A comparison of maxillary posterior changes following facemask therapy: Skeletal anchorage versus tooth-borne anchorage.

OBJECTIVE: To compare changes in the maxillary posterior structure as seen in cone-beam computed tomography (CBCT) images resulting from facemask therapy using skeletal (miniplate/FM) anchorage versus tooth-borne anchorage (RME/FM). MATERIALS AND METHODS: A retrospective study was conducted on 20 patients divided into the miniplate/FM group (nine patients aged 9.5 ± 1.4 years) and the RME/FM group (11 patients aged 9.2 ± 1.4 years). CBCT images before and after facemask therapy were evaluated to assess changes in the maxillary posterior structure. RESULTS: The miniplate/FM group had greater advancement of the maxilla and midface compared to the RME/FM group (p < .05). Specifically, there was about three times more advancement of the pterygomaxillary suture in the miniplate/FM group than in the RME/FM group (p < .05). Moreover, the advancement of the pterygomaxillary suture was about half the advancement of A point in the miniplate/FM group, while only about 25% in the RME/FM group. Finally, the miniplate/FM group showed an increase in the transverse dimension of the posterior and superior parts of the maxilla (p < .05). CONCLUSION: There was greater forward movement of the pterygomaxillary suture with facemask therapy using the skeletal anchorage compared to tooth-borne anchorage, leading to a more significant advancement of the maxilla and midface.

Facemask therapy with skeletal anchorage: A possible alternative to orthognathic surgery.

Treatment of skeletal Class III malocclusion in young patients is very challenging. Facemask therapy has been proven to be effective in early correction of Class III malocclusion. With the aid of skeletal anchorage, the orthopaedic effects are expected to be greater than the effects with conventional facemask with tooth-borne anchorage. However, only a few studies have reported on the long-term stability of facemask therapy combined with skeletal anchorage. This report examines two patients with skeletal Class III malocclusion who were treated with facemask and skeletal anchorage followed by orthodontic treatment using fixed orthodontic appliances. The long-term effects of facemask therapy with skeletal anchorage are discussed and compared with the conventional facemask therapy.

Porous TiO2 Nanotube Arrays for Drug Loading and Their Elution Sensing.

Porous TiO2 nanotube arrays have been attracting much attention as optical sensing layers and surface layers of dental implants because they are stable in acid and biocompatible. To use them as the optical sensing layers, TiO2 nanotube arrays with various structures were fabricated and obtained an optimized microstructure at 50 V, 50 min and 0.5 wt% of NH4F, 7.4 vol% deionized water in ethylene glycol. TiO2 nanotube arrays which had diameters of ~73.54 nm and lengths of ~3.39 µm showed the best sensing performance. A Ti implant was also anodized at 60 V for 4 hr in an ethylene glycol electrolyte and TiO2 nanotube arrays showed the pore diameter of 156.01 nm and the thickness of 6.87 µm. Recombinant human bone morphogenetic protein-2 (rhBMP-2), isobutylphenyl propionic acid, and sodium alendronate were loaded into the TiO2 nanotube arrays on the surface of the Ti implant. For elution of these drugs, optical thickness changes of 2.4 nm, 3.5 nm and 3.1 nm were respectively observed for about 2.2 hr, 3.6 hr and 3.1 hr. The TiO2 nanotube arrays were useful for drug loading and their elution interferometric sensing.

Botulinum Toxin Injection to Treat Masticatory Movement Disorder Corrected Mandibular Asymmetry in a Growing Patient.

An 8-year-old girl with masticatory movement disorder received botulinum toxin-A (BTX-A) injection and orthodontic treatment. She showed facial asymmetry with right masseter muscle hyperplasia. After BTX-A injection combined with orthodontic treatment, the transverse discrepancy between right and left maxillary dentition completely corrected. Cone-beam computed tomography images revealed that the height of the left mandibular ramus had increased by 2.3 mm, considerably more than on the right side, the discrepancy in mandibular ramus height between the left and the right decreased dramatically. In a short period, BTX-A injection combined with orthodontic treatment corrected a mandibular movement disorder with asymmetric mandibular growth in a growing patient.

Evaluation of anti-PD-1-based therapy against triple-negative breast cancer patient-derived xenograft tumors engrafted in humanized mouse models.

BACKGROUND: Breast cancer has been considered not highly immunogenic, and few patients benefit from current immunotherapies. However, new strategies are aimed at changing this paradigm. In the present study, we examined the in vivo activity of a humanized anti-programmed cell death protein 1 (anti-PD-1) antibody against triple-negative breast cancer (TNBC) patient-derived xenograft (PDX) tumor models. METHODS: To circumvent some of the limitations posed by the lack of appropriate animal models in preclinical studies of immunotherapies, partially human leukocyte antigen-matched TNBC PDX tumor lines from our collection, as well as human melanoma cell lines, were engrafted in humanized nonobese diabetic/severe combined immunodeficiency IL2Rγnull (hNSG) mice obtained by intravenous injection of CD34+ hematopoietic stem cells into nonlethally irradiated 3-4-week-old mice. After both PDXs and melanoma cell xenografts reached ~ 150-200 mm3, animals were treated with humanized anti-PD-1 antibody or anti-CTLA-4 and evaluated for tumor growth, survival, and potential mechanism of action. RESULTS: Human CD45+, CD20+, CD3+, CD8+, CD56+, CD68+, and CD33+ cells were readily identified in blood, spleen, and bone marrow collected from hNSG, as well as human cytokines in blood and engrafted tumors. Engraftment of TNBC PDXs in hNSG was high (~ 85%), although they grew at a slightly slower pace and conserved their ability to generate lung metastasis. Human CD45+ cells were detectable in hNSG-harbored PDXs, and consistent with clinical observations, anti-PD-1 antibody therapy resulted in both a significant reduction in tumor growth and increased survival in some of the hNSG PDX tumor lines, whereas no such effects were observed in the corresponding non-hNSG models. CONCLUSIONS: This study provides evidence associated with anti-PD-1 immunotherapy against TNBC tumors supporting the use of TNBC PDXs in humanized mice as a model to overcome some of the technical difficulties associated with the preclinical investigation of immune-based therapies.

Effect of drug-loaded TiO2 nanotube arrays on osseointegration in an orthodontic miniscrew: an in-vivo pilot study.

Osseointegration was evaluated for the surface of miniscrews with TiO2 nanotube arrays containing drugs in this in-vivo study. The diameter and length of the TiO2 nanotube arrays were about 70 nm and 5 µm, respectively. Recombinant human bone morphogenetic protein-2 (rhBMP-2) or ibuprofen was loaded in the TiO2 nanotube arrays with 12 miniscrews. The 12 drug-loaded miniscrews, 6 miniscrews with no drug-loaded TiO2 nanotube arrays and 6 conventional miniscrews, were placed on the tibias of New Zealand white rabbits. Histological osseointegration was assessed 8 weeks after implantation by measuring the bone-to-implant contact (BIC) ratio. Ibuprofen-loaded miniscrews showed a significantly higher BIC of 71.6% over conventional miniscrews of 44.3% on average. The mean BIC ratios of rhBMP-2-loaded miniscrews and no drug-loaded miniscrews was 24.6% and 60.1%, respectively. Our results suggest that TiO2 nanotube arrays on the surface of miniscrews could be used as carriers of drugs, and loading ibuprofen in TiO2 nanotube arrays may improve osseointegration of miniscrews. However, the effect of rhBMP-2 loaded in TiO2 nanotube arrays on osseointegration of miniscrews was questionable in this pilot study.

Antitumor activity of Cetuximab in combination with Ixabepilone on triple negative breast cancer stem cells.

BACKGROUND: Developing novel strategies against treatment-resistant triple negative breast cancer (TNBC) cells remains a significant challenge. The ErbB family, including epidermal growth factor receptor (EGFR), plays key roles in metastasis, tumorigenesis, cell proliferation, and drug resistance. Recently, these characteristics have been linked to a small subpopulation of cells classified as cancer stem cells (CSC) which are believed to be responsible for tumor initiation and maintenance. Ixabepilone is a new generation microtubule-stabilizing agent, which has been expected to be more efficacious than conventional taxanes. Here we aim to investigate whether the EGFR monoclonal antibody Cetuximab, in combination with Ixabepilone, is more effective in eliminating CSC populations compared to chemotherapy alone in TNBC. METHODS: Representative TNBC cell lines (MDA-MB-231 and SUM159) were used to evaluate breast CSC populations. We used fluorescence-activated cell sorter analysis (CD44(+) and CD24(-/low), or Aldefluor(+)) and a self-renewal assay called mammosphere formation efficiency (MSFE) to measure CSC population size after treatment with Cetuximab, or Cetuximab plus Ixabepilone in vitro. RESULTS: Although there was no significant decrease in cell viability, Cetuximab reduced MSFE and the CSC population in breast cancer cells in vitro and in vivo through inhibition of autophagy. Also, SUM159 and MDA-MB-231 orthotopic tumors demonstrated partial response to Centuximab or Ixabepilone monotherapy; however, the effect of the combination treatment was significant only in SUM159 tumors (p <0.0001), when compared to Ixabepilone alone. CONCLUSIONS: Overall, our findings demonstrate that EGFR-targeted therapy by Cetuximab effectively reduces the CSC population in TNBC tumors. However, combination therapy with Ixabepilone may be effective only in a small subset of TNBCs, warranting further investigation of alternative approaches to target multiple pathways for TNBC treatment.

Inhibition of iNOS as a novel effective targeted therapy against triple-negative breast cancer.

INTRODUCTION: Triple-negative breast cancer (TNBC) is an aggressive form of breast cancer with no effective targeted therapy. Inducible nitric oxide synthase (iNOS) is associated with poor survival in patients with breast cancer by increasing tumor aggressiveness. This work aimed to investigate the potential of iNOS inhibitors as a targeted therapy for TNBC. We hypothesized that inhibition of endogenous iNOS would decrease TNBC aggressiveness by reducing tumor initiation and metastasis through modulation of epithelial-mesenchymal transition (EMT)-inducing factors. METHODS: iNOS protein levels were determined in 83 human TNBC tissues and correlated with clinical outcome. Proliferation, mammosphere-forming efficiency, migration, and EMT transcription factors were assessed in vitro after iNOS inhibition. Endogenous iNOS targeting was evaluated as a potential therapy in TNBC mouse models. RESULTS: High endogenous iNOS expression was associated with worse prognosis in patients with TNBC by gene expression as well as immunohistochemical analysis. Selective iNOS (1400 W) and pan-NOS (L-NMMA and L-NAME) inhibitors diminished cell proliferation, cancer stem cell self-renewal, and cell migration in vitro, together with inhibition of EMT transcription factors (Snail, Slug, Twist1, and Zeb1). Impairment of hypoxia-inducible factor 1α, endoplasmic reticulum stress (IRE1α/XBP1), and the crosstalk between activating transcription factor 3/activating transcription factor 4 and transforming growth factor ß was observed. iNOS inhibition significantly reduced tumor growth, the number of lung metastases, tumor initiation, and self-renewal. CONCLUSIONS: Considering the effectiveness of L-NMMA in decreasing tumor growth and enhancing survival rate in TNBC, we propose a targeted therapeutic clinical trial by re-purposing the pan-NOS inhibitor L-NMMA, which has been extensively investigated for cardiogenic shock as an anti-cancer therapeutic.

SDF-1α stiffens myeloma bone marrow mesenchymal stromal cells through the activation of RhoA-ROCK-Myosin II.

Multiple myeloma (MM) is a B lymphocyte malignancy that remains incurable despite extensive research efforts. This is due, in part, to frequent disease recurrences associated with the persistence of myeloma cancer stem cells (mCSCs). Bone marrow mesenchymal stromal cells (BMSCs) play critical roles in supporting mCSCs through genetic or biochemical alterations. Previously, we identified mechanical distinctions between BMSCs isolated from MM patients (mBMSCs) and those present in the BM of healthy individuals (nBMSCs). These properties of mBMSC contributed to their ability to preferentially support mCSCs. To further illustrate mechanisms underlying the differences between mBMSCs and nBMSCs, here we report that (i) mBMSCs express an abnormal, constitutively high level of phosphorylated Myosin II, which leads to stiffer membrane mechanics, (ii) mBMSCs are more sensitive to SDF-1α-induced activation of MYL2 through the G(i./o)-PI3K-RhoA-ROCK-Myosin II signaling pathway, affecting Young's modulus in BMSCs and (iii) activated Myosin II confers increased cell contractile potential, leading to enhanced collagen matrix remodeling and promoting the cell-cell interaction between mCSCs and mBMSCs. Together, our findings suggest that interfering with SDF-1α signaling may serve as a new therapeutic approach for eliminating mCSCs by disrupting their interaction with mBMSCs.

Chloroquine eliminates cancer stem cells through deregulation of Jak2 and DNMT1.

Triple negative breast cancer (TNBC) is known to contain a high percentage of CD44(+) /CD24(-/low) cancer stem cells (CSCs), corresponding with a poor prognosis despite systemic chemotherapy. Chloroquine (CQ), an antimalarial drug, is a lysotropic reagent which inhibits autophagy. CQ was identified as a potential CSC inhibitor through in silico gene expression signature analysis of the CD44(+) /CD24(-/low) CSC population. Autophagy plays a critical role in adaptation to stress conditions in cancer cells, and is related with drug resistance and CSC maintenance. Thus, the objectives of this study were to examine the potential enhanced efficacy arising from addition of CQ to standard chemotherapy (paclitaxel) in TNBC and to identify the mechanism by which CQ eliminates CSCs in TNBCs. Herein, we report that CQ sensitizes TNBC cells to paclitaxel through inhibition of autophagy and reduces the CD44(+) /CD24(-/low) CSC population in both preclinical and clinical settings. Also, we are the first to report a mechanism by which CQ regulates the CSCs in TNBC through inhibition of the Janus-activated kinase 2 (Jak2)-signal transducer and activator of transcription 3 signaling pathway by reducing the expression of Jak2 and DNA methyltransferase 1.

Effect of TiO2 nanotubes arrays on osseointegration of orthodontic miniscrew.

To increase the stability of orthodontic miniscrews, TiO2 nanotube arrays were fabricated on the surface of Ti miniscrews and the effect of those arrays on the osseointegration of miniscrews was evaluated. Highly ordered TiO2 nanotube arrays were grown on the surface of orthodontic miniscrews. Ethylene glycol based electrolyte was used in the anodic oxidation process. Two-step anodic oxidation was conducted to obtain clean and open windows in TiO2 nanotube arrays. The diameter and length of the TiO2 nanotube arrays were ~ 70 nm and ~ 5 µm, respectively. The miniscrews with TiO2 nanotube arrays were implanted in the legs of New Zealand white rabbits for 8 weeks. Histological osseointegration was assessed by bone-to-implant contact ratio, and three-dimensional bone volume ratio was measured by micro-computed tomography analysis. The miniscrews with TiO2 nanotube arrays had a greater mean bone-to-implant contact ratio of 52.8 % than the control, 29.3 %. Mean bone volume ratio (BV/TV) was also higher in the miniscrews with TiO2 nanotube arrays, at 81.2 % than those in the control via micro-CT analysis. Our findings support that TiO2 nanotube arrays on the surface of miniscrews enhance osseointegration and improve the stability of the miniscrew.

Microfluidics separation reveals the stem-cell-like deformability of tumor-initiating cells.

Here we report a microfluidics method to enrich physically deformable cells by mechanical manipulation through artificial microbarriers. Driven by hydrodynamic forces, flexible cells or cells with high metastatic propensity change shape to pass through the microbarriers and exit the separation device, whereas stiff cells remain trapped. We demonstrate the separation of (i) a mixture of two breast cancer cell types (MDA-MB-436 and MCF-7) with distinct deformabilities and metastatic potentials, and (ii) a heterogeneous breast cancer cell line (SUM149), into enriched flexible and stiff subpopulations. We show that the flexible phenotype is associated with overexpression of multiple genes involved in cancer cell motility and metastasis, and greater mammosphere formation efficiency. Our observations support the relationship between tumor-initiating capacity and cell deformability, and demonstrate that tumor-initiating cells are less differentiated in terms of cell biomechanics.

Changes in natural head position after orthognathic surgery in skeletal Class III patients.

INTRODUCTION: The purpose of this study was to evaluate the change in natural head position (NHP) after orthognathic surgery in skeletal Class III patients. METHODS: We used pretreatment (T1) and posttreatment (T2) cephalometric radiographs and T1 and T2 lateral facial photographs of 20 skeletal Class III patients (mean age, 21.6 years), with 20 skeletal Class I patients (mean age, 22.2 years) as the controls. The Class III patients had undergone mandibular setback surgery, and the patients in the control group had received conventional orthodontic treatment. All lateral facial photographs were recorded in NHP. The true vertical line (TVL) was transferred from the photograph to the cephalometric radiograph, and then the angle between the TVL and the Frankfort horizontal plane (TVL/FH) was measured. A t test and a paired t test were used to verify the differences between the 2 groups, and between the T1 and T2 measurements in each group. RESULTS: The mean TVL/FH at T1 was significantly greater in the Class III group than in the Class I group; this indicated that the Class III group showed head flexion. However, the mean TVL/FH of the Class III group decreased by -3.1° at T2; this indicated head extension, and it did not significantly differ from that of the Class I group. Nineteen of the 20 Class I patients showed minimal or no change in their TVL/FH (-1.5° to 1.5°) at T2. On the other hand, 6 of the 20 Class III patients showed more than a 4.5° decrease in their TVL/FH at T2. CONCLUSIONS: Most of the Class I patients showed minimal or no change in their NHP at T2, but some Class III patients had changes in their NHP that tended toward head extension after mandibular setback surgery. Thus, soft tissue analysis using the TVL in NHP may not be reliable for some skeletal Class III patients who undergo mandibular setback surgery.

Antiangiogenic antitumor activities of IGFBP-3 are mediated by IGF-independent suppression of Erk1/2 activation and Egr-1-mediated transcriptional events.

Most antiangiogenic therapies currently being evaluated in clinical trials target the vascular endothelial growth factor pathway; however, the tumor vasculature can acquire resistance to vascular endothelial growth factor-targeted therapy by shifting to other angiogenesis mechanisms. Insulin-like growth factor binding protein-3 (IGFBP-3) has been reported to suppress tumor growth and angiogenesis by both IGF-dependent and IGF-independent mechanisms; however, understanding of its IGF-independent mechanisms is limited. We observed that IGFBP-3 blocked tumor angiogenesis and growth in non-small cell lung cancer and head and neck squamous cell carcinoma. Conditioned media from an IGFBP-3-treated non-small cell lung cancer cell line displayed a significantly decreased capacity to induce HUVEC proliferation and aortic sprouting. In cancer cells, IGFBP-3 directly interacted with Erk1/2, leading to inactivation of Erk1/2 and Elk-1, and suppressed transcription of early growth response protein 1 and its target genes, basic fibroblast growth factor and platelet-derived growth factor. These data suggest that IGF-independent Erk1/2 inactivation and decreased IGFBP-3-induced Egr-1 expression block the autocrine and paracrine loops of angiogenic factors in vascular endothelial and cancer cells. Together, these findings provide a molecular framework of IGFBP-3's IGF-independent antiangiogenic antitumor activities. Future studies are needed for development of IGFBP-3 as a new line of antiangiogengic cancer drug.

Comparison of facemask therapy effects using skeletal and tooth-borne anchorage.

OBJECTIVES: To investigate long-term outcomes of dentoskeletal changes induced by facemask therapy using skeletal anchorage in Class III patients and compare them to those of conventional tooth-borne anchorage. MATERIALS AND METHODS: This retrospective study included 20 patients who received facemask (FM) therapy with miniplates as anchorage for maxillary protraction (Miniplate/FM group, 10.6 ± 1.1 years old [mean ± SD]) and 23 patients who were treated with facemask with rapid maxillary expander (RME/FM group, 10.0 ± 1.5 years old [mean ± SD]). Dentoskeletal changes were evaluated using lateral cephalograms at pretreatment (T1), after facemask therapy (T2), and at the post-pubertal stage (T3). Cephalometric changes were compared between groups and clinical success rates at T3 were evaluated. RESULTS: SNA and A to N perpendicular to FH increased significantly more in the Miniplate/FM group than in the RME/FM group when comparing short-term effects of facemask therapy (T1-T2). ANB, Wits appraisal, Angle of convexity, mandibular plane angle, and overjet decreased significantly more in the RME/FM group than in the Miniplate/FM group after facemask therapy (T2-T3). A more favorable intermaxillary relationship was observed in the Miniplate/FM group than in the RME/FM group in long-term observations (T1-T3). Clinical success rate at T3 was 95% in the Miniplate/FM group and 85% in the RME/FM group. CONCLUSIONS: Facemask therapy with skeletal anchorage showed a greater advancement of the maxilla and more favorable stability for correction of Class III malocclusion in the long-term than conventional facemask therapy with tooth-borne anchorage.

Camouflage treatment by backward rotation of the mandible for a severe skeletal Class III malocclusion with aplastic anemia: A case report.

Orthognathic surgery is the primary treatment option for severe skeletal discrepancy. However, orthodontic camouflage should be considered as an alternative treatment option, considering the risks of surgery. A 19.5-year-old man presented with a severe prognathic mandible with a Class III molar relationship and an anterior crossbite. Orthognathic surgery could be considered because of his severe skeletal discrepancy and mandibular prognathism. However, the anesthetist for orthognathic surgery did not recommend surgery under general anesthesia because of risk factors associated with the patient's aplastic anemia, including bleeding and infections. Thus, a camouflage treatment to promote backward rotation of the mandible via orthodontic extrusion of the posterior teeth was planned. An anterior bite plate, intermaxillary elastics, and fixed orthodontic appliances were used to extrude the posterior teeth and to align the dentition. After 17 months of nonsurgical orthodontic treatment, normal occlusion was achieved, and the facial profile was dramatically improved. This case report describes the dentoskeletal and soft-tissue effects of mandibular rotation and its long-term stability.

Crown-root angulations of the maxillary anterior teeth according to malocclusions: A cone-beam computed tomography study in Korean population.

Objective: To compare crown-root angulations of the permanent maxillary anterior teeth in skeletal Class I, Class II, and Class III Korean malocclusion patients using cone-bean computed tomography (CBCT) images. Methods: Sixty CBCT images were collected from orthodontic patients archive based on skeletal Class I (0˚< A point-nasion-B point angle [ANB] < 4˚), Class II (ANB ≥ 4˚), and Class III (ANB ≤ 0˚) to have 20 samples in each group. Mesiodistal crown-root angulation (MDCRA) and labiolingual crown-root angulation (LLCRA) were evaluated after orientation of images. Crown-root angulations were compared among Class I, Class II, and Class III groups and among the maxillary anterior teeth in each group. Results: LLCRAs of the maxillary central incisor and the lateral incisor were significantly lower in Class III group than those in Class I group. However, those of the canine showed no significant differences among groups. MDCRAs of the maxillary anterior teeth did not significantly differ among groups either. Conclusions: Our results suggest that skeletal Class III malocclusion might affect LLCRA of the maxillary incisors, especially the central incisor.

Maxillary protraction with miniplates providing skeletal anchorage in a growing Class III patient.

Maxillary protraction headgear has been used in the treatment of Class III malocclusion with maxillary deficiency. However, loss of dental anchorage has been reported with tooth-borne anchorage such as lingual arches and expansion devices. This side effect can be minimized with skeletal anchorage devices such as implants, onplants, mini-implants, and miniplates. The use of miniplates for maxillary protraction in the mixed dentition has not been reported in the literature. This case report describes the treatment of an 8-year-old girl with a Class III malocclusion and maxillary deficiency. Miniplates were used as skeletal anchorage for maxillary protraction followed by phase 2 orthodontic treatment with fixed appliances. Skeletal, dental, and facial changes in response to orthopedic and orthodontic treatment are reported to illustrate the esthetics, function, and stability of treatment with this new technique.

Relationship between the lingual frenulum and craniofacial morphology in adults.

INTRODUCTION: The purpose of this study was to determine the relationship between the length of the lingual frenulum and craniofacial morphology and test the hypothesis that skeletal Class III malocclusion is related to tongue-tie, in which the lingual frenulum is short and restricts the mobility of the tongue. METHODS: The sample consisted of 50 skeletal Class I patients (0° < ANB angle < 4°), 50 skeletal Class II patients (ANB angle > 4°), and 50 skeletal Class III patients (ANB angle <0°). Direct and indirect measuring methods were used to quantify the length of the lingual frenulum. The median lingual frenulum length was measured directly with a lingual frenulum ruler. It was evaluated indirectly by measuring the differences between the maximum mouth opening with and without the tip of the tongue touching the incisive papilla. A lateral cephalogram was taken for each subject and a computerized cephalometric analysis was used to assess the cranial morphology. Analysis of variance (ANOVA) was used to compare the differences among the 3 groups. The Pearson correlation analysis was used to detect any relationship between the lingual frenulum length and cephalometric variables. RESULTS: The median lingual frenulum length was significantly longer in the skeletal Class III subjects compared with the skeletal Class I and Class II subjects. The maximum opening of the mouth was significantly reduced in the skeletal Class III subjects compared with Class I and Class II subjects. Significant correlations were also found among the median lingual frenulum length, maximum mouth opening reduction, and the cephalometric variables such as the SNB and ANB angles, Wits appraisal, mandibular length, and the interincisal angle. CONCLUSIONS: The present study supports the hypothesis that skeletal Class III malocclusion is related to long median lingual frenulum or a tongue-tie tendency. Patients diagnosed with tongue-tie might have a tendency toward skeletal Class III malocclusion.

Valuing water quality benefits from adopting best management practices: A spatial approach.

We developed a GIS-based tool that values, in a spatially explicit way, the ecosystem services generated by water quality improvements resulting from adoption of agricultural best management practices (BMPs). The tool is calibrated for watersheds in the Chesapeake Bay drainage and includes the benefits from water quality improvements within targeted watersheds, water quality improvements downstream from targeted watersheds, and reductions in pollutant loadings to Chesapeake Bay. The tool is used to investigate specific BMP scenarios adopted within specific watersheds. The results show that (i) BMP adoption generates large positive net benefits to society, with benefit/cost ratios ranging from 22 to 276; (ii) by selecting cost effective BMPs and placing them in the most appropriate places, the cost of meeting pollutant reduction targets would be reduced by 34-71%; and (iii) net benefits from BMP adoption are higher when they are implemented close to or upstream from population centers.