Cell circuits between leukemic cells and mesenchymal stem cells block lymphopoiesis by activating lymphotoxin beta receptor signaling.

Acute lymphoblastic and myeloblastic leukemias (ALL and AML) have been known to modify the bone marrow microenvironment and disrupt non-malignant hematopoiesis. However, the molecular mechanisms driving these alterations remain poorly defined. Using mouse models of ALL and AML, here we show that leukemic cells turn off lymphopoiesis and erythropoiesis shortly after colonizing the bone marrow. ALL and AML cells express lymphotoxin α1ß2 and activate lymphotoxin beta receptor (LTßR) signaling in mesenchymal stem cells (MSCs), which turns off IL7 production and prevents non-malignant lymphopoiesis. We show that the DNA damage response pathway and CXCR4 signaling promote lymphotoxin α1ß2 expression in leukemic cells. Genetic or pharmacological disruption of LTßR signaling in MSCs restores lymphopoiesis but not erythropoiesis, reduces leukemic cell growth, and significantly extends the survival of transplant recipients. Similarly, CXCR4 blocking also prevents leukemia-induced IL7 downregulation and inhibits leukemia growth. These studies demonstrate that acute leukemias exploit physiological mechanisms governing hematopoietic output as a strategy for gaining competitive advantage.

Mature B cells and mesenchymal stem cells control emergency myelopoiesis.

Systemic inflammation halts lymphopoiesis and prioritizes myeloid cell production. How blood cell production switches from homeostasis to emergency myelopoiesis is incompletely understood. Here, we show that lymphotoxin-ß receptor (LTßR) signaling in combination with TNF and IL-1 receptor signaling in bone marrow mesenchymal stem cells (MSCs) down-regulates Il7 expression to shut down lymphopoiesis during systemic inflammation. LTßR signaling in MSCs also promoted CCL2 production during systemic inflammation. Pharmacological or genetic blocking of LTßR signaling in MSCs partially enabled lymphopoiesis and reduced monocyte numbers in the spleen during systemic inflammation, which correlated with reduced survival during systemic bacterial and viral infections. Interestingly, lymphotoxin-α1ß2 delivered by B-lineage cells, and specifically by mature B cells, contributed to promote Il7 down-regulation and reduce MSC lymphopoietic activity. Our studies revealed an unexpected role of LTßR signaling in MSCs and identified recirculating mature B cells as an important regulator of emergency myelopoiesis.

Evaluation of drought propagations with multiple indices in the Yangtze River basin.

This paper explored the drought propagation phenomenon based on meteorological, hydrological, and agricultural aspects in the Yangtze River basin (YRB), China. To evaluate meteorological, hydrological, and agricultural droughts, this paper used three drought indices, standardized precipitation evapotranspiration index (SPEI), standardized runoff index (SRI), and standardized soil moisture index (SSMI), respectively. The community land model (CLM) in the YRB to generate the monthly evapotranspiration, soil moisture, runoff data, which are required for the estimation of drought index, were applied. Different mean durations (6-and 12-month) were used for drought estimation, and propagations of meteorological to hydrological and meteorological and agricultural droughts were investigated for different durations as SPEI6-SRI6, SPEI6-SSMI6, SPEI12-SRI12, SPEI12-SSMI12. The average drought propagation between 1950 and 2010 presented the highest autocorrelation and correlation with one-month lags in four combinations of drought indices in SPEI6-SRI6, SPEI6-SSMI6, SPEI12-SRI12, and SPEI12-SSMI12. Additionally, this paper estimated the optimal lags of SPEI-SRI and SPEI-SSMI drought propagations using mean 6-and 12-month lag times for six representative drought periods. Therefore, the propagation phenomenon of meteorological to hydrological and to agricultural droughts were confirmed in the YRB.

Metalloendopeptidase ADAM-like Decysin 1 (ADAMDEC1) in Colonic Subepithelial PDGFRα+ Cells Is a New Marker for Inflammatory Bowel Disease.

Metalloendopeptidase ADAM-Like Decysin 1 (ADAMDEC1) is an anti-inflammatory peptidase that is almost exclusively expressed in the gastrointestinal (GI) tract. We have recently found abundant and selective expression of Adamdec1 in colonic mucosal PDGFRα+ cells. However, the cellular origin for this gene expression is controversial as it is also known to be expressed in intestinal macrophages. We found that Adamdec1 mRNAs were selectively expressed in colonic mucosal subepithelial PDGFRα+ cells. ADAMDEC1 protein was mainly released from PDGFRα+ cells and accumulated in the mucosal layer lamina propria space near the epithelial basement membrane. PDGFRα+ cells significantly overexpressed Adamdec1 mRNAs and protein in DSS-induced colitis mice. Adamdec1 was predominantly expressed in CD45- PDGFRα+ cells in DSS-induced colitis mice, with only minimal expression in CD45+ CD64+ macrophages. Additionally, overexpression of both ADAMDEC1 mRNA and protein was consistently observed in PDGFRα+ cells, but not in CD64+ macrophages found in human colonic mucosal tissue affected by Crohn's disease. In summary, PDGFRα+ cells selectively express ADAMDEC1, which is localized to the colon mucosa layer. ADAMDEC1 expression significantly increases in DSS-induced colitis affected mice and Crohn's disease affected human tissue, suggesting that this gene can serve as a diagnostic and/or therapeutic target for intestinal inflammation and Crohn's disease.

Insights into the Pollutant Removal Performance of Stormwater Green Infrastructures: A Case Study of Detention Basins and Retention Ponds.

The quality of water has deteriorated due to urbanization and the occurrence of urban stormwater runoff. To solve this problem, this study investigated the pollutant reduction effects from the geometric and hydrological factors of green infrastructures (GIs) to more accurately design GI models, and evaluated the factors that are required for such a design. Among several GIs, detention basins and retention ponds were evaluated. This study chose the inflow, outflow, total suspended solids (TSS), total phosphorus (TP), watershed area, GI area (bottom area in detention basins and permanent pool surface area in retention ponds), and GI volume (in both detention basins and retention ponds) for analysis and applied both ordinary least squares (OLS) regression and multiple linear regression (MLR). The geometric factors do not vary within each GI, but there may be a bias due to the number of stormwater events. To solve this problem, three methods that involved randomly extracting data with a certain range and excluding outliers were applied to the models. The accuracies of these OLS and MLR models were analyzed through the percentage bias (PBIAS), Nash-Sutcliffe efficiency (NSE), and RMSE-observations standard deviation ratio (RSR). The results of this study suggest that models which consider the influent concentration combined with the hydrological and GI geometric parameters have better correlations than models that consider only a single parameter.

Extracellular Matrix Biomarkers in Colorectal Cancer.

The cellular microenvironment composition and changes therein play an extremely important role in cancer development. Changes in the extracellular matrix (ECM), which constitutes a majority of the tumor stroma, significantly contribute to the development of the tumor microenvironment. These alterations within the ECM and formation of the tumor microenvironment ultimately lead to tumor development, invasion, and metastasis. The ECM is composed of various molecules such as collagen, elastin, laminin, fibronectin, and the MMPs that cleave these protein fibers and play a central role in tissue remodeling. When healthy cells undergo an insult like DNA damage and become cancerous, if the ECM does not support these neoplastic cells, further development, invasion, and metastasis fail to occur. Therefore, ECM-related cancer research is indispensable, and ECM components can be useful biomarkers as well as therapeutic targets. Colorectal cancer specifically, is also affected by the ECM and many studies have been conducted to unravel the complex association between the two. Here we summarize the importance of several ECM components in colorectal cancer as well as their potential roles as biomarkers.

CXCL14 downregulation in human keratinocytes is a potential biomarker for a novel in vitro skin sensitization test.

To elucidate the roles of epidermal keratinocytes in the toxicological outcomes of chemically induced contact dermatitis, genome-scale transcriptional analyses were performed using normal human keratinocytes (NHKCs) treated with 10 µM sodium lauryl sulfate (SLS) or 5 µM urushiol. In Gene Ontology (GO) enrichment analyses, SLS- and urushiol-induced upregulated DEGs are commonly associated with the regulation of pro-inflammatory responses and epidermal differentiation processes in NHKCs whereas cellular protein metabolic process was also identified as a commonly downregulated DEG signature. Among the downregulated DEGs, CXCL14 was investigated as a potential biomarker for a new in vitro skin sensitization test using OECD TG429 reference chemicals. CXCL14 was significantly downregulated in NHKCs in response to 62.5% of the OECD TG429 sensitizers in a concentration-dependent manner. When the sensitizer-induced upregulation of chemokine CXCL8 was included in the analysis, 87.5% of the OECD TG429 reference sensitizing chemicals significantly induced either CXCL8 upregulation or CXCL14 downregulation in NHKCs. Only one OECD TG429 reference non-sensitizer changed the constitutive CXCL14 expression in NHKCs whereas five out of six non-sensitizers altered CXCL8 production. The reference irritating non-sensitizer SLS caused a false-positive outcome. The downregulation of constitutively expressed CXCL14 was regulated by both the MAPK/ERK and JAK3/STAT6 pathways in NHKCs. CXCL14 can be used as a mechanism-based biomarker in the development of in vitro skin sensitization tests and may help improve the distinction between allergenic sensitizers and non-sensitizers.

Novel linked butanolide dimer compounds increase adiponectin production during adipogenesis in human mesenchymal stem cells through peroxisome proliferator-activated receptor γ modulation.

Compounds inducing adiponectin production have therapeutic potential for metabolic diseases. During screening, heme oxygenase-1-inducing marliolide derivatives were identified as adiponectin-inducing compounds. Although some marliolide derivatives were directly bound to peroxisome proliferator-activated receptor γ (PPARγ), the adiponectin-inducing activity did not correlate with the PPARγ binding affinity. The most potent adiponectin inducing compound, (E,4S,5S)-3-butylidene-dihydro-4-hydroxy-5-methylfuran-2(3H)-one (1a), exhibited the weakest PPARγ binding activity. A docking simulation suggested that two 1a molecules can be present in two different sites within the PPARγ-ligand-binding pocket (LBP). Based on the docking model, novel linked butanolide dimer compounds were synthesized. A linked butanolide dimer compound, (3E,3'E,4S,4'S,5S,5'S)-3,3'-(decane-1,10-diylidene)bis(4-hydroxy-5-methyldihydrofuran-2(3H)-one) (3a), promoted adiponectin production in human bone marrow mesenchymal stem cells (hBM-MSCs) as a novel PPARγ full agonist (EC50, 4.34 µM). This linked butanolide dimer study provides novel insight into PPARγ biology, suggesting that small molecules can form multiple ligand interactions within the PPARγ-LBP and thereby affect the functional outcomes of PPARγ activation.

A long-wave UVA filter avobenzone induces obesogenic phenotypes in normal human epidermal keratinocytes and mesenchymal stem cells.

Avobenzone is the most commonly used ultraviolet (UV) A filter ingredient in sunscreen. To investigate the biological activity of avobenzone in normal human epidermal keratinocytes (NHEKs), the genome-scale transcriptional profile of NHEKs was performed. In this microarray study, we found 273 up-regulated and 274 down-regulated differentially expressed genes (DEGs) in NHEKs treated with avobenzone (10 µM). Gene Ontology (GO) enrichment analysis showed that avobenzone significantly increased the DEGs associated with lipid metabolism in NHEKs. In addition, avobenzone increased the gene transcription of peroxisome proliferator-activated receptor γ (PPARγ) and fatty acid binding protein 4 in NHEKs, implicating that avobenzone may be one of the metabolic disrupting obesogens. To confirm the obesogenic potential, we examined the effect of avobenzone on adipogenesis in human bone marrow mesenchymal stem cells (hBM-MSCs). Avobenzone (EC50, 14.1 µM) significantly promoted adipogenesis in hBM-MSCs as its positive control obesogenic chemicals. Avobenzone (10 µM) significantly up-regulated mRNA levels of PPARγ during adipogenesis in hBM-MSCs. However, avobenzone did not directly bind to PPARγ and the avobenzone-induced adipogenesis-promoting activity was not affected by PPARγ antagonists T0070907 and GW9662. Therefore, avobenzone promoted adipogenesis in hBM-MSCs through a PPARγ-independent mechanism. This study suggests that avobenzone functions as a metabolic disrupting obesogen.

Adiponectin-Secretion-Promoting Phenylethylchromones from the Agarwood of Aquilaria malaccensis.

The therapeutic potential of adiponectin regulation has received interest because of its association with diverse human disease conditions, such as diabetes, obesity, atherosclerosis, and cancer. Phenylethylchromone derivatives from Aquilaria malaccensis-derived agarwood promoted adiponectin secretion during adipogenesis in human bone marrow mesenchymal stem cells, and 5,6-dihydroxy-2-(2-phenylethyl)chromone (1) was identified as a new chromone derivative. A target identification study with the most potent adiponectin-secretion-promoting phenylethylchromones, 6-methoxy-2-(2-phenylethyl)chromone (3) and 7-methoxy-2-(2-phenylethyl)chromone (4), showed that they are PPARγ partial agonists. Therefore, the diverse therapeutic effects of agarwood are associated with a PPARγ-mediated adiponectin-secretion-promoting mechanism.

Leptin regulates the pro-inflammatory response in human epidermal keratinocytes.

The role of leptin in cutaneous wound healing process has been suggested in genetically obese mouse studies. However, the molecular and cellular effects of leptin on human epidermal keratinocytes are still unclear. In this study, the whole-genome-scale microarray analysis was performed to elucidate the effect of leptin on epidermal keratinocyte functions. In the leptin-treated normal human keratinocytes (NHKs), we identified the 151 upregulated and 53 downregulated differentially expressed genes (DEGs). The gene ontology (GO) enrichment analysis with the leptin-induced DEGs suggests that leptin regulates NHKs to promote pro-inflammatory responses, extracellular matrix organization, and angiogenesis. Among the DEGs, the protein expression of IL-8, MMP-1, fibronectin, and S100A7, which play roles in which is important in the regulation of cutaneous inflammation, was confirmed in the leptin-treated NHKs. The upregulation of the leptin-induced proteins is mainly regulated by the STAT3 signaling pathway in NHKs. Among the downregulated DEGs, the protein expression of nucleosome assembly-associated centromere protein A (CENPA) and CENPM was confirmed in the leptin-treated NHKs. However, the expression of CENPA and CENPM was not coupled with those of other chromosome passenger complex like Aurora A kinase, INCENP, and survivin. In cell growth kinetics analysis, leptin had no significant effect on the cell growth curves of NHKs in the normal growth factor-enriched condition. Therefore, leptin-dependent downregulation of CENPA and CENPM in NHKs may not be directly associated with mitotic regulation during inflammation.

2-Formyl-komarovicine promotes adiponectin production in human mesenchymal stem cells through PPARγ partial agonism.

Adiponectin is a major adipocytokine secreted from mammalian adipocytes. Relatively low expression of adiponectin is associated with various human metabolic diseases and some cancers. Adiponectin-secreting compounds have therapeutic potential for these diseases. Adipogenesis of human bone marrow-mesenchymal stem cells (hBM-MSCs) has been used as a phenotypic assay to find adiponectin secreting compounds. In a phytochemical library screen, 2-formyl-komarovicine, 1-(quinolin-8-yl)-1,3,4,9-tetrahydro-2H-pyrido[3,4-b]indole-2-carbaldehyde, isolated from Nitraria komarovii was identified as a potential adiponectin-secreting compound. To validate the results of the impure phytochemical, we synthesized 2-formyl-komarovicine. The synthetic 2-formyl-komarovicine significantly promoted adiponectin production during adipogenesis in hBM-MSCs. In a target identification experiment, 2-formyl-komarovicine bound to peroxisome proliferator-activated receptor γ (PPARγ) in a concentration-dependent manner. Notably, 2-formyl-komarovicine competitively inhibited the adiponectin-promoting activity of a full PPARγ agonist, troglitazone, in hBM-MSCs, which is a pharmacological feature of a partial agonist. The ligand-docking model showed that 2-formyl-komarovicine interacted with the hydrophobic pocket of the PPARγ ligand-binding domain, but lacked an interaction to stabilize helix H12, which is one of the major binding themes of PPARγ partial agonists. We concluded that 2-formyl-komarovicine provides a novel pharmacophore for PPARγ partial agonists to increase adiponectin production.

Phosphodiesterase 4B plays a role in benzophenone-3-induced phototoxicity in normal human keratinocytes.

Benzophenone-3 (BP-3), which is extensively used in organic sunscreen, has phototoxic potential in human skin. Phosphodiesterase 4B (PDE4B) has a well-established role in inflammatory responses in immune cells. Currently, it is unknown if PDE4B is associated with BP-3-induced phototoxicity in normal human keratinocytes (NHKs). We found that BP-3 significantly increased PDE4B expression in ultraviolet B (UVB)-irradiated NHKs. Notably, BP-8, a sunscreen agent that shares the 2-hydroxy-4-methoxyphenyl methanone moiety with BP-3, also upregulated PDE4B expression in NHKs. Upon UVB irradiation, BP-3 upregulated the expression of pro-inflammatory factors, such as prostaglandin endoperoxide synthase 2, tumor necrosis factor α, interleukin 8, and S100A7, and downregulated the level of cornified envelope associated proteins, which are important in the development of the epidermal permeability barrier. The additive effects of UVB-activated BP-3 on the expression of both pro-inflammatory mediators and cornified envelope associated proteins were antagonized by treatment with the PDE4 inhibitor rolipram. The BP-3 and UVB co-stimulation-induced PDE4B upregulation and its association with the upregulation of pro-inflammatory mediators and the downregulation of epidermal differentiation markers were confirmed in a reconstituted three dimensional human epidermis model. Therefore, PDE4B has a role in the mechanism of BP-3-induced phototoxicity.

Polypharmacology of N6-(3-Iodobenzyl)adenosine-5'-N-methyluronamide (IB-MECA) and Related A3 Adenosine Receptor Ligands: Peroxisome Proliferator Activated Receptor (PPAR) γ Partial Agonist and PPARδ Antagonist Activity Suggests Their Antidiabetic Potential.

A3 adenosine receptor (AR) ligands including A3 AR agonist, N6-(3-iodobenzyl)adenosine-5'-N-methyluronamide (1a, IB-MECA) were examined for adiponectin production in human bone marrow mesenchymal stem cells (hBM-MSCs). In this model, 1a significantly increased adiponectin production, which is associated with improved insulin sensitivity. However, A3 AR antagonists also promoted adiponectin production in hBM-MSCs, indicating that the A3 AR pathway may not be directly involved in the adiponectin promoting activity. In a target deconvolution study, their adiponectin-promoting activity was significantly correlated to their binding activity to both peroxisome proliferator activated receptor (PPAR) γ and PPARδ. They functioned as both PPARγ partial agonists and PPARδ antagonists. In the diabetic mouse model, 1a and its structural analogues A3 AR antagonists significantly decreased the serum levels of glucose and triglyceride, supporting their antidiabetic potential. These findings indicate that the polypharmacophore of these compounds may provide therapeutic insight into their multipotent efficacy against various human diseases.

Cystathionine metabolic enzymes play a role in the inflammation resolution of human keratinocytes in response to sub-cytotoxic formaldehyde exposure.

Low-level formaldehyde exposure is inevitable in industrialized countries. Although daily-life formaldehyde exposure level is practically impossible to induce cell death, most of mechanistic studies related to formaldehyde toxicity have been performed in cytotoxic concentrations enough to trigger cell death mechanism. Currently, toxicological mechanisms underlying the sub-cytotoxic exposure to formaldehyde are not clearly elucidated in skin cells. In this study, the genome-scale transcriptional analysis in normal human keratinocytes (NHKs) was performed to investigate cutaneous biological pathways associated with daily life formaldehyde exposure. We selected the 175 upregulated differentially expressed genes (DEGs) and 116 downregulated DEGs in NHKs treated with 200µM formaldehyde. In the Gene Ontology (GO) enrichment analysis of the 175 upregulated DEGs, the endoplasmic reticulum (ER) unfolded protein response (UPR) was identified as the most significant GO biological process in the formaldeyde-treated NHKs. Interestingly, the sub-cytotoxic formaldehyde affected NHKs to upregulate two enzymes important in the cellular transsulfuration pathway, cystathionine γ-lyase (CTH) and cystathionine-ß-synthase (CBS). In the temporal expression analysis, the upregulation of the pro-inflammatory DEGs such as MMP1 and PTGS2 was detected earlier than that of CTH, CBS and other ER UPR genes. The metabolites of CTH and CBS, l-cystathionine and l-cysteine, attenuated the formaldehyde-induced upregulation of pro-inflammatory DEGs, MMP1, PTGS2, and CXCL8, suggesting that CTH and CBS play a role in the negative feedback regulation of formaldehyde-induced pro-inflammatory responses in NHKs. In this regard, the sub-cytotoxic formaldehyde-induced CBS and CTH may regulate inflammation fate decision to resolution by suppressing the early pro-inflammatory response.

Microleakage under ceramic flash-free orthodontic brackets after thermal cycling.

OBJECTIVE: To compare microleakage under 3M Unitek's APC Flash-Free Adhesive Coated System bracket and the APC PLUS Adhesive Coated System bracket after thermal cycling. MATERIALS AND METHODS: Forty freshly extracted human maxillary premolars were randomly divided into two groups and bonded with either a Flash-Free bracket or a PLUS bracket. After bonding, the samples were incubated in a water bath at 37°C for 24 hours and thermocycled for 5000 cycles between 5°C and 50°C. All teeth were immersed in a 2% methylene blue solution for 24 hours, embedded in acrylic and sectioned in a buccolingual direction at approximately the center of the bracket. Microleakage was observed at the enamel-adhesive interface from the occlusal and gingival margins of the bracket base. Statistical analysis was conducted using the Mann-Whitney U-test. RESULTS: The median microleakage was higher in the Flash-Free group, but the difference between the two groups was not statistically significant (P > .05). CONCLUSION: In a laboratory setting, there is no significant difference between the extent of microleakage under the APC Flash-Free Adhesive Coated System bracket and the APC PLUS Adhesive Coated System bracket after thermal cycling.

Comparison of shear bond strength and bonding time of a novel flash-free bonding system.

OBJECTIVE: To evaluate the bonding time, shear bond strength (SBS), and adhesive residue index (ARI) of APC(TM) Flash-Free bonding system. MATERIALS AND METHODS: Thirty-six extracted human maxillary premolars were randomly divided into three groups (12 per group) and used for this in vitro study: group 1, APC Flash-Free Adhesive Coated Appliance System; group 2, Clarity ADVANCED Ceramic Bracket pasted manually; group 3 (control group), 3M APC PLUS Adhesive prepasted brackets bonded with the extruded flash removed. Bonding time was measured using a stopwatch. Bond strength was measured using an Instron at a cross-head speed of 1 mm/min. The ARI was graded on a scale from 1 to 5. Repeated-measures analysis of variance and post hoc Tukey tests were used for statistical analysis. RESULTS: It took significantly (P < .001) less time to bond in the APC Flash-Free Adhesive group (30.7 ± 3.3 seconds) compared with the control group (41.8 ± 4.0 seconds) and the manual group (39.2 ± 2.8 seconds). The APC Flash-Free Adhesive coated bracket had significantly (P < .001) greater SBS (13.7 ± 2.2 MPa) compared with the control group (10.8 ± 2.0 MPa) and the manual group (10.4 ± 1.4 MPa). The ARI was significantly (P < .001) greater with the APC Flash-Free Adhesive coated bracket compared with that of the other two groups. CONCLUSIONS: Compared with other methods of bonding, the APC Flash-Free Adhesive Coated System can potentially reduce bonding time while increasing SBS.

Evaluation of crown-root angulation of lateral incisors adjacent to palatally impacted canines.

BACKGROUND: The objective of this study is to explore differences in crown-to-root angulation between lateral incisors adjacent to palatally impacted canines (PICs) and lateral incisors adjacent to normally erupted canines (NECs). METHODS: Orthodontic records of 100 subjects (51 with PICs and 49 with NECs) were reviewed. Crown-to-root angulations of all lateral incisors were measured manually on the final panoramic radiographs. Also, three experienced orthodontists were asked to visually inspect the morphology of the lateral incisors on the panoramic radiographs. A mixed model was used to test the difference in crown-to-root angulation of the lateral incisor between the experimental and the control groups. The association between the examiners' observations and the presence of a canine impaction was assessed by means of a chi-square test. All analyses were performed at the 0.05 level of statistical significance. RESULTS: A significant (p = 0.009) difference of 2.3° in crown-to-root angulation was found between groups. Also, 66.7% of the lateral incisors that were identified as "abnormal" by the panel of orthodontists were adjacent to a PIC. A percentage of 65.2 of lateral incisors that were identified as "normal" were located adjacent to NECs. CONCLUSIONS: The root of lateral incisors adjacent to PICs is angulated more mesially compared to lateral incisors adjacent to NECs. In addition, clinicians are somewhat able to predict if a canine is palatally impacted by visually observing the crown-to-root angulation of the adjacent lateral incisor. Evaluating the crown-to-root angulation of a lateral incisor on a panoramic image might facilitate an early diagnosis of palatally impacted canines.

Newly defined landmarks for a three-dimensionally based cephalometric analysis: a retrospective cone-beam computed tomography scan review.

OBJECTIVES: To identify two novel three-dimensional (3D) cephalometric landmarks and create a novel three-dimensionally based anteroposterior skeletal measurement that can be compared with traditional two-dimensional (2D) cephalometric measurements in patients with Class I and Class II skeletal patterns. MATERIALS AND METHODS: Full head cone-beam computed tomography (CBCT) scans of 100 patients with all first molars in occlusion were obtained from a private practice. InvivoDental 3D (version 5.1.6, Anatomage, San Jose, Calif) was used to analyze the CBCT scans in the sagittal and axial planes to create new landmarks and a linear 3D analysis (M measurement) based on maxillary and mandibular centroids. Independent samples t-test was used to compare the mean M measurement to traditional 2D cephalometric measurements, ANB and APDI. Interexaminer and intraexaminer reliability were evaluated using 2D and 3D scatterplots. RESULTS: The M measurement, ANB, and APDI could statistically differentiate between patients with Class I and Class II skeletal patterns (P < .001). The M measurement exhibited a correlation coefficient (r) of -0.79 and 0.88 with APDI and ANB, respectively. CONCLUSIONS: The overall centroid landmarks and the M measurement combine 2D and 3D methods of imaging; the measurement itself can distinguish between patients with Class I and Class II skeletal patterns and can serve as a potential substitute for ANB and APDI. The new three-dimensionally based landmarks and measurements are reliable, and there is great potential for future use of 3D analyses for diagnosis and research.