Is periodontal phenotype modification therapy beneficial for patients receiving orthodontic treatment? An American Academy of Periodontology best evidence review

BackgroundOrthodontic treatment can greatly impact the periodontium, especially in dentitions with a thin periodontal phenotype. Orthodontic tooth movement can result into iatrogenic sequelae to these vulnerable anatomic conditions, such as development and exacerbation of bony dehiscence or fenestration defects, which can manifest loss of periodontal support and gingival recession (GR). This systematic review aimed to investigate whether periodontal phenotype modification therapy (PhMT) involving hard tissue augmentation (PhMT- b) or soft tissue augmentation (PhMT- s) has clinical benefits for patients undergoing orthodontic treatment.MethodsAn electronic search was performed in two major databases for journals published in English language from January 1975 to January 2019 and a hand search of printed journals was also performed to identify human clinical trials reporting clinical and radiographic outcomes of patients receiving orthodontic treatment with or without hard and soft tissue augmentation procedures. Data were extracted and organized into tables for qualitative assessment.ResultsEight studies were identified evaluating the outcomes of PhMT in patients undergoing orthodontic therapy. Six studies evaluated patients receiving PhMT- b via corticotomy- assisted orthodontic therapy (CAOT) and simultaneous bone augmentation while the other two received PhMT- s before tooth movement. No studies investigated PhMT- b alone without CAOT and most studies focused on the mandibular anterior decompensation movements. There was high heterogeneity in the study design and inconsistency of the reported outcomes; therefore, a meta- analysis was not performed. Evidence at this moment supports CAOT with hard tissue augmentation accelerated tooth movement. However, only two studies provided direct comparison to support that CAOT with PhMT- b reduced the overall treatment time compared with conventional orthodontic treatment. No periodontal complications or evidence of severe root resorption were reported for both groups. Four studies provided radiographic assessment of the PhMT- b and demonstrated increased radiographic density or thicker facial bone after the treatment. Two studies reported an expanded tooth movement. One study reported an increase in keratinized tissue width post- CAOT plus PhMT- b, while another study with a 10- year follow- up showed a lower degree of relapse using the mandibular irregularity index when compared with conventional tooth movement alone.Two studies examined the effect of PhMT- s before orthodontic treatment. Unfortunately, no conclusions can be drawn because of the limited number of studies with contradicting outcomes.ConclusionsWithin the limited studies included in this systematic review, PhMT- b via particulate bone grafting together with CAOT may provide clinical benefits such as modifying periodontal phenotype, maintaining or enhancing facial bone thickness, accelerating tooth movement, expanding the scope of safe tooth movement for patients undergoing orthodontic tooth movement. The benefits of PhMT- s alone for orthodontic treatment remain undetermined due to limited studies available. However, PhMT- b appears promising and with many potential benefits for patients undergoing orthodontic tooth movement. There is a need for a higher quality of randomized controlled trials or case control studies with longer follow- up to investigate the effects of different grafting materials and surgical sites other than mandibular anterior region.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/154653/1/jper10457.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/154653/2/jper10457_am.pd

Quantitative tooth mobility evaluation based on intraoral scanner measurements

BackgroundTooth mobility assessment is subjective and current techniques require the translation of a continuous variable to a categorical variable based on the perception of the examiner. The aim of this study was to evaluate the reliability of a novel technique to assess tooth mobility.MethodsThree experienced periodontists were asked to push tooth #16 into a buccal position to in a typodont model with different mobility (M1â M2). Tooth position was obtained using an intraoral scanner and files were compared in metrology software. Mobility was calculated at three reference points at the cervical (C), middle (M), and occlusal (O) regions of the buccal surface of the tooth to determine the linear deviation in the three axes (x, y, and z). Reliability was determined by intraclassâ correlation coefficient, differences between M1 and M2 determined by t test, and the analysis of variance (ANOVA) was used to compare the data at the Câ Mâ O regions.ResultsExcellent reliability was assessed by Cronbach alpha >0.9 on the xâ yâ z axes for both mobility tested, except for M1â C X (0.85), M1â M Y (0.89), and M2â M Z (0.89). The correlation between the examiners demonstrated excellent (Ë 0.90) or good (0.75Ë x Ë 0.90) consistency, except for M1â C Y (0.73; examiner 1 to 2) and M1â M X (0.69; examiners 1 to 3). Significant changes were detected in all axes at the three reference points comparing M1 and M2, and a similar proportional change was observed between Oâ Mâ C reference points for M1 and M2.ConclusionA novel technique to assess tooth mobility based on intraoral scanner measurements provided reliable data in an in vitro experiment.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/154459/1/jper10409_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/154459/2/jper10409.pd

ABL Genomic Editing Sufficiently Abolishes Oncogenesis of Human Chronic Myeloid Leukemia Cells In Vitro and In Vivo

Chronic myelogenous leukemia (CML) is the most common type of leukemia in adults, and more than 90% of CML patients harbor the abnormal Philadelphia chromosome (Ph) that encodes the BCR-ABL oncoprotein. Although the ABL kinase inhibitor (imatinib) has proven to be very effective in achieving high remission rates and improving prognosis, up to 33% of CML patients still cannot achieve an optimal response. Here, we used CRISPR/Cas9 to specifically target the BCR-ABL junction region in K562 cells, resulting in the inhibition of cancer cell growth and oncogenesis. Due to the variety of BCR-ABL junctions in CML patients, we utilized gene editing of the human ABL gene for clinical applications. Using the ABL gene-edited virus in K562 cells, we detected 41.2% indels in ABL sgRNA_2-infected cells. The ABL-edited cells reveled significant suppression of BCR-ABL protein expression and downstream signals, inhibiting cell growth and increasing cell apoptosis. Next, we introduced the ABL gene-edited virus into a systemic K562 leukemia xenograft mouse model, and bioluminescence imaging of the mice showed a significant reduction in the leukemia cell population in ABL-targeted mice, compared to the scramble sgRNA virus-injected mice. In CML cells from clinical samples, infection with the ABL gene-edited virus resulted in more than 30.9% indels and significant cancer cell death. Notably, no off-target effects or bone marrow cell suppression was found using the ABL gene-edited virus, ensuring both user safety and treatment efficacy. This study demonstrated the critical role of the ABL gene in maintaining CML cell survival and tumorigenicity in vitro and in vivo. ABL gene editing-based therapy might provide a potential strategy for imatinib-insensitive or resistant CML patient

EBV-encoded small RNA1 and nonresolving inflammation in rheumatoid arthritis

AbstractRheumatoid arthritis (RA) is a chronic autoimmune disease characterized by perpetuated inflammation in multiple joints. To date, there is no cure for RA, and the causal factor for non-resolving inflammation in RA remains unclear. In this study, we initially observed expression of Epstein–Barr virus-encoded small RNA1 (EBER1) in the synovial tissue of all five patients who showed nonresolving RA inflammation. By contrast, EBER1 was detected in the synovial tissue of only one out of seven patients with advanced osteoarthritis (OA; p < 0.01, Fisher’s exact test). To confirm this finding, we conducted a second study on synovial tissue samples taken from 23 patients with nonresolving RA inflammation and 13 patients with OA. All synovial samples from patients with nonresolving inflammation of RA showed positive expression of EBER1 (23/23, 100%), whereas none of the synovial samples from patients with OA showed expression of EBER1 (0/13, 0%; p < 0.001, by Fisher’s exact test). In vitro, transfection of RA synovial fibroblasts with EBER1 induced the production of interleukin-6. Taken together, these data strongly suggest that nonresolving RA inflammation is strongly related to the presence of EBER1, which might be, at least partially, responsible for synovial fibroblast interleukin-6 production

Evaluation of the Osteogenic Potential of Growth Factorâ Rich Demineralized Bone Matrix In Vivo

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/141502/1/jper0036.pd

Rural–urban disparities in the incidence and treatment intensity of periodontal disease among patients with diabetes

BackgroundDiabetes threatens population health, especially in rural areas. Diabetes and periodontal diseases have a bidirectional relationship. A persistence of rural–urban disparities in diabetes may indicate a rural–urban difference in periodontal disease among patients with diabetes; however, the evidence is lacking. This retrospective study aimed to investigate rural–urban discrepancies in the incidence and treatment intensity of periodontal disease among patients who were newly diagnosed with type 2 diabetes in the year 2010.MethodsThe present study was a retrospective cohort design, with two study samples: patients with type 2 diabetes and those who were further diagnosed with periodontal disease. The data sources included the 2010 Diabetes Mellitus Health Database at the patient level, the National Geographic Information Standardization Platform and the Department of Statistics, Ministry of Health and Welfare in Taiwan at the township level. Two dependent variables were a time-to-event outcome for periodontal disease among patients with type 2 diabetes and the treatment intensity measured for patients who were further diagnosed with periodontal disease. The key independent variables are two dummy variables, representing rural and suburban areas, with urban areas as the reference group. The Cox and Poisson regression models were applied for analyses.ResultsOf 68,365 qualified patients, 49% of them had periodontal disease within 10 years after patients were diagnosed with diabetes. Compared to urban patients with diabetes, rural (HR = 0.83, 95% CI: 0.75–0.91) and suburban patients (HR = 0.86, 95% CI: 0.83–0.89) had a lower incidence of periodontal disease. Among 33,612 patients with periodontal disease, rural patients received less treatment intensity of dental care (Rural: RR = 0.87, 95% CI: 0.83, 0.92; suburban: RR = 0.93, 95% CI: 0.92, 0.95) than urban patients.ConclusionGiven the underutilization of dental care among rural patients with diabetes, a low incidence of periodontal disease indicates potentially undiagnosed periodontal disease, and low treatment intensity signals potentially unmet dental needs. Our findings provide a potential explanation for the persistence of rural–urban disparities in poor diabetes outcomes. Policy interventions to enhance the likelihood of identifying periodontal disease at the early stage for proper treatment would ease the burden of diabetes care and narrow rural–urban discrepancies in diabetes outcomes

American Academy of Periodontology best evidence consensus statement on modifying periodontal phenotype in preparation for orthodontic and restorative treatment

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/154649/1/jper10498.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/154649/2/jper10498_am.pd

Predicting Inactive Conformations of Protein Kinases Using Active Structures: Conformational Selection of Type-II Inhibitors

Protein kinases have been found to possess two characteristic conformations in their activation-loops: the active DFG-in conformation and the inactive DFG-out conformation. Recently, it has been very interesting to develop type-II inhibitors which target the DFG-out conformation and are more specific than the type-I inhibitors binding to the active DFG-in conformation. However, solving crystal structures of kinases with the DFG-out conformation remains a challenge, and this seriously hampers the application of the structure-based approaches in development of novel type-II inhibitors. To overcome this limitation, here we present a computational approach for predicting the DFG-out inactive conformation using the DFG-in active structures, and develop related conformational selection protocols for the uses of the predicted DFG-out models in the binding pose prediction and virtual screening of type-II ligands. With the DFG-out models, we predicted the binding poses for known type-II inhibitors, and the results were found in good agreement with the X-ray crystal structures. We also tested the abilities of the DFG-out models to recognize their specific type-II inhibitors by screening a database of small molecules. The AUC (area under curve) results indicated that the predicted DFG-out models were selective toward their specific type-II inhibitors. Therefore, the computational approach and protocols presented in this study are very promising for the structure-based design and screening of novel type-II kinase inhibitors

Evaluation of the Osteogenic Potential of Growth Factor-Rich Demineralized Bone Matrix In Vivo

Background: The study evaluates the osteogenic properties and biocompatibility of growth factor-rich demineralized bone matrix (GDBM) by comparing with cancellous mineralized bone matrix (CMBM) and anorganic bovine bone matrix (ABBM). ;Methods: Thirty-six Sprague-Dawley rats were used (n = 6/group/time point). To assess biocompatibility and osteoinductivity, the respective bone matrices were randomly placed in subcutaneous pouches for 7 and 28 days and evaluated by histology and osteopontin expression. Osteoconductivity was assessed by randomly implanting respective bone matrices in osteotomies on femurs for 14 and 28 days and evaluated by microcomputed tomography and histology. ;Results: Neither acute inflammation nor mineralized tissue was noted in any of the subcutaneous specimens, whereas expression of osteopontin was more prominent in the GDBM group. Among the femoral specimens, the greatest relative bone volume (bone volume [BV] divided by trabecular volume [TV]) and trabecular thickness was noted in the ABBM group at both time points, whereas less BV/TV was noted in GDBM group at day 14. Residual matrix particles were noted in all examined groups at both time points, without significant differences regarding defect fill between groups. The GDBM group presented similar levels of newly formed bone compartment and marrow space to those of the ABBM group. ;Conclusions: GDBM demonstrated acceptable biocompatibility and osteogenic potential comparable to ABBM in vivo. Further investigations in a more clinically relevant model are warranted