A comprehensive patient-specific prediction model for temporomandibular joint osteoarthritis progression.

Temporomandibular joint osteoarthritis (TMJ OA) is a prevalent degenerative disease characterized by chronic pain and impaired jaw function. The complexity of TMJ OA has hindered the development of prognostic tools, posing a significant challenge in timely, patient-specific management. Addressing this gap, our research employs a comprehensive, multidimensional approach to advance TMJ OA prognostication. We conducted a prospective study with 106 subjects, 74 of whom were followed up after 2 to 3 y of conservative treatment. Central to our methodology is the development of an innovative, open-source predictive modeling framework, the Ensemble via Hierarchical Predictions through Nested cross-validation tool (EHPN). This framework synergistically integrates 18 feature selection, statistical, and machine learning methods to yield an accuracy of 0.87, with an area under the ROC curve of 0.72 and an F1 score of 0.82. Our study, beyond technical advancements, emphasizes the global impact of TMJ OA, recognizing its unique demographic occurrence. We highlight key factors influencing TMJ OA progression. Using SHAP analysis, we identified personalized prognostic predictors: lower values of headache, lower back pain, restless sleep, condyle high gray level-GL-run emphasis, articular fossa GL nonuniformity, and long-run low GL emphasis; and higher values of superior joint space, mouth opening, saliva Vascular-endothelium-growth-factor, Matrix-metalloproteinase-7, serum Epithelial-neutrophil-activating-peptide, and age indicate recovery likelihood. Our multidimensional and multimodal EHPN tool enhances clinicians' decision-making, offering a transformative translational infrastructure. The EHPN model stands as a significant contribution to precision medicine, offering a paradigm shift in the management of temporomandibular disorders and potentially influencing broader applications in personalized healthcare.

Three-dimensional decision support system for treatment of canine impaction.

INTRODUCTION: This study aimed to develop a 3-dimensional (3D) characterization of the severity of maxillary impacted canines and to test the clinical performance of this characterization as a treatment decision support tool. METHODS: Cone-beam computed tomography images obtained from 83 patients with 120 impacted maxillary canines were included. Quantitative information on the canine 3D position and qualitative assessment of root damage of adjacent teeth were evaluated. A severity index was constructed on the basis of the quantitative findings. Clinical applicability was tested by comparing clinical diagnosis and treatment planning for conventional records vs the 3D characterization via a 2-part survey. RESULTS: The average quantitative assessments of impacted maxillary canine position were 6.4 ± 3.6 mm from the midsagittal plane, 11.6 ± 3.1 mm in height relative to the occlusal plane, 31.5° ± 18° of roll, and 48.8° ± 14.3° of pitch. The severity index ranged from 0-13 with a mean score of 4.5 ± 2.2. Overlap with adjacent teeth was the greatest contributor (33%) to the index. Bicortically impacted canines caused the most severe root damage. Cone-beam computed tomography was preferred for assessing root damage and overall severity, whereas conventional imaging was sufficient for height and angulation assessment. The 3D report was very important or important for evaluating root damage, canine position, overall severity, and overlap. The 3D report changed most of the decisions relating to biomechanics, patient education, and treatment time estimate. The decision of exposure and traction vs extraction was changed 22% of the time after the presentation of the 3D report. CONCLUSIONS: The overlap with adjacent teeth frequently contributes the most to the severity index. The 3D report provided relevant clinical information regarding the canine position, damage to adjacent teeth, and the severity index, with a profound impact on the decisions of the clinicians regarding biomechanics, patient education, and treatment time estimate.

Comprehensive peri-implant tissue evaluation with ultrasonography and cone-beam computed tomography: A pilot study.

OBJECTIVES: The aim of the present study was to explore the feasibility of ultrasonography (US) for clinical imaging of peri-implant tissues. MATERIAL AND METHODS: Patients with ≥1 implant, a cone-beam computed tomography (CBCT) scan, an US scan, and clinical photographs taken during the surgery were included. The crestal bone thickness (CBT) and facial bone level (FBL) were measured on both US and CBCT modalities, and direct FBL measurements were also made on clinical images. US measurements were compared with CBCT and direct readings. RESULTS: A total of eight implants from four patients were included. For FBL measurements, US and direct (r2 = 0.95) as well as US and CBCT (r2 = 0.85) were highly correlated, whereas CBCT correlated satisfactorily with the direct reading (r2 = 0.75). In one implant without facial bone, CBCT was not able to measure CBT and FBL accurately. The estimated bias for CBT readings was 0.17 ± 0.23 mm (p = .10) between US and CBCT. US blood flow imaging was successfully recorded and showed a wide dynamic range among patients with different degrees of clinical inflammation. CONCLUSION: US is a feasible method to evaluate peri-implant facial crestal bone dimensions. Additional US features, for example, functional blood flow imaging, may be useful to estimate the extent and severity of inflammation.

Clinical decision support systems in orthodontics: A narrative review of data science approaches.

Advancements in technology and data collection generated immense amounts of information from various sources such as health records, clinical examination, imaging, medical devices, as well as experimental and biological data. Proper management and analysis of these data via high-end computing solutions, artificial intelligence and machine learning approaches can assist in extracting meaningful information that enhances population health and well-being. Furthermore, the extracted knowledge can provide new avenues for modern healthcare delivery via clinical decision support systems. This manuscript presents a narrative review of data science approaches for clinical decision support systems in orthodontics. We describe the fundamental components of data science approaches including (a) Data collection, storage and management; (b) Data processing; (c) In-depth data analysis; and (d) Data communication. Then, we introduce a web-based data management platform, the Data Storage for Computation and Integration, for temporomandibular joint and dental clinical decision support systems.

Mandibular condylar remodeling characteristics after simultaneous condylectomy and orthognathic surgery.

INTRODUCTION: The objectives of this study were to evaluate postsurgical condylar remodeling using a radiographical interpretation, quantify condylar volumetric asymmetry, and assess soft tissue symmetry after simultaneous unilateral high condylectomy and bimaxillary osteotomies. METHODS: Sixteen patients diagnosed with unilateral condylar hyperplasia underwent unilateral high condylectomy and orthognathic surgery to correct skeletal and facial asymmetries. Cone-beam computed tomography scans were acquired before and 1-year after surgery. A radiographic consensus was evaluated for signs of reparative or degenerative changes. The condyles were mirrored and registered for assessment of volumetric and morphologic asymmetry. Soft tissue symmetry was evaluated by measurement of the distance of soft tissue pogonion from the skeletal midsagittal plane. RESULTS: Patients who undergo unilateral high condylectomy and orthognathic surgery present radiographic signs suggestive of degenerative changes, including sclerosis, osteophytes, flattening, and erosion in both the surgical and nonsurgical condyles (P ≤0.01). There was an average volumetric improvement of 531.9 ± 662.3 mm3 1-year postsurgery (P = 0.006). Soft tissue symmetry improved in all patients, with an average improvement of 65.8% (4.0 mm ± 2.6 mm, P ≤ 0.01). There was no correlation between the change in condylar volumetric asymmetry and the stability of the soft tissue correction. CONCLUSIONS: High condylectomy for the correction of a skeletal asymmetry in patients with condylar hyperplasia successfully reduces the volumetric asymmetry between the condyles. Postsurgical dysmorphic remodeling and degenerative changes were noted in both the surgical and nonsurgical condyles. Despite remarkable changes and remaining joint asymmetry, the soft tissue correction is stable 1-year postsurgery.

Articular cartilage protection in Ctsk-/- mice is associated with cellular and molecular changes in subchondral bone and cartilage matrix.

Osteoarthritis (OA) is a degenerative disease and a major cause of chronic disability in aging individuals. Cathepsin K (CatK), encoded by the Ctsk gene, has been implicated in the pathogenesis of pycnodysostosis and osteoporosis. The use of a selective inhibitor of CatK was recently shown to delay OA progression in rabbits. However, the cellular mechanisms underlying these protective effects remain unexplored. We examined articular cartilage maintenance and joint bone remodeling using Ctsk null mice (Ctsk-/- ) which underwent destabilization of the medial meniscus (DMM). We found that Ctsk-/- mice displayed delayed remodeling of subchondral and calcified cartilage by osteoclasts and chodroclasts respectively in DMM-induced osteoarthritis. While WT mice displayed a more severe OA phenotype than Ctsk-/- mice at 16 weeks, higher subchondral bone volume and lower trabecular spacing were also observed in surgically-induced OA joints of Ctsk-/- mice. However, no differences were seen in non-surgical controls. During OA progression, TRAP+ osteoclast numbers were increased in both WT and Ctsk-/- mice. However, Ctsk-/- mice had fewer physis-derived chondroclasts than WT when OA was present. These data suggest that CatK may differentially regulate chondroclastogenesis in the growth plate. Targeted PCR arrays of RNA harvested from laser captured osteoclasts in the subchondral bone and chondroclasts in the growth plate demonstrated differential expression of Atp6v0d2, Tnfrsf11a, Ca2, Calcr, Ccr1, Gpr68, Itgb3, Nfatc1, and Syk genes between WT and Ctsk-/- mice at 8- and 16-weeks post-DMM. Our data provide insight into the cellular mechanisms by which cathepsin K deletion delays OA progression in mice.

Osteal macrophages support physiologic skeletal remodeling and anabolic actions of parathyroid hormone in bone.

Cellular subpopulations in the bone marrow play distinct and unexplored functions in skeletal homeostasis. This study delineated a unique role of osteal macrophages in bone and parathyroid hormone (PTH)-dependent bone anabolism using murine models of targeted myeloid-lineage cell ablation. Depletion of c-fms(+) myeloid lineage cells [via administration of AP20187 in the macrophage Fas-induced apoptosis (MAFIA) mouse model] reduced cortical and trabecular bone mass and attenuated PTH-induced trabecular bone anabolism, supporting the positive function of macrophages in bone homeostasis. Interestingly, using a clodronate liposome model with targeted depletion of mature phagocytic macrophages an opposite effect was found with increased trabecular bone mass and increased PTH-induced anabolism. Apoptotic cells were more numerous in MAFIA versus clodronate-treated mice and flow cytometric analyses of myeloid lineage cells in the bone marrow showed that MAFIA mice had reduced CD68(+) cells, whereas clodronate liposome-treated mice had increased CD68(+) and CD163(+) cells. Clodronate liposomes increased efferocytosis (clearance of apoptotic cells) and gene expression associated with alternatively activated M2 macrophages as well as expression of genes associated with bone formation including Wnt3a, Wnt10b, and Tgfb1. Taken together, depletion of early lineage macrophages resulted in osteopenia with blunted effects of PTH anabolic actions, whereas depletion of differentiated macrophages promoted apoptotic cell clearance and transformed the bone marrow to an osteogenic environment with enhanced PTH anabolism. These data highlight a unique function for osteal macrophages in skeletal homeostasis.

Polarization of prostate cancer-associated macrophages is induced by milk fat globule-EGF factor 8 (MFG-E8)-mediated efferocytosis.

Tumor cells secrete factors that modulate macrophage activation and polarization into M2 type tumor-associated macrophages, which promote tumor growth, progression, and metastasis. The mechanisms that mediate this polarization are not clear. Macrophages are phagocytic cells that participate in the clearance of apoptotic cells, a process known as efferocytosis. Milk fat globule- EGF factor 8 (MFG-E8) is a bridge protein that facilitates efferocytosis and is associated with suppression of proinflammatory responses. This study investigated the hypothesis that MFG-E8-mediated efferocytosis promotes M2 polarization. Tissue and serum exosomes from prostate cancer patients presented higher levels of MFG-E8 compared with controls, a novel finding in human prostate cancer. Coculture of macrophages with apoptotic cancer cells increased efferocytosis, elevated MFG-E8 protein expression levels, and induced macrophage polarization into an alternatively activated M2 phenotype. Administration of antibody against MFG-E8 significantly attenuated the increase in M2 polarization. Inhibition of STAT3 phosphorylation using the inhibitor Stattic decreased efferocytosis and M2 macrophage polarization in vitro, with a correlating increase in SOCS3 protein expression. Moreover, MFG-E8 knockdown tumor cells cultured with wild-type or MFG-E8-deficient macrophages resulted in increased SOCS3 expression with decreased STAT3 activation. This suggests that SOCS3 and phospho-STAT3 act in an inversely dependent manner when stimulated by MFG-E8 and efferocytosis. These results uncover a unique role of efferocytosis via MFG-E8 as a mechanism for macrophage polarization into tumor-promoting M2 cells.

A comparison of virtual reality and three-dimensional multiplanar educational methods for student learning of cone beam computed tomography interpretations.

OBJECTIVES: The purpose of this study was to compare student learning of cone beam computed tomography (CBCT) interpretation using immersive virtual reality (VR) and three-dimensional multiplanar (MP) reconstructions. METHODS: Sixty first-year dental students were randomly allocated to two groups, VR and MP, and underwent a one-on-one educational intervention to identify anatomic structures using CBCT data. All participants completed three multiple-choice questionnaires (MCQs) before (T1), immediately after (T2), and 2 weeks following (T3) the intervention. Additionally, pre-survey, post-survey, NASA Task Load Index (NASA-TLX), and presence questionnaires were completed. Analysis of objective measures of performance on MCQs and subjective data from the questionnaires was completed (α = 0.05). RESULTS: There was a significant increase in test performance and informational recall between T1-T2 and T1-T3 for VR and MP groups (p < 0.001). However, there were no significant differences in performance on MCQs between T2 and T3. Analysis of the Presence questionnaire indicated that the VR group felt decreased distraction (p = 0.013), increased realism (p = 0.035), and increased involvement (p = 0.047) during the educational intervention when compared with the MP group. Analysis of the NASA-TLX indicated that the VR group experienced more physical demand (p < 0.01) but similar cognitive demand when compared with the MP group. Qualitative responses indicated that the VR group had a more dynamic sense of visualization and manipulation compared to the MP group. CONCLUSION: Results from this study show that VR is as effective as traditional MP methods of CBCT interpretation learning. Further benefits of VR educational intervention include increased involvement, realism and less distraction.

A skeleton in a huff: insights in etiologies of osteosclerosis.

A 30-yr-old man developed right lower leg pain and a palpable solid mass. Radiographic imaging revealed a periosteal reaction with an exostotic mass arising from the right distal fibula. Generalized skeletal osteosclerosis with periosteal reaction was discovered on a radiographic skeletal survey. A biopsy of the right fibular mass revealed reactive woven bone. The patient was referred to a metabolic bone disease clinic, where laboratory values were consistent with secondary hyperparathyroidism and increased bone turnover. A DXA bone density scan revealed high bone density, with an L1-4 spine Z-score of +9.3, a left femoral neck Z-score of +8.5, and a total hip Z-score of +6.5. A dental exam revealed generalized gingival inflammation, teeth mobility, generalized horizontal alveolar bone loss and widening of the periodontal ligament space, increased bone density around the teeth, and thickening of the radicular lamina dura. An extensive evaluation was performed, with the result of a single test revealing the diagnosis. The differential diagnoses of osteosclerosis affecting the skeleton, teeth, and oral cavity are discussed.

A 30-yr-old man developed, over a short period, pain in his lower right leg accompanied by a hard mass. He also reported weight loss and night sweats for the past 6 months. After evaluation by his primary physician, an X-ray was ordered that reported a bony mass arising from the right fibula bone. A biopsy was performed of the mass, but no evidence of cancer or any other specific abnormality was found. The patient was then referred to a bone disease specialty clinic. Laboratory tests revealed a large increase in how quickly the patient's skeleton was remodeling, affecting the balance of bone formation and removal involved in maintaining a healthy skeleton. A bone density scan reported that the patient had very dense bones. Other unusual changes were also discovered in a dental exam, suggesting bone thickening. After an extensive evaluation, a single blood test revealed the cause of the fibular bone mass and dense bones.

The effects of zoledronic acid in the bone and vasculature support of hematopoietic stem cell niches.

Hematopoietic stem cells (HSC) are maintained in a tightly regulated bone microenvironment constituted by a rich milieu of cells. Bone cells such as osteoblasts are associated with niche maintenance as regulators of the endosteal microenvironment. Bone remodeling also plays a role in HSC mobilization although it is poorly defined. The effects of zoledronic acid (ZA), a potent bisphosphonate that inhibits bone resorption, were investigated on bone marrow cell populations focusing on HSCs, and the endosteal and vascular niches in bone. ZA treatment significantly increased bone volume and HSCs in both young and adult mice (4 week and 4 month old, respectively). ZA increased vessel numbers with no overall change in vascular volume in bones of young and had no effect on vasculature in adult mice. Since both young and adult mice had increased HSCs and bone mass with differing vasculature responses, this suggests that ZA indirectly supports HSCs via the osteoblastic niche and not the vascular niche. Additionally, gene expression in Lin- cells demonstrated increased expression of self-renewal-related genes Bmi1 and Ink4a suggesting a role of ZA in the modulation of cell commitment and differentiation toward a long-term self-renewing cell. Genes that support the osteoblastic niche, BMP2 and BMP6 were also augmented in ZA treated mice. In conclusion, ZA-induced HSC expansion occurs independent of the vascular niche via indirect modulation of the osteoblastic niche.

Student learning of head and neck anatomy using cone beam computed tomography and immersive virtual reality.

OBJECTIVES: The purpose of this study was to evaluate the efficacy of student learning of anatomy and 3D imaging concepts using cone beam computed tomography (CBCT) and immersive virtual reality (VR) technology. METHODOLOGY: Ninety (n = 90) first year dental students with no previous experience in 3D imaging were recruited. All participants completed a 10-item, multiple-choice questionnaire (MCQ) and a pre-survey prior to the educational intervention. Following a brief video orientation on CBCT and anatomy, each participant underwent a one-on-one educational intervention using immersive VR with calibrated instructors to identify head and neck anatomic structures using a VR/CBCT educational tool. Immediately following the intervention, all participants completed a postsurvey, a second MCQ, NASA task load index and presence questionnaires. Participants completed a third MCQ 2 weeks following the intervention. Analysis of objective measures of performance on MCQ's (p < 0.05) and subjective data from the questionnaires was completed. RESULTS: The students doubled their mean test scores 2.45 ± 1.274 to 5.99 ± 1.576 on MCQ's immediately following the educational intervention (p < 0.05). The significant increase in the MCQ test scores was maintained after 2 weeks, 5.73 ± 1.721 (p < 0.05). There were no gender differences in student test performance. Students rated the immersive VR/CBCT educational intervention experience highly for control, sensory, and realism factors with minimal distraction and frustration factors. CONCLUSION: Results from this study show that immersive VR/CBCT educational intervention improved test performance and contributed to information recall in students. Further benefits reported by participants include the sense of presence and increased engagement using immersive VR.

The multifaceted actions of PTHrP in skeletal metastasis.

PTHrP, identified during the elucidation of mediators of malignancy-induced hypercalcemia, plays numerous roles in normal physiology as well as pathological conditions. Recent data support direct functions of PTHrP in metastasis, particularly from tumors with strong bone tropism. Bone provides a unique metastatic environment because of mineralization and the diverse cell populations in the bone marrow. PTHrP is a key regulator of tumor-bone interactions and regulates cells in the bone microenvironment through proliferative and prosurvival activities that prime the 'seed' and the 'soil' of the metastatic lesion. This review highlights recent findings regarding the role of PTHrP in skeletal metastasis, including direct actions in tumor cells, as well as alterations in the bone microenvironment and future perspectives involving the potential roles of PTHrP in the premetastatic niche, and tumor dormancy.

Quantitative bone imaging biomarkers and joint space analysis of the articular Fossa in temporomandibular joint osteoarthritis using artificial intelligence models.

Temporomandibular joint osteoarthritis (TMJ OA) is a disease with a multifactorial etiology, involving many pathophysiological processes, and requiring comprehensive assessments to characterize progressive cartilage degradation, subchondral bone remodeling, and chronic pain. This study aimed to integrate quantitative biomarkers of bone texture and morphometry of the articular fossa and joint space to advance the role of imaging phenotypes for diagnosis of Temporomandibular Joint Osteoarthritis (TMJ OA) in early to moderate stages by improving the performance of machine-learning algorithms to detect TMJ OA status. Ninety-two patients were prospectively enrolled (184 h-CBCT scans of the right and left mandibular condyles), divided into two groups: 46 control and 46 TMJ OA subjects. No significant difference in the articular fossa radiomic biomarkers was found between TMJ OA and control patients. The superior condyle-to-fossa distance (p < 0.05) was significantly smaller in diseased patients. The interaction effects of the articular fossa radiomic biomarkers enhanced the performance of machine-learning algorithms to detect TMJ OA status. The LightGBM model achieved an AUC 0.842 to diagnose the TMJ OA status with Headaches and Range of Mouth Opening Without Pain ranked as top features, and top interactions of VE-cadherin in Serum and Angiogenin in Saliva, TGF-ß1 in Saliva and Headaches, Gender and Muscle Soreness, PA1 in Saliva and Range of Mouth Opening Without Pain, Lateral Condyle Grey Level Non-Uniformity and Lateral Fossa Short Run Emphasis, TGF-ß1 in Serum and Lateral Fossa Trabeculae number, MMP3 in Serum and VEGF in Serum, Headaches and Lateral Fossa Trabecular spacing, Headaches and PA1 in Saliva, and Headaches and BDNF in Saliva. Our preliminary results indicate that condyle imaging features may be more important in regards to main effects, but the fossa imaging features may have a larger contribution in terms of interaction effects. More studies are needed to optimize and further enhance machine-learning algorithms to detect early markers of disease, improve prediction of disease progression and severity to ultimately better serve clinical decision support systems in the treatment of patients with TMJ OA.

Ultrasound insonation angle and scanning imaging modes for imaging dental implant structures: A benchtop study.

INTRODUCTION: High frequency ultrasound has shown as a promising imaging modality to evaluate peri-implant tissues. It is not known if the ultrasound imaging settings might influence ultrasound's ability to differentiate implant structures. The aim of this benchtop study was to evaluate the dependence of ultrasound on imaging angles and modes to measure implant geometry-related parameters. METHODS: A clinical ultrasound scanner (ZS3, Mindray) with an intraoral probe (L30-8) offering combinations of harmonic and compound imaging modes was employed for imaging 16 abutments and 4 implants. The samples were mounted to a micro-positioning system in a water tank, which allowed a range of -30 to 30-degree imaging angles in 5-degree increment between the probe and samples. The abutment angle, implant thread pitch and depth were measured on ultrasound, compared to the reference readings. The errors were computed as a function of the image angles and modes. All samples were replicated 3 times for 3 image modes and 11 image angles, thus resulting in 2,340 images. RESULTS: The mean errors of ultrasound to estimate 16 abutment angles, compared to the reference values, were between -1.8 to 2.7 degrees. The root mean squared error (RMSE) ranged from 1.5 to 4.6 degrees. Ultrasound significantly overestimated the thread pitch by 26.1 µm to 36.2 µm. The error in thread depth measurements were in a range of -50.5 µm to 39.6 µm, respectively. The RMSE of thread pitch and depth of the tested 4 implants was in a range of 34.7 to 56.9 µm and 51.0 to 101.8 µm, respectively. In most samples, these errors were independent of the image angle and modes. CONCLUSIONS: Within the limitations of this study, high-frequency ultrasound was feasible in imaging abutments and implant fixtures independent of scanning angle within ±30° of normal incidence and for compounding and non-compounding-based imaging modes.

Automatic multi-anatomical skull structure segmentation of cone-beam computed tomography scans using 3D UNETR.

The segmentation of medical and dental images is a fundamental step in automated clinical decision support systems. It supports the entire clinical workflow from diagnosis, therapy planning, intervention, and follow-up. In this paper, we propose a novel tool to accurately process a full-face segmentation in about 5 minutes that would otherwise require an average of 7h of manual work by experienced clinicians. This work focuses on the integration of the state-of-the-art UNEt TRansformers (UNETR) of the Medical Open Network for Artificial Intelligence (MONAI) framework. We trained and tested our models using 618 de-identified Cone-Beam Computed Tomography (CBCT) volumetric images of the head acquired with several parameters from different centers for a generalized clinical application. Our results on a 5-fold cross-validation showed high accuracy and robustness with a Dice score up to 0.962±0.02. Our code is available on our public GitHub repository.

Leptin functions peripherally to regulate differentiation of mesenchymal progenitor cells.

Leptin functions through a well-documented central neuroendocrine pathway to regulate bone mass. However, the ability of leptin to modulate bone mass through a peripheral mechanism has been debated due to conflicting in vitro results and lack of sufficient in vivo models. We utilized mice with LoxP sites introduced into the long-form leptin receptor (ObRb) gene to determine how leptin regulates mesenchymal progenitor cell (MPC) differentiation and osteoblast function in vitro and in vivo. Rapid phosphorylation of Stat3 after leptin treatment of bone marrow stromal cells (BMSCs) from mice with conditional deletion of ObRb in macrophages (LysM(Cre+F/F)) confirmed expression of functional leptin receptors by BMSCs. Adenovirus-Cre mediated disruption of ObRb in primary stromal cells decreased mineralization and increased adipogenesis. In contrast, BMSCs harvested from leptin-signaling deficient Ob/Ob or Db/Db mice showed increased mineralization. To determine the physiologic relevance of these differences, mice with cell-specific deletion of ObRb in mesenchymal precursors (3.6(Cre+F/F)) or osteoblasts (2.3(Cre+F/F)) were generated. Although the 2.3(Cre+F/F) mice were grossly normal, the 3.6(Cre+F/F) mice displayed mild obesity that was not attributed to food intake. Femurs of 3.6(Cre+F/F) animals showed a 58%-61.9% increase in trabecular bone volume and a 65.5%-74% increase in bone mineral density. Cortical volume and mineral content were also increased 18%-22%. Primary 3.6(Cre+F/F) BMSCs recapitulated the high mineralization phenotype of Ob/Ob and Db/Db BMSCs. We conclude that leptin may have multiple peripheral roles depending on the differentiation state of MPC. Leptin (a) helps maintain MPCs in an undifferentiated state and (b) promotes mineralization of more differentiated osteoblasts.

Silver Diamine Fluoride and Progression of Incipient Approximal Caries in Permanent Teeth: A Retrospective Study.

Purpose: The purpose of this study was to evaluate the progression of incipient approximal caries lesions in permanent teeth of children and adolescents with and without silver diamine fluoride (SDF) application. Methods: A retrospective analysis of dental records and radiographs was performed. Baseline and follow-up bitewing radiographs were evaluated and scored using International Caries Classification and Management System (ICCMS) criteria to assess lesion progression. Results: A total of 131 lesions from 68 subjects (mean age equals 9.6 years) were evaluated radiographically and followed for up to 41 months (mean time equals 13.61±6.8 months); 23.6 percent of lesions in the SDF group progressed compared to 38.1 percent in the control group (P<0.001). On average, lesions in the control group increased more per month compared to the study group (P<0.001). The odds of lesion progression in the control group were 2.76 times the odds of progression in the study group. There was a statistically significant difference in lesion progression based on application method; lesions where SDF was applied with Superfloss progressed more per month, on average, versus microbrush application. Conclusions: Silver diamine fluoride may be an effective therapy to slow caries progression of incipient approximal lesions in permanent teeth in high caries-risk populations. Future studies are needed to detect differences in application methods.

Temporomandibular Joint Osteoarthritis Diagnosis Using Privileged Learning of Protein Markers.

Diagnosis of temporomandibular joint (TMJ) Osteoarthritis (OA) before serious degradation of cartilage and subchondral bone occurs can help prevent chronic pain and disability. Clinical, radiomic, and protein markers collected from TMJ OA patients have been shown to be predictive of OA onset. Since protein data can often be unavailable for clinical diagnosis, we harnessed the learning using privileged information (LUPI) paradigm to make use of protein markers only during classifier training. Three different LUPI algorithms are compared with traditional machine learning models on a dataset extracted from 92 unique OA patients and controls. The best classifier performance of 0.80 AUC and 75.6 accuracy was obtained from the KRVFL+ model using privileged protein features. Results show that LUPI-based algorithms using privileged protein data can improve final diagnostic performance of TMJ OA classifiers without needing protein microarray data during classifier diagnosis.

Radiographic interpretation using high-resolution Cbct to diagnose degenerative temporomandibular joint disease.

The objective of this study was to use high-resolution cone-beam computed images (hr- CBCT) to diagnose degenerative joint disease in asymptomatic and symptomatic subjects using the Diagnostic Criteria for Temporomandibular Disorders DC/TMD imaging criteria. This observational study comprised of 92 subjects age-sex matched and divided into two groups: clinical degenerative joint disease (c-DJD, n = 46) and asymptomatic control group (n = 46). Clinical assessment of the DJD and high-resolution CBCT images (isotropic voxel size of 0.08mm) of the temporomandibular joints were performed for each participant. An American Board of Oral and Maxillofacial Radiology certified radiologist and a maxillofacial radiologist used the DC/TMD imaging criteria to evaluate the radiographic findings, followed by a consensus of the radiographic evaluation. The two radiologists presented a high agreement (Cohen's Kappa ranging from 0.80 to 0.87) for all radiographic findings (osteophyte, erosion, cysts, flattening, and sclerosis). Five patients from the c- DJD group did not present radiographic findings, being then classified as arthralgia. In the asymptomatic control group, 82.6% of the patients presented radiographic findings determinant of DJD and were then classified as osteoarthrosis or overdiagnosis. In conclusion, our results showed a high number of radiographic findings in the asymptomatic control group, and for this reason, we suggest that there is a need for additional imaging criteria to classify DJD properly in hr-CBCT images.