What is the angular accuracy of regional voxel-based registration for segmental Le Fort I and genioplasty osteotomies?

Among the accuracy analysis techniques for orthognathic surgery, regional voxel-based registration (R-VBR) has robust data, but remains unvalidated for smaller jaw segments. The purpose of this study was to validate the angular accuracy of R-VBR for segmental Le Fort I (SLFI) and genioplasty osteotomies. Postoperative cone beam computed tomography (CBCT) of consecutive patients with three-piece SLFI or genioplasties was rotated to a known pitch/roll/yaw (P/R/Y). Using R-VBR, a copy of the raw CBCT was superimposed onto the rotated CBCT at four mutual regions of interest (ROI): anterior, right posterior, and left posterior maxilla, and chin. The P/R/Y of each was subtracted from those of the rotated CBCT to calculate the angular error. The predictor and outcome variables were ROI and absolute angular error, respectively. The accuracy threshold was 0.5°. Ten SLFI and 34 genioplasties were analyzed based on the sample size calculation. The one-sample t-test and Wilcoxon signed rank test were applied in the analysis. The mean absolute error was 0.20-0.54° for the maxillary segments (all P ≤ 0.01) and 0.83-2.51° for the genioplasty segments (all P < 0.001). R-VBR has variable angular accuracy for SLFI osteotomies and may be insufficient for genioplasty. The findings may allow the design and interpretation of studies on SLFI and genioplasty with greater rigor, thereby contributing to minimizing the discrepancy between planned and achieved outcomes.

The median lingual foramen in the era of orthognathic virtual surgical planning.

The median lingual foramen (MLF), which contains neurovascular bundles, is located in an area commonly considered safe for surgical procedures. However, published reports of severe complications after interventions in the mandibular symphysis area indicate the need for caution when approaching this region surgically. The aim of this study was to evaluate the vertical location of the MLF and the median lingual canal (MLC) by measuring the distances of these landmarks to the root apex of the lower central incisors (LCI) and to the menton cephalometric point (Me) on pre-orthognathic surgery cone beam computed tomography scans (N = 100). The results were analyzed in relation to the patients' type of deformity, age, sex, and number of foramina (single vs multiple). The median MLF-LCI and MLF-Me distances were 5.9 mm and 15.0 mm, respectively, while the mean MLC-LCI and MLC-Me distances were 9.7 mm and 11.6 mm, respectively. The mean LCI-Me distance was 21.3 mm, while the mean MLC length was 3.4 mm. Apart from the length of the MLC, the distances were all significantly greater in the male patients than in the female patients. The MLC-Me distance and MLC length differed significantly according to the number of foramina. In preoperative planning, the vertical locations of the MLF and respective MLC appear to be relevant for avoiding neurovascular complications.

Orthodontic correction of anterior open bite using skeletal anchorage: systematic review and meta-analysis.

The purpose of this study was to investigate the scientific evidence on the short- and long-term effects of orthodontic correction of anterior open bite (AOB) using skeletal anchorage (SA). Clinical studies on the use of SA for AOB in patients with permanent dentition, or at least 12 years of age, were searched. Short- and long-term (≥2 years) outcomes were collected. Mean differences were calculated from pooled data. Twenty-four eligible articles with a total of 362 subjects were selected for inclusion in the meta-analysis. There was a significant increase in overbite (3.88 mm, P < 0.001) and maxillary molar intrusion (-2.15 mm, P < 0.001). The mandible showed counterclockwise rotation with anterosuperior chin movement (all P < 0.001). Long term, the decrease in overbite was 19.9% and decrease in molar intrusion was 22.9%. The decrease in the mandibular projection was 14.6% for ANB (A-point-nasion-B-point angle) and 46.2% for mandibular anteroposterior position. The overall risk of bias in the included studies was rated as moderate to high, and publication bias existed for several key variables. SA for maxillary molar intrusion effectively improved dental and skeletal outcomes, but there was a long-term decrease in overbite and maxillary molar position. The variable data quality, heterogeneity, and publication bias in investigated outcomes are limitations in interpreting the findings.

A technique to verify adequacy of eminectomy for recurrent temporomandibular joint dislocation.

Recurrent dislocation of the temporomandibular joint (TMJ) can be highly debilitating, especially if the dislocation cannot be reduced by the patient. Despite being regarded as a 'gold standard' or 'salvage' procedure for refractory TMJ dislocations, complete mediolateral removal of the articular eminence can still lead to recurrences. A technique aimed at intraoperatively verifying the adequacy of osseous reduction in order to minimize the risk of re-dislocation of the TMJ is described.

Are we able to predict airway dimensional changes in isolated mandibular setback?

The goal of this study was to determine whether a relationship exists between the amount of mandibular setback and the amount of airway dimensional changes. Records and cone beam computed tomography (CBCT) of patients who had undergone isolated bilateral sagittal split osteotomy setback between January 1, 2013 and March 16, 2020 at a single institution were reviewed retrospectively. The primary outcome variable was upper airway volume dimension change, and the predictor variable was the magnitude of mandibular setback as measured by six different methods. Thirty-one patients were included in the study, with a mean mandibular setback ranging from 1.41 mm to 6.11 mm. None of the predictor variables showed an association with oropharyngeal (P = 0.54) or hypopharyngeal (P = 0.33) volume. Stepwise regression analysis failed to show any significant relationships. Similarly, there was no statistically significant association between any of the predictor variables and oropharyngeal (P = 0.44) or hypopharyngeal (P = 0.74) minimum axial area. The results showed that no correlation exists between the magnitude of mandibular setback and the amount of static airway dimensional changes; therefore, it may not be possible to predict whether obstructive sleep apnea will develop following mild to moderate mandibular setback based upon CBCT measurements.

Do positional changes of the inferior alveolar canal after sagittal split mandibular osteotomy affect neurosensory recovery?

The purpose of this study was to assess the pre- and postoperative position and dimensions of the inferior alveolar canal (IAC) following sagittal split osteotomy (SSO) and identify any association with postoperative neurosensory deficit (NSD) at 1 year. This retrospective cohort study enrolled consecutive patients who had SSO performed to correct skeletal malocclusion. The pre- and postoperative cone beam computed tomography data were superimposed to visualize differences in IAC position and dimensions. Subjective and objective neurosensory tests were used to determine NSD in the inferior alveolar nerve distribution. A total of 20 subjects were included. The preoperative distance from the lateral cortex of the IAC to the inner aspect of the lateral cortex of the mandible was significantly greater in sides with NSD when compared to sides without NSD (P = 0.01). A significantly greater reduction in the postoperative distance measurement was seen in sides with NSD when compared to sides without NSD (P = 0.01). The magnitude of mandibular movement was significantly increased in sides with NSD (P = 0.02). The preoperative location of the IAC, as well as certain changes in the mediolateral and vertical positions as a result of SSO, are risk factors for postoperative NSD.

BRCA1/2 somatic mutation detection in formalin-fixed paraffin embedded tissue by next-generation sequencing in Korean ovarian cancer patients.

INTRODUCTION: The detection of BRCA1/2 mutations is important because PARP1 inhibitors are approved for germline and/or somatic BRCA-mutated advanced ovarian cancer. Next-generation sequencing (NGS) is increasingly used in clinical practice for BRCA1/2 mutations. The purpose of this study was to consider several conditions of NGS BRCA1/2 assay applicable to clinical laboratory tests, in particular for using formalin fixed paraffin embedded (FFPE) ovarian tissues. MATERIALS AND METHODS: We selected 64 ovarian cancer patients and performed Oncomine™ BRCA assay using FFPE tissue. Effect of FFPE sample quality was analyzed by NGS quality parameters including deamination metric. Somatic variants were selected by removing germline variants of peripheral blood and interpreted as pathogenic, variants of unknown significance, and false positive. RESULTS: We found a positive relationship between the number of variants over the deamination metric and FFPE age (P < 0.001) with a cutoff values of approximately 0.7 and 60 months, respectively. When comparing NGS results with Sanger sequencing, NGS misreported 3 of 15 variants using default parameters which were corrected after changing parameters. We detected somatic variants in eight patients and classified them into pathogenic (n = 3), VUS (n = 3) and false positive (n = 2). CONCLUSIONS: This study is important for improving BRCA1/2 mutation detection capabilities of NGS analytical pipelines and strategy to overcome their limitations using FFPE tissue in ovarian cancer patients.

Sodium-calcium exchanger (NCX-1) and calcium modulation: NCX protein expression patterns and regulation of early heart development.

Ouabain-induced inhibition of early heart development indicated that Na/K-ATPase plays an important role in maintaining normal ionic balances during differentiation of cardiomyocytes (Linask and Gui [1995] Dev Dyn 203:93-105). Inhibition of the sodium pump is generally accepted to affect the activity of the Na(+)-Ca(++) exchanger (NCX) to increase intracellular [Ca(++)]. These previous findings suggested that Ca(++) signaling may be an important modulator during differentiation of cardiomyocytes. In order to identify a connection between heart development and NCX-mediated Ca(++) regulation, we determined the embryonic spatiotemporal protein expression pattern of NCX-1 during early developmental stages. In both chick and mouse embryos, NCX-1 (the cardiac NCX isoform) is asymmetrically expressed during gastrulation; in the right side of the Hensen's node in the chick, in the right lateral mesoderm in the mouse. At slightly later stages, NCX-1 is expressed in the heart fields at comparable stages of heart development, in the chick at stage 7 and in the mouse at embryonic day (ED) 7.5. By ED 8 in the mouse, the exchanger protein displays a rostrocaudal difference in cardiac expression and an outer curvature-inner curvature ventricular difference. By ED 9.5, cardiac expression has increased from that seen at ED8 and NCX-1 is distributed throughout the myocardium consistent with the possibility that it is important in regulating initial cardiac contractile function. Only a low level of expression is detected in inflow and outflow regions. To substantiate a role for the involvement of calcium-mediated signaling, using pharmacologic approaches, ionomycin (a Ca(++) ionophore) was shown to perturb cardiac cell differentiation in a manner similar to ouabain as assayed by cNkx2.5 and sarcomeric myosin heavy chain expression. In addition, we show that an inhibitor of NCX, KB-R7943, can similarly and adversely affect early cardiac development at stage 4/5 and arrests cardiac cell contractility in 12-somite embryos. Thus, based upon NCX-1 protein expression patterns in the embryo, experimental Ca(++) modulation, and inhibition of NCX activity by KB-R7943, these results suggest an early and central role for calcium-mediated signaling in cardiac cell differentiation and NCX's regulation of the initial heartbeats in the embryo.

N-cadherin/catenin-mediated morphoregulation of somite formation.

Somitogenesis during early stages in the chick and mouse embryo was examined in relation to N-cadherin-mediated adhesion. Previous studies indicated that N-cadherin localizes to the somite regions during their formation. Those observations were extended to include a spatiotemporal immunohistochemical analyses of beta-catenin and alpha-catenin, as well as a more detailed study of N-cadherin, during segmentation, compaction, and compartmentalization of the somite. N-cadherin and the catenins appear early within the segmental plate and are expressed as small patch-like foci throughout this tissue. The small foci of immunostaining coalesce into larger clusters of N-cadherin/catenin-expressing regions. The clusters subsequently coalesce into a region of centrally localized cells that express N-cadherin/catenins at their apical surfaces. The multiple clusters are spaced wide apart in the anterior segmental plates that form the first 6 somite pairs, as contrasted to segmental plates that form somites 7 and beyond. To examine the functional significance of N-cadherin, segmental plates were exposed to antibodies that perturb N-cadherin-mediated adhesion in the chick embryo. The multiple, anomalous somites that result in these experiments indicate that each N-cadherin/catenin-expressing cluster can give rise to a somitic structure. beta-Catenin involvement in somitogenesis suggests a role for Wnt-mediated signaling. Embryos treated with LiCl also show induction of similar anomalous somites indicating further the possibility that Wnt-mediated signaling may be involved in the clustering event. It is suggested that beta-catenin serves to initiate the adhesion process which is spread then by N-cadherin. Later during compartmentalization, N-cadherin/catenins remain expressed by the myotome compartment. Taken together, these results suggest that the Ca2+-dependent cell adhesion molecule N-cadherin and the intracellular catenins are important in segmentation and formation of the somite and myotome compartment. It is proposed that the N-cadherin-mediated adhesion process may serve as a common, evolutionarily conserved, link in the differentiation pathways of skeletal and cardiac muscle.

Analysis of the human gene encoding latent transforming growth factor-beta-binding protein-2.

Transforming growth factor (TGF)-beta is secreted as an inactive complex, which frequently contains a large molecular weight binding protein designated latent TGF-beta-binding protein (LTBP). Recently, the LTBPs have been shown to be a gene family that contains three known members and exhibits a multidomain structure containing cysteine-rich motifs that are also found in the fibrillin gene family. The present work seeks to characterize the gene encoding LTBP-2 and to compare its features to that of the other LTBPs and to the fibrillins. Human fibroblast libraries were used to isolate cDNA encoding LTBP-2 which was then used to identify LTBP-2 transcripts and to isolate the corresponding LTBP-2 gene. The cloned cDNA encodes a 195 kDa protein containing 20 epidermal growth factor (EGF)-like repeats, three repeats containing eight cysteines, and one segment that appears to be a hybrid of the two. Single exons encode EGF repeats while the eight-cysteine repeats are encoded in two exons. Northern analysis identified two transcripts of 7.5 and 9.0 kb, with the presently analyzed cDNA probably corresponding to the 7.5 transcript. Phylogenetic sequence comparisons demonstrated that LTBP-3 is more similar to LTBP-1 than LTBP-2, while LTBP-2 shows the most similarity to the fibrillins. These analyses suggest that LTBP-1 diverged from LTBP-3, and that LTBP-2 diverged from LTBP-1. Within the fibrillin family, fibrillin-1 is nearest to the LTBPs. While the domain structure of LTBP-2 is similar to that of the other LTBPs, LTBP-2 possesses unique regions that make it the largest member of the LTBP family. LTBP-2 may have dual functions as a member of the TGF-beta latent complex and as a structural component of microfibrils.

Microfibril-associated glycoprotein: characterization of the bovine gene and of the recombinantly expressed protein.

Microfibrils having a diameter of 10-12 nm, found either in association with elastin or independently, are an important component of the extracellular matrix of many tissues. Because isolation of native proteins composing the microfibrils has proven difficult, information on structure/function relationships is limited. In order to extend our understanding of the 31-kDa microfibril-associated glycoprotein (MAGP), the bovine gene has been cloned and characterized and the protein has been expressed in a eukaryotic system. The compact coding portion of the gene is contained in 4.5 kbp of genomic DNA and does not appear to share any domain motifs with other known proteins. The size, amino acid composition, and sequence of the amino terminus of the secreted recombinant protein (rMAGP) all agree with values predicted by the nucleotide sequence of the cDNA used in the expression vector. The rMAGP reacts with a monospecific antibody prepared against a defined amino acid sequence of the natural molecule and reacts specifically with recombinantly produced tropoelastin, suggesting that rMAGP will be a useful reagent with which to study its interaction with other extracellular matrix components.

Co-carcinogenic effects of several Korean foods on gastric cancer induced by N-methyl-N'-nitro-N-nitrosoguanidine in rats.

In study I, 48 ACI and Fisher inbred rats were given MNNG 100 micrograms/ml, with or without 1 per cent or 3 per cent red pepper diet; in study II, 164 Sprague-Dawley rats given MNNG 100 micrograms/ml, with or without 5 per cent or 10 per cent NaCl; in study III, 181 Wistar rats given MNNG 83 micrograms/ml with or without maejoo 10 gm per cent/diet; in study IV, 78 Wistar rats given MNNG 83 micrograms/ml with or without ginseng extract 150 micrograms/ml; in study V, 120 Wistar rats given MNNG 83 micrograms/ml with or without retinyl palmitate 150,000 IU/kg. Except for study II (28 weeks), all rats were fed the diets for 37 weeks and were examined at 38 weeks or 40 weeks. In study I, tumor incidence in rats fed a red pepper diet and MNNG solution were 57 per cent (ACI rats, 1 per cent red pepper) and 63 per cent (Fisher rats, 1 per cent or 3 per cent red pepper) which were higher than control group (44 per cent, 43 per cent); in study II, gastric cancer, 61.9 per cent (10 per cent NaCl-MNNG), 27.3 per cent (control); in study III, gastric cancer, 14.8 per cent (maejoo-MNNG), 24 per cent (control); in study IV, malignant tumor of gastroduodenum, 3.4 per cent (ginseng-MNNG), 32.1 per cent (control); in study V, forestomach papilloma, 10.7 per cent (retinoid-MNNG), 29.4 per cent (control), and cancer in duodenum and small intestine, 50.0 per cent (retinoid-MNNG), 17.6 per cent (control). Thus, gastric carcinogenesis was enhanced by red pepper and a high salt diet, was inhibited by a maejoo and ginseng diet and was not effected by vitamin A.