Melbourne Dental School - Research Publications
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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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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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ItemThe role of the brain-gut-microbiota axis in psychology: The importance of considering gut microbiota in the development, perpetuation, and treatment of psychological disorders.(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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ItemA dental workforce strategy to make Australian public dental services more efficient(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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ItemBilateral Distraction Osteogenesis of Vascularized Iliac Crest Free Flaps Used in Mandibular Reconstruction.(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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ItemKimura's disease: an uncommon cause of head and neck masses with potentially serious sequelae(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.
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ItemSupport for the Microgenderome: Associations in a Human Clinical Population.(Springer Science and Business Media LLC, 2016-01-13)The 'microgenderome' provides a paradigm shift that highlights the role of sex differences in the host-microbiota interaction relevant for autoimmune and neuro-immune conditions. Analysis of cross-sectional self-report and faecal microbial data from 274 patients with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) suggests that commensal gut microorganisms may play both protective and deleterious roles in symptom expression. Results revealed significant sex-specific interactions between Firmicutes (Clostridium, Streptococcus, Lactobacillus and Enterococcus) and ME/CFS symptoms (including neurological, immune and mood symptoms), regardless of compositional similarity in microbial levels across the sexes. Extending animal studies, we provide support for the microgenderome in a human clinical population. Applied and mechanistic research needs to consider sex-interactions when examining the composition and function of human microbiota.
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ItemExamining clinical similarities between myalgic encephalomyelitis/chronic fatigue syndrome and D-lactic acidosis: a systematic review.(Springer Science and Business Media LLC, 2017-06-07)BACKGROUND: The pursuit for clarity in diagnostic and treatment pathways for the complex, chronic condition of myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) continues. This systematic review raises a novel question to explore possible overlapping aetiology in two distinct conditions. Similar neurocognitive symptoms and evidence of D-lactate producing bacteria in ME/CFS raise questions about shared mechanisms with the acute condition of D-lactic acidosis (D-la). METHODS: D-la case reports published between 1965 and March 2016 were reviewed for episodes describing both neurological symptoms and high D-lactate levels. Fifty-nine D-la episodes were included in the qualitative synthesis comparing D-la symptoms with ME/CFS diagnostic criteria. A narrative review of D-la mechanisms and relevance for ME/CFS was provided. RESULTS: The majority of neurological disturbances reported in D-la episodes overlapped with ME/CFS symptoms. Of these, the most frequently reported D-la symptoms were motor disturbances that appear more prominent during severe presentations of ME/CFS. Both patient groups shared a history of gastrointestinal abnormalities and evidence of bacterial dysbiosis, although only preliminary evidence supported the role of lactate-producing bacteria in ME/CFS. LIMITATIONS: Interpretation of results are constrained by both the breadth of symptoms included in ME/CFS diagnostic criteria and the conservative methodology used for D-la symptom classification. Several pathophysiological mechanisms in ME/CFS were not examined. CONCLUSIONS: Shared symptomatology and underlying microbiota-gut-brain interactions raise the possibility of a continuum of acute (D-la) versus chronic (ME/CFS) presentations related to D-lactate absorption. Measurement of D-lactate in ME/CFS is needed to effectively evaluate whether subclinical D-lactate levels affect neurological symptoms in this clinical population.