SACM - United States of America
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Item Restricted Treatment Quality, Duration and Accuracy with LightForce™ 3D-Printed Custom Brackets and Clear Aligners(Unviversity at Buffalo, 0095-06) Hamiduddin, Aliyyah; Al-Jewair, Thikriat; Aszkler, Robert; Warunek, StephenIntroduction: New custom 3D-printed bracket workflows have emerged during the past few years. LightForceTM (LF, Burlington, MA) is a custom 3D-printed labial bracket that is indirectly bonded to teeth. The manufacturer claims that they are precise in delivering tooth movement, accurate in bracket placement, efficient in clinic visits. Clear Aligners (CA) have been utilized more commonly in clinical practice with similar claims to 3D-printed brackets in terms of its precision, accuracy, and efficiency. In Addition, CAs are more esthetic, better in oral hygiene maintenance, less susceptible to white spot lesions compared to fixed orthodontic brackets, however, they have some drawbacks such as patients’ compliance is required in wearing their aligners, the main movement produced is tipping and the predictability of controlled tipping ≤ 50% of the required tooth movement. To our knowledge, the treatment quality, duration, and accuracy of LF customized 3-D printed brackets in comparison to CAs has not been investigated in the literature Objectives: The aims of this study were to compare the treatment quality, duration and accuracy of LF bracket system and CA therapy. Methods: This was a retrospective comparative study of patients presenting for comprehensive orthodontic treatment with either LF or CAs (Invisalign®, San Jose, CA) in one private practice. A total of 70 subjects were included (37 in the LF group and 33 in the CA group). The mean age at the start of the treatment was 13.42 ± 1.09 in LF group and 15.8 ± 3.36 in the CA group. Pre- and post-comprehensive treatment records were compared. Treatment quality was evaluated on post-treatment 3-D printed models and panoramic radiographs using the ABO Cast-Radiograph evaluation (C-R Eval) grading system. Treatment duration was compared between the groups in months. Treatment accuracy was evaluated by comparing the predicted (TP) and the achieved (T1) arch width changes at the canine, first premolar and first molar between the groups. Results: The total C-R Eval score was 35.08 ± 9.99 in the LF group and 32.55 ± 8.85 in the CA group. The scores showed no significant difference between the two groups (P=0.503). The treatment duration was 15.89 ± 3.49 in the LF and 14.39 ± 4.69 in the CA group and the difference was not statistically significant (P= 0.138). There was significant difference between LF and CA groups in TP-T1 of the maxillary inter- canine width (LF= 0.87, CA=0.23, P= 0.013) Conclusion: Treatment quality and duration were comparable between LF and CAs in mild to moderate crowding cases. CAs demonstrated accuracy in archwidth predictions, whereas LF showed accuracy in predicting maxillary inter-canine width, mandibular intermolar and inter-premolar widths. CAs showed higher accuracy in the prediction of maxillary inter-canine width than LF.54 0Item Restricted The Role of Angiopoietin-Like 4 in Head and Neck Squamous Cell Carcinoma Progression and Dissemination(University of Maryland, 0022-07-19) Hefni, Eman; Montaner, SilviaDysregulation of cellular signaling and behavior are instrumental in promoting tumor cell metabolism, proliferation, tissue invasion and metastasis. Extensive investigations in human cancer development have identified various of these alterations within tumors and their microenvironments that have helped guide the direction of drug development in cancer. Different types of molecular-based therapies for this disease are designed to modulate or interact with cell surface receptors (monoclonal antibodies), intracellular cascades (small molecule tyrosine kinase inhibitors) as well as microenvironment components related to the functionality of the extracellular matrix, tumor vasculature and immune response. To design these cancer molecular-based therapies, an improved understanding of the molecular underpinnings leading to tumor formation and growth is essential. The overall aim of our investigation is the identification of the molecular mechanisms associated with the induction of tumor cell migration and proliferation induced by Angiopoietin-like 4 (ANGPTL4), a pro-tumorigenic and pro- angiogenic factor, in head and neck cancer squamous cell carcinoma (HNSCC). HNSCC accounts for approximately 900,000 cases and over 400,000 deaths annually, with around 54,000 new cases and 11,000 deaths per year in the United States. Unfortunately, the clinical management of this tumor remains challenging and there is an urgent need for novel therapeutic alternatives. Our studies, divided into two research aims, use in vitro cell- based models together with signal transduction and cell and molecular biology methods. Our results demonstrate that: 1) ANGPTL4 is upregulated in human-derived dysplastic oral keratinocytes (DOKs) and HNSCC cell lines, but not in normal oral keratinocytes (NOKs), suggesting an early and sustained role for ANGPTL4 in disease progression. ANGPTL4 is a molecular marker in biopsies from patients with mild-moderate or moderate oral epithelial dysplasia, primary HNSCC and metastatic HNSCC. ANGPTL4 is necessary and sufficient to promote cell migration in DOKs and HNSCCs lines. Binding of ANGPTL4 to neuropilin-1 (NRP1) leads to paxillin (PXN) phosphorylation and cell migration in an ABL1-dependent manner, exposing the ANGPTL4/NRP1/ABL1/PXN cascade as a vulnerable target for HNSCC treatment. 2) Epidermal Growth Factor (EGF)- and Hypoxia-inducible Factor-1 (HIF-1)-mediated pathways cooperate in the upregulation of ANGPTL4 in normal and dysplastic oral keratinocytes and HNSCC cells. Besides EGF, the EGF ligand, amphiregulin leads to an increase in ANGPTL4 and is upregulated in HNSCC lesions. ANGPTL4 activates the HNSCC molecular markers p38 MAPK, AKT and mTOR in NOKs; these kinases may act as potential intracellular regulators of the autocrine signals and paracrine secretions that ANGPTL4 activates to promote HNSCC tumorigenesis. Collectively, our findings are clinically relevant and suggest that ANGPTL4 and its associated signaling molecules are potential therapeutic targets in HNSCC clinical management.14 0Item Restricted THE ANTIM ICROBIAL ACTIVITY OF COMMIPHORA MOLM OL (MYRRHA) EXTRACT(Long Island University, 0019-07-15) Alenezi, Tahrir; Bhattacharjee, MrinalThe Commiphoramolmol (myrrha) has been used as a traditional medicine for centuries in different cultures. An ethanol extract o f myrrha was evaporated under vacuum to obtain an oil. A 20% solution o f this oil in ethanol was used to determine antimicrobial activity against the Gram-positive bacteria S. aureus, the Gram-negative bacteria, E. coli, MVlONal, and fungi, (yeast), Saccharomyces cerevisiae. The MIC forÆ’. coli and S. aureus were determined on phosphate buffer since the oil did not show antibiotic activity on growing cells. The MIC o f myrrha oil in phosphate buffer for E. coli was 0.56% (5.6 mg/ml) and for S. aureus was 0.1% (1 mg/ml). However, the oil could be used to kill cells in a nutrient-rich medium provided growth o f the bacteria is first stopped using a bacteriostatic antibiotic such as Chloramphenicol. The results show that chloramphenicol enhanced the antimicrobial activity o f myrrha oil. Zone o f inhibition test shows myrrha extract has antibacterial property against S. aureus. Furthermore, the antifungal activity of myrrha extract was prodigious since most o f the cells were killed in 10 minutes at a dose o f 0.05% (0.5 mg/ml) o f myrrha extract. Repeated attempts to obtain an E. coli or S. aureus strain that is resistant to myrrha oil were unsuccessful. A possible explanation o f this can be that myrrha oil is a membrane acting antibiotic. In conclusion, the results o f this study suggest that myrrha extract could be a prom ising antibacterial and antifungal drug.33 0Item Restricted IQGAP1 IS A NOVEL EFFECTOR OF GONADOTROPIN-RELEASING HORMONE RECEPTOR SIGNALING(Saudi Digital Library, 0100-12-17) Alqahatni, Huda; Amberg, GregoryStimulation of gonadotropin-releasing hormone (GnRH) receptors on the surface of anterior pituitary gonadotrope cells is a key signaling event for the hypothalamic-pituitary-gonadal axis. One important downstream component of GnRH receptor signaling is the activation of the mitogen-activated protein kinase ERK (extracellular signal-regulated kinase), which is essential for the production of the gonadotropin luteinizing hormone. Evidence suggests that GnRH receptors reside in low-density plasma membrane domains where they participate in multiprotein signaling complexes. Here, we used quantitative proteomics to identify proteins associated with low-density plasma membrane domains and to measure changes in their relative abundance in these domains in response to GnRH. Using αT3-1 gonadotropes, we identified 537 proteins in detergent-free subcellular fractions containing low-density plasma membranes. SILAC (stable isotope labeling by amino acids in cell culture), in combination with mass spectrometry, demonstrated that GnRH, within 10 min, altered the association of 87 proteins with this plasma membrane fraction. Ontology analysis revealed that GnRH promoted an enrichment of actin cytoskeletal and adherent junction-related proteins, including the molecular scaffold IQGAP1 and the small GTPase Rac1. Subsequent investigation revealed that the association between Rac1 and IQGAP1 increased with GnRH receptor stimulation and that GnRH increased Rac1 activity. Demonstrating functional relevance, inhibiting Rac1 reduced GnRH-dependent ERK activation. Our data reveals an upstream activation of signaling and structural molecules, including Ca2+, CDC42 and Rac1, E-cadherin, N-cadherin, and β-catenin. We also identified interactions between the scaffold protein IQGAP1 and these molecules, indicating that IQGAP1 is a fundamental regulator of GnRH-dependent signaling in gonadotropes. Furthermore, our data shows that IQGAP1 has a transcriptional regulatory role in gonadotropes treated with GnRH. In sum, these data indicate that IQGAP1 complexed with Rac1 modulates ERK activity and, as such, serves as an essential effector in modulating cell polarity and cell-cell contacts in gonadotropes. Altogether, our proteomics data show that acute stimulation of GnRH receptors (3 nM for 10 min) alters the PAM fraction abundance of proteins, such as IQGAP1, mechanistically linked to gonadotrope activation.5 0Item Restricted Unhealed Wounds: From Complex Trauma Exposure to Wellbeing and the Role of Coping(0023-07-23) Alsubaie, Mohammed; Bentley, JacobComplex Posttraumatic Stress Disorder (cPTSD) emerged as a theoretical construct reflecting symptoms beyond our current conceptualization of posttraumatic stress. Research examining its validity is still ongoing and cross-cultural research on the matter is emerging. An important risk factor to developing cPTSD is the experience of complex trauma, which constitutes experiences that reflect interpersonal violations of bodily boundary and integrity or betrayal (e.g., sexual assault and emotional abuse). There is still a gap in the literature linking complex trauma exposure to wellbeing or positive functioning in general. Survivors’ style of coping with trauma might influence later adjustment. With a sample of trauma survivors from Saudi Arabia, the present study evaluated the construct validity of cPTSD as well as examined the relationship between complex trauma and wellbeing as moderated by styles of coping. Results showed that all conceptualizations of complex trauma significantly predicted decreased wellbeing, but that such associations were not moderated by active nor passive style of coping. Factor and network analyses provided evidence for the construct validity of cPTSD, with the 6 first-order correlated factors model representing the best fit for the data, χ2 (155) = 431.373, p < .001, CFI = .941, TLI = .928, RMSEA = .064, 90% CI [.057, .071], SRMR = .041. Exploratory network analyses yielded 4-factor solutions distinguishing boundaries between PTSD, disturbance in self-organization (DSO), depression, and anxiety. Collectively, these findings call for systemic efforts to help increase access to well-researched and effective interventions as well as provide suggestions for central symptoms in these networks, and offer practitioners evidence for cPTSD validity and an assessment tool to utilize in Arabic.27 0