Treatment outcomes of digital nasoalveolar moulding in infants with cleft lip and palate: A systematic review with meta-analysis.

The aim of this systematic review was to compare the treatment outcomes of digital nasoalveolar moulding (dNAM) technique with conventional nasoalveolar moulding (cNAM) or non-presurgical intervention protocol in infants with unilateral (UCLP) or bilateral (BCLP) cleft lip and palate. A bibliometric search by MEDLINE (via Ovid), Embase, Cochrane Library, grey literature and manual method was conducted without language restriction until November 2023. Literature screening and data extraction were undertaken in Covidence. The risk of bias was evaluated using the Newcastle-Ottawa Scale and RoB-2. Pooled effect sizes were determined through random-effects statistical model using R-Software, and the certainty of evidence was assessed using the GRADE approach. Among 775 retrieved articles, nine studies were included for qualitative synthesis (6-UCLP, 3-BCLP), with only three eligible UCLP studies for meta-analysis. In the UCLP group, very low certainty of evidence indicated no difference in alveolar cleft width (SMD, 0.13 mm; 95% CI, -0.31 to 0.57; I2, 0%), soft tissue (lip) cleft gap, nasal width, nasal height, and columellar deviation angle changes between dNAM and cNAM. In the BCLP group, qualitative synthesis suggested similar changes in alveolar, lip, and nasal dimensions with dNAM and cNAM. In both cleft groups (UCLP, BCLP), reduced alveolar cleft width was observed in the dNAM group compared to the non-presurgical intervention protocol, along with fewer clinical visits and reduced chairside time for dNAM compared to cNAM. It can be concluded that the treatment outcomes with dNAM were comparable to cNAM in reducing malformation severity and were advantageous in terms of chairside time and clinical visit frequency. However, the overall quality of evidence is very low and standardization is needed for the virtual workflow regarding the alveolar movements and growth factor algorithms. Registration: PROSPERO-database (CRD42020186452).

Rationale for immune checkpoint inhibitors plus targeted therapy for advanced renal cell carcinoma.

Renal cell carcinoma (RCC) is a frequent urological malignancy characterized by a high rate of metastasis and lethality. The treatment strategy for advanced RCC has moved through multiple iterations over the past three decades. Initially, cytokine treatment was the only systemic treatment option for patients with RCC. With the development of medicine, antiangiogenic agents targeting vascular endothelial growth factor and mammalian target of rapamycin and immunotherapy, immune checkpoint inhibitors (ICIs) have emerged and received several achievements in the therapeutics of advanced RCC. However, ICIs have still not brought completely satisfactory results due to drug resistance and undesirable side effects. For the past years, the interests form researchers have been attracted by the combination of ICIs and targeted therapy for advanced RCC and the angiogenesis and immunogenic tumor microenvironmental variations in RCC. Therefore, we emphasize the potential principle and the clinical progress of ICIs combined with targeted treatment of advanced RCC, and summarize the future direction.

Customized planning of the visible maxillary arch width in harmony with interparopia width and smile width for female facial aesthetics.

BACKGROUND: The visible maxillary arch width (VAW) is an important aesthetic-determining feature. To date, there is no well-established methodology to determine the aesthetically optimal VAW in customized treatment planning. METHODS: In this study, the common traits of the dentofacial configuration were investigated in most attractive Asian and Caucasian female smiles. The smiling photo of a subject was digitally modified based on combined variations of VAW, smile width (SW), transverse facial dimensions (TFD), and vertical facial dimensions. These modified photos were assessed for aesthetics. The aesthetically essential parameters were identified, and their mathematic correlations and reference ranges were determined for different vertical facial patterns. Using the obtained results, a mathematic guidance was constructed for customized smile designing. The applicability of this guidance was tested in Asian females. RESULTS: The most attractive Asian and Caucasian female smiles have intraracial and interracial commonalities in the VAW-to-TFD ratios. The interparopia width (IPD) predominated over facial widths in determining well-matched VAW and SW. For optimal smile aesthetics, the VAW and SW were correlated as simulated by the formula 1.92 IPD ≤ VAW + 2.3 SW ≤ 2.17 IPD, plus the VAW-to-IPD ratio within 0.54 to 0.62 and the SW-to-IPD ratio within 0.61 to 0.71, ranges tailored to vertical facial patterns. This constitutes a mathematic guidance for customized planning of the aesthetically optimal VAW. This guidance was preliminarily validated to be applicable to Asian females. CONCLUSIONS: The VAW-to-TFD ratios were essential for Caucasian and Asian female smile aesthetics. The mathematic guidance could serve as a reference for customized smile designs for Asian females.

Inclination of the osseous components of the temporomandibular joint related with disc displacement: Magnetic resonance and cone beam computed tomography imaging-based study.

OBJECTIVE: To assess the association between three-dimensional inclination of the osseous structures of temporomandibular joints (TMJ) and the risk of disc displacement (DD). METHODS: The 120 TMJs of 60 patients were evaluated. According to magnetic resonance images, disc position was classified as normal, anterior DD with reduction (ADDWR) and without reduction (ADDWoR) and as normal, medial DD (MDD), and lateral DD (LDD) on the sagittal and coronal views, respectively. Condyle and eminence inclinations were measured using cone beam computed tomography. RESULTS: Smaller horizontal condylar inclination was associated with ADDWoR (p < 0.05). Larger coronal condylar inclination was associated with ADDWR (p < 0.05) and LDD (p < 0.05). There was no association between sagittal eminence inclination and DD (p < 0.05). CONCLUSION: Medial condylar rotation in the axial view may be associated with ADDWoR. The condyle head horizontally inclined in the coronal view may be associated with ADDWR and LDD.

Mycobacterial and Plasmodium ovale-associated destruction of the jaw bones.

OBJECTIVES: The project aims were to identify infectious mechanisms responsible for an extreme form of mandibular osteonecrosis and osteomyelitis in West African populations and test the hypothesis that Mycobacterium tuberculosis plays a pivotal role. MATERIALS AND METHODS: DNA was extracted from mandibular fragments of 9 of 19 patients previously included in a prospective study leading to the mycobacterial hypothesis. Amplified DNAs were used for preparing libraries suitable for next-generation sequencing. For comparison of the whole-genome sequencing data of the 9 patients with DNAs of both microbiota and human tissues, DIAMOND v0.9.26 was used to align sequencing reads to NCBI-nr database and MEGAN 6 for taxonomy binning and identification of Mycobacterium tuberculosis strains. RESULTS: The data show that mandibular bone fragments of all 9 patients not only contain Homo sapiens and Mycobacterium tuberculosis DNAs; they also contain DNAs of Plasmodium ovale wallikeri, Staphylococcus aureus, Staphylococcus hominis, and Prevotella P3-120/intermedia; as well as large numbers of DNAs from other infectious components. CONCLUSIONS: The data obtained provide direct evidence to support the conclusion that combinations of Mycobacterium tuberculosis, Plasmodium ovale wallikeri, and other oral bacteria are involved in this particular type of mandibular destruction in West African individuals of many ages.

Electroactive composite scaffold with locally expressed osteoinductive factor for synergistic bone repair upon electrical stimulation.

Tissue engineering is a promising strategy for the repair of large-scale bone defects, in which scaffolds and growth factors are two critical issues influencing the efficacy of bone regeneration. Unfortunately, the broad application of growth factors is limited by their poor stability in the scaffolds. In the present study, the strictly controlled expression of human bone morphogenetic protein-4 (hBMP-4) in the presence of doxycycline is achieved by adding an hBMP-4 gene fragment into a non-viral artificial restructuring plasmid vector (pSTAR) to form the pSTAR-hBMP-4 plasmid (phBMP-4). Furthermore, the controlled release of phBMP-4 is obtained with an electroactive tissue engineering scaffold, generated by combining a triblock copolymer of poly(l-lactic acid)-block-aniline pentamer-block-poly(l-lactic acid) (PLA-AP) with poly(lactic-co-glycolic acid)/hydroxyapatite (PLGA/HA). This PLGA/HA/PLA-AP/phBMP-4 composite scaffold, with controlled gene release and Dox-regulated gene expression upon electrical stimulation, operating synergistically, exhibits an improved cell proliferation ability, enhanced osteogenesis differentiation in vitro, and effective bone healing in vivo in a rabbit radial defect model. Taking these results together, the proposed smart PLGA/HA/PLA-AP/phBMP-4 scaffold lays a solid theoretical and experimental basis for future applications of such multi-functional materials in bone tissue engineering to help patients in need.

Osteoblast autophagy in glucocorticoid-induced osteoporosis.

Administration of glucocorticoids is an effective strategy for treating many inflammatory and autoimmune diseases. However, glucocorticoid treatment can have adverse effects on bone, leading to glucocorticoid-induced osteoporosis (GIO), the most common form of secondary osteoporosis. Although the pathogenesis of GIO has been studied for decades, over the past ten years the autophagy machinery has been implicated as a novel mechanism. Autophagy in osteoblasts, osteocytes, and osteoclasts plays a critical role in the maintenance of bone homeostasis. Herein, we specifically discuss how osteoblast autophagy responds to glucocorticoids and its role in the development of GIO.

YAP regulates periodontal ligament cell differentiation into myofibroblast interacted with RhoA/ROCK pathway.

During orthodontic tooth movement (OTM), periodontal ligament cells (PDLCs) receive the mechanical stimuli and transform it into myofibroblasts (Mfbs). Indeed, previous studies have demonstrated that mechanical stimuli can promote the expression of Mfb marker α-smooth muscle actin (α-SMA) in PDLCs. Transforming growth factor ß1 (TGF-ß1), as the target gene of yes-associated protein (YAP), has been proven to be involved in this process. Here, we sought to assess the role of YAP in Mfbs differentiation from PDLCs. The time-course expression of YAP and α-SMA was manifested in OTM model in vivo as well as under tensional stimuli in vitro. Inhibition of RhoA/Rho-associated kinase (ROCK) pathway using Y27632 significantly reduced tension-induced Mfb differentiation and YAP expression. Moreover, overexpression of YAP with lentiviral transfection in PDLCs rescued the repression effect of Mfb differentiation induced by Y27632. These data together suggest a crucial role of YAP in regulating tension-induced Mfb differentiation from PDLC interacted with RhoA/ROCK pathway.

Recycle the dental fairy's package: overview of dental pulp stem cells.

Adult stem cells are excellent cell resource for cell therapy and regenerative medicine. Dental pulp stem cells (DPSCs) have been discovered and well known in various application. Here, we reviewed the history of dental pulp stem cell study and the detail experimental method including isolation, culture, cryopreservation, and the differentiation strategy to different cell lineage. Moreover, we discussed the future potential application of the combination of tissue engineering and of DPSC differentiation. This review will help the new learner to quickly get into the DPSC filed.

Nonuniformity in ligaments is a structural strategy for optimizing functionality.

Ligaments serve as compliant connectors between hard tissues. In that role, they function under various load regimes and directions. The 3D structure of ligaments is considered to form as a uniform entity that changes due to function. The periodontal ligament (PDL) connects the tooth to the bone and sustains different types of loads in various directions. Using the PDL as a model, employing a fabricated motorized setup in a microCT, we demonstrate that the fibrous network structure within the PDL is not uniform, even before the tooth becomes functional. Utilizing morphological automated segmentation methods, directionality analysis, as well as second harmonic generation imaging, we find high correlation between blood vessel distribution and fiber density. We also show a structural feature in a form of a dense collar around the neck of the tooth as well as a preferred direction of the fibrous network. Finally, we show that the PDL develops as a nonuniform structure, with an architecture designed to sustain specific types of load in designated areas. Based on these findings, we propose that ligaments in general should be regarded as nonuniform entities, structured already at developmental stages for optimal functioning under variable load regimes.

Glucosamine oral administration as an adjunct to hyaluronic acid injection in treating temporomandibular joint osteoarthritis.

OBJECTIVE: To investigate the therapeutic effect of oral glucosamine (GS) as an adjunct to hyaluronic acid (HA) injection on patients with temporomandibular joint osteoarthritis (TMJ OA). METHODS: In this clinical trial, 136 participants, diagnosed as TMJ OA clinically and radiographically, were enrolled and randomized into two groups (group GS + HA: oral GS + HA injection; group placebo + HA: oral placebo + HA injection). Pain, maximum interincisal mouth opening (MMO), the levels of IL-1ß, IL-6, and TGF-ß in TMJ synovial were defined as the outcome measurements and conducted before operation, and at 1-month and 1-year follow-up. RESULTS: In both groups, pain scores were decreased and MMOs were increased at 1-month and 1-year follow-up, the changes at 1-year follow-up showed statistically significant intergroup differences. At 1-month follow-up, only IL-6 concentration was lower in group GS + HA than that in group placebo + HA. One year later, TGF-ß concentration was higher and IL-6 and IL-1ß concentrations were lower in group GS + HA than those in group placebo + HA. CONCLUSIONS: Both strategies alleviated symptoms in short term, but the patients treated with GS benefited more than those with placebo in long term, which may be due to the suppression of IL-1ß and IL-6 and the stimulation of TGF-ß.

Transversal changes, space closure, and efficiency of conventional and self-ligating appliances : A quantitative systematic review.

OBJECTIVE: Self-ligating brackets (SLBs) were compared to conventional brackets (CBs) regarding their effectiveness on transversal changes and space closure, as well as the efficiency of alignment and treatment time. METHODS: All previously published randomized controlled clinical trials (RCTs) dealing with SLBs and CBs were searched via electronic databases, e.g., MEDLINE, Cochrane Central Register of Controlled Trials, EMBASE, World Health Organization International Clinical Trials Registry Platform, Chinese Biomedical Literature Database, and China National Knowledge Infrastructure. In addition, relevant journals were searched manually. Data extraction was performed independently by two reviewers and assessment of the risk of bias was executed using Cochrane Collaboration's tool. Discrepancies were resolved by discussion with a third reviewer. Meta-analyses were conducted using Review Manager (version 5.3). RESULTS: A total of 976 patients in 17 RCTs were included in the study, of which 11 could be produced quantitatively and 2 showed a low risk of bias. Meta-analyses were found to favor CB for mandibular intercanine width expansion, while passive SLBs were more effective in posterior expansion. Moreover, CBs had an apparent advantage during short treatment periods. However, SLBs and CBs did not differ in closing spaces. CONCLUSIONS: Based on current clinical evidence obtained from RCTs, SLBs do not show clinical superiority compared to CBs in expanding transversal dimensions, space closure, or orthodontic efficiency. Further high-level studies involving randomized, controlled, clinical trials are warranted to confirm these results.

Association of malocclusion, self-reported bruxism and chewing-side preference with oral health-related quality of life in patients with temporomandibular joint osteoarthritis.

OBJECTIVES: The aim of this study was to evaluate the association of oral health-related quality of life (OHRQoL) with malocclusion and self-reported bruxism and chewing-side preference (CSP) in patients with temporomandibular joint osteoarthritis (TMJ-OA). METHODS: This study involved 511 patients diagnosed with TMJ-OA. Each participant completed the Chinese version of the 14-item Oral Health Impact Profile (OHIP-C14) questionnaire and received a clinical examination concerning malocclusion (posterior crossbite, overbite, overjet and anterior open bite). Also patients' self-reported awake bruxism (AB), sleep bruxism (SB) and CSP based on the Oral Behavior Checklist (OBC) were recorded. The associations of OHIP-C14 with malocclusion and self-reported bruxism and CSP were assessed using multiple linear regression analysis. RESULTS: Posterior crossbite, overbite, overjet and anterior open bite were not significantly associated with either the total OHIP-C14 score or the scores of each domain of OHIP-C14. AB was significantly associated with both the total OHIP-C14 score and the scores of each domain with the largest standardised coefficients. CSP was significantly associated with both the total OHIP-C14 score and the scores of the psychological and social domains. SB was significantly associated with the scores of both the function limitation and psychological disability domains. CONCLUSIONS: Malocclusion is not significantly associated with OHRQoL in patients with TMJ-OA. Self-reported AB is highly associated with OHRQoL in patients with TMJ-OA, while self-reported SB and CSP are both moderately associated with OHRQoL in patients with TMJ-OA.

PEGylated stereocomplex polylactide coating of stent for upregulated biocompatibility and drug storage.

Treatment of coronary heart disease by percutaneous coronary intervention (PCT) is usually limited to the high restenosis rate after implantation of bare-metal stent. To solve the problem, the coating of PEGylated stereocomplex poly(l-lactide) (PEG-cPLA) was utilized on the surface modification of stainless steel (SS) sheet. Specifically, the 3-aminopropyltriethoxysilane (APTES)-modified methoxy-poly(ethylene glycol)-poly(d-lactide) (mPEG-PDLA) was grafted onto the surface of hydroxylated SS sheet through coupling reaction, and poly(l-lactide)-poly(ethylene glycol)-poly(l-lactide) (PLLA-PEG-PLLA) was coated onto the surface through stereocomplex interaction between DLA and LLA units. The increase of contact angle firstly confirmed the changes of surface composition and hydrophilicity for the PEG-scPLA-modified SS sheet. The decreased fibrinogen adsorption, down-regulated platelet activation, and improved adhesion of human umbilical vein endothelial cells (HUVECs) indicated the excellent biocompatibility of PEG-scPLA-modified SS sheet. In addition, the drug loading capability of SS sheet was greatly upregulated through the formation of scPLA coating on the surface, where fluorescein (FLU) was chosen as a model molecule. Overall, the surface modification of SS sheet with PEG-scPLA could enhance the comprehensive performances, such as biocompatibility and drug loading capability, demonstrating that PEG-scPLA is a promising coating of coronary stent for PCT.

Differences between active and passive self-ligating brackets for orthodontic treatment : Systematic review and meta-analysis based on randomized clinical trials.

PURPOSE: In orthodontic treatment, the effects of differences in the design between active and passive self-ligating bracket (ASLB and PSLB, respectively) are usually neglected. This study investigated differences in effectiveness and efficiency between ASLBs and PSLBs. METHODS: To identify randomized, controlled clinical trials (RCTs) comparing ASLB with PSLB, the electronic databases Medline, Embase, Cochrane Central Register of Controlled Trials, Chinese Biomedical Literature Database, China National Knowledge Infrastructure, and Chinese Medical Journal Database were searched without language or time limits. Relevant available dental journals and reference lists from included studies were manually searched for applicable reports. Meta-analyses were conducted with the Review Manager program. Two independent reviewers performed all search processes; disagreements were discussed with a third reviewer. RESULTS: Eight studies were included in the systematic review, of which six were included in the meta-analysis due to the data consistency. Three had a low risk of bias, four had an unclear risk of bias, and one had a high risk of bias. With regard to alignment efficiency, meta-analysis favors ASLB [mean difference (MD) -10.24 days, 95% confidence interval (CI) -17.68 to -2.80]. However, the same analysis does not favor either design in terms of width change due to treatment for intercanine (MD -0.49 mm, 95% CI -1.10 to 0.13 mm) interfirst premolar (MD -0.07 mm, 95% CI -0.69, 0.56 mm) intersecond premolar (MD -0.58 mm, 95% CI -1.25 to 0.08 mm) and intermolar (MD 0.10 mm, 95% CI -0.82 to 1.02 mm) width. CONCLUSIONS: Based on current clinical evidence from RCTs, ASLB appears to be more efficient for alignment, while neither design shows an advantage for width change. Further research is needed to confirm present results.

Sclerostin Promotes Bone Remodeling in the Process of Tooth Movement.

Tooth movement is a biological process of bone remodeling induced by mechanical force. Sclerostin secreted by osteocytes is mechanosensory and important in bone remodeling. However, little is known regarding the role of sclerostin in tooth movement. In this study, models of experimental tooth movement were established in rats and mice. Sclerostin expression was investigated with immunohistochemistry staining, and osteoclastic activity was analyzed with tartrate-resistant acid phosphatase (TRAP) staining. MLO-Y4 osteocyte-like cells underwent uniaxial compression and tension stress or were cultured in hypoxia conditions. Expression of sclerostin was assessed by RT-qPCR and ELISA. MLO-Y4 cells were cultured with recombinant human sclerostin (rhSCL) interference and then co-cultured with RAW264.7 osteoclast precursor cells. Expressions of RANKL and OPG were analyzed by RT-qPCR, and osteoclastic activity was assessed by TRAP staining. During tooth movement, sclerostin was expressed differently in compression and tension sites. In SOST knock-out mice, there were significantly fewer TRAP-positive cells than in WT mice during tooth movement in compression sites. In-vitro studies showed that the expression of sclerostin in MLO-Y4 osteocyte-like cells was not different under a uniaxial compression and tension force, whereas hypoxia conditions significantly increased sclerostin expression in MLO-Y4 cells. rhSCL interference increased the expression of RANKL and the RANKL/OPG ratio in MLO-Y4 cells and the osteoclastic induction ability of MLO-Y4 cells in experimental osteocyte-osteoclast co-culture. These data suggest that sclerostin plays an important role in the bone remodeling of tooth movement.

Correlation between oral health-related quality of life and clinical dysfunction index in patients with temporomandibular joint osteoarthritis.

We evaluated the correlation between oral health-related quality of life (OHRQoL) and the Helkimo clinical dysfunction index (HDI) in patients with temporomandibular joint osteoarthritis (TMJ OA). Clinical data and scores for the Chinese version of the 14-item Oral Health Impact Profile (OHIP-C14) were recorded and analyzed for 541 patients with TMJ OA. Each patient was assigned an HDI score of 1 to 25, which was used to classify severity into three categories. OHRQoL was assessed by using OHIP-C14 score, which ranged from 0 to 56. Both HDI score and severity were significantly correlated with total OHIP-C14 score (P < 0.001 for both comparisons). The scores for all HDI domains except function impairment (P = 0.205) were significantly correlated with OHIP-C14 score. The scores for all seven OHIP-C14 domains were significantly correlated with HDI score and severity. Several correlations between OHIP-C14 domains and HDI domain scores were significant. HDI score and severity were correlated with OHIP-C14 score in TMJ OA patients. As compared with function-related domains, pain-related HDI domains were more strongly inversely related to OHRQoL.(J Oral Sci 58, 483-490, 2016).

Effect of sclerostin removal in vivo on experimental periodontitis in mice.

We explored the effects of sclerostin removal in vivo on experimental periodontitis in mice. A ligature of Porphyromonas gingivalis-saturated collagen silk was applied to the cervical region of the first molar tooth in 10 wild-type (WT) mice and 10 sclerostin-knockout (SOST-KO) mice, and the animals were fed 10% sucrose for 2 months. Another 10 WT mice and 10 SOST-KO mice were similarly treated, but then fed a normal diet for 2 months. The maxillae were then harvested for morphological and molecular examinations. The mice with periodontitis showed significantly more severe alveolar bone loss than control mice, the most significant absorption being observed in WT mice. Immunohistochemical staining demonstrated upregulation of RANKL and ERK1/2-MAPK expression and downregulation of OPG expression in mice with periodontitis, especially WT mice. Therefore, removal of sclerostin appears to modestly protect the alveolar bone from resorption in this experimental setting. (J Oral Sci 58, 271-276, 2016).

Inhibition of Ape1 Redox Activity Promotes Odonto/osteogenic Differentiation of Dental Papilla Cells.

Dentinogenesis is the formation of dentin, a substance that forms the majority of teeth, and this process is performed by odontoblasts. Dental papilla cells (DPCs), as the progenitor cells of odontoblasts, undergo the odontogenic differentiation regulated by multiple cytokines and paracrine signal molecules. Ape1 is a perfect paradigm of the function complexity of a biological macromolecule with two major functional regions for DNA repair and redox regulation, respectively. To date, it remains unclear whether Ape1 can regulate the dentinogenesis in DPCs. In the present study, we firstly examed the spatio-temporal expression of Ape1 during tooth germ developmental process, and found the Ape1 expression was initially high and then gradually reduced along with the tooth development. Secondly, the osteo/odontogenic differentiation capacity of DPCs was up-regulated when treated with either Ape1-shRNA or E3330 (a specific inhibitor of the Ape1 redox function), respectively. Moreover, we found that the canonical Wnt signaling pathway was activated in this process, and E3330 reinforced-osteo/odontogenic differentiation capacity was suppressed by Dickkopf1 (DKK1), a potent antagonist of canonical Wnt signaling pathway. Taken together, we for the first time showed that inhibition of Ape1 redox regulation could promote the osteo/odontogenic differentiation capacity of DPCs via canonical Wnt signaling pathway.

Effect of mesiodistal angulation of the maxillary central incisors on esthetic perceptions of the smile in the frontal view.

INTRODUCTION: The purpose of this study was to analyze the effect of mesiodistal angulation of the maxillary central incisors on the smiling esthetics in young adults. METHODS: Frontal smile photographs of a young man and a young woman were digitally modified to produce 28 smile images that were grouped into 4 series. These images were judged using visual analog scales by 52 orthodontists and 61 laypeople. The effects of the judges' professions, subjects' sexes, and photograph framings on the appreciation of smile esthetics with different mesiodistal angulations of the maxillary central incisors were evaluated. The data were analyzed with paired t tests, Dunnett t tests, and independent samples t tests; statistical significance was set at P <0.05. RESULTS: The images were ranked less attractive as the mesiodistal angulation of the maxillary central incisors increased during smiling. No relationship was found between the judges' professions and the esthetic evaluations of incisal angulation, but the statistical analysis showed that both the subject's sex and the photograph framing were significant variables (P <0.05). CONCLUSIONS: The mesiodistal angulation of the maxillary central incisors plays an essential role in smile esthetics in the frontal view. When formulating treatment plans, orthodontists should never underestimate the influence of mesiodistal angulation on smile attractiveness.