Melbourne Dental School - Research Publications
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ItemMaxillonasal dysplasia (Binder syndrome): a lateral cephalometric assessment.(Walter de Gruyter GmbH, 2002-11)Binder syndrome or maxillonasal dysplasia was first described by Binder in 1962, and is a disorder characterised by nasomaxillary hypoplasia. The records of 33 patients who had been diagnosed clinically with Binder syndrome at the Royal Children's Hospital of Melbourne were examined. Of these 33 patients, 14 were selected because they met the incusion criteria: that they had not had prior surgical and/or orthodontic treatment, and that high-quality lateral cephalometric radiographs were available. The craniofacial morphology of these patients was determined on lateral cephalometric radiographs and compared with published age- and sex-matched norms. In agreement with published studies, the anteroposterior lengths of the anterior cranial base and maxilla were reduced, and the majority of patients had a Class III skeletal relationship. Although the lower incisors tended to be prominent, both overjet and overbite 'ell within the ranges for the normal population. Despite the fact that the orthodontic and surgical treatment for patients with Binder syndrome is normally carried out within specialised units, clinicians should be aware of the variety of ways in which this condition may present.
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ItemNo Preview AvailableRegulation of the endosomal SNARE protein syntaxin 7 by colony-stimulating factor 1 in macrophages(AMER SOC MICROBIOLOGY, 2008-10)Colony-stimulating factor 1 (CSF-1) is the main growth factor controlling the development of macrophages from myeloid progenitor cells. However, CSF-1 also regulates some of the key effector functions of macrophages (e.g., phagocytosis and cytokine secretion). The endosomal SNARE protein syntaxin 7 (Stx7) regulates vesicle trafficking events involved in phagocytosis and cytokine secretion. Therefore, we investigated the ability of CSF-1 to regulate Stx7. CSF-1 upregulated Stx7 expression in primary mouse macrophages; it also upregulated expression of its SNARE partners Vti1b and VAMP8 but not Stx8. Additionally, CSF-1 induced the rapid serine phosphorylation of Stx7 and enhanced its binding to Vti1b, Stx8, and VAMP8. Bioinformatics analysis and results from experiments with kinase inhibitors suggested the CSF-1-induced phosphorylation of Stx7 was mediated by protein kinase C and Akt in response to phosphatidylinositol 3-kinase activation. Based on mutagenesis studies, CSF-1 appeared to increase the binding of Stx7 to its SNARE partners by inducing the phosphorylation of serine residues in the Habc domain and/or "linker" region of Stx7. Thus, CSF-1 is a key regulator of Stx7 expression and function in macrophages. Furthermore, the effects of CSF-1 on Stx7 may provide a mechanism for the regulation of macrophage effector functions by CSF-1.
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ItemEngineering highly effective antimicrobial selenium nanoparticles through control of particle size(Royal Society of Chemistry, 2019-08-21)The overuse of antibiotics has induced the rapid development of antibiotic resistance in bacteria. As a result, antibiotic efficacy has become limited, and infection with multidrug-resistant bacteria is considered to be one of the largest global human health threats. Consequently, new, effective and safe antimicrobial agents need to be developed urgently. One promising candidate to address this requirement is selenium nanoparticles (Se NPs), which are made from the essential dietary trace element Se and have antimicrobial activity against Gram-positive bacteria. The size of nanomaterials can strongly affect their biophysical properties and functions; however, the effects of the size of Se NPs on their antibacterial efficacy has not been systematically investigated. Therefore, in this work, spherical Se NPs ranging from 43 to 205 nm in diameter were fabricated, and their mammalian cytotoxicity and antibacterial activity as a function of their size were systematically studied. The antibacterial activity of the Se NPs was shown to be strongly size dependent, with 81 nm Se NPs showing the maximal growth inhibition and killing effect of methicillin-sensitive and methicillin-resistant Staphylococcus aureus (MSSA and MRSA). The Se NPs were shown to have multi-modal mechanisms of action that depended on their size, including depleting internal ATP, inducing ROS production, and disrupting membrane potential. All the Se NPs were non-toxic towards mammalian cells up to 25 μg mL−1. Furthermore, the MIC value for the 81 nm particles produced in this research is 16 ± 7 μg mL−1, significantly lower than previously reported MIC values for Se NPs. This data illustrates that Se NP size is a facile yet critical and previously underappreciated parameter that can be tailored for maximal antimicrobial efficacy. We have identified that using Se NPs with a size of 81 nm and concentration of 10 μg mL−1 shows promise as a safe and efficient way to kill S. aureus without damaging mammalian cells.
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ItemAntimicrobial nanoparticle coatings for medical implants: Design challenges and prospects(AMER INST PHYSICS, 2020-11)Microbial colonization, infection, and biofilm formation are major complications in the use of implants and are the predominant risk factors in implant failure. Although aseptic surgery and the administration of antimicrobial drugs may reduce the risk of infection, the systemic use of antibiotics can lead to a lack of efficacy, an increase in the risk of tissue toxicity, and the development of drug-resistant infections. To reduce implant-related infections, antimicrobial materials are increasingly being investigated and applied to implant surfaces using various methods depending on the agents and their microbicidal mechanisms. Through the development of biomaterials and nanotechnology, antimicrobial nanoparticles are becoming promising candidates for implant coatings, as their multifactorial antimicrobial mechanisms combat microbial adherence, viability, and biofilm formation. Despite their antimicrobial promise, the application of nanoparticles onto implant surfaces while retaining their antimicrobial potency faces many challenges. Herein, we review the potential and challenges associated with the design and implementation of antimicrobial nanoparticle coatings for the medical implant industry, particularly focusing on manufacturing considerations, sterilization, long-term stability, protein fouling, regulation, and safety, with a view to providing researchers the necessary tools to aid the translation of materials from the bench to the clinic.
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ItemMultifunctional Antimicrobial Polypeptide-Selenium Nanoparticles Combat Drug-Resistant Bacteria(AMER CHEMICAL SOC, 2020-12-16)Antibiotic-resistant bacteria are a severe threat to human health. The World Health Organization's Global Antimicrobial Surveillance System has revealed widespread occurrence of antibiotic resistance among half a million patients across 22 countries, with Staphylococcus aureus, Escherichia coli, and Klebsiella pneumoniae being the most common resistant species. Antimicrobial nanoparticles are emerging as a promising alternative to antibiotics in the fight against antimicrobial resistance. In this work, selenium nanoparticles coated with the antimicrobial polypeptide, ε-poly-l-lysine, (Se NP-ε-PL) were synthesized and their antibacterial activity and cytotoxicity were investigated. Se NP-ε-PL exhibited significantly greater antibacterial activity against all eight bacterial species tested, including Gram-positive, Gram-negative, and drug-resistant strains, than their individual components, Se NP and ε-PL. The nanoparticles showed no toxicity toward human dermal fibroblasts at the minimum inhibitory concentrations, demonstrating a therapeutic window. Furthermore, unlike the conventional antibiotic kanamycin, Se NP-ε-PL did not readily induce resistance in E. coli or S. aureus. Specifically, S. aureus began to develop resistance to kanamycin from ∼44 generations, whereas it took ∼132 generations for resistance to develop to Se NP-ε-PL. Startlingly, E. coli was not able to develop resistance to the nanoparticles over ∼300 generations. These results indicate that the multifunctional approach of combining Se NP with ε-PL to form Se NP-ε-PL is a highly efficacious new strategy with wide-spectrum antibacterial activity, low cytotoxicity, and significant delays in development of resistance.
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ItemComplementation in trans of Porphyromonas gingivalis Lipopolysaccharide Biosynthetic Mutants Demonstrates Lipopolysaccharide Exchange(American Society for Microbiology, 2021-04-21)Porphyromonas gingivalis, a bacterial pathogen contributing to human periodontitis, exports and anchors cargo proteins to its surface, enabling the production of black pigmentation using a type IX secretion system (T9SS) and conjugation to anionic lipopolysaccharide (A-LPS). To determine whether T9SS components need to be assembled in situ for correct secretion and A-LPS modification of cargo proteins, combinations of nonpigmented mutants lacking A-LPS or a T9SS component were mixed to investigate in trans complementation. Reacquisition of pigmentation occurred only between an A-LPS mutant and a T9SS mutant, which coincided with A-LPS modification of cargo proteins detected by Western blotting and coimmunoprecipitation/quantitative mass spectrometry. Complementation also occurred using an A-LPS mutant mixed with outer membrane vesicles (OMVs) or purified A-LPS. Fluorescence experiments demonstrated that OMVs can fuse with and transfer lipid to P. gingivalis, leading to the conclusion that complementation of T9SS function occurred through A-LPS transfer between cells. None of the two-strain crosses involving only the five T9SS OM component mutants produced black pigmentation, implying that the OM proteins cannot be transferred in a manner that restores function and surface pigmentation, and hence, a more ordered temporal in situ assembly of T9SS components may be required. Our results show that LPS can be transferred between cells or between cells and OMVs to complement deficiencies in LPS biosynthesis and hemin-related pigmentation to reveal a potentially new mechanism by which the oral microbial community is modulated to produce clinical consequences in the human host. IMPORTANCE: Porphyromonas gingivalis is a keystone pathogen contributing to periodontitis in humans, leading to tooth loss. The oral microbiota is essential in this pathogenic process and changes from predominantly Gram-positive (health) to predominantly Gram-negative (disease) species. P. gingivalis uses its type IX secretion system (T9SS) to secrete and conjugate virulence proteins to anionic lipopolysaccharide (A-LPS). This study investigated whether components of this secretion system could be complemented and found that it was possible for A-LPS biosynthetic mutants to be complemented in trans both by strains that had the A-LPS on the cell surface and by exogenous sources of A-LPS. This is the first known example of LPS exchange in a human bacterial pathogen which causes disease through complex microbiota-host interactions.
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ItemIADR 100 Years On: Driving Science, Engagement, and Globalization Post COVID-19(SAGE PUBLICATIONS INC, 2021-12)
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ItemLaboratory Evaluation of Novel Implant Metal-Acrylic Prosthesis Design: Influence of Monolithic Acrylic Veneer(QUINTESSENCE PUBLISHING CO INC, 2020)PURPOSE: To test a novel implant metal-acrylic prosthesis design in comparison to a conventional prosthesis design through simulation of cyclic masticatory loading. The novel design involved digital designing and fabrication of the framework and the matched veneering acrylic resin material. MATERIALS AND METHODS: Ten prostheses were fabricated for each group. All the prostheses exhibited a similar external design on two implants with a distal cantilever. The conventional group comprised a milled metal framework with mechanically retained acrylic denture teeth via vertical pins. The digital prosthesis group incorporated an inverted T-shape bar and a monolithic milled acrylic resin veneer. The resin veneer was subsequently adhesively attached on the bar. All prostheses were thermally aged and subjected to laboratory cyclic loading at the cantilever region. The load-to-failure and the number of cycles until failure were collected. Furthermore, failed specimens were analyzed to determine the mode of failure. RESULTS: The digital prostheses failed at significantly greater load-to-failure (1,570.0 N ± 116.0 N) and number of cycles (124,857 ± 21,608) than the conventional prostheses (load-to-failure = 1,015.0 N ± 47.4 N; number of cycles = 28,452 ± 6,559). The conventional prostheses failed by fracturing of the acrylic teeth and veneering material that led to exposure of the metal framework. Half of the digital prostheses failed by superficial chipping of the veneering material, while the other half failed by the deformation and fracture of screws. CONCLUSION: Within the limitations of this study, the digital prostheses with the novel design and monolithic veneering material showed significantly higher strength compared with the conventional prostheses. The mode of acrylic failure of the digital prostheses was more favorable.
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ItemSocial practice theory: An innovative approach to considering preschool children's poor oral health(WILEY, 2021-08)Oral disease in early childhood is highly prevalent and costly and impacts on the child and family with significant societal costs. Current approaches have largely failed to improve young children's oral health. This paper proposes a different approach to conceptualize poor oral health in preschool children (0-5 years) using social practices. Social practice theory offers an innovative perspective to understanding oral health by shifting emphasis away from the individual and onto how practical, social and material arrangements around the oral health of preschool children exist, change or become embedded in the social structures they inhabit. This novel approach contributes to the growing theoretical understanding in this area and has the potential to offer insights into the problem and ways it might be addressed.
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ItemPerceptions of oral health education and practice among nursing students in Malaysia and Australia(WILEY, 2021-05)OBJECTIVE: Representing the largest proportion of healthcare workers, nurses play a significant role in oral health (OH) maintenance as part of a larger effort to promote holistic patient care. The study aims to determine nursing students' perceptions of OH education and practice in Malaysian and Australian nursing schools. MATERIALS AND METHODS: A self-administered questionnaire (content- and face-validated) survey was undertaken, classroom style, amongst final-year nursing students from selected Malaysian (n = 122, Response rate=97.6%) and Australian (n = 299, Response rate=54.7%) institutions. Quantitative data were analysed via Statistical Package for Social Science software (Chi-square and Fisher's exact tests, p ≤ 0.01). RESULTS: Significantly more Malaysian nursing students, compared to those in Australia, reported having encountered patients with OH issues (98.4% vs. 82.9%), namely halitosis (87.7% vs. 62.2%), oral ulcers (63.1% vs. 41.1%), oral/dental trauma (36.9% vs. 21.1%) and caries in children (28.7% vs. 7.7%). Less than half of Malaysian and Australian nursing students reported that they received adequate OH training (48.4% vs. 36.6%, p ≤ 0.01), especially in detecting oral cancer (18.0.0% vs. 22.6%, p ≤ 0.01) and preventing oral diseases (46.7% vs. 41.7%, p ≤ 0.01). Students in both countries demonstrated positive attitudes and believed in their role in OH care. Most students agreed that they should receive training in OH, especially in smoking cessation and providing OH care for patients with special needs. They also opined that a standardized evidence-based oral hygiene protocol is needed. CONCLUSION: Support for education and practice in this area of patient care suggested positive implications for further development of nurses' roles in OH promotion and management.