Publications by authors named "Szu-Ting Chou"

29 Publications

  • Page 1 of 1

Importance in the Occurrence Distribution of Minimum Oropharyngeal Cross-Sectional Area in the Different Skeletal Patterns Using Cone-Beam Computed Tomography.

Biomed Res Int 2021 4;2021:5585629. Epub 2021 May 4.

Department of Orthodontics, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan.

Purpose: Obstructive sleep apnea is a condition involving repetitive partial or complete collapse of the pharyngeal airway, especially in patient with mandibular hypoplasia. The present study investigated the differences between the volume of the oropharyngeal airway and the minimum axial area in three skeletal patterns through the use of cone-beam computed tomography (CBCT).

Materials And Methods: CBCT scans of 147 patients were collected to measure the upper oropharyngeal airway volume (UOV), lower oropharyngeal airway volume (LOV), upper oropharyngeal airway area (UOA), minimum upper oropharyngeal airway area (MUOA), lower oropharyngeal airway area (LOA), minimum lower oropharyngeal airway area (MLOA), anatomical structures (orbitale, Or; porion, Po; pogonion, Pog; hyoid, H; second cervical vertebra, C2; fourth cervical vertebra, C4), and relevant angles. Statistical analysis was performed using analysis of variance and Pearson's test.

Results: Compared with patients in Class II, those in Class III and Class I exhibited a significantly anterior position of H and Pog. The vertical positions of H and Pog revealed no significant difference between the three skeletal patterns. Patients in skeletal Class III exhibited significantly larger oropharyngeal area (UOA, MUOA, LOA, MLOA) and oropharyngeal airway (UOV and LOV) than those in skeletal Class II did. The horizontal position of Pog had a moderately significant correlation with UOA ( = 0.471) and MUOA ( = 0.455).

Conclusion: Patients in skeletal Class II had significantly smaller oropharyngeal airway areas and volumes than those in Class III did. The minimum oropharyngeal cross-sectional area had a 67% probability of occurrence in the upper oropharyngeal airway among patients in Class I and Class II and a 50% probability of occurrence among patients in Class III.
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http://dx.doi.org/10.1155/2021/5585629DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8116163PMC
May 2021

Morphology of Sella Turcica and Bridging Prevalence Correlated with Sex and Craniofacial Skeletal Pattern in Eastern Asia Population: CBCT Study.

Biomed Res Int 2021 22;2021:6646406. Epub 2021 Mar 22.

School of Dentistry, College of Dental Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.

Purpose: Sella turcica bridging (STB) refers to a rare anatomical variation formed by the ossification of the ligament between the anterior and posterior clinoid processes. The presence of the STB was significantly correlated with craniofacial skeleton classification and a higher prevalence rate in skeletal Class III. The current study is aimed at investigating the dimensions of sella turcica and the prevalence of STB in different sexes and on the three craniofacial skeletal patterns using cone beam computed tomography (CBCT).

Materials And Methods: A total of 159 adults (66 males and 93 females), including 3 different craniofacial skeletal patterns (skeletal Classes I, II, and III), were included in the study. The sella turcica dimensions and the prevalence of STB were calculated. An independent -test and generalized linear model were used to compare the differences in the sella turcica dimensions and the skeletal relations. The Spearman rank correlation coefficient was used to analyze the correlations between sella turcica dimensions and skeletal relation.

Results: The sella length (SL) was 11.05 ± 1.80 mm for males and 10.77 ± 1.56 mm for females. The anterior clinoid distance (ACD) which was measured for the anterior width of sella turcica showed 25.83 ± 2.04 mm and 24.04 ± 2.28 mm for males and females, respectively ( < 0.0001). The overall percentage of complete bridging and partial bridging was 6.6% and 56.9%, respectively. Complete bridges were more common in males (males: 9.1%, females: 4.8%), and partial bridges were more frequent in females (males: 49.2%, females: 62.4%). Both sexes differed with respect to sella turcica dimensions. Moreover, males had a significantly larger ACD, posterior clinoid distance (PCD), and diameter of sella turcica (DST), on both sides, relative to females.

Conclusion: The prevalence rate of complete STB in the Taiwanese population was 6.6%. Significant differences between sexes were found in sella turcica dimensions. The prevalence rates of STB as well as the sella turcica dimensions did not significantly differ between different craniofacial skeletal patterns (skeletal Classes I, II, and III).
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http://dx.doi.org/10.1155/2021/6646406DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8009724PMC
May 2021

Evaluation of pharyngeal airway volume for different dentofacial skeletal patterns using cone-beam computed tomography.

J Dent Sci 2021 Jan 16;16(1):51-57. Epub 2020 Aug 16.

School of Dentistry, Kaohsiung Medical University, Kaohsiung, Taiwan.

Background/purpose: Understanding of the three-dimensional airway space in three skeletal patterns is important in orthodontic treatment. This study investigated differences between the volume of pharyngeal airway sections and the smallest cross-sectional area in three skeletal patterns by using cone-beam computed tomography (CBCT).

Materials And Methods: The 90 patients were collected to measure total pharyngeal airway volume (TP), velopharyngeal airway volume (VP), glossopharyngeal airway volume (GP), oropharyngeal airway volume (OP), hypopharyngeal airway volume (HP), and the smallest cross-sectional areas (SCA) of the upper respiratory tract as well as other relevant anatomical structures. The mean values differences between classes were analyzed using ANOVA. Pearson's test was used to compare classes in terms of the correlations between different factors.

Results: Patients in skeletal classes I and III exhibited significantly higher SCA values (322.6 mmand 344.5 mm respectively) than those in skeletal class II (240.8 mm). Subjects from skeletal classes I and III exhibited significantly higher values of VP, HP, and OP than those in skeletal class II. Skeletal classes I and III exhibited significantly higher TP values (31190.1 mm and 30696.2 mm, respectively) than those in skeletal class II (22386.0 mm). Non-significant relationships were discovered between pharyngeal airway and skeletal pattern. Conversely, significant relationships were found between TP and gender, ANB, SNB, hyoid and pogonion positions.

Conclusion: The skeletal class II has smaller airway volume than those in skeletal class I and III. The pharyngeal airway volumes could serve as a guide in differentiating the different skeletal classes in clinical settings.
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http://dx.doi.org/10.1016/j.jds.2020.07.015DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7770282PMC
January 2021

Importance in the occurrence rate of shortest buccal bone marrow distance (<1 mm) for sagittal split ramus osteotomy.

J Formos Med Assoc 2021 Jan 1;120(1 Pt 3):697-704. Epub 2020 Aug 1.

School of Dentistry and Graduate Program of Dental Science, College of Dental Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan; Department of Orthodontics, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan. Electronic address:

Background/purpose: The neurosensory disturbance is a common complication following sagittal split ramus osteotomy (SSRO) whereas the shortest buccal bone marrow (SBM) is an important risk factor. The present study aimed to investigate the relationship between the occurrence rates of SBM among three skeletal patterns.

Methods: The cone-beam computed tomography (CBCT) images of 90 participants were divided into skeletal Class I, II, and III. There were six horizontal planes separated apart by a 2 mm interval; it started with plane 0 (original intact mandibular canal) to plane 5 which was 10 mm below. The data of SBM were divided into two groups (SBM ≥ 1 mm and SBM < 1 mm). With an SBM value < 1 mm, we defined a high occurrence rate of postoperative neurosensory abnormality or unfavorable split.

Results: The Class III patients had the smallest SBM value (1.31-1.75 mm) whereas the Class II patients had the largest SBM value (1.57-2.09 mm). For the Class III patients, the highest and lowest occurrence rates of SBM were 56.5% and 43.5% respectively. For the Class II patients, the highest and lowest occurrence rates of SBM were 37.1% and 17.7% respectively. The patients with Class III malocclusion had higher occurrence rates of SBM than the patients with Class II malocclusion.

Conclusion: Class III had a significantly higher occurrence of probability (SBM < 1 mm) than Class II. Therefore, patients with Class III were more likely to experience postoperative neurosensory abnormalities and unfavorable split than patients with Class II.
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http://dx.doi.org/10.1016/j.jfma.2020.07.030DOI Listing
January 2021

Effects of cortical bone thickness and trabecular bone density on primary stability of orthodontic mini-implants.

J Dent Sci 2019 Dec 20;14(4):383-388. Epub 2019 Jul 20.

School of Dentistry and Graduate Program of Dental Science (Orthodontics), College of Dental Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.

Background/purpose: Mini-implant screws are now routinely used as anchorage devices in orthodontic treatments. This study used synthetic bone models to investigate how the primary stability of an orthodontic mini-implant (OMI) as measured by resonance frequency (RF) is affected by varying cortical bone thickness and trabecular bone density.

Materials And Methods: Three synthetic cortical shells (thicknesses of 1, 2, and 3 mm) and three polyurethane foam blocks (densities of 40, 20, and 10 pound/cubic foot) were used to represent jawbones of varying cortical bone thicknesses and varying trabecular bone densities. Twenty-five stainless steel OMIs (2 × 10 mm) were sequentially inserted into artificial bone blocks to depths of 2, 4, and 6 mm. Five experimental groups of bone blocks with OMIs were examined by Implomates® RF analyzer. Statistical and correlation analyses were performed by Kruskal-Wallis test, Wilcoxon rank-sum test, and simple linear regression.

Results: As trabecular bone density decreased, RF decreased; as cortical bone thickness decreased, RF also decreased. Simple linear regression analysis showed highly linear correlations between trabecular bone density and RF (  > 0.99;  < 0.0001) and between cortical bone thickness and RF (  > 0.98;  < 0.0001).

Conclusion: The stability of an OMI at the time of placement is influenced by both cortical bone thickness and trabecular bone density. Both cortical bone thickness and trabecular bone density have strong linear correlations with RF.
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http://dx.doi.org/10.1016/j.jds.2019.06.002DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6921117PMC
December 2019

Recognizing the peak bone mass (age 30) as a cutoff point to achieve the success of orthodontic implants.

Odontology 2020 Jul 4;108(3):503-510. Epub 2019 Dec 4.

School of Dentistry, College of Dental Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.

The aim of present study was to investigate the critical risk factor (age 30: peak bone mass) to evaluate the success of orthodontic implants. A total of 426 orthodontic implants were placed in 270 patients as orthodontic anchorages. Data were analyzed according to patient's characteristics, location of placement, implant categories, and orthodontic force. The young patients were the age ≤ 30 years and the older patients were the age > 30 years. Statistical analysis was performed and a p value < 0.05 was considered to indicate statistical significance. The Chi-square or Fisher exact test was used depending on sample sizes. The null hypothesis was no statistically significant correlation between age ≤ 30 years and age > 30 years. The overall success rate (with and without predrill) was 89.2%. The success rate of orthodontic implants was significantly larger in younger patients (89.9%) than in older patients (76.1%). Recognizing age-related factor in the success rates, older patient (> 30 years) were significant lower than young patients (≤ 30 years) in the gender (female and male), malocclusion (Class II), facial pattern (ortho and hyperdivergent), location (infrazygomatic crest), jaw (maxilla), side (right), material (titanium and stainless), length (9 mm and 10 mm), diameter (2 mm), load (< 3 weeks), and force (intrusion). Therefore, the null hypothesis was rejected. Age 30 is a cutoff point to achieve the success of orthodontic implants. The success rates of older patients (age > 30 years) were significant lower than young patients (age ≤ 30 years), especially in female.
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http://dx.doi.org/10.1007/s10266-019-00476-wDOI Listing
July 2020

Targeting Cancer with Peptide RNAi Nanoplexes.

Methods Mol Biol 2019 ;1974:161-180

AparnaBio, Inc., Gaithersburg, MD, USA.

With the recent explosion of genomic information on the root causes of disease, there is an increased interest in nucleic acid therapeutics, including siRNA and gene therapy, all of which require delivery of highly charged nucleic acids from siRNA with a molecular weight of about 1.4 × 10 to plasmids with an approximate molecular weight of 2.0-3.0 × 10. This chapter describes the delivery of shRNA via plasmid or siRNA with a peptide-based carrier. We focus on the histidine-lysine peptide which serves as an example for other peptides and polymeric carrier systems. When the HK peptide and nucleic acids are mixed together and interact with one another through ionic and nonionic interactions, nanoplexes are formed. These nanoplexes, carrying either shRNA or siRNA that target oncogenes, provide promising options for the treatment of cancer. We describe methods of preparation and characterization of these nanoplexes using dynamic light scattering, zeta potential, and gel retardation assays. We also provide protocols for transfection in vitro and in vivo for these nanoplexes.
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http://dx.doi.org/10.1007/978-1-4939-9220-1_12DOI Listing
November 2019

Comparison of Pharyngeal Airway between Mandibular Setback Surgery Patients (Skeletal Class III) and Nonsurgery Patients (Skeletal Classes I and II).

Biomed Res Int 2019 17;2019:5012037. Epub 2019 Mar 17.

Graduate Institute of Dental Sciences, School of Dental Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.

Purpose: We investigated the pharyngeal airway dimensions and their correlations in patients who underwent mandibular setback surgery versus those who did not.

Materials And Methods: One hundred and sixty cephalometric radiographs (120 patients) were obtained from patients with three skeletal malocclusion classifications: Class I and Class II in the nonsurgery group and Class III in the surgery group (preoperative and postoperative cephalograms). The following dimensions were measured: nasopharyngeal airway (NOP), uvulopharyngeal airway (UOP), shortest distance from the posterior tongue to the pharyngeal wall (TOP), and distance from the epiglottis to the pharyngeal wall (EOP). Paired test, one-way analysis of variance, and Pearson correlation coefficients were used for statistical analysis.

Results: Preoperatively, UOP and TOP of skeletal Class III patients (15.2 mm and 16.6 mm) were significantly larger than those of skeletal Class II (11.5 mm and 12 mm) and Class II (12.3 mm and 12.9 mm) patients, respectively. No differences were observed in EOP between the three skeletal patterns. The hyoid bone of Class III patients was significantly anterior to that of Class I/II patients. Furthermore, UOP had a moderate negative correlation with soft palate length. Postoperatively, no significant difference (UOP, TOP, EOP, soft palate width, and hyoid bone) was found between the skeletal classes.

Conclusion: Preoperatively, UOP and TOP of skeletal Class III patients were significantly wider than those of skeletal Class I/II patients. Pre- and postoperatively, EOP did not exhibit significant differences among the three skeletal classifications. No differences were found in all postoperative pharyngeal airway dimensions between Class III patients and nonsurgery patients (Class I and Class II).
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http://dx.doi.org/10.1155/2019/5012037DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6441503PMC
August 2019

A prospective study of factors associated with orthodontic mini-implant survival.

J Oral Sci 2016 ;58(4):515-521

School of Dentistry, Kaohsiung Medical University.

The orthodontic mini-implant (MI) is a widely used anchorage device in orthodontic treatment. This prospective study analyzed MI survival and factors associated with MI survival in 139 patients (114 females and 25 males; average age, 25.7 years; age range, 12-56 years) who had received orthodontic treatment with MIs. Survival analysis and Kaplan-Meier curves were used to identify clinical variables associated with MI survival. For the 254 MIs investigated, the overall success rate was 85.8%, and the 1-year cumulative survival rate was 81.6%. MI survival was significantly associated with patient age and MI size. Notably, MI survival was significantly longer in patients aged 20-30 years than in older patients. The Cox proportional-hazards model revealed a 5% increase in failure risk for every 1-year increase in age among participants older than 30 years. Additionally, MI failure risk was inversely associated with MI length. MIs are generally reliable anchorage devices for orthodontic treatment but should be used with caution in older patients, due to the higher rate of failure in that population. Another important factor in MI survival is implant size. Future studies should attempt to clarify associations between MI survival and clinical variables.(J Oral Sci 58, 515-521, 2016).
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http://dx.doi.org/10.2334/josnusd.16-0145DOI Listing
November 2017

Simultaneous blockade of interacting CK2 and EGFR pathways by tumor-targeting nanobioconjugates increases therapeutic efficacy against glioblastoma multiforme.

J Control Release 2016 12 5;244(Pt A):14-23. Epub 2016 Nov 5.

Nanomedicine Research Center, Department of Neurosurgery, Cedars-Sinai Medical Center, Los Angeles, California, USA.

Glioblastoma multiforme (GBM) remains the deadliest brain tumor in adults. GBM tumors are also notorious for drug and radiation resistance. To inhibit GBMs more effectively, polymalic acid-based blood-brain barrier crossing nanobioconjugates were synthesized that are delivered to the cytoplasm of cancer cells and specifically inhibit the master regulator serine/threonine protein kinase CK2 and the wild-type/mutated epidermal growth factor receptor (EGFR/EGFRvIII), which are overexpressed in gliomas according to The Cancer Genome Atlas (TCGA) GBM database. Two xenogeneic mouse models bearing intracranial human GBMs from cell lines LN229 and U87MG that expressed both CK2 and EGFR at different levels were used. Simultaneous knockdown of CK2α and EGFR/EGFRvIII suppressed their downstream prosurvival signaling. Treatment also markedly reduced the expression of programmed death-ligand 1 (PD-L1), a negative regulator of cytotoxic lymphocytes. Downregulation of CK2 and EGFR also caused deactivation of heat shock protein 90 (Hsp90) co-chaperone Cdc37, which may suppress the activity of key cellular kinases. Inhibition of either target was associated with downregulation of the other target as well, which may underlie the increased efficacy of the dual nanobioconjugate that is directed against both CK2 and EGFR. Importantly, the single nanodrugs, and especially the dual nanodrug, markedly suppressed the expression of the cancer stem cell markers c-Myc, CD133, and nestin, which could contribute to the efficacy of the treatments. In both tumor models, the nanobioconjugates significantly increased (up to 2-fold) animal survival compared with the PBS-treated control group. The versatile nanobioconjugates developed in this study, with the abilities of anti-cancer drug delivery across biobarriers and the inhibition of key tumor regulators, offer a promising nanotherapeutic approach to treat GBMs, and to potentially prevent drug resistance and retard the recurrence of brain tumors.
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http://dx.doi.org/10.1016/j.jconrel.2016.11.001DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5308909PMC
December 2016

Palatal bone thickness and associated factors in adult miniscrew placements: A cone-beam computed tomography study.

Kaohsiung J Med Sci 2015 May 5;31(5):265-70. Epub 2015 Mar 5.

Department of Orthodontics, Dental Clinics, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan. Electronic address:

Palatal bone thickness measurements obtained by cone-beam computed tomography (CBCT) in 30 men and 28 women were evaluated for associated factors. Palatal bone thickness was measured at 20 locations unilateral to the midpalatal suture and posterior to the incisive foramen. Tongue position, presence of posterior crossbite, and palatal morphology were recorded. Lateral cephalograms acquired from CBCT data were used to calculate Frankfort-mandibular plane angles (FMA). At almost all sites, bone thickness was greater in males than in females, but the difference was statistically significant at only seven sites. Bone thickness showed no associations with tongue position, palatal morphology, or presence of posterior crossbite. In women, FMA significantly correlated with bone thickness at 12 locations. In conclusion, palatal bone thickness is unassociated with tongue position, posterior crossbite, or palatal morphology. In hyperdivergent women, however, available bone may be smaller than normal in the middle and posterior palatal areas; in such cases, a shorter than normal miniscrew may be needed to avoid penetrating the nasal cavity.
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http://dx.doi.org/10.1016/j.kjms.2015.02.002DOI Listing
May 2015

siRNA nanoparticles: the future of RNAi therapeutics for oncology?

Nanomedicine (Lond) 2014 Oct;9(15):2251-4

Department of Pathology, University of Maryland School of Medicine, 10 South Pine Street, University of Maryland, Baltimore, MD 21201, USA.

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http://dx.doi.org/10.2217/nnm.14.157DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4788000PMC
October 2014

Increased tumor distribution and expression of histidine-rich plasmid polyplexes.

J Gene Med 2014 Sep-Oct;16(9-10):317-28

Department of Pathology, University Maryland School of Medicine, Baltimore, MD, USA.

Background: Selecting nonviral carriers for in vivo gene delivery is often dependent on determining the optimal carriers from transfection assays in vitro. The rationale behind this in vitro strategy is to cast a net sufficiently wide to identify the few effective carriers of plasmids for in vivo studies. Nevertheless, many effective in vivo carriers may be overlooked by this strategy because of the marked differences between in vitro and in vivo assays.

Methods: After solid-phase synthesis of linear and branched histidine/lysine (HK) peptides, the two peptide carriers were compared for their ability to transfect MDA-MB-435 tumor cells in vitro and then in vivo.

Results: By contrast to their transfection activity in vitro, the linear H2K carrier of plasmids was far more effective in vivo compared to the branch H2K4b. Surprisingly, negatively-charged polyplexes formed by the linear H2K peptide gave higher transfection in vivo than did those with a positive surface charge. To examine the distribution of plasmid expression within the tumor from H2K polyplexes, we found widespread expression by immunohistochemical staining. With a fluorescent tdTomato expressing-plasmid, we confirmed a pervasive distribution and gene expression within the tumor mediated by the H2K polyplex.

Conclusions: Although mechanisms underlying the efficiency of gene expression are probably multifactorial, unpacking of the H2K polyplex within the tumor appears to have a significant role. Further development of these H2K polyplexes represents an attractive approach for plasmid-based therapies of cancer.
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http://dx.doi.org/10.1002/jgm.2807DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4242722PMC
June 2015

Direct observation of dynamic mechanical regulation of DNA condensation by environmental stimuli.

Angew Chem Int Ed Engl 2014 Sep 21;53(40):10631-5. Epub 2014 Aug 21.

Fischell Department of Bioengineering, University of Maryland, College Park, MD 20742 (USA).

Gene delivery is a promising way to treat hereditary diseases and cancer; however, there is little understanding of DNA:carrier complex mechanical properties, which may be critical for the protection and release of nucleic acids. We applied optical tweezers to directly measure single-molecule mechanical properties of DNA condensed using 19-mer poly-L-lysine (PLL) or branched histidine-lysine (HK) peptides. Force-extension profiles indicate that both carriers condense DNA actively, showing force plateaus during stretching and relaxation cycles. As the environment such as carrier concentration, pH, and the presence of zinc ions changes, DNA:HK complexes showed dynamically regulated mechanical properties at multiple force levels. The fundamental knowledge from this study can be applied to design a mechanically tailored complex which may enhance transfection efficiency by controlling the stability of the complex temporally and spatially.
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http://dx.doi.org/10.1002/anie.201403499DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5517097PMC
September 2014

Enhancement of antifungal activity by integrin-targeting of branched histidine rich peptides.

J Drug Target 2014 Jul 14;22(6):536-42. Epub 2014 Apr 14.

Aparna Biosciences Corp , Rockville, MD , USA .

The treatment of invasive candidiasis associated with growing numbers of immunocompromised patients remains a major challenge complicated by increasing drug resistance. A novel class of branched histidine-lysine (bHK) peptides has promising antifungal activity, and exhibits a mechanism similar to natural histatins, and thus may avoid drug resistance. The present studies evaluate ligand targeting of bHK peptides to fungal surface integrins by determining whether a cyclic RGD (cRGD) peptide with a large PEG linker could enhance bHK peptide antifungal activity. Whereas conjugates containing only the PEG linker reduced bHK peptide activity, conjugates with the cRGD-PEG ligand resulted in marked enhancement of activity against Candida albicans. This study provides the first demonstration of benefit from ligand targeting of antifungal agents to fungal surface receptors.
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http://dx.doi.org/10.3109/1061186X.2014.905948DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4072455PMC
July 2014

Orthodontic treatment for a mandibular prognathic girl of short stature under growth hormone therapy.

J Formos Med Assoc 2013 Dec 5;112(12):801-6. Epub 2012 Sep 5.

Department of Dentistry, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan; School of Dentistry, College of Dental Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan. Electronic address:

This report presents a case of a 12-year-old girl with maxillary deficiency, mandibular prognathism, and facial asymmetry, undergoing growth hormone (GH) therapy due to idiopathic short stature. Children of short stature with or without GH deficiency have a deviating craniofacial morphology with overall smaller dimensions; facial retrognathism, especially mandibular retrognathism; and increased facial convexity. However, a complete opposite craniofacial pattern was presented in our case of a skeletal Class III girl with idiopathic short stature. The orthodontic treatment goal was to inhibit or change the direction of mandibular growth and stimulate the maxillary growth of the girl during a course of GH therapy. Maxillary protraction and mandibular retraction were achieved using occipitomental anchorage (OMA) orthopedic appliance in the first stage of treatment. In the second stage, the patient was treated with a fixed orthodontic appliance using a modified multiple-loop edgewise archwire technique of asymmetric mechanics and an active retainer of vertical chin-cup. The treatment led to an acceptable facial profile and obvious facial asymmetry improvement. Class I dental occlusion and coincident dental midline were also achieved. A 3½-year follow-up of the girl at age 18 showed a stable result of the orthodontic and dentofacial orthopedic treatment. Our case shows that the OMA orthopedic appliance of maxillary protraction combined with mandibular retraction is effective for correcting skeletal Class III malocclusion with midface deficiency and mandibular prognathism in growing children with idiopathic short stature undergoing GH therapy.
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http://dx.doi.org/10.1016/j.jfma.2012.07.021DOI Listing
December 2013

Enhanced silencing and stabilization of siRNA polyplexes by histidine-mediated hydrogen bonds.

Biomaterials 2014 Jan 22;35(2):846-55. Epub 2013 Oct 22.

Department of Pathology, University of Maryland Baltimore, MSTF Building, 10 South Pine Street, Baltimore, MD 21201, United States; Department of Chemical and Biomolecular Engineering, University of Maryland, College Park, MD 20742, United States. Electronic address:

Branched peptides containing histidines and lysines (HK) have been shown to be effective carriers for DNA and siRNA. We anticipate that elucidation of the binding mechanism of HK with siRNA will provide greater insight into the self-assembly and delivery of the HK:siRNA polyplex. Non-covalent bonds between histidine residues and nucleic acids may enhance the stability of siRNA polyplexes. We first compared the polyplex biophysical properties of a branched HK with those of branched asparagine-lysine peptide (NK). Consistent with siRNA silencing experiments, gel electrophoresis demonstrated that the HK siRNA polyplex maintained its integrity with prolonged incubation in serum, whereas siRNA in complex with NK was degraded in a time-dependent manner. Isothermal titration calorimetry of various peptides binding to siRNA at pH 7.3 showed that branched polylysine, interacted with siRNA was initially endothermic, whereas branched HK exhibited an exothermic reaction at initial binding. The exothermic interaction indicates formation of non-ionic bonds between histidines and siRNA; purely electrostatic interaction is entropy-driven and endothermic. To investigate the type of non-ionic bond, we studied the protonation state of imidazole rings of a selectively (15)N labeled branched HK by heteronuclear single quantum coherence NMR. The peak of Nδ1-H tautomers of imidazole shifted downfield (in the direction of deprotonation) by 0.5-1.0 ppm with addition of siRNA, providing direct evidence that histidines formed hydrogen bonds with siRNA at physiological pH. These results establish that histidine-rich peptides form hydrogen bonds with siRNA, thereby enhancing the stability and biological activity of the polyplex in vitro and in vivo.
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http://dx.doi.org/10.1016/j.biomaterials.2013.10.019DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3920840PMC
January 2014

Morphometric analysis of the cranial base in Asians.

Odontology 2014 Jan 2;102(1):81-8. Epub 2013 Feb 2.

Department of Orthodontics, Dental Clinics, Kaohsiung Medical University Hospital, Kaohsiung, 80756, Taiwan,

This study tested the hypothesis that developmental heterogeneity in cranial base morphology increases the prevalence of Class III malocclusion and mandibular prognathism in Asians. Thin-plate spline (TPS) graphical analysis of lateral cephalometric radiographs of the cranial base and the upper midface configuration were compared between a European-American group (24 females and 31 males) and four Asian ethnic groups (100 Chinese, 100 Japanese, 100 Korean and 100 Taiwanese; 50 females and 50 males per group) of young adults with clinically acceptable occlusion and facial profiles. Procrustes analysis was performed to identify statistically significant differences in each configuration of landmarks (P < 0.001). The TPS graphical analysis revealed that the greatest differences of Asians were the horizontal compression and vertical expansion in the anterior portion of the cranial base and upper midface region. The most posterior cranial base region also showed horizontal compression between the basion and Bolton point, with forward displacement of the articulare. Facial flatness and anterior displacement of the temporomandibular joint, resulting from a relative retrusion of the nasomaxillary complex and a relative forward position of the mandible were also noted. These features that tend to cause a prognathic mandible and/or retruded midface indicate a morphologic predisposition of Asian populations for Class III malocclusion.
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http://dx.doi.org/10.1007/s10266-012-0096-8DOI Listing
January 2014

Surface-modified HK:siRNA nanoplexes with enhanced pharmacokinetics and tumor growth inhibition.

Biomacromolecules 2013 Mar 14;14(3):752-60. Epub 2013 Feb 14.

Department of Pathology, University of Maryland Baltimore, MSTF Building, 10 South Pine Street, Baltimore, MD 21201, USA.

We characterized in this study the pharmacokinetics and antitumor efficacy of histidine-lysine (HK):siRNA nanoplexes modified with PEG and a cyclic RGD (cRGD) ligand targeting αvβ3 and αvβ5 integrins. With noninvasive imaging, systemically administered surface-modified HK:siRNA nanoplexes showed nearly 4-fold greater blood levels, 40% higher accumulation in tumor tissue, and 60% lower luciferase activity than unmodified HK:siRNA nanoplexes. We then determined whether the surface-modified HK:siRNA nanoplex carrier was more effective in reducing MDA-MB-435 tumor growth with an siRNA targeting Raf-1. Repeated systemic administration of the selected surface modified HK:siRNA nanoplexes targeting Raf-1 showed 35% greater inhibition of tumor growth than unmodified HK:siRNA nanoplexes and 60% greater inhibition of tumor growth than untreated mice. The improved blood pharmacokinetic results and tumor localization observed with the integrin-targeting surface modification of HK:siRNA nanoplexes correlated with greater tumor growth inhibition. This investigation reveals that through control of targeting ligand surface display in association with a steric PEG layer, modified HK: siRNA nanoplexes show promise to advance RNAi therapeutics in oncology and potentially other critical diseases.
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http://dx.doi.org/10.1021/bm3018356DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3595641PMC
March 2013

Influence of different implant materials on the primary stability of orthodontic mini-implants.

Kaohsiung J Med Sci 2012 Dec 28;28(12):673-8. Epub 2012 Jul 28.

Department of Orthodontics, Dental Clinics, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan.

This study evaluates the influence of different implant materials on the primary stability of orthodontic mini-implants by measuring the resonance frequency. Twenty-five orthodontic mini-implants with a diameter of 2 mm were used. The first group contained stainless steel mini-implants with two different lengths (10 and 12 mm). The second group included titanium alloy mini-implants with two different lengths (10 and 12 mm) and stainless steel mini-implants 10 mm in length. The mini-implants were inserted into artificial bones with a 2-mm-thick cortical layer and 40 or 20 lb/ft(3) trabecular bone density at insertion depths of 2, 4, and 6 mm. The resonance frequency of the mini-implants in the artificial bone was detected with the Implomates(®) device. Data were analyzed by two-way analysis of variance followed by the Tukey honestly significant difference test (α = 0.05). Greater insertion depth resulted in higher resonance frequency, whereas longer mini-implants showed lower resonance frequency values. However, resonance frequency was not influenced by the implant materials titanium alloy or stainless steel. Therefore, the primary stability of a mini-implant is influenced by insertion depth and not by implant material. Insertion depth is extremely important for primary implant stability and is critical for treatment success.
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http://dx.doi.org/10.1016/j.kjms.2012.04.037DOI Listing
December 2012

Buffering capacity and size of siRNA polyplexes influence cytokine levels.

Mol Ther 2012 Dec 2;20(12):2282-90. Epub 2012 Oct 2.

Department of Pathology, University of Maryland School of Medicine, Baltimore, MD 21201, USA.

Induction of cytokines by small interfering RNA (siRNA) polyplexes has been a significant concern of researchers attempting to minimize the toxicity of this promising therapy. Although cationic carriers of siRNA are known to increase cytokine levels, few systematic studies have been done to determine what properties of the carrier are important to modulate cytokines. Because branched histidine-lysine (HK) peptides are effective carriers of siRNA and their sequence can be readily modified, we selected this class of carrier to determine which sequences of the peptide were important for cytokine induction. With the use of peripheral blood mononuclear cells (PBMCs), the HK peptide with a higher number of histidines (H3K(+H)4b) in complex with siRNA induced lower levels of cytokines compared with other HK (e.g., H2K4b, H3K4b, H3K(+N)4b) siRNA nanoplexes. Notably, these peptides' siRNA polyplexes showed a similar pattern of cytokine induction when injected intravenously in a mouse model, i.e., the HK with higher content of histidines induced cytokines the least. As indicated by the pH-sensitive dye within acidic endosomes, the greater pH-buffering capacity of H3K(+H)4b compared with other HK peptides may explain why cytokine levels were reduced. In addition to buffering capacity, the size of HK polyplexes markedly influenced cytokine production.
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http://dx.doi.org/10.1038/mt.2012.206DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3519993PMC
December 2012

An interdisciplinary treatment approach combining orthodontic forced eruption with immediate implant placement to achieve a satisfactory treatment outcome: a case report.

Clin Implant Dent Relat Res 2013 Feb 11;15(1):113-20. Epub 2011 Jul 11.

Division of Periodontics, Kaohsiung Medical University Hospital, No. 100 Shih-Chuan 1st Rd., Kaohsiung, Taiwan.

Background: Periodontal disease often results in severely bony defects around the teeth and leads to eventual extraction. Remaining bone morphology often compromises ideally restoration-driven positions and deteriorates the success rates for dental implants.

Purpose: The present investigation illustrates the clinical outcome of immediately installing an implant following orthodontic forced eruption and atraumatic extraction.

Material And Methods: The subject of this study is a 40-year-old Asian female with a right mandibular first molar that had a deep probing depth on the mesial side and mobility. Via the aid of radiographic examination, the tooth that had an angular bony defect and apical lesion was diagnosed as having deep caries and chronic periodontitis with a poor prognosis. After consultation with the patient, we developed a treatment plan incorporating a forced eruption with immediate implantation, intended to augment the alveolar bone volume and increase the width of keratinized gingivae, in a nonsurgical manner.

Results: Following 12 months of orthodontic treatment, the tooth was successfully moved occlusally in conjunction with an 8 mm vertical interdental bone augmentation. Because of sufficient volume of bone and satisfactory gingival dimensions, the implant showed adequate initial stability in the correct position to facilitate physiological and aesthetic prerequisites. After 6 months of osteointegration, a customized impression coping was utilized to transfer the established emergence profile to a definitive cast for the fabrication of a customized abutment. The final prosthesis was made using a customized metal abutment and ceramometal crown.

Conclusion: In the face of difficult clinical challenges, meticulous inspection and a comprehensive treatment plan were crucial. Interdisciplinary treatment through the careful integration of multiple specialists suggests the possibility of optimal results with high predictability.
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http://dx.doi.org/10.1111/j.1708-8208.2011.00363.xDOI Listing
February 2013

Craniofacial skeletal dysplasia of opposite-sex dizygotic twins.

J Formos Med Assoc 2011 May;110(5):342-6

Department of Orthodontics, Kaohsiung Medical University Hospital, and Faculty of Dentistry, College of Dental Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.

Craniofacial skeletal dysplasia can lead to different skeletal malocclusions. Both environmental factors and heredity contribute to the formation of malocclusions. There are strong familial tendencies in the development of Angle's Class II and III malocclusions. Cases such as opposite-typed (Class II and III) malocclusions with skeletal and dentoalveolar discordance in siblings or dizygotic (DZ) twins have seldom been reported. We describe the rare case of a pair of opposite-sex DZ twins with completely different skeletal malocclusions, and discuss the clinical considerations for treatment. The patients were twins aged 13 years and 4 months. The girl had mandibular prognathism and a Class III dentoskeletal relationship, whereas the boy had skeletal Class II with mandibular retrusion. Several morphological traits have been implicated with hormonal effect. However, there was no evidence of whether the masculinization effect had any impact on jaw size in the female fetus or whether this effect lasted into adolescence. We suggest that, although DZ twins share the same growth environment, genetic or other unknown extrinsic factors can result in discordance of characteristics of the craniofacial skeleton, dentition, and occlusion.
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http://dx.doi.org/10.1016/S0929-6646(11)60051-XDOI Listing
May 2011

Treatment of adult Class III malocclusions with orthodontic therapy or orthognathic surgery: receiver operating characteristic analysis.

Am J Orthod Dentofacial Orthop 2011 May;139(5):e485-93

Faculty of Dentistry, College of Dental Medicine, Kaoshiung Medical University, Taiwan.

Introduction: The aim of this study was to distinguish between orthodontic patients with skeletal Class III malocclusions requiring surgery and those not requiring surgery by conducting a receiver operating characteristic analysis of cephalometric variables.

Methods: We used lateral cephalometric radiographs of 80 subjects (40 nonsurgical and 40 surgical patients) with Class III malocclusions and obtain 25 cephalometric measurements using computerized cephalometry. Of these, 14 measurements showed statistically significant differences between the 2 groups. Receiver operating characteristic analysis was used to determine the ability of the 14 cephalometric measurements in distinguishing between the 2 groups. Six statistically validated and clinically relevant measurements were used to obtain the optimum discriminant effectiveness.

Results: For a Class III malocclusion patient with any 4 of these 6 measurement criteria, the sensitivity was 88% and the specificity was 90% in determining the need for surgical treatment: overjet, ≤-4.73 mm; Wits appraisal, ≤-11.18 mm; L1-MP angle, ≤80.8°; Mx/Mn ratio, ≤65.9%; overbite, ≤-0.18 mm; and gonial angle, ≥120.8°.

Conclusions: We selected 6 cephalometric measurements as the minimum number of discriminators required to obtain the optimum discriminant effectiveness of diagnosis between surgical and nonsurgical treatment of skeletal Class III malocclusions.
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http://dx.doi.org/10.1016/j.ajodo.2010.12.014DOI Listing
May 2011

Vaccines targeting the neovasculature of tumors.

Vasc Cell 2011 Mar 8;3(1). Epub 2011 Mar 8.

Department of Pathology, University of Maryland Baltimore, MSTF Building, 10 South Pine Street, Baltimore, MD 21201, USA.

Angiogenesis has a critical role in physiologic and disease processes. For the growth of tumors, angiogenesis must occur to carry sufficient nutrients to the tumor. In addition to growth, development of new blood vessels is necessary for invasion and metastases of the tumor. A number of strategies have been developed to inhibit tumor angiogenesis and further understanding of the interplay between tumors and angiogenesis should allow new approaches and advances in angiogenic therapy. One such promising angiogenic approach is to target and inhibit angiogenesis with vaccines. This review will discuss recent advances and future prospects in vaccines targeting aberrant angiogenesis of tumors. The strategies utilized by investigators have included whole endothelial cell vaccines as well as vaccines with defined targets on endothelial cells and pericytes of the developing tumor endothelium. To date, several promising anti-angiogenic vaccine strategies have demonstrated marked inhibition of tumor growth in pre-clinical trials with some showing no observed interference with physiologic angiogenic processes such as wound healing and fertility.
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http://dx.doi.org/10.1186/2045-824X-3-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3061948PMC
March 2011

Sex determination using discriminant function analysis in children and adolescents: a lateral cephalometric study.

Int J Legal Med 2010 Mar 22;124(2):155-60. Epub 2010 Jan 22.

Department of Anatomy and Department of Public Health, College of Medicine, Kaoshiung Medical University, 100 Shih-Chuan 1st Road, Kaohsiung, Taiwan.

The objective of this study is to test the validity of sex determination in children and adolescents using lateral radiographic cephalometry and discriminant function analysis. Fifty male and 50 female cephalograms of Taiwanese children were used (males and females with mean age of 15.52 +/- 1.38 and 15.67 +/- 1.54 years, respectively). Twenty-two cephalometric measurements were performed using computerized cephalometry. Statistical analysis shows that all measurements were sexually dimorphic (p < 0.05). Nine measurements, statistically validated and clinically relevant, were used for discriminant function analysis. A stepwise discriminant procedure selected seven of the nine variables, producing 95% accuracy in sex determination. Resubstitution classification reveals the same discriminant rate. Cross-validation classification (the leave-one-out method) reveals that the correct sex determination rate is 91%. However, the combination of four variables using both the stepwise procedure and the resubstitution method achieves a 92% accuracy rate. A cross-validation classification procedure with the same four variables resulted in a 91% accuracy rate. Therefore, this study uses four cephalometric measurements as the minimum number of traits yielding the maximum discriminant effectiveness of sex determination in children and adolescents.
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http://dx.doi.org/10.1007/s00414-009-0412-1DOI Listing
March 2010

Immunization with virus-like particles of enterovirus 71 elicits potent immune responses and protects mice against lethal challenge.

Vaccine 2008 Mar 25;26(15):1855-62. Epub 2008 Feb 25.

Department of Chemical Engineering, National Tsing Hua University, Hsinchu 300, Taiwan.

Enterovirus 71 (EV71) is an etiologic agent responsible for seasonal epidemics of hand-foot-and-mouth disease and causes outbreaks with significant mortality among young children. To develop the vaccine, we have produced and purified the EV71 virus-like particle (VLP) that resembles the authentic virus in appearance, capsid structure and protein composition. In this study, we further evaluated the potential of VLP as a vaccine by comparing the humoral and cellular immune responses elicited by the purified VLP, denatured VLP and heat-inactivated EV71 virus. After immunization of BALB/c mice, EV71 VLP induced potent and long-lasting humoral immune responses as evidenced by the high total IgG titer and neutralization titer. The splenocytes collected from the VLP-immunized mice exhibited significant cell proliferation and produced high levels of IFN-gamma, IL-2 and IL-4 after stimulation, indicating the induction of Th1 and Th2 immune responses by VLP immunization. More importantly, the VLP immunization of mother mice conferred protection (survival rate up to 89%) to neonatal mice against the lethal (1000 LD(50)) viral challenge. Compared with the VLP immunization, immunization with denatured VLP and heat-inactivated EV71 elicited lower neutralization titers and conferred less effective protection to newborn mice, although they induced comparable levels of total IgG and cellular immune responses. These data collectively indicate the importance of the preservation of VLP structure and implicate the potential of VLP as a vaccine to prevent EV71 infection.
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http://dx.doi.org/10.1016/j.vaccine.2008.01.058DOI Listing
March 2008

Combination of baculovirus-mediated gene delivery and packed-bed reactor for scalable production of adeno-associated virus.

Hum Gene Ther 2007 Nov;18(11):1161-70

Department of Chemical Engineering, National Tsing Hua University, Hsinchu 300, Taiwan.

The production of recombinant adeno-associated virus (rAAV) commonly requires plasmid cotransfection, which hinders its mass production. Herein we describe the development of a novel process for rAAV production by combining the advantages of baculovirus-mediated gene delivery and BelloCell bioreactor (a novel packed-bed reactor for animal cell culture; CESCO Bioengineering, Hsinchu, Taiwan). We constructed three baculoviral vectors: Bac-LacZ carries the lacZ gene flanked by AAV inverted terminal repeats, Bac-RC harbors AAV rep and cap genes, and Bac-Helper carries helper genes derived from adenovirus. Cotransduction of HEK-293 cells with these three baculoviruses resulted in successful production of rAAV, and the protein and rAAV yield did not decrease with Bac-RC passage for up to four passages. By adjusting the dose ratio of Bac-LacZ to Bac-RC, adding sodium butyrate, and transferring the production process to the BelloCell-500-AP (500 ml), which allowed for high-density culture and effective baculovirus-mediated transduction of HEK-293 cells, the maximal specific rAAV yield reached approximately 3.8 x 10(4) vector genome (VG) or 247 infectious viral particles (IVP) per cell, which corresponded to approximately 1 x 10(14) VG or 8.5 x 10(11) IVP per reactor run. The yield was comparable or superior to those obtained with other production systems. Baculoviral transduction is simple and cost-effective and the BelloCell-500-AP offers high-density culture of HEK-293 cells. Altogether, the combination of baculoviral transduction and BelloCell reactor culture provides a novel and economically viable approach for rAAV production.
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http://dx.doi.org/10.1089/hum.2007.107DOI Listing
November 2007

Morphometric analysis of the mandible in subjects with Class III malocclusion.

Kaohsiung J Med Sci 2006 Jul;22(7):331-8

Department of Orthodontics, Kaohsiung Medical University Hospital, Taiwan.

This study evaluated the deformations that contribute to Class III mandibular configuration, employing geometric morphometric analysis. Lateral cephalograms of male and female groups of 100 young adults and 70 children with Class III malocclusion were compared to those of counterparts with normal occlusion. The sample included an equal number of both genders. The cephalographs were traced, and 12 homologous landmarks were identified and digitized. Average mandibular geometries were generated by means of Procrustes analysis. Thin-plate spline analysis was then applied to mandibular configurations to determine local form differences in male and female groups of adults and children with normal occlusion and Class III mal-occlusion. The mandibular morphology was significantly different between these two groups of male and female adults, and children (p < 0.0001). This spline analysis revealed an anteroposterior elongation of the mandible along the condylion-gnathion axis, showing an extension in the regions of the mandibular condyle and ramus, and of the anteroinferior portion of the mandibular symphysis in Class III groups. More extension was evident in Class III adults. The deformations in subjects with Class III malocclusion may represent a developmental elongation of the mandible anteroposteriorly, which leads to the appearance of a prognathic mandibular profile.
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http://dx.doi.org/10.1016/S1607-551X(09)70319-5DOI Listing
July 2006
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