Evaluating Dental Arch Relationships in Indonesian Patients with Operated Bilateral Cleft Lip and Palate Using Modified Huddart/Bodenham Index and Bauru-bilateral cleft lip and palate (BCLP) Yardstick.

Background: Patients with complete bilateral cleft lip and palate (CBCLP) have the most complex orofacial abnormalities despite its lowest incidence among cleft lip and palate (CLP) types. Impaired maxillary growth can result from surgical procedures in patients with CBCLP. This study evaluates dental arch relationships in Indonesian patients with CBCLP after undergoing CLP repair at Harapan Kita Children and Mother Hospital in Jakarta. Material and Methods: Using the modified Huddart and Bodenham (MHB) index and Bauru bilateral cleft lip and palate (BCLP) yardstick, three examiners assessed 17 study models in the 9-year age group and 13 study models in the 12-year age group, as well as two intraoral clinical photographs of two patients with CBCLP. The assessments were repeated three times within two weeks of each assessment time. Results: Patients with operated CBCLP (aged 9 and 12 years) had edge-to-edge tooth relations, which were categorized as a mild crossbite or mild deviation, and only required orthodontic treatment according to the two specified indicators. Conclusions: The CLP repair protocol used at the Harapan Kita Hospital effectively manages CBCLP cases with satisfactory results, suggesting the effectiveness of the MHB index and Bauru-BCLP yardstick in assessing dental arch relationships in patients with operated CBCLP. Key words:Bilateral, cleft lip and palate, dental arch relationship, lip repair, palate repair.

Developmental process of the modern house shrew's molars: implications for the evolution of the tribosphenic molar in Mesozoic mammals.

Phylogenetically, the tribosphenic molars-prototypes of multi-cusped cheek teeth in marsupial and placental mammals-are derived from the single-cusped conical teeth of reptiles through the addition of cusps. Ontogenetically, mammalian molars are formed through the interface between the dental epithelium and mesenchyme (future enamel-dentin junction), becoming geometrically complex by adding epithelial signaling centers, called enamel knots, which determine future cusp positions. To reevaluate cusp homologies in Mesozoic mammals from an ontogenetic perspective, this study tracked molar development in a living placental mammal species, the house shrew (Suncus murinus), whose molars are morphologically the least derived from tribosphenic prototypes. The development of shrew molars proceeded as if it replayed the evolutionary process of tribosphenic molars. The first formed enamel knots gave rise to the evolutionarily oldest cusps-upper paracone and lower protoconid. The order of formation of other enamel knots and their location in development seemed to trace the order of cusp appearance in evolution. The parallel relationship between ontogeny and phylogeny of mammalian molars, if any, suggests that a change in the timing between developmental events rather than a change in the morphogenetic mechanism itself, should have been a major causal factor for the evolutionary transformation of tooth morphology.

Early induction of Hes1 by bone morphogenetic protein 9 plays a regulatory role in osteoblastic differentiation of a mesenchymal stem cell line.

Bone morphogenic protein 9 (BMP9) is one of the most potent inducers of osteogenic differentiation among the 14 BMP members, but its mechanism of action has not been fully demonstrated. Hes1 is a transcriptional regulator with basic helix-loop-helix (bHLH) domain and is a well-known Notch effector. In this study, we investigated the functional roles of early induction of Hes1 by BMP9 in a mouse mesenchymal stem cell line, ST2. Hes1 mRNA was transiently and periodically induced by BMP9 in ST2, which was inhibited by BMP signal inhibitors but not by Notch inhibitor. Interestingly, Hes1 knockdown in ST2 by siRNA increased the expression of osteogenic differentiation markers such as Sp7 and Ibsp and matrix mineralization in comparison with control siRNA transfected ST2. In contrast, forced expression of Hes1 by using the Tet-On system suppressed the expression of osteogenic markers and matrix mineralization by BMP9. We also found that the early induction of Hes1 by BMP9 suppressed the expression of Alk1, an essential receptor for BMP9. In conclusion, BMP9 rapidly induces the expression of Hes1 via the SMAD pathway in ST2 cells, which plays a negative regulatory role in osteogenic differentiation of mesenchymal stem cells induced by BMP9.

Prognostic value of inflammatory biomarkers in aged patients with oral squamous cell carcinoma.

Background: Better prognostic biomarkers for oral squamous cell carcinoma (OSCC) must be developed, particularly within the realm of clinically and frequently administered tests, to advise appropriate clinical therapy and follow-up. In this study, we retrospectively investigated which of the several inflammation-nutrition indicators might predict the prognosis of patients with OSCC. Methods: The preoperative neutrophil-lymphocyte ratio (NLR), lymphocyte-monocyte ratio (LMR), platelet-lymphocyte ratio (PLR), CRP-albumin ratio (CAR), Glasgow prognostic score (GPS), modified GPS (mGPS), prognostic nutritional index (PNI), controlling nutrition status (CONUT), and modified CONUT (mCONUT) were retrospectively evaluated using blood samples collected 1-5 days before surgery. To estimate the effect on the prognosis of tumor progression, the mean values of the markers between stages I/II and III/IV were used for subgroup analysis. The multivariate Cox proportional hazards model included all independent variables significantly associated with survival in the univariate analysis to determine the independent variables. Results: A total of 112 patients (69 males and 43 females) with primary OSCC who underwent surgical treatment at our hospital were included. There were statistically significant differences in the mean values of monocytes, platelets, and albumin between stages I/II and III/IV. According to the multivariate Cox proportional hazards regression, a low PNI was associated with shorter overall survival (OS) and disease-free survival (DFS); women were associated with shorter DFS. Conclusion: The pretreatment PNI had excellent predictive value for the 5-year OS and DFS of patients with OSCC. Future large-scale prospective studies with a high sample size are needed to verify our findings in OSCC patients.

Lipoteichoic Acid and Lipopolysaccharides Are Affected by p38 and Inflammatory Markers and Modulate Their Promoting and Inhibitory Effects on Osteogenic Differentiation.

Lipoteichoic acid (LTA) and lipopolysaccharide (LPS) are cell wall components of Gram-positive and Gram-negative bacteria, respectively. Notably, oral microflora consists of a variety of bacterial species, and osteomyelitis of the jaw caused by dental infection presents with symptoms of bone resorption and osteosclerosis. However, the effects of LTA and LPS on osteogenic differentiation have not yet been clarified. We examined the effects of LTA and LPS on osteoblasts and found that LTA alone promoted alizarin red staining at low concentrations and inhibited it at high concentrations. Additionally, gene expression of osteogenic markers (ALP, OCN, and OPG) were enhanced at low concentrations of LTA. High concentrations of LPS suppressed calcification potential, and the addition of low concentrations of LTA inhibited calcification suppression, restoring the gene expression levels of suppressed bone differentiation markers (ALP, BSP, and OCN). Moreover, the suppression of p38, a signaling pathway associated with bone differentiation, had opposing effects on gene-level expression of tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6), suggesting that mixed LTA and LPS infections have opposite effects on bone differentiation through concentration gradients, involving inflammatory markers (TNF-α and IL-6) and the p38 pathway.

Three-Dimensional Quantification of Postoperative Facial Asymmetry in Patients With Unilateral Cleft lip and Palate Using Facial Symmetry Plane.

OBJECTIVE: To quantitatively assess three-dimensional (3D) soft tissue facial asymmetry in patients with unilateral cleft lip and palate (UCLP) who have undergone primary lip repair. DESIGN: Clinical, retrospective, comparative, methodological study. PATIENTS/PARTICIPANTS: Twenty patients with UCLP were selected after a review of the records. INCLUSION CRITERIA: Complete UCLP; surgically treated without secondary repair. An age-matched and sex-matched Control group was employed. MAIN OUTCOME MEASURES: A 3D facial symmetry plane (FSP) was obtained by superimposing the point clouds of the original 3D facial image excluding the surgical site and including lip and nose areas and those of a mirrored facial image using the iterative closest point (ICP) adjustment method. The discrepancies in the depth and angle of the normal vector of the facial surface of each point cloud between right and left sides (cleft and non-cleft sides in the UCLP group, respectively) based on FSP were calculated. RESULTS: Facial asymmetry in the UCLP group was significantly greater than in the Control group regarding both the discrepancies in the depth (1.34 ± 0.62, 0.73 ± 0.32 pixels, respectively) (P = .0004) and surface angle (18.0 ± 5.88, 12.8 ± 4.0°, respectively) (P = .0024). Biaxial assessment of the discrepancies in the depth and surface angle allowed us to visually extract UCLP patients with greater facial asymmetry. CONCLUSIONS: Facial asymmetry analysis based on 3D FSP effectively facilitates the facial asymmetry quantification and soft tissue surgical outcome evaluation in patients with UCLP.

Effects of immune checkpoint inhibitor therapy resumption in patients with malignant tumors after moderate-to-severe immune-related adverse events.

BACKGROUND AND AIMS: Immune checkpoint inhibitors (ICIs) are used to treat several cancers, but they sometimes induce immune-related adverse events (irAEs). Patients with irAEs often have improved antitumor responses, but discontinuation of ICIs after irAEs is considered necessary. Resuming the use of ICIs after irAEs is preferable, but few studies have investigated the safety of ICI resumption after irAEs. Therefore, we evaluated the factors associated with the recurrence of irAEs after ICI resumption to investigate the safety of this approach. METHODS: In this observational study, we enrolled patients treated with ICIs from September 2014 to March 2020 at our institution. Patient characteristics, ICIs, grades of irAEs, ICI discontinuation or resumption rates, and recurrence rates of irAEs after ICI therapy were analysed. RESULTS: Two-hundred eighty-seven patients were included in the present study, and 76 patients experienced grade 2 or higher irAEs. Forty-two patients underwent ICI resumption after recovering from irAEs, and 13 of them had a recurrence of irAEs. Among those 13 patients, six had a recurrence of the same irAE, and seven experienced other irAEs. Ten of the 13 patients had grade ≥2 irAEs, and none had fatal irAEs. In the grade 2 or higher irAE group, more patients had irAEs associated with multiple organs and of initial grade ≥2 than those in the grade 1 and no recurrent irAEs group. CONCLUSIONS: Patients with initial multisystemic irAEs and irAEs of grade ≥2 were more likely to experience relapse or develop new grade ≥2 irAEs after ICI resumption.

HIF-1α plays an essential role in BMP9-mediated osteoblast differentiation through the induction of a glycolytic enzyme, PDK1.

Bone homeostasis is regulated by bone morphogenic proteins (BMPs), among which BMP9 is one of the most osteogenic. Here, we have found that BMP9 rapidly increases the protein expression of hypoxia-inducible factor-1α (HIF-1α) in osteoblasts under normoxic conditions more efficiently than BMP2 or BMP4. A combination of BMP9 and hypoxia further increased HIF-1α protein expression. HIF-1α protein induction by BMP9 is not accompanied by messenger RNA (mRNA) increase and is inhibited by the activation of prolyl hydroxylase domain (PHD)-containing protein, indicating that BMP9 induces HIF-1α protein expression by inhibiting PHD-mediated protein degradation. BMP9-induced HIF-1α protein increase was abrogated by inhibitors of phosphoinositide 3-kinase (PI3K) and protein kinase B (AKT) kinase, indicating that it is mediated by PI3K-AKT signaling pathway. BMP9 increased mRNA expression of pyruvate dehydrogenase kinase 1 (PDK1), a glycolytic enzyme, and vascular endothelial growth factor-A (VEGF-A), an angiogenic factor, in osteoblasts. Notably, BMP9-induced mRNA expression of PDK1, but not that of VEGF-A, was significantly inhibited by small interference RNA-mediated knockdown of Hif-1α. BMP9-induced matrix mineralization and osteogenic marker gene expressions were significantly inhibited by chemical inhibition and gene knockdown of either Hif-1α or Pdk-1, respectively. Since increased glycolysis is an essential feature of differentiated osteoblasts, our findings indicate that HIF-1α expression is important in BMP9-mediated osteoblast differentiation through the induction of PDK1.

Intercellular signaling between ameloblastoma and osteoblasts.

Ameloblastoma is an odontogenic tumor located in the bone jaw with clinical characteristics of extensive bone resorption. It is a locally invasive tumor with a high recurrence rate despite adequate surgical removal. In bone disease, tumors and other cells including osteoblasts, osteoclasts, and osteocytes in the bone microenvironment contribute to the pathogenesis of tumor growth. However, the effect of osteoblasts on ameloblastoma cells is not well-understood, and there has been limited research on interactions between them. This study investigated interactions between ameloblastoma cells and osteoblasts using a human ameloblastoma cell line (AM-3 ameloblastoma cells) and a murine pre-osteoblast cell line (MC3T3-E1 cells). We treated each cell type with the conditioned medium by the other cell type. We analyzed the effect on cytokine production by MC3T3-E1 cells and the production of MMPs by AM-3 cells. Treatment with AM-3-conditioned medium induced inflammatory cytokine production of IL-6, MCP-1, and RANTES from MC3T3-E1 cells. The use of an IL-1 receptor antagonist suppressed the production of these inflammatory cytokines by MC3T3-E1 cells stimulated with AM-3-conditioned medium. The MC3T3-E1-conditioned medium triggered the expression of MMP-2 from AM-3 cells. Furthermore, we have shown that the proliferation and migration activity of AM-3 cells were accelerated by MC3T3-E1 conditioned media. In conclusion, these intercellular signalings between ameloblastoma cells and osteoblasts may play multiple roles in the pathogenesis of ameloblastoma.

Complete sequences of epidermin and nukacin encoding plasmids from oral-derived Staphylococcus epidermidis and their antibacterial activity.

Staphylococcus epidermidis is a commensal bacterium in humans. To persist in the bacterial flora of the host, some bacteria produce antibacterial factors such as the antimicrobial peptides known as bacteriocins. In this study, we tried to isolate bacteriocin-producing S. epidermidis strains. Among 150 S. epidermidis isolates from the oral cavities of 287 volunteers, we detected two bacteriocin-producing strains, KSE56 and KSE650. Complete genome sequences of the two strains confirmed that they carried the epidermin-harboring plasmid pEpi56 and the nukacin IVK45-like-harboring plasmid pNuk650. The amino acid sequence of epidermin from KSE56 was identical to the previously reported sequence, but the epidermin synthesis-related genes were partially different. The prepeptide amino acid sequences of nukacin KSE650 and nukacin IVK45 showed one mismatch, but both mature peptides were entirely similar. pNuk650 was larger and had an additional seven ORFs compared to pIVK45. We then investigated the antibacterial activity of the two strains against several skin and oral bacteria and found their different activity patterns. In conclusion, we report the complete sequences of 2 plasmids coding for bacteriocins from S. epidermidis, which were partially different from those previously reported. Furthermore, this is the first report to show the complete sequence of an epidermin-carrying plasmid, pEpi56.

Effectiveness of fibreoptic endoscopic evaluation of swallowing and dietary intervention during home-visit dental care in older individuals.

BACKGROUND: Currently, patients with dysphagia are receiving dietary management that deviates from their original swallowing function. OBJECTIVE: To evaluate the clinical significance of fibreoptic endoscopic evaluation of swallowing (FEES) and dietary intervention (DI) by multi-professional collaboration during visit care for determining the actual oral intake status in patients with dysphagia. METHODS: Five hundred and eighteen patients with dysphagia underwent FEES, focusing on the penetration-aspiration scale, and DI. Oral intake status was categorised using the functional oral intake scale (FOIS). FOIS scores at the first visit, after FEES, and at the reassessment were compared. RESULTS: At the first visit, 34.7% of the patients had an FOIS score of level 1 (no oral intake) and 65.3% had a score of level 2 or higher (capable of oral intake). Following FEES, 7.1% of patients had an FOIS score of level 1, and 44.4% had a score of level 2 with resumption of oral intake. At the reassessment, 489 patients (94.4%) were capable of oral ingestion (FOIS level 2 or higher). There were significant differences between the distributions of FOIS scores at the first visit and following FEES (P < .01) and between those at the first visit and at the reassessment (P < .01). Regarding tube feeding, 17 (5.9%) of 289 patients, who had received tube feeding at the first visit, were completely capable of oral intake following FEES and at the reassessment. CONCLUSION: Appropriate evaluation of swallowing function using FEES and DI helps to understand the definite swallowing function in patients with dysphagia.

Comparison of recurrence rate and speech outcome between two different techniques for cleft palatal fistula closure: A retrospective cohort study.

The aim of this retrospective cohort study was to compare the recurrence rate and speech outcomes between two techniques for palatal fistula closure of cleft palate (CP). Patients with CP who underwent secondary palatal fistula closure using the single hinge-flap method with double-breasted mattress suture (hinge-flap group) and those who were treated with the conventional sliding palatal flap method (sliding-flap group) were retrospectively evaluated for demographic and perioperative variables. Recurrence rate of palatal fistula, perceptual speech outcomes, and nasalance scores were further reviewed in patients who met the inclusion criteria. A total of 31 patients, 21 in the hinge-flap group and 10 in the sliding-flap group, were included in this study. The fistula recurrence rate in the hinge-flap group (0%) was significantly lower than that in the sliding-flap group (30.0%) (P = 0.027). In the speech assessment, hypernasality and nasalance scores decreased post-operatively in both groups and significance was observed in the hinge-flap group (P = 0.013, P < 0.001, respectively). Articulation disorders were significantly improved in the hinge-flap group (P = 0.001). Within the limitations of the study it seems that the single hinge-flap method with double-breasted mattress suture should be preferred whenever appropriate.

A Follow-Up Study on the Clinical Outcomes of Alveolar Reconstruction Using Octacalcium Phosphate Granules and Atelocollagen Complex.

PURPOSE: To observe the long-term postoperative bone formation and eruption of adjacent teeth after octacalcium phosphate granule and atelocollagen complex (OCP/Col) grafting in the treatment of alveolar cleft of patients with unilateral cleft lip with or without cleft palate (UCL ± P). METHODS: Four patients with UCL ± P who underwent OCP/Col grafting (OCP group), and 55 patients with UCL ± P who underwent autologous bone grafting (AB group) were enrolled in this study. OCP/Col or autologous bone grafting was performed before the eruption of canines or lateral incisors in mixed dentition, followed by orthodontic management. Patients in the OCP group underwent radiography before and after surgery at 1, 2, 3, 6, and over 30 months postoperatively. The volume and area of the bony defect in the alveolar cleft area were compared between the OCP and AB groups before and after 6 months of surgery. RESULTS: The bone bridge in all patients in the OCP/Col group was successfully formed, and by 6 months postoperatively, the permanent teeth adjacent to the alveolar cleft had erupted at the site of the OCP/Col complex graft. Comparison of the pre- and postoperative bone defects between the 2 groups revealed almost the same extent of bone bridge formation. CONCLUSIONS: OCP/Col grafting could be considered as an alternative to autologous bone grafting as it yielded successful bone bridge formation and facilitated permanent tooth eruption.

Prognostic Role of Preoperative Sarcopenia Evaluation of Cervical Muscles with Long-Term Outcomes of Patients with Oral Squamous Cell Carcinoma.

Accumulating evidence has shown that sarcopenia in patients with oral squamous cell carcinoma (OSCC) is at a risk of poor prognosis. There is no universal consensus on how to assess sarcopenia in patients with OSCC in daily practice. It is important to validate the usefulness of sarcopenia assessment from cervical muscles, which are frequently used in routine clinical practice in patients with OSCC. In this study, we investigated whether preoperative lumbar (L3) skeletal muscle mass and adiposity in OSCC patients were associated with cervical (C3) skeletal muscle mass and adiposity from CT measurements. We also investigated whether skeletal muscle mass and adiposity in the C3 muscles were associated with survival rates in patients with OSCC. We demonstrated that both the quality and quantity of muscle between the C3 and L3 levels were positively correlated with each other. We also demonstrated that the survival rates in patients with low sternocleidomastoid muscle mass index, high processus spinosus muscle-intramuscular adipose tissue content, and the combination of both were significantly lower than those in the controls. These results suggest that the assessment of sarcopenia from multiple neck muscles by preoperative CT measurements may be useful in predicting the prognosis of patients with OSCC.

In Vivo Analyses of Osteogenic Activity and Bone Regeneration Capacity of Demineralized Freeze-Dried Bovine Bone Xenograft: A Potential Candidate for Alveolar Bone Fillers.

BACKGROUND: Deproteinized bovine bone mineral (DBBM) particle is the commonly used bone graft substitute in implant surgery which is mainly osteoconductive and has very slow degradation. Demineralized freeze-dried bovine bone xenograft (DFDBBX) particle is being developed as a novel xenogeneic bone filler. OBJECTIVES: The study aimed to analyze osteogenic activity and bone-forming capacity of DFDBBX particles compared to DBBM particles in alveolar bone defects in rabbit mandibles models. Material and Methods. This study investigated bone defects whether filled with DBBM particles or DFDBBX particles or left unfilled in 30 rabbit mandibles. Specimens were processed for histology, immunohistochemistry, and micro-CT scanning. Statistical difference was set at a p value < 0.05. RESULTS: The quantitative assessment showed a significantly lower number of osteoclasts and a higher number of osteoblasts in the DFDBBX group compared to the DBBM group in 2 and 4 weeks (p < 0.05). Immunostaining analyses showed significantly higher expression of RUNX2, collagen type I, alkaline phosphatase, and osteocalcin in the DFDBBX group compared to the DBBM group in 2 and 4 weeks. Bone healing score in the DFDBBX group was comparable to the DBBM group. Micro-CT presented no significant difference in the volume percentage of the mineralized tissue in the DBBM and DFDBBX groups in spite of the different healing patterns in both groups. CONCLUSION: DFDBBX particles induced higher osteoblastic activities than DBBM particles at the early stage of healing. Meanwhile, the capacity of bone formation in DFDBBX particles was comparable with DBBM particles at the later stage of healing. Considering the limitation of this study, the results presented DFDBBX particles as potential bone filler candidates.

Molecular biological findings of ameloblastoma.

Ameloblastoma is benign odontogenic tumours that mainly occur in the jawbone. This tumour induces aggressive invasion into the surrounding bone and has a high recurrence rate after surgery. Therefore, mandibular resection is performed in many patients with this tumour, causing aesthetic and functional problems. It is necessary to develop a novel treatment strategy for ameloblastoma, but there are currently no innovative treatments. Although our understanding of the molecular biological mechanisms of ameloblastoma is still insufficient, there have been many recent reports of new molecular biological findings on ameloblastoma. Therefore, bioactive factors that have potential for novel therapeutic methods, such as molecular targeted therapy, have been discovered in ameloblastoma. In this review, we summarize the molecular biological findings of ameloblastoma reported over several decades, focusing on factors involved in invasion into surrounding tissues and disease-specific gene mutations. We also mention the effect of the interaction between tumour cells and stromal components in ameloblastoma on tumour development. Scientific field of dental Science: Oral surgery, Odontogenic tumor, Ameloblastoma.

In vivo degradation and bone formation behaviors of hydroxyapatite-coated Mg alloys in rat femur.

Various coatings have been developed for biodegradable Mg alloys to control the degradation speed and to improve the bone conductivity. In this study, hydroxyapatite (HAp) coatings were formed on pure Mg, Mg-0.8mass% Ca (MgCa), Mg-4mass% Y-3mass% rare earth (RE) (WE43), Mg-3mass% RE-1mass% Y (EW31) and Mg-4mass% RE (RE4) alloy rods with a chemical solution deposition method. The HAp-coated and uncoated Mg/Mg alloy rods were implanted in the femurs of rats for 3-6 months, and the corrosion suppression and bone formation abilities of the HAp coating were examined using a scanning electron microscope. The corrosion rate of WE43 was suppressed by 1/3 with the HAp coating for 6 months, and the corrosion product showed very slow dissolution. The effect of the HAp coating for pure Mg and MgCa disappeared in 1-2 months with the thinning of the rods accompanying with the obvious dissolution of the corrosion products. The effect of the HAp coating for EW31 and RE4 was not stable due to the expansion and collapse of the corrosion products. The bone formation was enhanced on the HAp layers. Eventually, the HAp coating basically suppressed the corrosion initiation and corrosion progress of Mg substrates. The magnitude of the suppression effect depended mainly on the chemical and physical stability of the corrosion products.

Bone morphogenetic protein 9 (BMP9) directly induces Notch effector molecule Hes1 through the SMAD signaling pathway in osteoblasts.

Bone morphogenetic protein (BMP) 9 is one of the most osteogenic BMPs, but its mechanism of action has not been fully elucidated. Hes1, a transcriptional regulator with a basic helix-loop-helix domain, is a well-known effector of Notch signaling. Here, we find that BMP9 induces periodic increases of Hes1 mRNA and protein expression in osteoblasts, presumably through an autocrine negative feedback mechanism. BMP9-mediated Hes1 induction is significantly inhibited by an ALK inhibitor and overexpression of Smad7, an inhibitory Smad. Luciferase and ChIP assays revealed that two Smad-binding sites in the 5' upstream region of the mouse Hes1 gene are essential for transcriptional activation by BMP9. Thus, our data indicate that BMP9 induces Hes1 expression in osteoblasts via the Smad signaling pathway.

PCP4/PEP19 and HER2 Are Novel Prognostic Markers in Mucoepidermoid Carcinoma of the Salivary Gland.

Mucoepidermoid carcinoma (MEC) is one of the most common malignant salivary gland carcinomas, but no effective treatment strategy has been established other than surgical resection. Purkinje cell protein (PCP) 4/peptide (PEP) 19 is a calmodulin-binding antiapoptotic peptide that is expressed and inhibits apoptosis in human breast cancer cells. Human epidermal growth factor receptor 2 (HER2) is an epidermal growth factor that has been implicated in the pathogenesis of many carcinomas, particularly breast and gastric carcinomas. In the present study, we performed immunohistochemical analyses of samples from 73 patients who underwent surgical resection for MEC of the salivary gland using antibodies against PCP4/PEP19 and HER2. PCP4/PEP19 expression was related to better prognosis, while HER2 expression was associated with worse prognosis. Patients that were PCP4/PEP19-positive and HER2-negative showed similar outcomes to PCP4/PEP19 and HER2 alone. Therefore, PCP4/PEP19 and HER2 are predicted to play important roles in the pathogenesis and progression of MEC.

Using three-dimensional nasal forms to compare definitive unilateral cleft lip nose correction with/without a cross-lap joint cartilage graft technique.

To compare three-dimensional (3D) nasal forms after definitive correction of unilateral cleft lip (UCL)-nose using an extended spreader cartilage graft with/without a cross-lap joint cartilage graft technique. Twenty-four patients with UCL who underwent definitive nose correction using an extended spreader cartilage graft with a cross-lap joint technique (CLJ group) and fifteen patients with UCL who underwent nose correction without a cross-lap joint technique (non-CLJ group) were enrolled in this study. Pre- and postoperative 3D nasal forms were compared between the two groups. The CLJ group demonstrated more successful recovery of the nasal tip and anterior nasal ridge in the center of the face (P < 0.01), and the higher nasal tip was maintained for more than 1 year (P = 0.008). The differences in the cephalo-caudal heights of the nasal alar groove and curvatures of the alar groove arch were successfully improved in both CLJ and non-CLJ groups. The nasal angles on lateral profiles did not change in either group. An extended spreader cartilage graft with a cross-lap joint technique facilitates satisfactory recovery of the nasal tip in the center of the face and a higher nasal tip, avoiding over-projection in the definitive correction of UCL-nose.