ORCID Profile
0000-0002-0631-2975
Current Organisations
Anzac Research Institute
,
Concord Repatriation General Hospital
,
The University of Sydney Institute for Infectious Diseases
,
Sydney Medical School
,
Sydney School of Public Health, University of Sydney
,
University of Sydney
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Publications
Preventing osteolytic lesions and osteomyelitis in multiple myeloma
Publisher: Elsevier BV
Date: 12-2022
What’s New in Cryptococcus gattii: From Bench to Bedside and Beyond
Publisher: MDPI AG
Date: 27-12-2022
DOI: 10.3390/JOF9010041
Abstract: Cryptococcus species are a major cause of life-threatening infections in immunocompromised and immunocompetent hosts. While most disease is caused by Cryptococcus neoformans, Cryptococcus gattii, a genotypically and phenotypically distinct species, is responsible for 11–33% of global cases of cryptococcosis. Despite best treatment, C. gattii infections are associated with early mortality rates of 10–25%. The World Health Organization’s recently released Fungal Priority Pathogen List classified C. gattii as a medium-priority pathogen due to the lack of effective therapies and robust clinical and epidemiological data. This narrative review summarizes the latest research on the taxonomy, epidemiology, pathogenesis, laboratory testing, and management of C. gattii infections.
Disease-modifying interactions between chronic kidney disease and osteoarthritis: a new comorbid mouse model
Publisher: BMJ
Date: 08-2023
DOI: 10.1136/RMDOPEN-2023-003109
Abstract: The prevalence of comorbid chronic kidney disease (CKD) and osteoarthritis (OA) is increasing globally. While sharing common risk factors, the mechanism and consequences of concurrent CKD-OA are unclear. The aims of the study were to develop a preclinical comorbid model, and to investigate the disease-modifying interactions. Seventy (70) male 8–10 week-old C57BL/6 mice were subjected to 5/6 nephrectomy (5/6Nx)±destabilisation of medial meniscus (DMM) or sham surgery. OA pathology and CKD were assessed 12 weeks postinduction by blinded histology scoring, micro-CT, immunohistochemistry for osteoclast and matrix metalloproteinase (MMP)-13 activity, and serum analysis of bone metabolic markers. The 5/6Nx model recapitulated characteristic features of CKD, with renal fibrosis and deranged serum alkaline phosphatase, calcium and phosphate. There was no histological evidence of cartilage pathology induced by 5/6Nx alone, however, synovial MMP-13 expression and subchondral bone osteoclastic activity were increased (p .05), with accompanying reductions (p .05) in subchondral trabecular bone, bone volume and mineral density. DMM significantly (p .05) increased tibiofemoral cartilage damage, subchondral bone sclerosis, marginal osteophytes and synovitis, in association with increased cartilage and synovial MMP-13. DMM alone induced (p .05) renal fibrosis, proteinuria and increased (p .05) 5/6Nx-induced serum urea. However, DMM in 5/6Nx-mice resulted in significantly reduced (p .05) cartilage pathology and marginal osteophyte development, in association with reduced subchondral bone volume and density, and inhibition of 5/6Nx-induced subchondral bone osteoclast activation. This study assessed a world-first preclinical comorbid CKD-OA model. Our findings demonstrate significant bidirectional disease-modifying interaction between CKD and OA.
Highly substituted calcium silicates 3D printed with complex architectures to produce stiff, strong and bioactive scaffolds for bone regeneration
Publisher: Elsevier BV
Date: 12-2021
Synthesis and Characterization of Bone Binding Antibiotic-1 (BBA-1), a Novel Antimicrobial for Orthopedic Applications
Publisher: MDPI AG
Date: 11-03-2021
DOI: 10.3390/MOLECULES26061541
Abstract: Osteomyelitis and orthopedic infections are major clinical problems, limited by a lack of antibiotics specialized for such applications. In this paper, we describe the design and synthesis of a novel bone-binding antibiotic (BBA-1) and its subsequent structural and functional characterization. The synthesis of BBA-1 was the result of a two-step chemical conjugation of cationic selective antimicrobial-90 (CSA-90) and the bisphosphonate alendronate (ALN) via a heterobifunctional linker. This was analytically confirmed by HPLC, FT-IR, MS and NMR spectroscopy. BBA-1 showed rapid binding and high affinity to bone mineral in an in vitro hydroxyapatite binding assay. Kirby—Baur assays confirmed that BBA-1 shows a potent antibacterial activity against Staphylococcus aureus and methicillin-resistant S. aureus comparable to CSA-90. Differentiation of cultured osteoblasts in media supplemented with BBA-1 led to increased alkaline phosphatase expression, which is consistent with the pro-osteogenic activity of CSA-90. Bisphosphonates, such as ALN, are inhibitors of protein prenylation, however, the amine conjugation of ALN to CSA-90 disrupted this activity in an in vitro protein prenylation assay. Overall, these findings support the antimicrobial, bone-binding, and pro-osteogenic activities of BBA-1. The compound and related agents have the potential to ensure lasting activity against osteomyelitis after systemic delivery.
Personalized Baghdadite scaffolds: stereolithography, mechanics and in vivo testing
Publisher: Elsevier BV
Date: 09-2021
MLST-Based Population Genetic Analysis in a Global Context Reveals Clonality amongst Cryptococcus neoformans var. grubii VNI Isolates from HIV Patients in Southeastern Brazil
Publisher: Public Library of Science (PLoS)
Date: 18-01-2017
Murine models of orthopedic infection featuring Staphylococcus aureus biofilm
Publisher: Copernicus GmbH
Date: 07-03-2023
Abstract: Abstract. Introduction: Osteomyelitis remains a major clinical challenge. Many published rodent fracture infection models are costly compared with murine models for rapid screening and proof-of-concept studies. We aimed to develop a dependable and cost-effective murine bone infection model that mimics bacterial bone infections associated with biofilm and metal implants. Methods: Tibial drilled hole (TDH) and needle insertion surgery (NIS) infection models were compared in C57BL/6 mice (female, N=150). Metal pins were inserted selectively into the medullary canal adjacent to the defect sites on the metaphysis. Free Staphylococcus aureus (ATCC 12600) or biofilm suspension (ATCC 25923) was locally inoculated. Animals were monitored for physiological or radiographic evidence of infection without prophylactic antibiotics for up to 14 d. At the end point, bone swabs, soft-tissue biopsies, and metal pins were taken for cultures. X-ray and micro-CT scans were performed along with histology analysis. Results: TDH and NIS both achieved a 100 % infection rate in tibiae when a metal implant was present with injection of free bacteria. In the absence of an implant, inoculation with a bacterial biofilm still induced a 40 %–50 % infection rate. In contrast, freely suspended bacteria and no implant consistently showed lower or negligible infection rates. Micro-CT analysis confirmed that biofilm infection caused local bone loss even without a metal implant as a nidus. Although a metal surface permissive for biofilm formation is impermeable to create progressive bone infections in animal models, the metal implant can be dismissed if a bacterial biofilm is used. Conclusion: These models have a high potential utility for modeling surgery-related osteomyelitis, with NIS being simpler to perform than TDH.
Modeling anabolic and antiresorptive therapies for fracture healing in a mouse model of osteogenesis imperfecta.
Publisher: Wiley
Date: 21-07-2022
DOI: 10.1002/JOR.25414
Abstract: Osteogenesis imperfecta (OI) is a genetic bone fragility disorder that features frequent fractures. Bone healing outcomes are contingent on a proper balance between bone formation and resorption, and drugs such as bone morphogenetic proteins (BMPs) and bisphosphonates (BPs) have shown to have utility in modulating fracture repair. While BPs are used for OI to increase BMD and reduce pain and fracture rates, there is little evidence for using BMPs as local agents for fracture healing (alone or with BPs). In this study, we examined wild-type and OI mice (Col1a2
Bacillus Calmette-Guérin vaccination for protection against recurrent herpes labialis
Publisher: Elsevier BV
Date: 10-2023
The application of ceragenins to orthopedic surgery and medicine
Publisher: Wiley
Date: 10-02-2020
DOI: 10.1002/JOR.24615
Abstract: Osteomyelitis and infections associated with orthopedic implants represent a significant burden of disease worldwide. Ceragenins (CSAs) are a relatively new class of small-molecule antimicrobials that target a broad range of Gram-positive and Gram-negative bacteria as well as fungi, viruses, and parasites. This review sets the context of the need for new antimicrobial strategies by cataloging the common pathogens associated with orthopedic infection and highlighting the increasing challenges of managing antibiotic-resistant bacterial strains. It then comparatively describes the antimicrobial properties of CSAs with a focus on the CSA-13 family. More recently developed members of this family such as CSA-90 and CSA-131 may have a particular advantage in an orthopedic setting as they possess secondary pro-osteogenic properties. In this context, we consider several new preclinical studies that demonstrate the utility of CSAs in orthopedic models. Emerging evidence suggests that CSAs are effective against antibiotic-resistant Staphylococcus aureus strains and can prevent the formation of biofilms. There remains considerable scope for developing CSA-based treatments, either as coatings for orthopedic implants or as local or systemic antibiotics to prevent bone infection.
Randomized Trial of BCG Vaccine to Protect against Covid-19 in Health Care Workers
Publisher: Massachusetts Medical Society
Date: 27-04-2023
BCG vaccination to reduce the impact of COVID-19 in healthcare workers: Protocol for a randomised controlled trial (BRACE trial)
Publisher: BMJ
Date: 10-2021
DOI: 10.1136/BMJOPEN-2021-052101
Abstract: BCG vaccination modulates immune responses to unrelated pathogens. This off-target effect could reduce the impact of emerging pathogens. As a readily available, inexpensive intervention that has a well-established safety profile, BCG is a good candidate for protecting healthcare workers (HCWs) and other vulnerable groups against COVID-19. This international multicentre phase III randomised controlled trial aims to determine if BCG vaccination reduces the incidence of symptomatic and severe COVID-19 at 6 months (co-primary outcomes) compared with no BCG vaccination. We plan to randomise 10 078 HCWs from Australia, The Netherlands, Spain, the UK and Brazil in a 1:1 ratio to BCG vaccination or no BCG (control group). The participants will be followed for 1 year with questionnaires and collection of blood s les. For any episode of illness, clinical details will be collected daily, and the participant will be tested for SARS-CoV-2 infection. The secondary objectives are to determine if BCG vaccination reduces the rate, incidence, and severity of any febrile or respiratory illness (including SARS-CoV-2), as well as work absenteeism. The safety of BCG vaccination in HCWs will also be evaluated. Immunological analyses will assess changes in the immune system following vaccination, and identify factors associated with susceptibility to or protection against SARS-CoV-2 and other infections. Ethical and governance approval will be obtained from participating sites. Results will be published in peer-reviewed open-access journals. The final cleaned and locked database will be deposited in a data sharing repository archiving system. ClinicalTrials.gov NCT04327206
Off-target effects of bacillus Calmette–Guérin vaccination on immune responses to SARS-CoV-2: implications for protection against severe COVID-19
Publisher: Wiley
Date: 2022
DOI: 10.1002/CTI2.1387
Abstract: Because of its beneficial off‐target effects against non‐mycobacterial infectious diseases, bacillus Calmette–Guérin (BCG) vaccination might be an accessible early intervention to boost protection against novel pathogens. Multiple epidemiological studies and randomised controlled trials (RCTs) are investigating the protective effect of BCG against coronavirus disease 2019 (COVID‐19). Using s les from participants in a placebo‐controlled RCT aiming to determine whether BCG vaccination reduces the incidence and severity of COVID‐19, we investigated the immunomodulatory effects of BCG on in vitro immune responses to SARS‐CoV‐2. This study used peripheral blood taken from participants in the multicentre RCT and BCG vaccination to reduce the impact of COVID‐19 on healthcare workers (BRACE trial). The whole blood taken from BRACE trial participants was stimulated with γ‐irradiated SARS‐CoV‐2‐infected or mock‐infected Vero cell supernatant. Cytokine responses were measured by multiplex cytokine analysis, and single‐cell immunophenotyping was made by flow cytometry. BCG vaccination, but not placebo vaccination, reduced SARS‐CoV‐2‐induced secretion of cytokines known to be associated with severe COVID‐19, including IL‐6, TNF‐α and IL‐10. In addition, BCG vaccination promoted an effector memory phenotype in both CD4 + and CD8 + T cells, and an activation of eosinophils in response to SARS‐CoV‐2. The immunomodulatory signature of BCG’s off‐target effects on SARS‐CoV‐2 is consistent with a protective immune response against severe COVID‐19.
Related Organisations
Sydney School Of Public Health, University Of Sydney
Location: No location found
National Centre For Immunisation Research And Surveillance Of Vaccine Preventable Diseases
Location: Australia
The University Of Sydney Institute For Infectious Diseases
Location: Australia
Sydney School Of Public Health, University Of Sydney
Location: Australia
Related Funding Activities
No related grants have been discovered for Aiken Dao.