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  • Publication
    Following Surgically Assisted Rapid Palatal Expansion, Do Tooth-Borne or Bone-Borne Appliances Provide More Skeletal Expansion and Dental Expansion?
    (2019-01-02) Hamedi-Sangsari, Adrien
    Abstract Purpose: The aim of this study is to compare the outcome measures of skeletal and dental expansion with Bone-Borne (BB) versus Tooth-Borne (TB) appliances following SARPE. This study is being done to provide quantitative measurements that will help the oral surgeon and orthodontist in selecting the appliance with, on average, the greatest amount of skeletal expansion and the least amount of dental expansion. Methods: A computerized database search was performed using PubMed, EBSCO, Cochrane, Scopus, Web of Science, and Google Scholar on publications in reputable oral surgery and orthodontic journals. A systematic review and meta-analysis was then completed with the predictor variables of expansion appliance (TB versus BB) and outcome measure of expansion (in millimeters). Results:A total of 487 articles were retrieved from the six databases. 5 articles were included, 4 with CBCT data and 1 with non-CBCT 3D cast data. There was a significant difference in the skeletal expansion (SMD = 0.92, 95% CI [0.54, 1.30], p = Conclusion: The literature points to the fact that in order to achieve more effective skeletal expansion and minimize dental expansion after SARPE, a Bone-Borne (BB) appliance should be favored. Keywords: Bone Borne; Tooth Borne; Rapid Palatal Expansion; SARME; SARPE; Surgically Assisted Rapid Palatal Expansion; Surgically Assisted Rapid Maxillary Expansion.
  • Publication
    Factors associated with survival of teeth following initial endodontic therapy
    (2021-12-01) Choi, Minyoung
    Aim: The aim of this retrospective study is to review the tooth retention rate of primary endodontically treated teeth at University of Pennsylvania Graduate Endodontics department (PGE) and faculty practice (PDFP) and compare it to the tooth retention rate of non-surgical retreatment and surgical retreatment and test the hypothesis-- the survival rate of secondary RCT is lower than the rate of initial RCT. Also, this study analyzed systemic and local co-factors affecting longevity of these endodontically treated teeth. Systemic factors included smoking, diabetes, and drug allergy. Local factors included tooth position, presence of core buildup, post and core, and full coverage crown. These patients were reviewed to observe if they had periodontal conditions and if other periodontal treatments were provided. Material and methods: Electronic health records of patients who had primary endodontic treatment at PDM Graduate Endodontic clinic and PDFP of the University of Pennsylvania from January 1, 2017 to December 31, 2020 were analyzed and followed until June, 10, 2021 Results: 9107 patients (11854 teeth) had RCT done at PDM from 2017 to 2020. Of these patients, 990 patients (1627 teeth) were excluded because they had initial RCT somewhere else other than at PGE or PDFP. 8117 patients (10227 teeth) were reviewed for extractions and secondary treatments. Of 10227 teeth, 393 teeth were extracted. Of 393 teeth, 384 teeth were extracted without any type of retreatments. 9 teeth were extracted after retreatment. Of these 9 teeth, 7 teeth had nonsurgical retreatment and 2 teeth had surgical retreatment. Chi square and logistic regression analyses showed that there is no statistical significance between extraction rate of primary RCT teeth and extraction rate of NS retx teeth. Also, these analyses demonstrated that there is no statistically significant difference between extraction rate of primary RCT teeth and that of surgical retx teeth. Most extractions and NS retx occurred after 12+ months unlike surgical retx which happened more commonly in the first 0-6 months. Systemic factors such as diabetes, smoking, and drug allergy were reviewed. 342 patients underwent extractions. Chi square analysis showed statistical difference for smokers, diabetic patients, and drug allergy patients in relation to tooth loss. Logistic regression and Kaplan Meier analysis showed only drug allergy and tooth loss are correlated. Of drug allergy patients, 38.8% were allergic to penicillin. Local factors such as tooth position, restorations, periodontal conditions were reviewed. Based on chi square, patients with buildup, full coverage crown, PD≤ 5mm before and after RCT showed statistically significant difference. However, tooth position, post and core, CLP, and SRP did not show statistically significant difference. Based on logistic regression, results were similar except for SRP which demonstrated statistical significance. Based on Kaplan Meier analysis, core buildup, full coverage crowns, presence of PD≥5mm after RCT, and SRP made a statistical difference. However, tooth position, post and core, PD≥ before RCT, CLP did not make a statistical significance. Conclusion: This study concluded that endodontic treatment is a viable option if RCT gets performed properly using the proper techniques, material, and technologies. Patient’s health history (eg. diabetes, smoking, and drug allergy) and dental history (eg. build up, crowns, periodontal treatments) can result in difference in the outcome of the endodontic therapy regardless of the treatment modalities.
  • Publication
    The Role of Specific Integrase Strand Transfer Inhibitors (INSTIs) in the Alteration of Oligodendrocyte Maturation and Myelination in Hand
    (2019-03-13) Zidane, Bassam N
    Currently, thirty-seven million people are infected with human immunodeficiency virus-1 (HIV-1) worldwide. Thankfully, the development of combined antiretroviral therapy (cART) regimens has decreased mortality and significantly improved the overall quality of life for these patients. However, approximately half of all patients clinically manifest with HIV-associated neurocognitive disorder (HAND), a spectrum of cognitive, motor, and behavioral abnormalities which histologically present as non-specific gliosis, synaptodendritc damage and loss of white matter and myelin. Furthermore, the severity of white matter damage correlates with the length of ART duration. However, almost no studies have been performed to determine how the myelin sheath or the oligodendrocytes that synthesize the sheath are damaged. Thus, we hypothesized that the administration of ART contributed in part to the myelin loss in the CNS of HIV-positive patients. Previously, we have reported that the protease inhibitor class of ART drugs hampered the in vitrodifferentiation of oligodendrocytes. Given that the new US guidelines for treating HIV patients recommends anew class of drugs, the integrasestrand transferinhibitors(INSTIs)as front-line therapy, we examined if two specific INSTIs, Elvitegravir (EVG) and raltegravir (RAL), altered the survival and/or maturation of developing oligodendrocytes in vitroand in vivo. We found that treatment of oligodendrocyte precursor cells (OPCs) with EVG, but not RAL, during differentiation reduced the number of cells positive for immature oligodendrocyte marker galactosylceramide (GalC) and mature oligodendrocyte marker myelin basic protein (MBP) in vitro, as well as the synthesis of myelin proteins. However, neither EVG or RAL induced cell loss or apoptosis, as determined by cell counts and TUNEL assays, suggesting that EVG does not affect OPC viability but instead, inhibits differentiation. EVG-induced oligodendrocyte differentiation deficits could be reversed by pre-treating the cells with a drug that pharmacologically inhibits the phosphorylation of eukaryotic initiation factor 2α(eIF2α) throughthe cellular integrated stress response (ISR). Finally, in vivo,mice receiving EVG/COBI failed to remyelinate the corpus callosum during the three week recovery period following demyelination, after cuprizone treatment. Although EVG/COBI treatment by itself did not cause overt white matter loss in this brain region. Our study demonstrates that EVG, but not RAL, inhibits oligodendrocyte precursor cell differentiation both in vitroand in vivo. Furthermore, EVG may be inhibiting oligodendrocyte precursor cell differentiation though activation of the ISR. Also, we found thatthe effects of EVG on oligodendrocyte differentiation could be attenuated in vitroby inhibiting the ISR. These studies suggest that ART may contribute to cognitive impairment by inhibiting renewal and replacement of oligodendrocytes in adults or development of oligodendrocytes in children. Further, our results suggest an ISR inhibitor might attenuate the negative effect of EVG on the maturation of oligodendrocytes. Our findings also suggest that development of less toxic ART compounds and adjunctive therapies are needed to minimize the side effects of ART on the CNS.
  • Publication
    Do Buffered Local Anesthetics Provide More Successful Anesthesia Over Non-Buffered Solutions in Patients Requiring Dental Therapy? – A Systematic Review & Meta-Analysis.
    (2017-05-18) Kattan, Sereen; Karabucak, Bekir; Hersh, Elliot V; Korostoff, Johnathan M; Hunter, Paul
    Background: The pH of commercially available local anesthetics (LAs) is purposefully low (pH 3–4). Decreasing the pH extends the shelf life of the solution and prevents its early oxidation. However, a low pH may produce a burning sensation on the injection site, a slower onset of anesthesia, and a decrease in its clinical efficacy. Buffering of local anesthetics (alkalinization) by adding sodium bicarbonate has been suggested to achieve better pain control, reduce the pain of injection and produce a faster onset of local anesthetics. The aim of this review is to utilize a systematic review to collate evidence on the use of buffering agents with local anesthetics and its effect on causing profound pulpal anesthesia in patients requiring dental therapy and its side effects. Methods: Electronic searches were conducted in MEDLINE, Scopus, Cochrane Library, and, World Health Organization (WHO) International Trials Registry Platform, OpenGrey & Google Scholar beta. Hand searching of two books “Handbook of Local Anesthesia” & “Successful Local Anesthesia for Restorative Dentistry and Endodontics” was conducted. Also, the reference lists of all included and excluded studies were checked to identify any further trials. Weighted anesthesia success rates and 95% confidence intervals (CIs) were estimated and compared by using a random-effects model. Results: 14,011 studies were initially identified from the search; 5 double-blind, randomized clinical trials met the inclusion criteria. For combined studies, buffered local anesthetics were more likely than non-buffered solutions to achieve successful anesthesia (odds ratio [OR], 2.29; 95% confidence interval [CI], 1.11–4.71; P = 0.0232; I2 = 66%). Conclusion: This systematic review of double-blind, randomized clinical trials comparing the use of buffered and non-buffered local anesthetics in patients requiring dental therapy provides level ‘A’ evidence that is based on the criteria given by the Strength of Recommendation Taxonomy (SORT). In conclusion, the present meta-analysis showed that in patients receiving dental therapy, buffered local anesthetics are more effective than non-buffered solutions when used for mandibular or maxillary anesthesia. Buffering local anesthetics has 2.29 times greater likelihood of achieving successful anesthesia.
  • Publication
    The Role of MRGPRX2/Mrgprb2 in Regulating Mast Cell Function
    (2019-06-21) Alkanfari, Ibrahim S
    Mast"cells"(MCs)"are"derived"from"bone"marrow"pluripotent"hematopoietic" stem" cells" and" are" located" in" close" proximity" to" the" external" environment." MCs" expresses"several"receptors"on"their"surface"such"as"the"high"affinity"IgE"receptor" (Fc!RI)"and"G"ProteinECoupled"Receptors"(GPCRs)."MRGPRX2"is"a"GPCR,"which" consists"of"seven"transmembrane"domains"and"is"expressed"exclusively"in"MCs" but" no" other" immune" cells." This" receptor" is" activated" by" multiple" amphipathic" ligands" including" neuropeptides," US" Food" and" Drug" Administration" (FDA)E approved"peptidergic"drugs"and"host"defense"peptides"such"as"LL_37."HDPs"also" known" as" antimicrobial" peptides" (AMPs)" have" been" investigated" in" depth" as" an" alternative"to"overcome"antibiotic"resistance"crisis."However,"their"susceptibility"to" degradation,"cytotoxicity"and"high"production"expenses"have"limited"their"use."To" overcome" these" limitations," nonEpeptide" small" molecule" HDP" mimetics" (smHDPMs)" that" structurally" resemble" the" AMPs" properties" but" have" better" stability"and"less"cytotoxicity"have"been"developed."We"utilized"five"smHDPMs"and" found" that" these" compounds" demonstrated" its" ability" to" activate" MCs" via" MRGPRX2."This"raises"an"interesting"possibility"that"its"function"as"antimicrobial" agent"could"be"as"a"result"of"harnessing"MCs"host"defense"functions"beside"their" antimicrobial"activities."" MCs" can" also" participate" in" chronic" inflammatory" diseases" when" innate" immunity" is" dysregulated." Rosacea" is" a" chronic" skin" disease" that" is" common" among"middle"aged"Caucasians."Human"rosacea"skin"samples"exhibited"higher" 3 number"of"MCs"compared"to"normal"subjects."AMP"LL37"and"neuropeptide"(NP)" substance"P"(SP)"are"upregulated"in"rosacea."LL37"and"SP"activate"MCs"through" MRGPRX2"in#vitro.#Utilizing"Mrgprb2"knockout"mice"(Mrgprb2E/E)"we"demonstrated" a" reduction" in" erythema" presentation," inflammatory" cell" recruitment," MMP+9" and" CXCL+2"mRNA"expression"compared"to"WT"mice"following"intradermal"injection" of" LLE37" and" SP" to" rosacea" model." Calcium" signaling" is" essential" for" MC" degranulation" and" function." In" this" dissertation" we" present" an" evidence" that" STIM1/Orai1" plays" an" important" role" in" MRGPRX2" mediated" calcium" influx" and" mediators"release"when"stimulated"with"LLE37"and"SP."" Moreover,"this"dissertation"showed"naturally"occurring"missense"mutations" of" MRGPRX2" both" within" and" outside" the" receptor’s" predicted" ligand" binding" pocket" (G165E," D184H," W243R" and" H259Y)" renders" it" unresponsive" neuropeptides," HDPs" and" peptidergic" drugs" for" MC" degranulation." Thus," individuals" harboring" these" mutations" may" develop" resistance" to" drugEinduced" allergic"reactions"and"rosacea"but"may"display"increased"susceptibility"to"microbial" infection.""
  • Publication
    Dentin Remineralization Around Ceramir Restoration
    (2016-08-15) Alhuwayrini, Lujain S
    AIM: To determine the efficacy of Ceramir, a modified glass ionomer cement and a surfactant mono-n-dodecyl phosphate in remineralization of dentin around root caries restorations. MATERIALS & METHODS: 45 permanent intact teeth were embedded in self-cured dental acrylic resin to expose buccal or lingual surfaces. The buccal/lingual surfaces were wet ground with carbide paper, final polishing were accomplished with aluminum to obtain highly polished dentin surface. Baseline Knoop micro hardness values were recorded. All specimens were then etched using 37% phosphoric acid for 5 seconds to demineralize dentin and to expose dentin collagen. The Knoop indenter micro hardness measurements were again performed for each sample four indentations in dentin surface within an area of 75 μm. The mean of Knoop microhardness was calculated. Cavities, 6.35 mm width and 3 mm depth were prepared within the etched area of each tooth with round carbide bur. Samples were divided into 4 groups: 2 samples used as control with no restoration, 13 samples were restored with plain Ceramir, 13 sample were restored with Ceramir containing 2% mono-n-dodecyl phosphate restoration and 13 samples were restored with Ceramir containing 5% mono-n-dodecyl phosphate. Samples were stored in SBF a 37° C incubator. Knoop micro hardness values were recorded at a distance of 75 um from the margins of the restoration at 10,20 and 38 day intervals. RESULTS: Knoop hardness of dentin (KHN) was reduced by 33.7% after etching. Knoop hardness of dentin around Ceramir restorations returned to pre-etching levels after 10 days of restoration. There was no statistically significant difference in Knoop micro-hardness (KHN) between the plain Ceramir compared to the Ceramir with surfactant after 10 days. Also, there was no statistically significant difference between the plain Ceramir and Ceramir with 2% surfactant after 20 days. Knoop hardness around cavities restored with Plain Ceramir and Ceramir with 2% Surfactant were significantly higher than around cavities restored with Ceramir with 5% surfactant after 20 and 38 days. CONCLUSIONS: The result of this study shows that Ceramir restorations of dentin lesions lead to remineralization of dentin around the restoration margins in the area of 75 μm where the micro-indentations performed. It shows that addition of 2% surfactant to Ceramir tend to increase the remineralization over time. Toward the end of the observation period samples restored with Ceramir containing 2% surfactant appeared to remineralize at a faster rate than plain Ceramir. On the other hand addition of 5% surfactant was not beneficial as it led to a decrease in the remineralizing effect of Ceramir.
  • Publication
    Comparison of Bone- and Tooth-Anchored, Bone-Anchored, and Surgically Assisted Bone-Anchored Rapid Palatal Expansion: a Pilot Retrospective CBCT Study
    (2020-06-11) Kim, Douglas
    Introduction: The purpose of this retrospective pilot study is to evaluate and compare the transverse dental and skeletal changes in three different approaches to miniscrew-assisted rapid palatal expansion (MARPE) including bone- and tooth-anchored (BTAME), bone-anchored (BAME), and surgically assisted bone-anchored maxillary expansion (SRBAME) maxillary expansion. The secondary purpose is to formulate new research questions and develop methods for future MARPE studies. Materials and Methods: Pre- (T1) and post-expansion (T2) Cone Beam Computed Tomography (CBCT) radiographs from 12 patients treated with BAME (median age = 15.5, 95% CI 14.0-18.1), 7 patients treated with BTAME (median age = 19, 95% CI 14.8-26.9), and 5 patients treated with SRBAME (median age = 38, 95% CI 21.6-56.0) were included in the study. All skeletal, alveolar, and dental changes were standardized using suture opening at first molar for intergroup comparisons. There were seven linear and two angular measurements evaluated at the first premolar, second premolar, first molar, and second molar levels for intra- and intergroup comparisons. Results: BTAME and BAME approaches both resulted in significant changes to transverse skeletal and alveolar transverse dimension with some dental tipping. Alveolar bone tipping at the first molar level in BAME was greater than in BTAME (p0.05) while it was significantly greater in the anterior than posterior in BAME (p Conclusions: Both BTAME and BAME result in significant transverse skeletal, alveolar, and dental expansion. BAME resulted in greater alveolar bone bending while BTAME resulted in greater dental tipping. Among the three groups, BTAME suture opening was closest to parallel from anterior to posterior. Contribution of skeletal expansion to intermolar width increase is more favorable in BAME than BTAME.
  • Publication
    (2021-06-03) Qali, Mohammad Taqi
    Background: Prosthetically compromised teeth (e.g., insufficient ferrule) and hopeless teeth (e.g., due to extensive caries or endodontic failure) present a number of restorative treatment challenges. In cases with pristine adjacent teeth and intact periodontium or a hopeless tooth that demands vertical alveolar bone augmentation, forced eruption is a conservative treatment approach. Current evidence in the literature is lacking in regard to the long-term (> 1 year) prognosis of forced erupted teeth. Aim: To evaluate the long-term (>1 year) stability of teeth that have been orthodontically treated with forced eruption for restorative purposes. Materials and Methods: This study is an investigator-initiated, retrospective. clinical study. Inclusion criteria: Patients receiving orthodontic extrusion in PDM between the years of 2012 to 2020, all ages, systemically healthy, medical records consist of radiographs, clinical pictures prior to and after extrusion. Exclusion Criteria: patients with active periodontal disease or patients with acute endodontic infection. Radiographic measurements were done before and after treatment to measure 1) crown margin to the crest of the alveolar bone, 2) root length. Clinical parameters measured included 1) activation time, 2) retention time, 3) total treatment time, 4) additional treatment required to restore the teeth, 5) pre/post-surgical complication, and 6) associations between clinician training and complication rate. Results: Twenty-five (25) participants with a total of thirty-six (36) orthodontically extruded teeth were included in the study. Mean activation time was 5.11 weeks. Mean retention before prosthetics and tooth extraction was 5.11 weeks and 12.3 weeks, respectively. The overall treatment period ranged from 3-16 months with a mean of 7.05 months. 96.0% survival rate of force erupted teeth and 4.0% failure rate due to non-restorable caries. When more than 1.0 mm extrusion was completed, there was a statistically higher chance that the tooth required additional surgeries (p < 0.05). Complications during treatment was higher in clinicians who did not have orthodontic training (43.0%) when compared to clinicians with orthodontic training (10.0%). Conclusion: Forced eruption for prosthetic treatment and implant site development is a viable and successful treatment option in the long-term.
  • Publication
    Effect of Expansive Force on Mesenchymal Stem Cells Isolated From the Mid-Palatal Suture of Mice
    (2018-07-12) Mojarrad, Samaneh
    Understanding the mechanisms by which craniofacial sutures respond to mechanical force is essential for improving orthodontic treatment strategies. However, the innate ability to regenerate bone from calvarial stem cells is still unknown. Therefore, we have initiated a study to isolate cells from the mid-palatal suture of mice. The aim of our study is to evaluate mesenchymal stem cell (MSC) characteristics of cells isolated from the mid-palatal suture and their ability for osteogenic differentiation when subjected to cyclic tensile force in vitro. A total of 10, 6-week old male C57BL/6 mice were used to obtain mid-palatal suture cells. Cultured cells were evaluated for MSC markers using flow cytometry and their potential for multi-lineage differentiation was evaluated using Alizarin Red S , Oil Red O, and Toluidine Blue staining. Cultured cells were subjected to cyclic tensile force with 15% elongation and a frequency of 0.5 Hz for 2 hours on the Flexcell-FX5000 tension system. Both stretched and control cells were cultured in osteogenic medium and the effect of tensile force on osteogenic differentiation was evaluated using Western Blot analysis and Alizarin Red S staining. Our results showed that mid-palatal suture cells formed colony-forming-units (CFU-F), expressed MSC-markers CD73, CD90, CD105, and Sca-1, and were negative for hematopoietic markers CD34 and CD45. In addition, these cells showed multi-lineage differentiation to osteogenic, chondrogenic, and adipogenic cell lines. Western blot analysis showed an upregulation in expression of osteoblastic markers, including ALP, OCN, and RUNX2 in the stretch group compared to control which was confirmed by a marked increase in extracellular matrix deposit in the stretched group using Alizarin Red S staining. In summary, our findings show that cells isolated from the mid-palatal suture of mice have MSC characteristics in vitro and that cyclic mechanical tensile strain can promote osteogenic differentiation through an upregulation of osteogenic markers and an increase in production of mineralized matrix.
  • Publication
    FOXO1 Differentially Regulates Both Normal and Diabetic Gingival Wound Healing
    (2016-07-29) Jeon, Hyeran H
    We have previously demonstrated that keratinocyte-specific forkhead box O1 (FOXO1) deletion interferes with keratinocyte migration in normal skin wounds. However it has an opposite effect in diabetic skin wounds, significantly improving the healing response. In addition we found that skin epithelium regulates connective tissue healing mediated by FOXO1, which is strongly associated with wound angiogenesis in our microarray results. However, a role for keratinocytes in this complex process has yet to be investigated. To this end, we investigated possible involvement of gingival keratinocytes in connective tissue healing under both normal and diabetic conditions. We found that keratinocyte-specific FOXO1 deletion interfered with normal gingival connective tissue healing by decreasing granulation tissue formation and angiogenesis, which were mediated by vascular endothelial growth factor A (VEGF-A). In particular this is the first evidence that avascular epithelium regulates angiogenesis involving the VEGF-A secretion mediated by FOXO1. Furthermore, we investigated the possible role of epithelial to mesenchymal transition (EMT) during wound healing using the lineage tracing in transgenic mice. But we did not find any keratinocyte-specific reporter activity in the connective tissue indicating that there was no apparent trans-differentiation of keratinocytes into typical fibroblasts or myofibroblasts during wound healing. These results establish an important role of epithelial cells in accelerating wound angiogenesis and connective tissue healing through a FOXO1-dependent mechanism.