Melbourne Dental School - Research Publications

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    Maxillonasal dysplasia (Binder syndrome): a lateral cephalometric assessment.
    Carach, B ; Woods, M ; Scott, P (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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    Regulation of the endosomal SNARE protein syntaxin 7 by colony-stimulating factor 1 in macrophages
    Achuthan, A ; Masendycz, P ; Lopez, JA ; Nguyen, T ; James, DE ; Sweet, MJ ; Hamilton, JA ; Scholz, GM (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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    Engineering highly effective antimicrobial selenium nanoparticles through control of particle size
    Huang, T ; Holden, JA ; Heath, DE ; O'Brien-Simpson, NM ; O'Connor, AJ (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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    Antimicrobial nanoparticle coatings for medical implants: Design challenges and prospects
    Li, X ; Huang, T ; Heath, DE ; O'Brien-Simpson, NM ; O'Connor, AJ (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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    Multifunctional Antimicrobial Polypeptide-Selenium Nanoparticles Combat Drug-Resistant Bacteria
    Huang, T ; Holden, JA ; Reynolds, EC ; Heath, DE ; O'Brien-Simpson, NM ; O'Connor, AJ (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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    Laboratory Evaluation of Novel Implant Metal-Acrylic Prosthesis Design: Influence of Monolithic Acrylic Veneer
    El-adHdad, H ; Judge, RB ; Abduo, J ; Palamara, J (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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    The role of the brain-gut-microbiota axis in psychology: The importance of considering gut microbiota in the development, perpetuation, and treatment of psychological disorders.
    Ganci, M ; Suleyman, E ; Butt, H ; Ball, M (Wiley, 2019-11)
    INTRODUCTION: The prevalence of psychological disorders remains stable despite steady increases in pharmacological treatments suggesting the need for auxiliary treatment options. Consideration of the brain-gut-microbiota axis (BGMA) has made inroads into reconceptualizing psychological illness from a more holistic perspective. While our understanding of the precise role of gut microbiota (GM) in psychological illness is in its infancy, it represents an attractive target for novel interventions. METHOD: An extensive review of relevant literature was undertaken. RESULTS: Gut microbiota are proposed to directly and indirectly influence mood, cognition, and behavior which are key components of mental health. This paper outlines how GM may be implicated in psychological disorders from etiology through to treatment and prevention using the Four P model of case formulation. CONCLUSION: Moving forward, integration of GM into the conceptualization and treatment of psychological illness will require the discipline of psychology to undergo a significant paradigm shift. While the importance of the GM in psychological well-being must be respected, it is not proposed to be a panacea, but instead, an additional arm to a multidisciplinary approach to treatment and prevention.
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    A dental workforce strategy to make Australian public dental services more efficient
    Tan, MN ; Tonmukayakul, U ; Calache, H (BMC, 2019-05-30)
    BACKGROUND: Dental services can be provided by the oral health therapy (OHT) workforce and dentists. This study aims to quantify the potential cost-savings of increased utilisation of the OHT workforce in providing dental services for children under the Child Dental Benefits Schedule (CDBS). The CDBS is an Australian federal government initiative to increase dental care access for children aged 2-17 years. METHODS: Dental services billed under the CDBS for the 2013-2014 financial year were used. Two OHT-to-dentist workforce mix ratios were tested: Model A National Workforce (1:4) and Model B Victorian Workforce (2:3). The 30% average salary difference between the two professions in the public sector was used to adjust the CDBS fee schedule for each type of service. The current 29% utilisation rate of the CDBS and the government target of 80% were modelled. RESULTS: The estimated cost-savings under the current CDBS utilisation rate was AUD 26.5M and AUD 61.7M, for Models A and B, respectively. For the government target CDBS utilisation rate, AUD 73.2M for Model A and AUD 170.2M for Model B could be saved. CONCLUSION: An increased utilisation of the OHT workforce to provide dental services under the CDBS would save costs on public dental service funding. The potential cost-savings can be reinvested in other dental initiatives such as outreach school-based dental check programmes or resource allocation to eliminate adult dental waiting lists in the public sector.
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    Bilateral Distraction Osteogenesis of Vascularized Iliac Crest Free Flaps Used in Mandibular Reconstruction.
    Bobinskas, AM ; Subramaniam, SS ; Vujcich, NJ ; Nastri, AL (Ovid Technologies (Wolters Kluwer Health), 2016-03)
    Vascularized free flaps have become the gold standard in reconstructing large segmental mandibular defects; however, even when bony union and soft-tissue coverage is achieved, insufficient bone stock and altered facial contour can create functional and cosmetic problems for the patient. There have been limited case reports on the use of secondary distraction osteogenesis to address these issues. The authors report a case of bilateral mandibular distraction of deep circumflex iliac artery free flaps, used for mandibular reconstruction after total mandibulectomy for treatment of osteosarcoma. Performed for reasons of retrognathia and facilitation of dental prosthetic rehabilitation, this is the first case of bilateral horizontal distraction osteogenesis of deep circumflex iliac artery free flaps reported in the literature.
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    Kimura's disease: an uncommon cause of head and neck masses with potentially serious sequelae
    Bobinskas, AM ; Chandu, A ; Nastri, AL (OXFORD UNIV PRESS, 2015-10)
    Kimura's disease (KD) typically presents as a mass in the head and neck region in association with eosinophilia and elevated serum IgE. Excisional biopsy is often required in order to obtain an adequate sample for histological diagnosis and exclude malignancy. If suspected, patients should also be investigated for renal involvement as this may complicate KD. Treatment options include surgical excision and medical therapies such as corticosteroids depending on the extent and severity of disease.