Penn Dental Medicine

Established in 1878, Penn Dental Medicine is among the oldest university-affiliated dental schools in the nation. The school's mission is to transform global oral health and well-being through exceptional clinical care, innovation, education, and research.

Search results

Now showing 1 - 10 of 107
  • Publication
    The Active Subunit of the Cytolethal Distending Toxin, CdtB, Derived From Both Haemophilus ducreyi and Campylobacter jejuni Exhibits Potent Phosphatidylinositol-3,4,5-Triphosphate Phosphatase Activity
    (2021-03-29) Huang, Grace; Boesze-Battaglia, Kathleen; Walker, Lisa P.; Zekavat, Ali; Schaefer, Zachary P.; Blanke, Steven R.; Shenker, Bruce J.
    Human lymphocytes exposed to Aggregatibacter actinomycetemcomitans (Aa) cytolethal distending toxin (Cdt) undergo cell cycle arrest and apoptosis. In previous studies, we demonstrated that the active Cdt subunit, CdtB, is a potent phosphatidylinositol (PI) 3,4,5-triphosphate phosphatase. Moreover, AaCdt-treated cells exhibit evidence of PI-3-kinase (PI-3K) signaling blockade characterized by reduced levels of PIP3, pAkt, and pGSK3β. We have also demonstrated that PI-3K blockade is a requisite of AaCdt-induced toxicity in lymphocytes. In this study, we extended our observations to include assessment of Cdts from Haemophilus ducreyi (HdCdt) and Campylobacter jejuni (CjCdt). We now report that the CdtB subunit from HdCdt and CjCdt, similar to that of AaCdt, exhibit potent PIP3 phosphatase activity and that Jurkat cells treated with these Cdts exhibit PI-3K signaling blockade: reduced levels of pAkt and pGSK3β. Since non-phosphorylated GSK3β is the active form of this kinase, we compared Cdts for dependence on GSK3β activity. Two GSK3β inhibitors were employed, LY2090314 and CHIR99021; both inhibitors blocked the ability of Cdts to induce cell cycle arrest. We have previously demonstrated that AaCdt induces increases in the CDK inhibitor, p21CIP1/WAF1, and, further, that this was a requisite for toxin-induced cell death via apoptosis. We now demonstrate that HdCdt and CjCdt also share this requirement. It is also noteworthy that p21CIP1/WAF1 was not involved in the ability of the three Cdts to induce cell cycle arrest. Finally, we demonstrate that, like AaCdt, HdCdt is dependent upon the host cell protein, cellugyrin, for its toxicity (and presumably internalization of CdtB); CjCdt was not dependent upon this protein. The implications of these findings as they relate to Cdt’s molecular mode of action are discussed. © Copyright © 2021 Huang, Boesze-Battaglia, Walker, Zekavat, Schaefer, Blanke and Shenker.
  • Publication
    (2021-06-17) Hakim Shoushtari, Reza
    Aim: The aim of this retrospective study was to determine the implant failure rate and associated factors in the academic setting by using electronic health records (Axium) and hard copies of patients who received dental implants at in Penn Dental Medicine (PDM) and at Penn Dental Faculty Ppractices (PDFP) ofat the University of Pennsylvania from 06/01/2016 to 08/31/201920. In addition, evaluation of electronic health records and hard copies were reviewed for patients who had implants removed due to bone loss or lack of osseointegration atin PDM and Faculty practicesPDFP of the University of Pennsylvania from 06/01/2016 to 02/29/2020. Secondary objective was to investigate the co-contributing factors for implant failure at the patient level. Method and Material: Electronic health records and hard copies of patients who had implants placed and removed due to bone loss or lack of osseointegration atin PDM and Faculty practicesPDFP of the University of Pennsylvania from 06/01/2016 to 02/29/2020 were analyzed. Results: Data was evaluated at patient count and implant count for this retrospective study. 1609 patients received implants. 883 patients had implant placement at PDM and 726 patients had implant placement at PDFP. Of the total patients, 3180 implants were placed during the study period. 2162 implants were placed at PDM and 1018 implants were placed at PDFP. The total patient failure rate was 4.97% and the failure rate was of 6.0% and 3.7% for PDM and PDFP, respectively. The total implant failure rate was 3.49% and the implant failure rate was 3.7% and 3% for PDM and PDFP, respectively. Based on the chi-square test results, patients with bisphosphonate IV+PO (12%, P-value=0.004) were significantly overrepresented in the failure group. In contrast, patients with no bisphosphonate use (4.60%, P-value=0.004) were significantly underrepresented in the failure group. No overrepresentation (or underrepresentation) of patients with different gender, different age group, diabetes mellitus, history of periodontal disease, current smoking status, penicillin allergy, and recall were noted amongst failures. Based on the chi-square test, implants for bisphosphonate IV variable (11.5%, P-value=0.025) were significantly overrepresented in the failure group. In contrast, implants for no bisphosphonate use (3.20%, P-value<0.001) were significantly underrepresented in the failure group. No overrepresentation (or underrepresentation) of implants for different gender, different age group, diabetes mellitus, history of periodontal disease, current smoking status, penicillin allergy, and recall was noted amongst failures. Based on the multivariate conditional logistic regression, estimated odds of implant failure in participants with multiple implants were about three times than the participants with single implant (Adj OR=2.99, P-value=0.002); estimated odds of implant failure for bisphosphonate use of IV and PO was about four times that of the participants with no bisphosphonate use (Adj. OR=4.09, P-value=0.003). Diabetes and history of failed implants did not show any significant association with implant failure (with P-values>0.05). Conclusion: This study concluded that bisphosphonate use and patients with multiple implants were shown to have a significant contribution to implant failure. There was no difference in the failure rate of patients with different gender, different age group, diabetes mellitus, history of periodontal disease, current smoking status, penicillin allergy, and recallamongst failures. It is important to note that due to limitations and the retrospective nature of this study, only the co-contributing factors were evaluated and not the etiology of the implant failure. To further investigate the etiology, randomized clinical trial should be conducted.
  • Publication
    Crosstalk Between Dysfunctional Mitochondria and Inflammation in Glaucomatous Neurodegeneration
    (2021-07-21) Jassim, Assraa Hassan; Inman, Denise M.; Mitchell, Claire H.
    Mitochondrial dysfunction and excessive inflammatory responses are both sufficient to induce pathology in age-dependent neurodegenerations. However, emerging evidence indicates crosstalk between damaged mitochondrial and inflammatory signaling can exacerbate issues in chronic neurodegenerations. This review discusses evidence for the interaction between mitochondrial damage and inflammation, with a focus on glaucomatous neurodegeneration, and proposes that positive feedback resulting from this crosstalk drives pathology. Mitochondrial dysfunction exacerbates inflammatory signaling in multiple ways. Damaged mitochondrial DNA is a damage-associated molecular pattern, which activates the NLRP3 inflammasome; priming and activation of the NLRP3 inflammasome, and the resulting liberation of IL-1β and IL-18 via the gasdermin D pore, is a major pathway to enhance inflammatory responses. The rise in reactive oxygen species induced by mitochondrial damage also activates inflammatory pathways, while blockage of Complex enzymes is sufficient to increase inflammatory signaling. Impaired mitophagy contributes to inflammation as the inability to turnover mitochondria in a timely manner increases levels of ROS and damaged mtDNA, with the latter likely to stimulate the cGAS-STING pathway to increase interferon signaling. Mitochondrial associated ER membrane contacts and the mitochondria-associated adaptor molecule MAVS can activate NLRP3 inflammasome signaling. In addition to dysfunctional mitochondria increasing inflammation, the corollary also occurs, with inflammation reducing mitochondrial function and ATP production; the resulting downward spiral accelerates degeneration. Evidence from several preclinical models including the DBA/2J mouse, microbead injection and transient elevation of IOP, in addition to patient data, implicates both mitochondrial damage and inflammation in glaucomatous neurodegeneration. The pressure-dependent hypoxia and the resulting metabolic vulnerability is associated with mitochondrial damage and IL-1β release. Links between mitochondrial dysfunction and inflammation can occur in retinal ganglion cells, microglia cells and astrocytes. In summary, crosstalk between damaged mitochondria and increased inflammatory signaling enhances pathology in glaucomatous neurodegeneration, with implications for other complex age-dependent neurodegenerations like Alzheimer’s and Parkinson’s disease. © Copyright © 2021 Jassim, Inman and Mitchell.
  • Publication
    Neural EGFL Like 1 as a Potential Pro-Chondrogenic, Anti-Inflammatory Dual-Functional Disease-Modifying Osteoarthritis Drug
    (2020-01-01) Li, Chenshuang; Zheng, Zhong; Ha, Pin; Jiang, Wenlu; Berthiaume, Emily A.; Lee, Seungjun; Mills, Zane; Pan, Hsinchuan; Chen, Eric C.; Jiang, Jie; Culiat, Cymbaline T.; Zhang, Xinli; Ting, Kang; Soo, Chia
    Arthritis, an inflammatory condition that causes pain and cartilage destruction in joints, affects over 54.4 million people in the US alone. Here, for the first time, we demonstrated the emerging role of neural EGFL like 1 (NELL-1) in arthritis pathogenesis by showing that Nell-1-haploinsufficient (Nell-1+/6R) mice had accelerated and aggravated osteoarthritis (OA) progression with elevated inflammatory markers in both spontaneous primary OA and chemical-induced secondary OA models. In the chemical-induced OA model, intra-articular injection of interleukin (IL)1β induced more severe inflammation and cartilage degradation in the knee joints of Nell-1+/6R mice than in wildtype animals. Mechanistically, in addition to its pro-chondrogenic potency, NELL-1 also effectively suppressed the expression of inflammatory cytokines and their downstream cartilage catabolic enzymes by upregulating runt-related transcription factor (RUNX)1 in mouse and human articular cartilage chondrocytes. Notably, NELL-1 significantly reduced IL1β-stimulated inflammation and damage to articular cartilage in vivo. In particular, NELL-1 administration markedly reduced the symptoms of antalgic gait observed in IL1β-challenged Nell-1+/6R mice. Therefore, NELL-1 is a promising pro-chondrogenic, anti-inflammatory dual-functional disease-modifying osteoarthritis drug (DMOAD) candidate for preventing and suppressing arthritis-related cartilage damage. © 2019 Elsevier Ltd
  • Publication
    In Vitro Comparative Study Between Full-Arch Conventional Implant Impressions and Full-Arch Digital Implant Impressions with Snap-on Scan Bodies
    (2022-06-24) Yoo, Thomas H.
    Statement of Problem: Digital impression techniques are widely used in everyday cases. There is sufficient evidence to support this technique in partially edentulous patients but the evidence supporting the use of intraoral scanners (IOS) in restorative digital workflows for edentulous patients is still limited. Purpose: The aim of the present in vitro study was to measure and compare the accuracy of full- arch conventional implant impressions with open and closed-trays, full-arch digital implant impressions with intraoral scanners (IOS), and three-dimensional (3D) printed casts from the full-arch digital implant impressions. Material and methods: Six implants were placed into a mandibular model. Snap-on scan bodies were inserted into the implants and scanned with a high-resolution reference scanner and exported in standard tessellation language (.STL) format (Group Control). Splinted open-tray impressions (Group 1, n=5) and closed-tray impressions (Group 2, n=5) were made and stone casts were fabricated. Digital impressions (Group 3, n=5) were made with an intra-oral scanner and the .STL files were exported to fabricate 3D printed casts. Snap-on scan bodies were inserted into analogs in Groups 1, 2, and 3 and scanned with the reference scanner. Using a 3D inspection software, impression techniques were compared to the control. Root mean square (RMS) values were calculated from the control and superimposed digitized casts from different impression techniques. Results: Group 3 had the lowest mean dimensional difference when superimposed with Group Control, then Groups 4, 1, and 2. Significant differences were found in RMS values between Group Control and digitized models fabricated from different techniques (P<0.05). Post Hoc (Tukey) test revealed that Group 3 (P<0.001) was significantly different from other groups while no significant difference was found between Groups 1, 2, and 4 (P>0.001). Conclusions: 3D printed models from full-arch digital impression of Snap-on scan bodies seem to be as accurate as stone models fabricated from full-arch conventional impression techniques. Closed-tray full-arch impression technique using dual-functioning Snap-on scan bodies seem to be as accurate as the splinted open-tray full-arch technique.
  • Publication
    18F-FDG-PET/CT in Radiation Therapy-Induced Cerebellar Inflammation
    (2022-06-22) Abu Kar, Mohammad; Alavi, Abass; Korostoff, Johnathan M; Fiorellini, Joseph P; Chang, Yu-Cheng
    ABSTRACT Background 18F-fluorodeoxyglucose-positron emission tomography/computed tomography (18FDG- PET/CT) is used in the clinical diagnosis and management of oncologic and inflammatory pathologies. It may also have utility in detecting tissue damage induced by radiotherapy (RT) used to treat various types of cancer. The aim of the present study was to use 18FDG-PET/CT to evaluate the effect of RT on the uptake of 18FDG by the cerebellum. Methods Thirty patients with head and neck cancer (HNC) were included in this retrospective study. The patients were treated with photon, proton, or combined photon/proton RT, in addition to chemotherapy. All patients received 18FDG- PET/CT imaging pre-treatment and 3 months post-treatment. The global mean standardized uptake value (SUVmean) of the cerebellum was determined for every patient by global assessment of 18FDG activity using OsiriX MD software. A two-tailed paired t-test was used to compare global SUVmean pre- and post-RT. Results The pre-treatment and post-treatment global SUVmean for the photon group were 5.26 and 5.51 (p: 0.42), respectively. As for the proton only group, the pre- and post-treatment global SUVmeans were 7.06 and 6.05, respectively. In the combined RT group, the pre- and post-treatment global SUVmeans were 6.14 and 6.19 respectively (p: 0.92). The differences between the pre- and post-treatment values failed to reach statistical significance for any of the treatment groups but it should be noted that there was a trend of increased 18FDG uptake in the cerebellum following photon therapy. This trend was not clear in the combined group. As for the proton group, p-value was not calculated as only two patients were included. Conclusion Although not statistically significant, the results showed an incremental increase in global SUVmean following treatment with photon RT likely reflecting the presence of mild radiation-induced inflammation in the cerebellum.
  • Publication
  • Publication
    Evoked and Spontaneous Pain Assessment During Tooth Pulp Injury
    (2020-12-01) Rossi, Heather Lynn; See, Lily Pachanin; Foster, William; Pitake, Saumitra; Gibbs, Jennifer; Schmidt, Brian; Mitchell, Claire H.; Abdus-Saboor, Ishmail
    Injury of the tooth pulp is excruciatingly painful and yet the receptors and neural circuit mechanisms that transmit this form of pain remain poorly defined in both the clinic and preclinical rodent models. Easily quantifiable behavioral assessment in the mouse orofacial area remains a major bottleneck in uncovering molecular mechanisms that govern inflammatory pain in the tooth. In this study we sought to address this problem using the Mouse Grimace Scale and a novel approach to the application of mechanical Von Frey hair stimuli. We use a dental pulp injury model that exposes the pulp to the outside environment, a procedure we have previously shown produces inflammation. Using RNAscope technology, we demonstrate an upregulation of genes that contribute to the pain state in the trigeminal ganglia of injured mice. We found that mice with dental pulp injury have greater Mouse Grimace Scores than sham within 24 hours of injury, suggestive of spontaneous pain. We developed a scoring system of mouse refusal to determine thresholds for mechanical stimulation of the face with Von Frey filaments. This method revealed that mice with a unilateral dental injury develop bilateral mechanical allodynia that is delayed relative to the onset of spontaneous pain. This work demonstrates that tooth pain can be quantified in freely behaving mice using approaches common for other types of pain assessment. Harnessing these assays in the orofacial area during gene manipulation should assist in uncovering mechanisms for tooth pulp inflammatory pain and other forms of trigeminal pain. © 2020, The Author(s).
  • Publication
    3D Printed Complete Removable Dental Prostheses: a Narrative Review
    (2020-12-01) Anadioti, Eva; Musharbash, Leen; Blatz, Markus B.; Papavasiliou, George; Kamposiora, Phophi
    Background: The purpose of this paper is to review the available literature on three-dimensionally printed complete dentures in terms of novel biomaterials, fabrication techniques and workflow, clinical performance and patient satisfaction. Methods: The methodology included applying a search strategy, defining inclusion and exclusion criteria, selecting studies and forming tables to summarize the results. Searches of PubMed, Scopus, and Embase databases were performed independently by two reviewers to gather literature published between 2010 and 2020. Results: A total of 126 titles were obtained from the electronic database, and the application of exclusion criteria resulted in the identification of 21 articles pertaining to printed technology for complete dentures. Current innovations and developments in digital dentistry have successfully led to the fabrication of removable dental prostheses using CAD/CAM technologies. Milled dentures have been studied more than 3D printed ones in the currently available literature. The limited number of clinical studies, mainly case reports, suggest current indications of 3D printing in denture fabrication process to be custom tray, record bases, trial, interim or immediate dentures but not definitive prostheses fabrication. Limitations include poor esthetics and retention, inability to balance occlusion and low printer resolution. Conclusions: Initial studies on digital dentures have shown promising short-term clinical performance, positive patient-related results and reasonable cost-effectiveness. 3D printing has potential to modernize and streamline the denture fabrication techniques, materials and workflows. However, more research is required on the existing and developing materials and printers to allow for advancement and increase its application in removable prosthodontics. © 2020, The Author(s).