in matrix-producing osteoblasts and plays an essential role in osteoblastogenesis. Although the bone anabolic activity of proteasome inhibitors has been demonstrated, the roles of ER stress induced by proteasome inhibition in osteoblastogenesis remain largely unknown. Here we show that bortezomib translationally increases protein levels of activating transcription factor 4 (ATF4), a downstream mediator of ER stress, in bone marrow stromal cells and MC3T3-E1 preosteoblastic cells. The suppression of ATF4 expression by siRNA abrogated osteocalcin expression and mineralized nodule formation by MC3T3-E1 cells induced by bortezomib, indicating a critical role for ATF4 in bortezomib-mediated osteoblastogenesis. However, bortezomib at 20 nM or higher abolished the mineralized nodule formation along with reductions in the expression of osteoblastogenesis mediators β-catenin and Osterix. Furthermore, at 50 nM, bortezomib induced the expression of C/EBP homologous protein (CHOP), suggesting activation of the ATF4-CHOP pro-apoptotic pathway. These results suggest that a low dose of bortezomib induces osteogenic activity, but that, in contrast, excessive ER stress caused by bortezomib at higher doses hampers osteoblastogenesis. Therefore, dosing schedules for proteasome inhibitors warrant further study to maximize anabolic actions without compromising anti-MM activity in patients with multiple myeloma (MM).

Cancer stem cells have been proposed to be responsible for tumorigenesis and recurrence in various neoplastic diseases, including multiple myeloma (MM). We have previously reported that MM cells specifically express HLA class I at high levels and that single-chain Fv diabody against this molecule markedly induces MM cell death. Here we investigated the effect of a new diabody (C3B3) on cancer stem cell-like side population (SP) cells. SP fraction of MM cells highly expressed ABCG2 and exhibited resistance to chemotherapeutic agents; however, C3B3 induced cytotoxicity in both SP cells and main population (MP) cells to a similar extent. Moreover, C3B3 suppressed colony formation and tumorigenesis of SP cells in vitro and in vivo. Crosslinking of HLA class I by C3B3 mediated disruption of lipid rafts and actin aggregation, which led to inhibition of gene expression of β-catenin and pluripotency-associated transcription factors such as Sox2, Oct3/4 and Nanog. Conversely, knockdown of Sox2 and Oct3/4 mRNA reduced the proportion of SP cells, suggesting that these factors are essential in maintenance of SP fraction in MM cells. Thus, our findings reveal that immunotherapeutic approach by engineered antibodies can overcome drug resistance, and provide a new basis for development of cancer stem cell-targeted therapy.

We investigated whether advanced parental age and assisted reproductive technology (ART) are risk factors in autism spectrum disorders (ASDs), attention deficit hyperactivity disorder (ADHD), and Tourette syndrome (TS). Clinical charts of Japanese outpatients with ASD (n = 552), ADHD (n = 87), and TS (n = 123) were reviewed. Parental age of individuals with ASD, ADHD, or TS was compared with parental age in the general population (GP) of Tokyo after adjusting for year of birth. Paternal and maternal ages were significantly higher in persons with ASD and ADHD, but not those with TS. In final steps of stepwise logistic regression analysis, both maternal and paternal age were associated with ASD after controlling for the other parent's age, gender, and birth order. In cases where the presence or absence of ART could be ascertained (ASD n = 467; ADHD n = 64; TS n = 83), the rate of ART in cases of persons with ASD (4.5%) was 1.8 times the frequency expected in the GP, while ART was not present in cases of persons with ADHD and TS. These preliminary results remain tentative pending replication with larger, community-based samples.

A 6-year-old boy, diagnosed with Crouzon syndrome, had moderate exorbitism, a concave profile, an anterior crossbite of -4.0 mm, and a skeletal Class III jaw-base relationship caused by midfacial hypoplasia. At age 8 years 9 months, a LeFort III osteotomy was performed, and distraction osteogenesis was immediately started with the rigid external distractor system. The midface was advanced approximately 10.0 mm for 6 days, including overcorrection. After the distraction, a reverse headgear was used for 6 years to prevent relapse and to accelerate expected growth. At age 16 years 5 months, after extraction of the maxillary first premolars and mandibular third molars, 0.022-in preadjusted edgewise brackets were placed to treat the edge-to-edge incisor relationship and minor crowding. After 13 months of treatment, the facial profile was significantly improved, and an acceptable occlusion was achieved. During the 9-year observation period after the distraction, acceptable facial growth occurred, and no relapse of the maxillary advancement was observed. However, syndrome-specific growth and methodologically induced relapse should be considered when planning a LeFort III distraction in children for the treatment of Crouzon syndrome.