Virtually-Planned Orthognathic Surgery Achieves an Accurate Condylar Position.

PURPOSE: Accuracy in orthognathic surgery with virtual planning has been reported, but detailed analysis of accuracy according to anatomic location, including the mandibular condyle, is insufficient. The purpose of this study was to compare the virtual plan and surgical outcomes and analyze the degree and distribution of errors according to each anatomic location. PATIENTS AND METHODS: This retrospective cohort study evaluated skeletal class III patients, treated with bimaxillary surgery. The primary predictor was anatomic locations that consisted of right and left condyles, maxilla, and the distal segment of the mandible. Other variables were age and gender. The primary outcome was surgical accuracy, defined as mean 3-dimensional distance error, mean absolute error, and mean error along the horizontal, vertical, and anteroposterior axes between the virtual plan and surgical outcomes. Landmarks were compared using a computational method based on affine transformation with a 1-time landmark setting. The mean errors were visualized with multidimensional scattergrams. Bivariate and regression statistics were computed. RESULTS: This study included 52 patients, 26 men and 26 women, with a mean age of 21 years and 3 months. The mean 3D distance errors for condylar landmarks, maxillary landmarks, and landmarks on the distal segment of the mandible were 1.03, 1.25, and 2.24 mm, respectively. Condylar landmarks, maxillary landmarks, and the landmarks on the distal segment of the mandible were positioned at 0.49 mm inferior, 0.28 mm anterior, and 1.25 mm inferior, respectively. The landmark errors for the distal segment of the mandible exhibited a wider distribution than those for condylar and maxillary landmarks. CONCLUSIONS: Agreement between the planned and actual outcome aided by virtual surgical planning was highest for the condyles, followed by the maxilla, and the distal segment of the mandible. It is important to consider the tendency for surgical errors in each anatomic location during operations.

Investigation of Postoperative Complications of Intrabony Cystic Lesions in the Oral and Maxillofacial Region.

PURPOSE: The purpose of this study was to identify factors that can complicate the surgical removal of intrabony cysts and any relevant correlations between them. PATIENTS AND METHODS: The medical records of 249 patients who underwent surgical removal of intrabony cysts were retrospectively reviewed. Outcome variables were postoperative complications, infection, and recurrence. Predictor variables were patient age, gender, comorbidities, anatomic location, pathologic diagnosis, preoperative infection, previous marsupialization, and bone graft methods. Logistic regression analysis was performed to identify risk factors of postoperative infection and recurrence. RESULTS: The cystic lesion was smallest in patients who did not receive a bone graft and increased steadily in those who received a xenogeneic bone graft and an autogenous bone graft, in that order. Paresthesia occurred after enucleation of the cystic lesion in 38 cases. Pathologic fractures were observed in 4 cases. There were 59 postoperative infections. The postoperative infection rate was as high as 63.6% in patients who underwent autogenous bone grafting. In contrast, infection rates were as low as 26.8 and 19.5% in those who underwent xenogeneic bone grafting and no bone grafting, respectively. Location of the cystic lesion in the maxilla or mandible affected the infection rate. When cysts were located in the anterior mandible, no postoperative infection occurred. In contrast, the infection rate was highest for cysts in the mandibular ramus, followed by those in the posterior mandible. Cystic lesion recurrence was observed in 7 cases: 5 cases of odontogenic keratocysts, 1 case of periapical cyst, and 1 case of dentigerous cyst. These findings suggest that cyst pathologic identity affects the recurrence rate. Cyst size was meaningfully correlated with recurrence rate. CONCLUSIONS: These results suggest that autogenous bone grafts increase the risk of postoperative infection compared with absence of a bone graft.

TSG-6 secreted by mesenchymal stem cells suppresses immune reactions influenced by BMP-2 through p38 and MEK mitogen-activated protein kinase pathway.

Bone morphogenetic protein 2 (BMP-2) has a critical function in bone and cartilage development and in repairing damaged organs and tissue. However, clinical use of BMP-2 at doses of 0.5-1 mg/ml for orthopedics has been associated with severe postoperative swelling requiring emergency surgical intervention. We determined whether a high concentration of BMP-2 induces inflammatory responses in macrophages and the suppression of osteogenesis in hMSCs. We obtained human periodontal ligament stem cells and bone marrow stem cells from the maxilla, i.e., human mesenchymal stem cells (hMSCs), from the periodontal ligament of extracted third molar teeth and from the bone marrow of the maxilla, respectively. Osteogenic differentiation was measured by alkaline phosphatase activity and alizarin red S staining. Proteins were assessed by flow cytometry, enzyme-linked immunosorbent assay, Western blot and immunocytochemistry. Changes of gene expression were measured by reverse transcription plus the polymerase chain reaction (RT-PCR) and real-time PCR. A high BMP-2 concentration inhibited the early stages of osteogenesis in hMSCs. Co-culturing THP-1 cells (human monocytic cells) with hMSCs reduced the late stages of osteogenesis compared with those seen in hMSCs alone. In addition, high-dose BMP-2 induced the expression of inflammatory cytokines in THP-1 cells and the expression of the anti-inflammatory cytokine tumor-necrosis-factor-α-inducible gene 6 protein (TSG-6) in hMSCs. Consistent with the anti-inflammatory effects of hMSCs when co-cultured with THP-1 cells, interleukin-1ß expression was downregulated by TSG-6 treatment of THP-1 cells. Our findings suggest that a high BMP-2 concentration triggers inflammation that causes inflammatory cytokine release from THP-1 cells, leading to the suppression of osteogenesis, whereas TSG-6 secreted by hMSCs suppresses inflammatory reactions through p38 and ERK in the mitogen-activated protein kinase pathway.

Extensive Surgical Procedures Result in Better Treatment Outcomes for Bisphosphonate-Related Osteonecrosis of the Jaw in Patients With Osteoporosis.

PURPOSE: To identify the risk factors associated with relapse or treatment failure after surgery for bisphosphonate-related osteonecrosis of the jaw (BRONJ) in patients with osteoporosis. PATIENTS AND METHODS: We performed a retrospective cohort study of BRONJ in patients with osteoporosis who had undergone surgical procedures from 2004 to 2016 at the Department of Oral and Maxillofacial Surgery, Seoul National University Dental Hospital. The predictor variables were a set of heterogeneous variables, including demographic (age, gender), anatomic (maxilla or mandible, or both, affected location), clinical (disease stage, etiology, comorbidities, history of intravenous bisphosphonate intake), time (conservative treatment before surgery, bisphosphonate treatment before the development of BRONJ, discontinuation of the drug before surgery, interval to final follow-up, interval to reoperation in the case of relapse or treatment failure), and perioperative variables (type of anesthesia, type of surgical procedures). The primary outcome variable was relapse after surgery that required reoperation (yes vs no). The descriptive and bivariate statistics were computed to assess the relationships between the study variables and the outcome. To determine the risk factors, we conducted a survival analysis using the Cox model. RESULTS: The final sample included 325 subjects with a median age of 75 years, and 97% were women. After surgery, 30% of patients did not completely recuperate and underwent repeat surgery. The interval from the first surgery to reoperation ranged from 10 days to 5.6 years. Relapse or treatment failure most often occurred immediately after surgery. The type of surgical procedure and mode of anesthesia were the most important factors in the treatment outcome. A drug holiday did not appear to influence the likelihood of relapse after surgery. CONCLUSIONS: Treatment of BRONJ in patients with osteoporosis might benefit from more careful and extensive surgical procedures rather than curettage performed with the patient under local anesthesia.

Three-Dimensional Computed Tomographic Assessment of Temporomandibular Joint Stability After Orthognathic Surgery.

PURPOSE: Ensuring that the condyle is appropriately positioned and that positional changes are minimal is considered crucial for the temporomandibular joint (TMJ) to function without symptoms after orthognathic surgery. The purposes of this study were to evaluate condylar changes after surgery and to examine the association between these changes and TMJ symptoms. PATIENTS AND METHODS: A retrospective cohort study was conducted in patients with mandibular prognathism who underwent orthognathic surgery. Linear and angular changes in the positioning of the condyle were measured by superimposing 3-dimensional computed tomograms taken before surgery and 3 months after surgery. Clinical symptoms of TMJ pain and sound were recorded at 3, 6, 9, and 12 months after surgery. Possible associations between TMJ symptoms and clinical variables, such as postoperative condylar changes, were investigated using multiple logistic regression analysis. RESULTS: Linear condylar displacement after orthognathic surgery occurred predominantly in the anterior, medial, and inferior directions, with minimal changes (<1 mm) observed. Most angular condylar changes were smaller than 4° and occurred in the inward direction in the axial plane and the posterior direction in the sagittal plane. The best predictor of postoperative TMJ signs and symptoms was the preoperative status of TMJ signs and symptoms. Neither linear nor angular condylar displacement showed a relevant influence on postoperative pain and sound. CONCLUSIONS: Within the ranges of linear (<1 mm) and angular (<4°) condylar displacement noted in this study, displacement was not associated with postoperative TMJ pain and sound.

miR-124 negatively regulates osteogenic differentiation and in vivo bone formation of mesenchymal stem cells.

MicroRNAs are novel key regulators of cellular differentiation. Dlx transcription factors play an important role in osteoblast differentiation, and Dlx5 and Dlx2 are known targets of miR-124. Therefore, in the present study, we investigated the regulatory effects of miR-124 on the osteogenic differentiation and in vivo bone formation of mesenchymal stem cells (MSCs). During osteogenic induction by BMP2, the expression levels of miR-124 were inversely correlated with those of osteogenic differentiation marker genes in human and mouse bone marrow-derived MSCs, MC3T3-E1 cells and C2C12 cells. The overexpression of a miR-124 mimic significantly decreased the expression levels of Dlx5, Dlx3, and Dlx2, whereas the silencing of miR-124 with hairpin inhibitors significantly increased the expression of these Dlx genes. Luciferase reporter assays demonstrated that miR-124 directly targets the 3'UTRs of Dlx3, Dlx5, and Dlx2. The overexpression of a miR-124 mimic suppressed the osteogenic marker gene expression levels, alkaline phosphatase activity and matrix mineralization, which were all significantly increased by the overexpression of a miR-124 inhibitor. When ectopic bone formation was induced by the subcutaneous transplantation of human bone marrow-derived MSCs in nude mice, MSCs overexpressing a miR-124 inhibitor significantly enhanced woven bone formation compared with control MSCs. However, MSCs overexpressing a miR-124 mimic exhibited increased adipocyte differentiation at the expense of ectopic bone formation. These results suggest that miR-124 is a negative regulator of osteogenic differentiation and in vivo bone formation and that the targeting of Dlx5, Dlx3, and Dlx2 genes partly contributes to this inhibitory effect exerted by miR-124.

Identification of tendon stem/progenitor cells and the role of the extracellular matrix in their niche.

The repair of injured tendons remains a great challenge, largely owing to a lack of in-depth characterization of tendon cells and their precursors. We show that human and mouse tendons harbor a unique cell population, termed tendon stem/progenitor cells (TSPCs), that has universal stem cell characteristics such as clonogenicity, multipotency and self-renewal capacity. The isolated TSPCs could regenerate tendon-like tissues after extended expansion in vitro and transplantation in vivo. Moreover, we show that TSPCs reside within a unique niche predominantly comprised of an extracellular matrix, and we identify biglycan (Bgn) and fibromodulin (Fmod) as two critical components that organize this niche. Depletion of Bgn and Fmod affects the differentiation of TSPCs by modulating bone morphogenetic protein signaling and impairs tendon formation in vivo. Our results, while offering new insights into the biology of tendon cells, may assist in future strategies to treat tendon diseases.

Cpne7 deficiency induces cellular senescence and premature aging of dental pulp.

Once tooth development is complete, odontoblasts and their progenitor cells in the dental pulp play a major role in protecting tooth vitality from external stresses. Hence, understanding the homeostasis of the mature pulp populations is just as crucial as understanding that of the young, developing ones for managing age-related dentinal damage. Here, it is shown that loss of Cpne7 accelerates cellular senescence in odontoblasts due to oxidative stress and DNA damage accumulation. Thus, in Cpne7-null dental pulp, odontoblast survival is impaired, and aberrant dentin is extensively formed. Intraperitoneal or topical application of CPNE7-derived functional peptide, however, alleviates the DNA damage accumulation and rescues the pathologic dentin phenotype. Notably, a healthy dentin-pulp complex lined with metabolically active odontoblasts is observed in 23-month-old Cpne7-overexpressing transgenic mice. Furthermore, physiologic dentin was regenerated in artificial dentinal defects of Cpne7-overexpressing transgenic mice. Taken together, Cpne7 is indispensable for the maintenance and homeostasis of odontoblasts, while promoting odontoblastic differentiation of the progenitor cells. This research thereby introduces its potential in oral disease-targeted applications, especially age-related dental diseases involving dentinal loss.

Effect of maxillary impaction on mandibular surgical accuracy in virtually-planned orthognathic surgery: A retrospective study.

Although surgical accuracy has been evaluated in bi-maxillary procedures, few studies have investigated the relationship between maxillary and mandibular accuracy. The present study evaluated the effect of maxillary impaction accuracy on mandibular surgical outcome. This cohort study analyzed skeletal class III patients who underwent planned maxillary impaction in bi-maxillary surgery. The primary predictor was the difference between the virtual plan and surgical outcome in the maxilla, as determined by three-dimensional (3D) and vertical differences. The secondary predictors were the planned 3D distances in the maxilla and mandible. The primary outcome was mandibular surgical accuracy, defined as the difference between the planned and actual outcomes, calculated as 3D Euclidean distance. The study included 73 patients. Increased differences between the planned and actual outcomes in the maxilla were associated with increased differences in the mandible. The post-operative position of the mandible was closer to the planned position when the position of the impacted maxilla was superior than when it was inferior to the planned position. Moving the maxilla closer to the planned position resulted in a more accurate mandibular position. These findings suggest that careful surgical procedures are needed to avoid inferior positioning of the maxilla during maxillary impaction surgery.

Effects of VEGF and FGF-2 on proliferation and differentiation of human periodontal ligament stem cells.

Human periodontal ligament stem cells (PDLSCs) from extracted third molar teeth are a type of adult stem cell originating from dental tissue. PDLSCs are known to have a self-renewal capacity and multi-lineage differentiation potential. Vascular endothelial growth factor (VEGF), an angiogenic/vasculogenic factor, has been shown to stimulate endothelial cell mitogenesis and cell migration. Another growth factor, fibroblast growth factor-2 (FGF-2), a mitogenic factor, enhances osteogenesis in mesenchymal stem cells (MSCs). This study examines the effects of VEGF and FGF-2 on PDLSCs in vitro and in vivo compared with those on bone marrow stem cells (BMSCs) as a positive control. Treatment of PDLSCs with VEGF increases the accumulation of calcium nodules, alkaline phosphatase (ALP) activity and the formation of hard tissue and up-regulates the mRNA level of runt-related transcription factor 2 (Runx2). In contrast, FGF-2 enhances the proliferation of PDLSCs in vitro in cell culture, where it significantly decreases calcium accumulation and ALP activity and down-regulates the expression of osteogenic gene markers (i.e., Runx2, ALP, type I collagen) involved in osteogenic induction. We have also transplanted PDLSCs with hydroxyapatite/tricalcium phosphate particles (HA/TCP) as carriers for each factor (VEGF, FGF-2) into nude mice and, after 8 weeks, observed the in vivo formation of hard tissue at the dorsal surface. Based on our results, we suggest that VEGF has positive effects on odonto-/osteogenic differentiation in vitro and on the formation of mineralized structure in vivo. FGF-2 might be a powerful promoter of the proliferation of progenitor cells in hard tissue regeneration but exogenous FGF-2 might inhibit terminal differentiation.

Dental follicle cells and cementoblasts induce apoptosis of ameloblast-lineage and Hertwig's epithelial root sheath/epithelial rests of Malassez cells through the Fas-Fas ligand pathway.

Hertwig's epithelial root sheath (HERS), epithelial rests of Malassez (ERM) cells, and reduced ameloblasts undergo apoptosis during tooth development. This study examined the effects of dental follicle cells and cementoblasts on the apoptosis of ameloblast-lineage and HERS/ERM cells derived from the enamel organ. We also elucidated the induction pathways and identified the apoptotic pathway involved in this process. Here, we showed terminal deoxynucleotidyl transferase-mediated biotin-dUTP nick-end labeling (TUNEL)-positive HERS cells and reduced ameloblasts near dental follicle cells during tooth development. Co-culturing ameloblast-lineage cell line (ALC) ameloblasts and HERS/ERM cells with either dental follicle cells or OCCM-30 cementoblasts markedly enhanced the apoptosis of ameloblasts and HERS/ERM cells compared with cells cultured alone. However, dental follicle cells and cementoblasts did not modulate the apoptotic responses of co-cultured non-odontogenic MCF10A or KB cells. When ameloblasts + HERS and cementoblasts + dental follicle cells were co-cultured, the expression of Fas ligand (FasL) increased in cementoblasts + dental follicle cells, while the expression of Fas increased in ameloblasts + HERS. Interestingly, recombinant FasL induced ameloblast apoptosis while the cementoblast-induced ameloblast apoptosis was suppressed by the Fas/FasL antagonist Kp7-6. These results suggest that during tooth development, dental follicle cells and cementoblasts induce apoptosis of ameloblast-lineage and HERS/ERM cells through the Fas-FasL pathway, but do not induce the apoptosis of non-odontogenic epithelial cells.

A more accurate method of predicting soft tissue changes after mandibular setback surgery.

PURPOSE: To propose a more accurate method to predict the soft tissue changes after orthognathic surgery. PATIENTS AND METHODS: The subjects included 69 patients who had undergone surgical correction of Class III mandibular prognathism by mandibular setback. Two multivariate methods of forming prediction equations were examined using 134 predictor and 36 soft tissue response variables: the ordinary least-squares (OLS) and the partial least-squares (PLS) methods. After fitting the equation, the bias and a mean absolute prediction error were calculated. To evaluate the predictive performance of the prediction equations, a 10-fold cross-validation method was used. RESULTS: The multivariate PLS method showed significantly better predictive performance than the conventional OLS method. The bias pattern was more favorable and the absolute prediction accuracy was significantly better with the PLS method than with the OLS method. CONCLUSIONS: The multivariate PLS method was more satisfactory than the conventional OLS method in accurately predicting the soft tissue profile change after Class III mandibular setback surgery.

Surgical ciliated cyst of the mandible after orthognathic surgery: a case report with review of the literature.

BACKGROUND: Surgical ciliated cysts, also known as postoperative maxillary cysts or implantation cysts, occur mainly in the posterior maxilla after radical maxillary sinus surgery; they rarely develop in the mandible. They are thought to occur when the sinonasal epithelium is infiltrated by a surgical instrument during surgery or as a result of transplantation of bone or cartilage with respiratory epithelium attached. CASE PRESENTATION: We report a case in which a surgical ciliated cyst developed in the anterior part of the mandible, presumably as a result of bimaxillary orthognathic surgery and genioplasty performed 24 years earlier. We then review the few similar cases reported in the literature. CONCLUSION: Surgical ciliated cysts in the mandible are extremely rare, but they could occur after simultaneous surgery on the maxilla and mandible, even decades later. To prevent surgical ciliated cysts in the mandible, we recommend that the surgical instruments, especially the saw blade used during bimaxillary surgery, be new or cleaned and that previously placed plates and screws be removed at an appropriate time.

FAM83H mutations in families with autosomal-dominant hypocalcified amelogenesis imperfecta.

Amelogenesis imperfecta (AI) is a collection of diverse inherited disorders featuring dental-enamel defects in the absence of significant nondental symptoms. AI phenotypes vary and are categorized as hypoplastic, hypocalcified, and hypomaturation types. Phenotypic specificity to enamel has focused research on genes encoding enamel-matrix proteins. We studied two families with autosomal-dominant hypocalcified AI and have identified nonsense mutations (R325X and Q398X) in the FAM83H gene on chromosome 8q24.3. The mutations perfectly cosegregate with the disease phenotype and demonstrate that FAM83H is required for proper dental-enamel calcification.

Nonsyndromic multiple mandibular supernumerary premolars.

PURPOSE: The purpose of this study was to estimate the frequency of and describe the clinical characteristics and complications of patients with nonsyndromic multiple mandibular supernumerary premolars. PATIENTS AND METHODS: Among 110,500 patients seen between July 2003 and January 2007, 32 cases of multiple (2 or more) mandibular supernumerary premolars were found. Data including age, gender, number, distribution, and location of supernumerary premolars, extraction procedure, and related complications (such as cystic changes, root resorption, or adjacent teeth eruption disturbance) were collected. RESULTS: Six of 32 patients were female; the male to female ratio was 4.3:1. Prevalence of non-syndromic multiple mandibular supernumerary premolars was 0.029%. Mean age was 17.8 years. Root resorption of an adjacent tooth was found in 1 patient. Eruption anomalies were found in 5 patients and included impaction of a permanent tooth, prolonged retention of a deciduous tooth, and displacement of an adjacent tooth. Supernumerary teeth locations were predominantly lingual except for 4 teeth. CONCLUSION: Prevalence found in this study was lower compared with previous studies. However, the rate of related complications was higher, even though the mean age was relatively low. Surgical intervention should be considered to prevent unwanted sequelae for any signs of complication.

TGF-ß2 downregulates osteogenesis under inflammatory conditions in dental follicle stem cells.

Bone formation is important for the reconstruction of bone-related structures in areas that have been damaged by inflammation. Inflammatory conditions such as those that occur in patients with rheumatoid arthritis, cystic fibrosis, and periodontitis have been shown to inhibit osteoblastic differentiation. This study focussed on dental follicle stem cells (DFSCs), which are found in developing tooth germ and participate in the reconstruction of alveolar bone and periodontal tissue in periodontal disease. After bacterial infection of inflamed dental tissue, the destruction of bone was observed. Currently, little is known about the relationship between the inflammatory environment and bone formation. Osteogenic differentiation of inflamed DFSCs resulted in decreased alkaline phosphatase (ALP) activity and alizarin red S staining compared to normal DFSCs. Additionally, in vivo transplantation of inflamed and normal DFSCs demonstrated severe impairment of osteogenesis by inflamed DFSCs. Protein profile analysis via liquid chromatography coupled with tandem mass spectrometry was performed to analyse the differences in protein expression in inflamed and normal tissue. Comparison of inflamed and normal DFSCs showed significant changes in the level of expression of transforming growth factor (TGF)-ß2. Porphyromonas gingivalis (P.g.)-derived lipopolysaccharide (LPS) was used to create in vitro inflammatory conditions similar to periodontitis. The osteogenic differentiation of LPS-treated DFSCs was suppressed, and the cells displayed low levels of TGF-ß1 and high levels of TGF-ß2. DFSCs treated with TGF-ß2 inhibitors showed significant increases in alizarin red S staining and ALP activity. TGF-ß1 expression was also increased after inhibition of TGF-ß2. By examining inflamed DFSCs and LPS-triggered DFSCs, these studies showed both clinically and experimentally that the increase in TGF-ß2 levels that occurs under inflammatory conditions inhibits bone formation.

A crucial role of caspase-3 in osteogenic differentiation of bone marrow stromal stem cells.

Caspase-3 is a critical enzyme for apoptosis and cell survival. Here we report delayed ossification and decreased bone mineral density in caspase-3-deficient (Casp3(-/-) and Casp3(+/-)) mice due to an attenuated osteogenic differentiation of bone marrow stromal stem cells (BMSSCs). The mechanism involved in the impaired differentiation of BMSSCs is due, at least partially, to the overactivated TGF-beta/Smad2 signaling pathway and the upregulated expressions of p53 and p21 along with the downregulated expressions of Cdk2 and Cdc2, and ultimately increased replicative senescence. In addition, the overactivated TGF-beta/Smad2 signaling may result in the compromised Runx2/Cbfa1 expression in preosteoblasts. Furthermore, we demonstrate that caspase-3 inhibitor, a potential agent for clinical treatment of human diseases, caused accelerated bone loss in ovariectomized mice, which is also associated with the overactivated TGF-beta/Smad2 signaling in BMSSCs. This study demonstrates that caspase-3 is crucial for the differentiation of BMSSCs by influencing TGF-beta/Smad2 pathway and cell cycle progression.

Modern trends in Class III orthognathic treatment: A time series analysis.

OBJECTIVE: To examine the current trends in surgical-orthodontic treatment for patients with Class III malocclusion using time-series analysis. MATERIALS AND METHODS: The records of 2994 consecutive patients who underwent orthognathic surgery from January 1, 2004, through December 31, 2015, at Seoul National University Dental Hospital, Seoul, Korea, were reviewed. Clinical data from each surgical and orthodontic treatment record included patient's sex, age at the time of surgery, malocclusion classification, type of orthognathic surgical procedure, place where the orthodontic treatment was performed, orthodontic treatment modality, and time elapsed for pre- and postoperative orthodontic treatment. RESULTS: Out of the orthognathic surgery patients, 86% had Class III malocclusion. Among them, two-jaw surgeries have become by far the most common orthognathic surgical treatment these days. The age at the time of surgery and the number of new patients had seasonal variations, which demonstrated opposing patterns. There was neither positive nor negative correlation between pre- and postoperative orthodontic treatment time. Elapsed orthodontic treatment time for both before and after Class III orthognathic surgeries has been decreasing over the years. CONCLUSION: Results of the time series analysis might provide clinicians with some insights into current surgical and orthodontic management.

Modified Fisher method for unilateral cleft lip-report of cases.

BACKGROUND: Rehabilitation of normal function and form is essential in cleft lip repair. In 2005, Dr. David M. Fisher introduced an innovative method, named "an anatomical subunit approximation technique" in unilateral cleft lip repair. According to this method, circumferential incision along the columella on cleft side of the medial flap is continued to the planned top of the Cupid's bow in straight manner, which runs parallel to the unaffected philtral ridge. Usually, small inlet incision is needed to lengthen the medial flap. On lateral flap, small triangle just above the cutaneous roll is used to prevent unesthetic shortening of upper lip. This allows better continuity of the Cupid's bow and ideal distribution of tension. CASE PRESENTATION: As a modification to original method, orbicularis oris muscle overlapping suture is applied to make the elevated philtral ridge. Concomitant primary rhinoplasty also results in good esthetic outcome with symmetric nostrils and correction of alar web. As satisfactory results were obtained in three incomplete and one complete unilateral cleft lip patients, indicating Fisher's method can be useful in cleft lip surgery with functional and esthetic outcome. CONCLUSIONS: Clinically applied Fisher's method in unilateral cleft lip patients proved the effectiveness in improving the esthetic results with good symmetry. This method also applied with primary rhinoplasty.

Valproic Acid Modulates the Multipotency in Periodontal Ligament Stem Cells via p53-Mediated Cell Cycle.

Human periodontal ligament stem cells (PDLSCs), a type of mesenchymal stem cell, are a promising source for dental regeneration and are identified in human periodontal ligaments from extracted third molars. Valproic acid (VPA) is a histone deacetylase inhibitor that has been used as a wide-spectrum antiepileptic drug and a medication for mood disorders. VPA has shown several effects on increasing the pluripotency of embryonic stem cells and controlling osteogenic differentiation, besides the prevention of seizures. However, its effect on proliferation and osteogenesis depends on the cell type and concentration. The aim of this study was to investigate the effects of cyclic and constant VPA treatment on PDLSCs. Proliferation and apoptosis of PDLSCs were determined with cyclic and constant VPA treatment. In cemento/osteogenic differentiation, osteogenic markers decreased significantly after cyclic treatment with 0.5 mM VPA. In contrast, VPA enhanced osteogenic differentiation after constant treatment. With cyclic VPA treatment, p53 levels related to apoptotic pathway decreased to induce proliferation. These findings indicated that VPA has different roles in proliferation and differentiation of PDLSCs in vitro and in vivo via p53-related pathway.