Saudi Cultural Missions Theses & Dissertations
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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 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 Identification and Functional Characterization of Novel Variants Associated with Sepsis Identified by Whole Exome Sequencing(Saudi Digital Library, 0098-11-04) Alsaif, Hessa Saad; Knight, Julian; Jia, AliciaBackground Sepsis is a life-threatening organ dysfunction caused by a dysregulated host response to infection. It is a leading cause of global mortality. Although sepsis is not considered a classic monogenic trait, there is strong evidence of the role of genetics in its susceptibility. Methods and Results This project uses the previously collected sepsis-affected cohort of 484 whole-exome sequenced (WES) samples to bring insights into genetics of sepsis. The two variants in GNLY gene encoding for antimicrobial peptide granulysin, NM_006433.5:c.255+2T>C and NM_006433.5:c.304C>T, have been prioritised using in silico variant pathogenicity prediction tools for further in vitro evaluation. These variants were present in three patients from sepsis cohort. The criteria for prioritisation were the rarity of the variants in non-affected population, the high impact consequences of the variants on GNLY transcripts and proteins, and the essential role of the GNLY gene as a key component of the immune response. NM_006433.5:c.304C>T variant introduces a premature stop codon and is predicted to lead to truncation of GNLY protein by third: from 148 aa to 102 aa. NM_006433.5:c.255+2T>C variant was predicted to affect splicing of exons 3-4 of GNLY transcript. The presence of the variants in three patients from the cohort in a heterozygous state has been confirmed through Sanger sequencing. In vitro ExonTrap minigene assays have confirmed that NM_006433.5:c.255+2T>C variant leads to aberrant splicing. It has been also investigated whether the two variants are presented in compound heterozygote state using cloning assay. The overall conclusion was that the variants are not likely to be present in the compound heterozygote state in two patients. Conclusion Potential of GNLY being a novel sepsis-susceptibility gene, caveats of variant pathogenicity predictions and the potential genetic mechanisms by which the two variants can contribute to the genetics of susceptibility of sepsis are further discussed.12 0