Evaluation of Aligners and Root Resorption: An Overview of Systematic Reviews.

Background: To evaluate the current evidence on clear aligners and root resorption using 3D and/or combined 2D and 3D methods from available systematic reviews and meta-analyses and to determine the relationship between root resorption and clear aligners using the AMSTAR 2 tool. Methods: A comprehensive literature search of systematic reviews investigating aligners and root resorption, published up until 31 December 2022, was conducted. The following electronic databases were searched: MEDLINE via PubMed, EMBASE, Google Scholar, Science Direct, Web of Science, Scopus, LIVIVO, and LILACS. There were no language restrictions. The inclusion criteria were restricted to studies focusing on root resorption utilizing either 3D methods exclusively or a combination of 2D and 3D techniques. Data were screened and analyzed for quality using the "A Measurement Tool to Assess Systematic Reviews (AMSTAR 2)" tool. Data extraction was conducted independently by two authors. The gathered information was categorized and synthesized narratively based on the primary findings elucidated within the reviews. Results: Out of a total of 1221 potentially eligible studies initially identified, 4 systematic reviews met the inclusion criteria following the exclusion of irrelevant studies. Among these, two systematic reviews (50%) were classified as low-quality, while the remaining two (50%) were deemed to be of critically low quality. Conclusions: Based on the findings of four systematic reviews, the root resorption rate was lower with the use of clear aligners than with fixed aligners. It is advisable to approach the interpretation of this conclusion with caution, as the quality of the available evidence is assessed to be very low. Higher quality systematic reviews are needed to substantiate this conclusion.

Three-dimensional evaluation of the association between tongue position and upper airway morphology in adults: A cross-sectional study.

Objective: This study aimed to evaluate the association between low tongue position (LTP) and the volume and dimensions of the nasopharyngeal, retropalatal, retroglossal, and hypopharyngeal segments of the upper airway. Methods: A total of 194 subjects, including 91 males and 103 females were divided into a resting tongue position (RTP) group and a LTP group according to their tongue position. Subjects in the LTP group were divided into four subgroups (Q1, Q2, Q3, and Q4) according to the intraoral space volume. The 3D slicer software was used to measure the volume and minimum and average cross-sectional areas of each group. Airway differences between the RTP and LTP groups were analyzed to explore the association between tongue position and the upper airway. Results: No significant differences were found in the airway dimensions between the RTP and LTP groups. For both retropalatal and retroglossal segments, the volume and average cross-sectional area were significantly greater in the patients with extremely low tongue position. Regression analysis showed that the retroglossal airway dimensions were positively correlated with the intraoral space volume and negatively correlated with A point-nasion-B point and palatal plane to mandibular plane. Males generally had larger retroglossal and hypopharyngeal airways than females. Conclusions: Tongue position did not significantly influence upper airway volume or dimensions, except in the extremely LTP subgroup.

Serendipitous Discovery of T Cell-Produced KLK1b22 as a Regulator of Systemic Metabolism.

In order to study mechanistic/mammalian target of rapamycin's role in T cell differentiation, we generated mice in which Rheb is selectively deleted in T cells (T-Rheb-/- C57BL/6J background). During these studies, we noted that T-Rheb-/- mice were consistently heavier but had improved glucose tolerance and insulin sensitivity as well as a marked increase in beige fat. Microarray analysis of Rheb-/- T cells revealed a marked increase in expression of kallikrein 1-related peptidase b22 (Klk1b22). Overexpression of KLK1b22 in vitro enhanced insulin receptor signaling, and systemic overexpression of KLK1b22 in C57BL/6J mice also enhances glucose tolerance. Although KLK1B22 expression was markedly elevated in the T-Rheb-/- T cells, we never observed any expression in wild-type T cells. Interestingly, in querying the mouse Immunologic Genome Project, we found that Klk1b22 expression was also increased in wild-type 129S1/SVLMJ and C3HEJ mice. Indeed, both strains of mice demonstrate exceptionally improved glucose tolerance. This prompted us to employ CRISPR-mediated knockout of KLK1b22 in 129S1/SVLMJ mice, which in fact led to reduced glucose tolerance. Overall, our studies reveal (to our knowledge) a novel role for KLK1b22 in regulating systemic metabolism and demonstrate the ability of T cell-derived KLK1b22 to regulate systemic metabolism. Notably, however, further studies have revealed that this is a serendipitous finding unrelated to Rheb.

Electrochemical and fluorescent dual-mode sensor of acetylcholinesterase activity and inhibition based on MnO2@PD-coated surface.

We developed an electrochemical and fluorescent dual-mode sensor for assessing acetylcholinesterase (AChE) activity and inhibition by taking advantage of the high redox sensitivity of surface-coated mesoporous MnO2@polymer dot (MnO2@PD) towards AChE. The following phenomena constitute the basis of the detection mechanism: fluorescence resonance energy transfer (FRET) effect between MnO2 and PD; catalytic hydrolysis of acetylthiocholine (ATCh) to thiocholine (TCh) by AChE expressed by PC-12 cells, inducing fluorescence restoration and change in the conductivity of the system due to MnO2 decomposition; the presence of the inhibitor neostigmine preventing the conversion of ATCh to TCh. The surface-coated biosensor presents both fluorescence-based and electrochemical approaches for effectively monitoring AChE activity and inhibition. The fluorescence approach is based on the fluorescent "on/off" property of the system caused by MnO2 breakdown after interaction with TCh and the subsequent release of PDs. The conductivity of the coated electrode decreased dramatically as AChE concentration increased, resulting in electrochemical sensing of AChE activity and inhibition screening. Real-time wireless sensing can be conducted using a smartphone to monitor the resistance change, investigating the potential use of MnO2@PD nanocomposites in biological studies, and offering a real-time redox-fluorescent test for AChE activity monitoring and inhibitor screening.

GOT1 regulates CD8+ effector and memory T cell generation.

T cell activation, proliferation, function, and differentiation are tightly linked to proper metabolic reprogramming and regulation. By using [U-13C]glucose tracing, we reveal a critical role for GOT1 in promoting CD8+ T cell effector differentiation and function. Mechanistically, GOT1 enhances proliferation by maintaining intracellular redox balance and serine-mediated purine nucleotide biosynthesis. Further, GOT1 promotes the glycolytic programming and cytotoxic function of cytotoxic T lymphocytes via posttranslational regulation of HIF protein, potentially by regulating the levels of α-ketoglutarate. Conversely, genetic deletion of GOT1 promotes the generation of memory CD8+ T cells.

Cutting Edge: mTORC2 Regulates CD8+ Effector and Memory T Cell Differentiation through Serum and Glucocorticoid Kinase 1.

The mechanistic target of rapamycin is an essential regulator of T cell metabolism and differentiation. In this study, we demonstrate that serum- and glucocorticoid-regulated kinase 1 (SGK1), a downstream node of mechanistic target of rapamycin complex 2 signaling, represses memory CD8+ T cell differentiation. During acute infections, murine SGK1-deficient CD8+ T cells adopt an early memory precursor phenotype leading to more long-lived memory T cells. Thus, SGK1-deficient CD8+ T cells demonstrate an enhanced recall capacity in response to reinfection and can readily reject tumors. Mechanistically, activation of SGK1-deficient CD8+ T cells results in decreased Foxo1 phosphorylation and increased nuclear translocation of Foxo1 to promote early memory development. Overall, SGK1 might prove to be a powerful target for enhancing the efficacy of vaccines and tumor immunotherapy.

Long-term follow-up implant site development in the submerged mandibular primary second molars: a case report.

Treatment of ankylosed and submerged primary molars without permanent successors is challenging, as normal vertical dentoalveolar growth is compromised. Thus, grafting techniques and distraction osteogenesis are performed for ridge augmentation before implant restoration. However, these techniques are invasive with limited success. Another treatment for implant site development is noninvasive forced eruption. This case report describes long-term follow-up of alveolar ridge augmentation in the submerged mandibular primary second molars using subluxation and orthodontic forced eruption for implant site development. A 19-year old female had Class II molar relationships, upper anterior crowding with large overjet, missing four second premolars and submerged mandibular primary second molars with inadequate vertical development of alveolar bone. For the vertical alveolar bone alterations in the mandible, forced eruption with subluxation of ankylosed lower primary second molars was applied. Treatment outcome was evaluated over 5 years with stable occlusion, healthy periodontal tissues, and successful radiographic results.

Comparison of short-term condylar positional changes in mandibular prognathism after surgery-first approach: Symmetric setback versus asymmetric setback.

The aim of this study was to compare how the displacement of the mandibular condyle changed after symmetric or asymmetric mandibular setback surgery using the surgery-first approach (SFA). Patients who underwent mandibular setback surgery using the SFA were selected and divided into a symmetry group (n = 18) with differences of less than 2 mm between the right and left setback, and an asymmetry group (n = 18) with a difference of greater than 2 mm. Cone-beam computed tomography (CBCT)-generated cephalograms were obtained after three-dimensional superimposition of CBCT images taken before surgery (T0), within one week after surgery (T1), and seven months after surgery (T2). The condylar positions were measured. Condylar positional changes according to time were compared between the two groups and correlation analysis was performed. There were significant positional changes in mandibular condyles over time in both groups. However, most of these changes returned to their initial state. In the asymmetry group, there was a greater internal rotation of the mandibular condyle on the lesser setback side. The correlation analysis results revealed that only the setback difference was associated with rotational displacement of the condyle on the lesser setback side at two time points (T1-T0, T2-T0). In the SFA, significant condylar displacement occurred immediately after both symmetric and asymmetric mandibular setback surgery, and the right/left difference in mandibular setback showed a significant positive correlation with rotational displacement. Although more significant rotational displacement of the mandibular condyle was observed after asymmetric mandibular setback surgery, the amount was not large enough to be clinically significant.

CCL5 production in lung cancer cells leads to an altered immune microenvironment and promotes tumor development.

Current immunotherapies for lung cancer are only effective in a subset of patients. Identifying tumor-derived factors that facilitate immunosuppression offers the opportunity to develop novel strategies to supplement and improve current therapeutics. We sought to determine whether expression of driver oncogenes in lung cancer cells affects cytokine secretion, alters the local immune environment, and influences lung tumor progression. We demonstrate that oncogenic EGFR and KRAS mutations, which are early events in lung tumourigenesis, can drive cytokine and chemokine production by cancer cells. One of the most prominent changes was in CCL5, which was rapidly induced by KRASG12V or EGFRL858R expression, through MAPK activation. Immunocompetent mice implanted with syngeneic KRAS-mutant lung cancer cells deficient in CCL5 have decreased regulatory T cells (Tregs), evidence of T cell exhaustion, and reduced lung tumor burden, indicating tumor-cell CCL5 production contributes to an immune suppressive environment in the lungs. Furthermore, high CCL5 expression correlates with poor prognosis, immunosuppressive regulatory T cells, and alteration to CD8 effector function in lung adenocarcinoma patients. Our data support targeting CCL5 or CCL5 receptors on immune suppressive cells to prevent formation of an immune suppressive tumor microenvironment that promotes lung cancer progression and immunotherapy insensitivity.

Association of the three-dimensional skeletal variables with self-recognition of facial asymmetry in skeletal Class III patients.

OBJECTIVES: To investigate the association between three-dimensional (3D) skeletal variables and self-recognition of facial asymmetry in skeletal Class III patients. MATERIALS AND METHODS: Questionnaires and cone beam computed tomography of 74 patients (42 men and 32 women; mean age: 22.8 ± 4.5 years) with skeletal Class III and facial asymmetry were collected retrospectively. Patients were classified into three groups: group Sy (recognition of symmetry), group NS (not sure), and group Asy (recognition of asymmetry), according to their responses to the questionnaires. To assess 3D anatomic differences in the maxillomandibular region, six 3D hard tissue variables: maxillary height, ramal length, frontal ramal inclination (FRI), lateral ramal inclination (LRI), mandibular body length (Mn BL), and mandibular body height (Mn BH) were compared among the three self-recognition groups. Six 3D hard tissue variables and Menton deviation were reduced into three factors and their association with the self-recognition of facial asymmetry was investigated. RESULTS: Maxillary height, FRI, LRI, Mn BH, and Menton deviation demonstrated significant differences among the three self-recognition groups. The reduced factors, which consisted of transverse and vertical parameters, and vertical parameter of the mandibular corpus, demonstrated significant differences among the three self-recognition groups. The difference in Mn BH influenced the self-recognition of facial asymmetry. CONCLUSIONS: Both the transverse and vertical parameter of the skeleton were determinant in self-recognition of facial asymmetry. Identification of the skeletal difference in the lateral view involving LRI and Mn BH should be included for assessment of facial asymmetry.

Infrared Clinical Enamel Crack Detector Based on Silicon CCD and Its Application: A High-Quality and Low-Cost Option.

Enamel cracks generated in the anterior teeth not only affect the function but also the aesthetics of the teeth. Chair-side tooth enamel crack detection is essential for clinicians to formulate treatment plans and prevent related dental disease. This study aimed to develop a dental imaging system using a near-IR light source to detect enamel cracks and to investigate the relationship between anterior enamel cracks and age in vivo. A total of 68 subjects were divided into three groups according to their age: young, middle, and elderly. Near-infrared radiation of 850 nm was used to identify enamel cracks in anterior teeth. The results of the quantitative examination showed that the number of enamel cracks on the teeth increased considerably with age. For the qualitative examination, the results indicated that there was no significant relationship between the severity of the enamel cracks and age. So, it can be concluded that the prevalence of anterior cracked tooth increased significantly with age in the young and middle age. The length of the anterior enamel cracks tended to increase with age too; however, this result was not significant. The silicon charge-coupled device (CCD) with a wavelength of 850 nm has a good performance in the detection of enamel cracks and has very good clinical practicability.

mTORC1 Signaling Regulates Proinflammatory Macrophage Function and Metabolism.

Metabolic programming is integrally linked to immune cell function. Nowhere is this clearer than in the differentiation of macrophages. Proinflammatory M1 macrophages primarily use glycolysis as a rapid energy source but also to generate antimicrobial compounds, whereas alternatively activated M2 macrophages primarily rely on oxidative phosphorylation for the longevity required for proper wound healing. mTOR signaling has been demonstrated to be a key regulator of immune cell metabolism and function. mTORC2 signaling is required for the generation of M2 macrophages, whereas the role of mTORC1 signaling, a key regulator of glycolysis, has been controversial. By using genetic deletion of mTORC1 signaling in C57BL/6 mouse macrophages, we observed enhanced M1 macrophage function in vitro and in vivo. Surprisingly, this enhancement occurred despite a significant defect in M1 macrophage glycolytic metabolism. Mechanistically, enhanced M1 function occurred because of inhibition of the class III histone deacetylases the sirtuins, resulting in enhanced histone acetylation. Our findings provide a counterpoint to the paradigm that enhanced immune cell function must occur in the presence of increased cellular metabolism and identifies a potential, pharmacologic target for the regulation of inflammatory responses.

Part II. What drives Korean adults to seek orthodontic treatment: Factors contributing to orthodontic treatment decisions.

OBJECTIVE: This study aimed to identify the perceptions of orthodontic treatment among Korean adults and determine the factors that drive them to seek orthodontic treatment. METHODS: A total of 2,321 adults aged 19-64 years were surveyed using an internet research system from a specialized research company. The participants were divided into the following groups based on their experience of and willingness to undergo orthodontic treatment: experience, acceptance, and non-acceptance groups. The characteristics of the participants were compared using analysis of variance with post-hoc analysis. Multinomial logistic regression analysis was performed in all three models with the non-acceptance group as a reference. RESULTS: In terms of demographic characteristics, age, gender, marital status, and education had significant influences on orthodontic treatment decisions in adults in the experience and acceptance groups (p < 0.001). When all the factors were analyzed, age, marital status, past dental treatment experience, regular oral examinations, demand for orthodontic treatment, optimal treatment period, health insurance coverage, information on orthodontic treatments, perceptions regarding orthodontic treatment, and psychosocial impact of dental esthetics significantly influenced orthodontic treatment decisions in adults in the experience and acceptance groups (p < 0.001). CONCLUSIONS: These findings suggest that various factors influence orthodontic treatment decisions in adults. Individuals who seek orthodontic treatment were found to undergo more regular dental treatment and oral examination than those who did not. They also had a better perception of orthodontic treatment and more negative values for the psychosocial impact of dental esthetics.

Part I. What drives Korean adults to seek orthodontic treatment: Reliability and validity of a measurement instrument for the perception of orthodontic treatment.

OBJECTIVE: To develop a standardized instrument to measure the level of cognition for orthodontic treatment in adults, and verify its reliability and validity for assessing perceptions of orthodontic treatment in adults. METHODS: A total of 406 adults aged 19-64 years were surveyed by an internet research system. A tool was developed through the instrument development and verification stages. The data were analyzed by correlation analysis, exploratory factor analysis, confirmatory factor analysis, and Cronbach's α test. RESULTS: The instrument consisted of 11 items covering four factors related to orthodontic treatment. Three items were related to general perception, four described the perception of the treatment for adults, two related to the treatment effects, and two related to the retention of orthodontic treatment. In the reliability test, Cronbach's α was 0.845 for the 11 items. In assessments for individual components, Cronbach's α was 0.764 for the general perception of orthodontic treatment, 0.705 for the perception of this treatment for adults, 0.707 for the effects of the treatment, and 0.701 for the retention of orthodontic treatment. Finally, a measurement instrument for the perception of orthodontic treatment in adults was designed to assess the 11 items on a four-point Likert scale. CONCLUSIONS: This study developed a standard measurement instrument for assessing the perception of orthodontic treatment in adults. The proposed instrument will enable additional studies on the influence of an adult's perception of orthodontic treatment on the decision to undergo treatment.

The three-dimensional morphology of mandible and glenoid fossa as contributing factors to menton deviation in facial asymmetry-retrospective study.

BACKGROUND: The aim of this study is to evaluate whether the three-dimensional (3D) morphology of the mandibular condyle, glenoid fossa, and mandible correlated with menton deviation in facial asymmetry. SUBJECTS AND METHODS: Thirty adults (15 males and 15 females; mean age, 23.2 ± 3.8 years) with facial asymmetry were included. Linear, angular, and volumetric measurements of the 3D morphology of the mandibular condyle, glenoid fossa, and mandible were recorded using computed tomography (CT) images. The right/left differences were obtained by subtracting the left value from the right value, and an independent t test was used to compare the differences between the females and males. Multiple regression analysis was performed to identify the correlation between the right/left difference of the 3D morphology and menton deviation. RESULTS: The results of the comparative analysis did not show any statistical difference between the females and males (P > .05), so the females and males were combined. Multiple regression analysis for the mandibular condyle, glenoid fossa, and mandible showed that neck length, ramus length, and frontal ramal inclination had positive influences on menton deviation, with 76.5% of explanatory power. The neck length and head volume of the mandibular condyle when only the mandibular condyle was considered, and the ramus length and frontal ramal inclination when only the mandible was considered had positive influence on menton deviation with 69.9% and 68.6% explanatory power, respectively. On the other hand, when only considering glenoid fossa, the glenoid fossa had little effect on menton deviation with 15.7% of explanatory power. CONCLUSIONS: In facial asymmetry, the right/left differences in mandibular condyle and mandible have more impact on the menton deviation than the right/left differences in glenoid fossa. TRIAL REGISTRATION: CNUDH, CNUDH-EXP-2017-016 . Registered 28 September 2017.

Construction reproducibility of a composite tooth model composed of an intraoral-scanned crown and a cone-beam computed tomography-scanned root.

OBJECTIVE: To evaluate the construction reproducibility of a composite tooth model (CTM) composed of an intraoral-scanned crown and a cone-beam computed tomography (CBCT)-scanned root. METHODS: The study assessed 240 teeth (30 central incisors, 30 canines, 30 second premolars, and 30 first molars in the maxillary and mandibular arches) from 15 young adult patients whose pre-treatment intraoral scan and CBCT were available. Examiner-Reference (3 years' experience in CTM construction) and Examiners-A and Examiner-B (no experience) constructed the individual CTMs independently by performing the following steps: image acquisition and processing into a three-dimensional model, integration of intraoral-scanned crowns and CBCT-scanned teeth, and replacement of the CBCT-scanned crown with the intraoral-scanned crown. The tooth axis angle in terms of mesiodistal angulation and buccolingual inclination of the CTMs constructed by the three examiners were measured. To assess the construction reproducibility of CTMs, intraclass correlation coefficient (ICC) assessments were performed. RESULTS: The ICC values of mesiodistal angulation and buccolingual inclination among the 3 examiners showed excellent agreement (0.950-0.992 and 0.965-0.993; 0.976-0.994 and 0.973-0.995 in the maxillary and mandibular arches, respectively). CONCLUSIONS: The CTM showed excellent construction reproducibility in mesiodistal angulation and buccolingual inclination regardless of the construction skill and experience levels of the examiners.

Targeting glutamine metabolism enhances tumor-specific immunity by modulating suppressive myeloid cells.

Myeloid cells comprise a major component of the tumor microenvironment (TME) that promotes tumor growth and immune evasion. By employing a small-molecule inhibitor of glutamine metabolism, not only were we able to inhibit tumor growth, but we markedly inhibited the generation and recruitment of myeloid-derived suppressor cells (MDSCs). Targeting tumor glutamine metabolism led to a decrease in CSF3 and hence recruitment of MDSCs as well as immunogenic cell death, leading to an increase in inflammatory tumor-associated macrophages (TAMs). Alternatively, inhibiting glutamine metabolism of the MDSCs themselves led to activation-induced cell death and conversion of MDSCs to inflammatory macrophages. Surprisingly, blocking glutamine metabolism also inhibited IDO expression of both the tumor and myeloid-derived cells, leading to a marked decrease in kynurenine levels. This in turn inhibited the development of metastasis and further enhanced antitumor immunity. Indeed, targeting glutamine metabolism rendered checkpoint blockade-resistant tumors susceptible to immunotherapy. Overall, our studies define an intimate interplay between the unique metabolism of tumors and the metabolism of suppressive immune cells.

Glutamine blockade induces divergent metabolic programs to overcome tumor immune evasion.

The metabolic characteristics of tumors present considerable hurdles to immune cell function and cancer immunotherapy. Using a glutamine antagonist, we metabolically dismantled the immunosuppressive microenvironment of tumors. We demonstrate that glutamine blockade in tumor-bearing mice suppresses oxidative and glycolytic metabolism of cancer cells, leading to decreased hypoxia, acidosis, and nutrient depletion. By contrast, effector T cells responded to glutamine antagonism by markedly up-regulating oxidative metabolism and adopting a long-lived, highly activated phenotype. These divergent changes in cellular metabolism and programming form the basis for potent antitumor responses. Glutamine antagonism therefore exposes a previously undefined difference in metabolic plasticity between cancer cells and effector T cells that can be exploited as a "metabolic checkpoint" for tumor immunotherapy.