Research Showcase 2023

Sajal K. Saha^1,2, David Kong³, Karin Thursky² and Danielle Mazza⁴ and Eugene Athan¹

Affiliations

1. Centre for Innovation in Infectious Disease and Immunology Research, School of Medicine, IMPACT, Deakin University, Geelong VIC 3220
2. National Centre for Antimicrobial Stewardship (NCAS), The Peter Doherty Institute for Infection and Immunity, Melbourne, Victoria, VIC 3000, Australia
3. Centre for Medicine Use and Safety, Monash University, 381 Royal Parade Parkville Victoria 3052, Australia
4. Department of General Practice, Monash University, VIC 3168, Australia

Background

The estimate suggests that 30-50% of antibiotic prescriptions are inappropriate either in choice, dose or duration in primary care. We aim to design a general practitioner-pharmacist antimicrobial stewardship (GPPAS) health service model to optimise antibiotic use in Australian primary care by addressing diagnostic uncertainty, patient demand for antibiotics and gaps in GP-pharmacist collaboration.

Methods

Since 2017-2023, a systematic review, a scoping review, a rapid review, nationwide surveys and qualitative studies of GPs and pharmacists in Australia and a pilot study were conducted to inform the GPPAS model.  Systems Engineering Initiative for Patient Safety framework guided the theoretical structure of the GPPAS model.

Results

A novel GPPAS health service model has been successfully designed to guide implementation of i) antimicrobial stewardship education program, ii) antimicrobial audits, iii) point-of-care diagnostic testing, iv) delayed antibiotic prescribing and v) routine review of antibiotic prescription by fostering GP-pharmacist collaboration. A GPPAS pilot program involving stewardship education demonstrated improvements of appropriateness of antimicrobial prescribing by GPs in Australia; choice of antimicrobial from 73.9% to 92.8% (p < 0.001), duration from 53.1% to 87.7% (p < 0.001) and guideline compliance from 42.2% to 58.5% (p < 0.001) post-intervention. A national clinical governance structure has been built to foster the implementation of the GPPAS model.

Conclusions

The GPPAS model will impact evidence-based antibiotic use practices and policies in primary care, and guide how future care should be delivered in the community for safe use of antibiotics. Future randomised controlled trial is needed to better understand the model’s effectiveness and cost-effectiveness.

Dr Christine Roder^1,2*, Dr Jacqui Richmond^1,3, Inga Tribe¹, Professor Eugene Athan, Dr Jack Wallace³, Dr Amanda Wade^1-3

Affiliations

1. Barwon Public Health Unit, Barwon Health, Australia;
2. Centre for Innovation in Infectious Disease and Immunology Research (CIIDIR), Institute for Mental and Physical Health and Clinical Translation (IMPACT) and School of Medicine, Deakin University, Australia
3. Disease Elimination Program, Burnet Institute, Australia

Background

Australia is not on track to meet the World Health Organization (WHO) targets for hepatitis B elimination. Access to care is a major barrier for people living in regional Victoria. This study aims to gain insight into the needs of people living with hepatitis B in the Barwon South West region of Victoria. This will involve mapping the distribution and prevalence of the population requiring care and interviewing healthcare workers to understand their experience and gain insight into their perspectives on hepatitis B models of care. Outcomes will inform an improved care model that will support community-based hepatitis B care.

Methods

Data mapping: at-risk population data was collected from the Australian Bureau of Statistics 2021 census, hepatitis B notifications data collected from the Victorian Department of Health and hepatitis B testing data collected from Australian Clinical Labs. Data mapped using ArcGIS.

Interviews and thematic analysis: Up to 30 interviews with healthcare workers will be conducted. These include general practitioners (GPs), S100 Hepatitis B prescriber GPs, community and refugee health nurses, specialists and nurses from the Liver Clinic and interpreters.

Results

The Local Government Area (LGA) with the highest notification rate was Greater Geelong 11.2 notifications/100,000 people/year). The at-risk population for postal areas (POA) within this LGA ranged from 1.1% to 15.5%.

Recruitment for the qualitative interviews is currently underway.

Conclusion

Improving access to care in the Barwon South West Region will require culturally competent and multidisciplinary approaches that overcome the challenges routinely faced by patients living in regional Victoria.

McNamara BJ^1,2,3 Blasdell KR⁴, O’Brien D^1,2,5, Yeramilli A², Smith IL⁶, Clayton SL⁴, Dunn M⁴,  Tay EE⁷, Gibney KB⁵, Waidyatillake NT^3,8 Hussain MA^1,2, Muleme M¹, Athan E^1,2,8

Affiliations

1. Centre for Innovation in Infectious Disease and Immunology Research, Geelong, Australia.

2. Barwon South West Public Health Unit, Barwon Health, Geelong, Australia

3. Centre for Epidemiology and Biostatistics, University of Melbourne, Melbourne, Australia

4. Australian Centre for Disease Preparedness, Commonwealth Scientific and Industrial Research Organisation, Geelong, Victoria, Australia

5. Department of Infectious Diseases, University of Melbourne, Melbourne, Australia

6. Commonwealth Scientific and Industrial Research Organisation, Canberra, Australia

7. Victoria Department of Health, Melbourne Victoria, Australia

8. School of Medicine, Deakin University, Waurn Ponds, Victoria, Australia

Background

Mycobacterium ulcerans infection (Buruli Ulcer, BU) incidence in Victoria has been increasing and in new geographic locations. Reasons for this remain unclear. This detailed case-control study explored host, environmental and behavioural risk and protective factors associated with BU.

Methods

Postal questionnaire data for 245 BU cases notified to the Victorian Department of Health between June 2018 and June 2020, and 481 postcode-matched controls were analysed. Age- and sex-adjusted odds ratio (aOR) for factors associated with BU were obtained using conditional logistic regression.

Results

The likelihood of BU was higher for individuals with diabetes mellitus, aOR 2.26 (95%CI 1.13, 4.49), but lower among those with a history of BCG vaccination (aOR 0.59 (0.39, 0.90)). Working outside with soil contact had a higher odds of BU than working indoors in endemic areas.  A strong dose-response relationship was observed between the number of possums at residential properties and likelihood of BU; aOR 4.52 (1.48, 13.81) in residents with 1-2 possums, 6.06 (1.85, 19.83) with ≥ 5 possums, compared to residents on properties with no possums. BU was associated with ponds and bore water use at the residence. Insect repellent, covering arms and legs during outdoor activity and immediately washing wounds were observed to be protective; undertaking multiple protective behaviours was associated with the lowest odds of BU.

Conclusion

Our findings suggest that skin hygiene and protection behaviours and previous BCG vaccination may provide protection against BU in endemic areas, especially for those at increased risk due to health, occupational, or environmental risks.

Aseel Al-Araji^1,2, Peter Vuillermin^1,2,3,4, and Eugene Athan^1,2,3

Affiliations

1. Centre for Innovation in Infectious Diseases and Immunology Research, Geelong, VIC 3220, Australia;
2. Deakin University, School of Medicine, Geelong, VIC 3220, Australia;
3. Barwon Health, University Hospital Geelong, Geelong, VIC 3220 Australia;
4. The Murdoch Children’s Research Institute, Parkville, Victoria, 3052, Australia.

Background

In recent years, carriage of antimicrobial resistance (AMR) genes has increased dramatically among infants. The reasons for this, however, remain poorly understood. Here we aim to identify potential determinants of AMR, the sites in which AMR genes are carried, and the most prevalent resistant infections.

Methods

Following PRISMA guidelines, we performed a systematic review using PubMed and Web of Science databases covering the years 2000 to 2021. We included studies which investigated AMR genes in infants using next-generation sequencing. Our search yielded 1840 articles, of which 32 were included in the final sample.

Results

The most common identified determinants of AMR were delivery in neonatal intensive care units (n=4), antibiotic exposure in infants’ gut microbiome (n=7), caesarean section as mode of delivery (n=3), and mother-to-child bacterial transmission (n=3). 9 of the 32 studies identified two main biological reservoirs of AMR including gut and the nasopharyngeal microbiota. The most common antibiotic resistance classes identified were aminoglycoside, β-lactams, macrolide, and tetracycline. Last-resort antibiotic resistance genes were also detected in infants' guts. Finally, we found the bacteria from order Enterobacterales and Bacteroidetes are commonly identified as carrying AMR genes.

Conclusion

Neonatal intensive care unit, antibiotic use, caesarean section, and maturity of the infant’s gut are each independently associated with increased AMR carriage. More comprehensive studies regarding healthy infants and factors such as antibiotic use, mode of delivery and other factors are required. Furthermore, uniformity of AMR databases and bioinformatics pipelines should be addressed to promote inter-study comparisons.

Dr Christine Roder1-3* Dr Carl Cosgrave1, Kathryn Mackie1, Dr Bridgette McNamara1,2, Associate Professor Joseph Doyle3,4, Dr Amanda Wade1-3

Affiliations

1. Barwon Public Health Unit, Barwon Health, Australia;
2. Centre for Innovation in Infectious Disease and Immunology Research (CIIDIR), Institute for Mental and Physical Health and Clinical Translation (IMPACT) and School of Medicine, Deakin University, Australia
3. Disease Elimination Program, Burnet Institute, Australia
4. Department of Infectious Disease, Alfred Health and Monash University.

Background

Key to achieving micro-elimination of hepatitis C in Western Victoria is developing targeted, data-driven strategies to increase testing and linkage to care. This study aimed to assess the proportion of patients who are at risk of, or living with, hepatitis C infection, and the number who were tested and linked to care, whilst attending University Hospital Geelong.

Methods

A retrospective study of adults admitted as hospital inpatients or Emergency Department patients from November 2018 to November 2021. Data were collected from the hospital admissions, Australian Clinical Labs, hospital pharmacy, and hospital outpatient Liver Clinic databases. Separations were selected if they had an ICD-10 code indicating intravenous drug use (IDU) or hepatitis C infection.

Results

There were 1345 patients with IDU-coded separations and 628 patients with hepatitis C-coded separations (total n=1892. Overall, 323 (17.1%) of patients had hepatitis C virus (HCV) antibody testing (253/323 positive, 70/323 negative), 165 (8.7%) had HCV RNA testing (101/165 detected, 64/165 not detected) and 43 (3.1%) received treatment.

The Emergency Department had increased odds of not providing hepatitis C care (OR 3.29, 95% CI 2.42-4.48). The Mental Health Unit had the highest odds of HCV antibody testing (OR 2.12, 95% CI 1.24-3.63). Obstetrics and Gynaecology had the highest odds of HCV RNA testing (OR 4.38, 95% CI 1.55-12.37).

Conclusion

A targeted intervention that increases hepatitis C antibody testing of people with a history of IDU whilst hospital inpatients is likely to improve linkage to hepatitis C care at our health service, and contribute to micro-elimination.

O’Brien DP^1,2,3,Blasdell K⁴, Muhi S^3,5, McNamara BJ¹, Athan E^1,2,6.

Affiliations

1. Center for Innovation in Infectious Disease and Immunology Research, Geelong, Australia.

2. Department of Infectious Diseases, Barwon Health, Geelong, Australia

3. Department of Infectious Diseases, Royal Melbourne Hospital, University of Melbourne, Melbourne, Australia

4. Australian Centre for Disease Preparedness, Commonwealth Scientific and Industrial Research Organisation, Geelong, Victoria, Australia.

5. The Peter Doherty Institute for Infection and Immunity, University of Melbourne

6. Deakin University, Waurn Ponds, Australia

Background

Buruli ulcer (BU), caused by Mycobacterium ulcerans, is endemic in Victoria, Australia, with an increasing incidence, severity and spread of the disease. It is a potentially severe disease often leading to serious long-term consequences and resulting in significant community costs and concern. Evidence suggests that possums are a zoonotic reservoir for M. ulcerans. Currently there are no proven public health interventions to address this worsening disease.

Methods

We will provide the evidence, rationale and research plan for a novel proposal to vaccinate possums in the wild with oral-bait BCG.

Results

A M. ulcerans infection model of ringtail possums has recently been developed at the CSIRO research facility in Geelong. Next steps include possum vaccination with BCG before M. ulcerans challenge to assess the level and durability of protection by comparing vaccine with control groups. This could utilise tools developed previously by a BCG-based oral-bait vaccination scheme for brushtail possums against M. bovis in New Zealand. In the proposed study, blood samples would be collected to measure the immune responses to BCG vaccination, which would be correlated with immune protection. If effective, attempts would be made to optimize the palatability and feasibility of oral-bait BCG delivery. Finally, testing the effectiveness of oral-bait BCG vaccine against M. ulcerans in ringtail possums would be performed in laboratory and real-life field settings.

Conclusion

Vaccination of possums in the wild with oral-bait BCG provides hope for an acceptable, safe and feasible intervention benefiting human and possum populations by reducing the transmission of M. ulcerans.

Cooper D¹, Rofe A², Athan E^1,3,Aboltins C^4,5, Davis JS^6,7,8 andManning L^9,10 on behalf of the Australasian Society for Infectious Diseases Clinical Research Network

Affiliations

1. Deakin University, School of Medicine, IMPACT, Institute for innovation in Physical and Mental health and Clinical Translation, Geelong, Australia.​​​​​​​
2. Department of Infectious Diseases, Northern Health, Epping, Melbourne, Vic, Australia
3. Barwon Health, Deakin University, Geelong, Vic, Australia.
4. Northern Clinical School, University of Melbourne, Melbourne, Vic, Australia
5. Menzies School of Health Research and Charles Darwin University, Darwin, NT, Australia
6. Department of Infectious Diseases, Northern Health, Epping, Melbourne, Vic, Australia
7. Department of Infectious Diseases, John Hunter Hospital, Newcastle, NSW, Australia
8. School of Medicine and Public Health, University of Newcastle, Newcastle, NSW, Australia
9. Department of Infectious Diseases, Fiona Stanley Hospital, Murdoch, WA, Australia
10. Medical School, University of Western Australia, Perth, Australia

Category:

Bacterial diseases and infections

Introduction:

Joint replacement improves overall quality of life, but few prospective data describe patient-reported outcome measures (PROMs) in patients with peri-prosthetic joint infection (PJI). Using the Short Form Health Survey version 2 (SF-12v2), we aimed to describe the patient-reported physical (PCS) and mental health scores (MCS) at the time of PJI diagnosis and for 2-years.

Methods:

Data from the PIANO cohort study were analysed for PROMS. An SF-12v2 questionnaire was administered at baseline, 3, 12 and 24 months. MCS and PCS were scored against age-adjusted population norms.

Results:

Of the 783 participants in PIANO, 522 had complete SF-12v2 data across baseline, 3, 12 and 24 months. There were no significant differences between PCS and MCS for hip, knee and shoulder PJI. At baseline, the median (IQR) PCS was 36.9 (30.1 – 45.6) whilst the MCS was closer to the population norm (47.9 [37.5-57.4]). Chronic PJI had lower baseline median PCS and MCS than late acute PJI (LA-PJI; 34.0 vs. 39.5, P=0.007 and 41.2 vs. 51.2, respectively). By 12 months, both the PCS (median difference 3.1) and MCS (3.4) had improved, but the PCS remained well below population age-adjusted norms. There were no further improvements between 12 and 24 months. Clinical cure at 12 months was associated with higher PCS (43.8 vs. 37.9, P<0.0001) as well as higher MCS (55.4 vs. 50.0, P<0.0001).

Conclusion:

At baseline, patients with PJI have impaired QoL and despite limited improvement, this is sustained beyond 12 months. Achieving clinical cure is associated with significant improvements in QoL.

Disclosure of Interest Statement:

This work was supported by seed funding grants from Heraeus Medical GmbH and the John Hunter Charitable Trust Fund.

Authors: Murray HC^1,2, Muleme M^2,3#, Cooper D^1,3, McNamara BJ^2,3, Hussain MA² , Bartolo C^1,2,4, O’Brien DP ^1,2,5, Athan E^1,2,3,4

¹Department of Infectious Diseases, Barwon Health

²Barwon Southwest Public Health Unit, Barwon Health

³Centre for Innovation in Infectious Disease and Immunology Research

⁴School of Medicine, Deakin University

⁵Department of Medicine and Infectious Diseases, Royal Melbourne Hospital, University of Melbourne

Presenting author: Muleme Michael, Epidemiologist, Barwon South West Public Health Unit

Category:

CIIDIR

Introduction: Secondary infections complicate COVID-19 management resulting in longer hospital and ICU length of stay (LOS), and increased mortality. There is limited information on the prevalence of secondary infections among Victorian COVID-19 patients and variability in reported prevalence (6.9-24%) globally.

Methods: We performed a retrospective cohort study estimating the prevalence of secondary infections complicating COVID-19 and post-COVID admissions in Victoria from January 2020 to May 2023. Admissions were identified from the Victorian Admitted Episodes Dataset (VAED). All relevant secondary viral, bacterial, and fungal infections were identified using corresponding ICD-10 codes. The impact of secondary infections was determined using outcome measures including hospital/ICU LOS using negative binomial regression models, and mortality using Cox proportional-hazard models.

Results: 194660 COVID-19 and post-COVID admissions were identified with 13467 (6.9%) having a secondary infection; 11,651 (6.0%) bacterial, 1,691 (0.9%) viral, and 385 (0.2%) fungal. The odds of secondary infection increased with age (odds ratio (OR), 3.76 (95%CI 3.43, 4.14) amongst those ≥70 years and were higher amongst individuals with chronic conditions (OR: 3.15; 95%CI: 2.88). Patients with a secondary infection had 2.43 (95%CI 2.39, 2.48) times longer hospital LOS, and 9.60 times (95%CI 8.62, 10.73) longer ICU LOS compared to those without. The mortality risk was higher (hazard ratio 2.17; 95%CI: 2.06, 2.27) in those with secondary infections. Admissions of those aged ≥70 years, those with chronic disease, the unvaccinated, those from the most socio-economically disadvantaged areas were associated with increased risk of secondary infections and poor outcomes.

Conclusion:

Secondary infection occurred in 6.9% of COVID-19 associated hospital admissions in Victoria from 2020 to 2023 and were associated with increasing hospital length of stay, ICU admission and length of stay, and mortality, with bacterial secondary infections being the most prevalent (6.0%).

Charles A. Narh^1,2,3*, Gloria Amegatcher³, Maame E. Acquah³, Rachael Obeng³, Deborah Tetteh³, Kyerewaa A. Boateng³, Lydia Mosi³

Affiliations

1. School of Medicine, Deakin University, Australia
2. Centre for Innovation in Infectious Disease and Immunology Research (CIIDIR), Australia.
3. West African Centre for Cell Biology of Infectious Pathogens (WACBIP), University of Ghana.

*Corresponding author: charles.narh@deakin.edu.au

Abstract

Malaria control and surveillance in sub-Sahara Africa has stalled in the past three years, partly due to reallocation of resources for COVID-19 interventions. In Ghana where malaria transmission is high and COVID-19 is widespread, Plasmodium falciparum and SARS-CoV-2 co-infection rates remain unknown; Subsequently, clinical misdiagnosis poses a threat to control efforts. Therefore, this study aimed to evaluate the epidemiological, clinical, and diagnostic factors to inform malaria and COVID-19 co-surveillance.

Between October-December 2022, 1,065 participants were recruited through multi-site prospective cross-sectional surveys in 12 communities within Greater Accra (metropolitan) and Central (semi-urban) regions of Ghana. Others were recruited through community health programs in the study communities. Each participant provided nasal/throat swabs for COVID-19 PCR-testing, with optional finger-prick blood for malaria RDT-testing; Their data including malaria infection and antimalarial treatment in the past two weeks were recorded in REDCap.

The majority of the study population comprised of adults (18-59 years) and females, 73.6 and 61.1%, respectively, with COVID-19 positivity and vaccination rate being 22.8% and 54.6%, respectively. Overall, 18.1% of participants self-reported having malaria, and this was associated (adjusted odds ratio ≥ 1.55, P-value ≤ 0.022) with study community, COVID-19 clinical disease and positivity. All malaria cases were reportedly self-medicated or clinically treated with antimalarials. Malaria testing (N=136) resulted in P. falciparum prevalence of 6.0%, with 2.0% being co-infected with SARS-CoV-2, without overt symptoms.

In communities with active malaria and COVID-19 transmissions, co-surveillance for both infections will provide programmatic synergies, which will be crucial to inform national control and elimination efforts.

Zahra Razook ^1,2, Kirsty McCann ^1,2, Somya Mehra ^1,2 Bourama Traore ³, ³, Mahamoudou Touré ³, Daouda Sanogo ³, Fousseyni Kané ³, Drissa Konaté ³, Soumba Keita ³, Seydou Doumbia³, Mahamadou Diakité ³and Alyssa E. Barry^1,2

Affiliations

1. Centre for Innovation in Infectious Disease and Immunology Research (CIIDIR), Institute of Mental and Physical Health and Clinical Translation (IMPACT) and School of Medicine, Faculty of Health, Deakin University, Geelong, Victoria, Australia
2. Life Sciences Discipline, Burnet Institute, Melbourne, Victoria, Australia
3. West African International Center for Excellence in Malaria Research,University Clinical Research Center, University of Sciences, Techniques and Technologies of Bamako, Mali

Abstract

Seasonal Malaria Chemoprevention (SMC)has been proven to be effective in high-transmission areas of seasonal malaria in sub- Saharan regions. Although studies have shown the potential effectiveness of this intervention, no studies have been done to elucidate the impact of this intervention in the changes of parasite population. We conducted a pilot study as part of the International Centre of Excellence in Malaria Research (ICEMR) programme to evaluate the impact of SMC intervention on parasite genetics by hypothesizing that SMC would lead to a reduction in parasite genetic diversity. We examined samples from cross-sectional surveys collected before and during the implementation of SMC from the Dangassa, Mali in 2015. Genotyping was done using SNP barcoding of 81 samples collected between 2013 – 2019. The barcodes included 175 biallelic SNP markers and further used for downstream population genetic analyses. We obtained 69 high quality genotypes and identified 80 polymorphic SNPs to measure patterns of population diversity and structure (minor allele frequency > 0.10). We then compared parasite populations before and during SMC using nucleotide diversity statistics, Principal Co-ordinate Analysis and pairwise Identity-by-decent to observe population diversity and structure and parasite relatedness. Preliminary analyses revealed no clear genetic differentiation, reduced diversity or increased clustering patterns comparing the parasite populations collected before and during treatment. The study demonstrated a limited impact of the SMC intervention on the parasite population suggesting that further sustained control efforts will be needed to interrupt transmission.  The study also demonstrates the utility of this SNP barcode for parasite genomic surveillance in West Africa.

Carly Botheras¹, Eugene Athan^1,3,4

Affiliations

1. Centre for Innovation in Infectious Disease and Immunology Research (CIIDIR), Institute of mental and physical health and clinical translation (IMPACT), School of Medicine, Deakin University, Geelong, Victoria, Australia
2. Department of Infectious Disease, Barwon Health, Geelong, Victoria, Australia
3. Barwon South West Public Health Unit, Geelong, Victoria, Australia

Background

Approximately 30% of the population are permanently colonised with Staphylococcus aureus. S. aureus killed over 1 million people globally in 2019 alone. Being colonised gives you a 3x increased odds of having an infection. It has also been seen that colonisation of S. aureus can change the immune makeup against S. aureus. What is currently unknown is the role it has when combined with other co-morbidities. Does being colonised plus a specific comorbidity make even more at risk of infection. Does being colonised exacerbate a condition not directly linked to S. aureus. This preliminary scope of the literature investigated what is currently known in this field

Methods

Literature from 2000-2022 was sought with the key words of S. aureus colonisation and co-morbidity. Articles were included if they were human focused research, interventional, observational, or systematic studies. Articles not in English, reviews, case studies, animal studies were not included.

Results

Colonisation of S. aureus was observed within the literature to increase the risk of infection in specific co-morbidities such as haemodialysis patients. It was also observed to be associated with increased severity of symptoms in other diseases such as asthma. Not many of these studies were performed in the Australian context.

Conclusion

It is proposed by the authors that S. aureus colonisation prevalence needs to be surveyed in the Australian population and further investigation of the impact of these bacteria in disease is warranted. This would be a good collaborative opportunity for multiple disciplinary research across multiple diseases.

Katelyn Stanhope^1*, Jessy Vibin², Kirsty McCann³, Zahra Razook³, Montana Spiteri⁴, Zuleima Pava¹, Nimol Khim⁵, Anais Pepey⁵, Thomas Obadia⁶, Mirco Sandfort⁷, Michael White⁶, Amelie Vantaux⁸, Benoit Witkowski⁵, Leanne J. Robinson^1,9, Ivo Mueller⁹ and Alyssa E. Barry^1,3

Affiliation

1. Disease Elimination, Burnet Institute, Melbourne, Australia, 
2. School of Medicine, Deakin University, Waurn Ponds, Australia,
3. Centre for Innovation in Infectious Disease and Immunology Research (CIIDIR), Institute for Mental and Physical Health and Clinical Treatment (IMPACT), School of Medicine, Deakin University, Waurn Ponds, Australia, 
4. Walter and Eliza Hall Institute, Melbourne, Australia,
5. Institut Pasteur du Cambodge, Phnom Penh, Cambodia,
6. Institut Pasteur, Paris, France,
7. Department for Infectious Disease Epidemiology, Robert Koch Institut, Berlin, Germany
8. Institut Pasteur de Madagascar, Antananarivo, Madagascar,
9. Population Health and Immunity Division, Walter and Eliza Hall Institute, Melbourne, Australia,

Background

A cross-sectional survey conducted in Kaev Seima District, Mondulkiri Province in Cambodia by the Asia Pacific International Centre for Malaria Research (ICEMR) demonstrated that living and working in forested areas is a risk factor for both P. falciparum and P. vivax malaria. It is not known whether infections outside the forest are driven by infections acquired inside the forest. Population genetic analyses can reveal transmission dynamics and population structure, as well as the origins and flow of infections between villages.

Methods

This project aimed to apply SNP barcoding to P. falciparum and P. vivax isolates from the cross-sectional study to allow population genetic analysis.

Results

This SNP barcoding of 176 informative, validated SNPs in 34 P. falciparum isolates resulted in 127 successfully genotyped SNPs, 9 of which were polymorphic in this Cambodia population. For P. vivax, SNP barcoding of 178 informative, validated SNPs in 65 isolates resulted in 53 successfully genotyped SNPs, 19 of which were polymorphic. The analysis revealed low population diversity for both species with no evidence of clustering or population structure between village and forest. Further, genotypes originating from different geographical locations were seen to be highly related.

Conclusion  

These results support the hypothesis that parasites originate in forest areas and are the likely source of infections in villages outside the forest as demonstrated by the high gene flow to and between areas. This information may be used by malaria programs to successfully interrupt and monitor impacts of control efforts on malaria transmission.

McNamara BJ^1,2,3, Cornish J², Blasdell B⁴, Athan E^1,2,5, Clarke N², Pe T², Hussain MA^1,2, Muleme M^1,2, Tay E⁶, Dunn M⁴, Boyd V⁴, O’Brien DP^1,2,7,8.

Affiliations

1. Centre for Innovation in Infectious Disease and Immunology Research, Geelong, Australia.
2. Barwon South West Public Health Unit, Barwon Health, Geelong, Australia
3. Centre for Epidemiology and Biostatistics, University of Melbourne, Melbourne, Australia
4. Australian Centre for Disease Preparedness, Commonwealth Scientific and Industrial Research Organisation, Geelong, Australia
5. School of Medicine, Deakin University, Waurn Ponds, Australia
6. Victoria Department of Health, Melbourne, Australia
7. Department of Infectious Diseases, Barwon Health, Geelong, Australia
8. Department of Infectious Diseases, Royal Melbourne Hospital, University of Melbourne, Melbourne, Australia

Background

Buruli ulcer (BU), is a necrotising skin condition, caused by the environmental pathogen Mycobacterium ulcerans. Case numbers in Victoria, of this potentially severe disease, have increased from 77 BU cases in 2012 to 339 cases in 2022, and BU endemic areas have been expanding. Previously, BU incidence centred in coastal areas of the Mornington and Bellarine Peninsulas. Importantly, new urban, non-coastal areas of inner Geelong and Melbourne are now contributing significantly to the rise in case numbers.

Methods

In this study, we describe the changing epidemiology, incidence and spatial distribution of BU cases in Geelong. We compare the distribution and timeline of human BU cases to the distribution of M. ulcerans DNA-positive possum faeces from surveys in 2020 and 2022.

Results

A total of 80 BU cases have been notified for people living in central Geelong areas from 2011-2022.  Spatiotemporal analysis showed a clear clustering of cases in areas of Belmont (2019-2022) and Highton (2022), with clustering also noted in Newtown (2020-2021). Clusters occurred in highly focal geographic areas and were close to M.ulcerans-positive possum faecal samples (median 199m (IQR 88, 393) from case residence) detected within 8-31 months prior to the human case diagnosis.

Conclusion

Epidemiological analyses and faecal possum surveys has allowed the rapid detection of new BU endemic areas in Geelong. This enabled important public health opportunities for targeted prevention messaging and for community and clinician education towards reducing exposures and improving early detection and treatment of BU disease to improve clinical outcomes.

Alyna Turner ¹ , Heather Smith ¹ , Jade Doonan ¹ , Anna L Wrobel ¹ , Alison Kennedy ^{1 2} , Olivia M Dean ¹ , Sarah Baker ² , Isabelle Manson ¹ , Tara Johnson ¹ , Mohammadrezza Mohebbi ¹ , Rochelle Shackleton ³ , Ian I Kneebone ⁴

Affiliations

1. Deakin University, Geelong, Victoria, Australia
2. Western District Health Service, Hamilton, Victoria, Australia
3. Albury Wodonga Health, Wodonga, Victoria, Australia
4. University of Technology, Sydney, Ultimo, NSW, Australia

Background

Return to work (RTW) after stroke is an important rehabilitation outcome. In rural areas specialised RTW support might not be available. We evaluated feasibility of a telecommunication delivered RTW support service, designed to increase access to people who have had a stroke. The overall aims of the study were to evaluate intervention satisfaction and acceptability of procedures.

Methods

We recruited people aged 18-74, who experienced a stroke up to 2.5 months previously, at four Victorian sites (Barwon Health, Western District Health, Albury Wodonga Health and South West Health Care). Participants were assessed at baseline, 3- and 6-months post-stroke. Intervention satisfaction evaluated through qualitative interviews at each timepoint and the Client Satisfaction Questionnaire-8 (CSQ-8; score range 8-32). RTW rates and other employment variables, as well as measures of mood, anxiety, fatigue and cognition, were collected.

Results

Twenty-one participants were recruited. Telehealth delivery was feasible and associated with high satisfaction (CSQ-8 median score=32). Eighteen of 21 (86%) participants RTW within 6 months, with 16 of 20 (80%) participants employed and working at 6-months post-stroke. For those working at 6-months post-stroke, no change in hours of work was seen from pre-stroke (m=30.5, SD=24.1 hours/week) to 6-months post-stroke (m=29.6, SD=11.9 hours/week, t=.12, p=.91). Measures of depression, anxiety, fatigue and cognition improved from baseline to 6-months post-stroke (Cohen’s d =.30 to .50).

Conclusion

Remote delivery of a RTW support service was feasible and acceptable to people who had recently experienced a stroke. High RTW rates were reported however a randomised controlled trial is required to confirm intervention effectiveness.

Olivia Dean^1,2,, Adam Walker¹, Melanie Ashton¹, Lesley Berk¹, Alyna Turner¹

Affiliations

1. Deakin University and Barwon Health, Geelong, Australia
2. Florey Institute of Neuroscience and Mental Health

Background

Conventional antidepressants are generally useful for treating major depressive disorder (MDD), but shortfalls remain in recovery for many individuals. At present there is little to guide who is best suited to a given treatment. Immune pathways are implicated in MDD, making them an adjunctive target. Minocycline has shown efficacy as an adjunctive antidepressant. This presentation will provide an overview of the clinical findings and supporting basic science regarding adjunctive minocycline for MDD.

Methods

Over the past several years, our team have investigated the clinical potential and underlying biological treatment response of adjunctive minocycline. This presentation will review the current clinical trial data and supporting biological investigations to enhance the translation of adjunctive minocycline.

Results

Our clinical trial and our pooled data in an international collaboration have demonstrated the efficacy of adjunctive minocycline for MDD. This is supplemented by recent systematic reviews, creating sufficient evidence for adjunctive minocycline to be included in the recent Royal Australian and New Zealand College of Psychiatrist Guidelines for the Treatment of Mood Disorders. Our team is now focusing on exploring the underlying biological mechanisms associated with the treatment response to adjunctive minocycline. This presentation will explore some of that data.

Conclusion

With a paucity of novel treatment for depression and a shortfall in recovery for many individuals experiencing symptoms and diminished quality of life, adjunctive minocycline represents a safe, off-patent treatment option. Our work in understanding the treatment response will further assist in enhancing agent selection and reducing individual symptoms response variation.

Samantha E Russell¹, Anna L Wrobel^1,2, Dave Skvarc³, Mojtaba Lotfaliany¹, Pedro C Magalhães⁴, Melanie M Ashton¹, Michael Berk^1,2,5,6,7, Olivia Dean^1,5 and Alyna Turner^1,8

Affiliations

1. Deakin University, IMPACT, the Institute for Mental and Physical Health and Clinical Translation, School of Medicine, Barwon Health, Geelong, Australia
2. Orygen, Parkville, Victoria, Australia
3. School of Psychology, Faculty of Health, Deakin University, Geelong, Australia
4. Institute of Social Sciences, University of Lisbon, Lisboa, Portugal
5. Florey Institute for Neuroscience and Mental Health, University of Melbourne, Kenneth Myer Building, Parkville, Victoria, Australia
6. University of Melbourne, Department of Psychiatry, Royal Melbourne Hospital, Parkville, Victoria, Australia
7. Centre for Youth Mental Health, The University of Melbourne, Parkville, Victoria, Australia
8. School of Medicine and Public Health, Faculty of Health, The University of Newcastle, Callaghan, Australia

Background

Post Traumatic Stress Disorder (PTSD) is more prevalent in the those with Bipolar Disorder (BD) compared to the general population, with rates at high as 55% in some BD cohorts. Despite this, effective pharmacotherapy treatments have not been explored in those with comorbid BD and PTSD.

Methods

The Systematic Treatment Enhancement Program for BD (STEP-BD) cohort was utilized to examine and compare symptoms and pharmacotherapy treatments between those with BD alone (n=3393), and those with comorbid BD and PTSD (n=304). Regression models were conducted comparing those with and without comorbid PTSD. Models included measures of depression, mania, functioning and quality of life over 24 months of the STEP-BD study. Baseline pharmacotherapies (lithium, valproate, antidepressants, antipsychotics, and benzodiazepines) were utilized as a predictor variable in models.

Results

At baseline, reported use of lithium was lower in the comorbid PTSD group, while the use of antidepressants, antipsychotics, and benzodiazepines was significantly higher in the comorbid PTSD compared to the BD alone group. Those with comorbid PTSD experienced higher levels of mania and depression symptoms and lower functioning and quality of life compared to BD alone. Benzodiazepine use was associated with a small improvement in depression symptom scores and poorer quality of life in those with comorbid PTSD.

Conclusion

These results highlight the importance of considering comorbidity in the treatment of mental health conditions, specifically BD. This study also emphasizes the need for a better understanding of this comorbidity to ensure individuals achieve recovery and improve symptoms and quality of life.

Olivia Dean^1,2, Sarah Healy¹, Eslam Ahmed¹, Bonnie Beasant¹, Adam Walker¹, Carly Botheras¹

Affiliations

1. Deakin University and Barwon Health, Geelong, Australia
2. Florey Institute of Neuroscience and Mental Health

Introduction

Community engagement and translation preside at the forefront of novel research. This is in parallel with an increasing contribution of lived experience both in co-design and translation of research.

Method

In 2013, A/Prof Dean established the Community and Research Network (CARN), a forum for any health-related stakeholders to meet and provide reciprocal opportunities for research and community translation. Since then, CARN has grown to include a series of community-focused activities, seminars, and garnered philanthropic support.

Results

Examples of CARN’s success include the employment of the McIntosh CARN Engagement Officer, Sarah Healy. This role was made possible by collaborative grants from the McIntosh Family and Western Alliance.  Sarah is growing the CARN membership, improving the reciprocity between researchers and the community and, with the support of Western Alliance, engaging with rural and regional partners. The CARN Student Seminar Series is a further example of community engagement, led by IMPACT postgraduate students; Bonnie Beasant and Eslam Ahmed. Dr Carly Botheras’ role, taking over from Dr Adam Walker, as the CARN Co-Chair has breadthened the scope of CARN; Carly also writes a community-focused blog about general science topics. Partnerships with CARN include the Geelong Music Community Collective (GMCC) - a Geelong collective aiming to promote mental health and generously providing the GMCC Dean McInnes Travel Award to IMPACT.

Conclusion

To have maximum impact, research needs to address the needs of the people it is targeting. Lived experience provides expertise that is unavailable through traditional research methods and is integral to translating high quality research. This presentation will provide an overview of ways to engage that voice within research.

Samantha E Russell¹, Anna L Wrobel^1,2, Mojtaba Lotfaliany¹, Melanie M Ashton¹, Ravleen Kaur³, Anastasia K Yocum³, Elizabeth R Duval³, Claudia Diaz-Byrd³, Tobin J Ehrlich⁴, David F Marshall³, Michael Berk^1,2,5,6,7, Melvin G McInnis³, Olivia Dean^1,5 and Alyna Turner^1,8

Affiliations

1. Deakin University, IMPACT, the Institute for Mental and Physical Health and Clinical Translation, School of Medicine, Barwon Health, PO Box 281, Geelong, 3220, Australia
2. Orygen, Parkville, Victoria, Australia
3. Department of Psychiatry, University of Michigan Medical School, Ann Arbor, Michigan USA
4. Department of Neurology, University of Utah School of Medicine, Salt Lake City, Utah, USA
5. Florey Institute for Neuroscience and Mental Health, University of Melbourne, Kenneth Myer Building, Parkville, 3052, Australia
6. University of Melbourne, Department of Psychiatry, Royal Melbourne Hospital, Parkville, Victoria, Australia
7. Centre for Youth Mental Health, The University of Melbourne, Parkville, Victoria, Australia
8. School of Medicine and Public Health, Faculty of Health, The University of Newcastle, Callaghan, 2308, Australia

Background

It is estimated that up to 50% of people with bipolar disorder also have comorbid post-traumatic stress disorder (PTSD). However, little is known about the presentation and treatment of people with this comorbidity.

Methods

Data from 577 individuals diagnosed with bipolar disorder participating in the Heinz C. Prechter Longitudinal Study of Bipolar Disorder (PLS-BD) were explored at baseline, year two and year four. Three trauma groups were created according to participants’ responses to the Life Events Checklist and the Diagnostic Interview for Genetic Studies: (i) one trauma (n = 75), (ii) multiple traumas (n = 417), and comorbid PTSD (n = 85). Measures of depression, mania, sleep, number of hospitalisations and suicide attempts, and medication use were analysed using regression modelling to determine differences between the three trauma groups.

Results

There was a significant increase in depression, mania, and sleep scores and a higher number of hospitalisations in participants with comorbid PTSD compared to those experiencing one trauma. A significant increase was also seen in mania and depression scores in participants experiencing multiple traumas compared to those who reported one trauma. There was no difference in medication use between those who experienced one trauma when compared to those diagnosed with PTSD. However, participants who experienced multiple traumas were significantly less likely to use lithium compared to those who experienced one trauma.

Conclusion

The comorbidity of bipolar disorder and PTSD is associated with worse mania and depression symptoms scores and worse sleep scores compared to participants reporting one trauma.

Background

Cardiac rehabilitation (CR) significantly reduces the risk of recurrent cardiovascular events and improves quality of life. Psychosocial well-being and healthy eating are essential components of CR and are included in the current National Heart Foundation of Australia’s standardised program content. However, little is known regarding practitioners’ attitudes and practices towards these components.

Methods

We conducted a national survey to establish attitudes and practices regarding psychosocial well-being and healthy eating. Practitioners were recruited through professional networks. The survey was completed via redcap and asked multiple-choice and rating scale questions about the practitioner and their program (n=6), psychosocial well-being (n=11) and healthy eating (n=6). Descriptive statistics were performed.

Results

The survey was completed by 98 CR practitioners, representing approximately 25% of Australian CR programs.

All participants were familiar with the standardised program content for CR (8% slightly, 36.8% moderately, 36.8% very, and 18.4% extremely familiar). Figure 1 describes practitioners’ attitudes and competencies. All but one practitioner screened for psychosocial well-being during CR, 72.5% screen at program commencement, 25.5% screen throughout the program, and 49.0% screen or rescreen at program completion. Healthy eating education was reported by 98.8% of participants. However, only 54.9% offered an individualised consultation with health professionals such as a dietitian.

Conclusion/implications

CR practitioners commonly report that psychosocial well-being and healthy eating play an important role in recovery and preventing subsequent events. However, psychosocial well-being assessment across the course of CR is less common, as is offering individualised dietary counselling with trained health professionals such as a dietitian.

Figure 1. The mean response from rating scales on practitioners’ attitudes towards psychosocial well-being and healthy eating in CR

Emma Todd(1)^, Bec Orr(1), Elizabeth Gamage(1), Emma West(1), Victoria George(1), Lara Voglsanger(1), Kate Phuong-Nguyen(1), Lisa Angwenyi(1), Abbas Khosravi(2), Felice Jacka(1)*, and Samantha Dawson(1)*

Affiliations

(1) Institute for Mental and Physical Health and Clinical Translation (IMPACT), School of Medicine, Faculty of Health, Deakin University

(2) Institute for Intelligent Systems Research and Innovation (IISRI), Deakin University

*joint senior authors
^presenting author

Background

Depression and anxiety, known as common mental disorders (CMDs), affect millions worldwide and impose great burden on individuals and communities (1). Recently, machine learning (ML) has been used to interrogate large datasets and develop models that predict CMDs based on lifestyle, demographic, and/or biological risk factors. This review aims to synthesise the existing literature from such studies and assess whether lifestyle factors are consistently reported to be more predictive of CMDs than less-modifiable factors, such as demographics. This knowledge could provide new avenues for prevention through targeted lifestyle interventions and/or future risk prediction tools.

Methods

The systematic review was performed in accordance with the PRISMA statement and registered with PROSPERO. Databases searched included MEDLINE, EMBASE, PsycInfo, IEEE Xplore, and Engineering Village. The search strategy aimed to identify studies that used ML to predict CMDs in adults. Studies were included if they used a method that produces a measure of variable ‘importance’ (e.g. Shapley Values, Gini importance) and differentiated people with CMDs from controls. Search terms included CMD terms in the title, ‘diagnosis or differentiation’ terms and ML methods that perform ‘variable importance analyses’ in the abstract. The search was limited to English language articles. All screening and extraction steps were performed in duplicate using Covidence and Microsoft Excel.

Results

The initial search yielded 2318 results (858 duplicates). 1452 papers that were screened using title and abstract, 1099 studies were found to be irrelevant. Thus, 361 studies were screened for full-text eligibility, with 245 excluded to date (26 TBC). 90 studies are currently eligible for extraction. Preliminary results for extracted papers and risk of bias analyses will be presented. Numbers of papers included can be updated on request.

Conclusion  

Studies using ML to predict CMDs show reasonable accuracy on average, but also have a high risk of bias and low applicability to real world use-cases. This indicates greater methodological rigour is required to ensure results can be trusted. Specifically, there is a lack of external validation, small sample sizes, and improper handling of outcome data in many studies.

Reference

[1] Institute of Health Metrics and Evaluation, Global Health Data Exchange (2019), https://ghdx.healthdata.org/gbd-results-tool?params=gbd-api-2019-permalink/87120109249ceec600942153d36ee021

Rebecca Orr¹, Erin Hoare¹, Deborah N Ashtree¹, Mojtaba Lotfaliany², Brenda Penninx^3,4, Mariska Bot^3,4, Felice N Jacka*¹ & Adrienne O’Neil*¹

Affiliations

1. Food & Mood Centre, the Institute for Mental and Physical Health and Clinical Translation, Deakin University, Geelong, Australia
2. The Institute for Mental and Physical Health and Clinical Translation, Deakin University, Geelong, Australia
3. Amsterdam UMC location Vrije Universiteit Amsterdam, Department of Psychiatry, Boelelaan 1117, Amsterdam, The Netherlands
4. Amsterdam Public Health, Mental Health program, Amsterdam, The Netherlands

*Shared senior authorship.

Background

Common mental disorders, including depression and anxiety, are a major source of disease burden, and despite considerable efforts to improve treatment access and stigma, prevalence remains high(1). Additional methods to address this burden are urgently needed, including identifying modifiable risk factors. Research repeatedly suggests that lifestyle behaviours (diet, physical activity, sleep, tobacco smoking, and alcohol use) are associated with depression and anxiety risk(2).However, the potential impact of clustering lifestyle behaviours is underexplored. The aim of this study is to identify clusters of lifestyle behaviours and assess how these clusters associate with depression and anxiety presence and/or severity.

Methods

We will use latent profile analysis to identify clusters of lifestyle behaviours in wave 6 of the Netherlands Study of Depression and Anxiety (NESDA). We will then assess the associations between lifestyle behaviour clusters and depression and/or anxiety presence and severity using regression models.

Results

NESDA included 2069 individuals with and without depression and/or anxiety. Participants were aged 26-75 years old (mean=50.8) and 66.1% were female. Of these, 27.5% had a current depressive and/or anxiety disorder; 53.4% had a remitted depressive and/or anxiety disorder; and 19.1% had no lifetime history of depressive and/or anxiety disorder. Full results are expected by early October.

Conclusion  

This study will assist with identifying individuals who may be at an increased risk of common mental disorders by observing their lifestyle behaviour patterns. Understanding how modifiable lifestyle behaviours cluster together may also provide important insights for developing effective common mental disorder prevention and treatment interventions.

References

1. Jorm AF, Patten SB, Brugha TS, Mojtabai R. Has increased provision of treatment reduced the prevalence of common mental disorders? Review of the evidence from four countries. World Psychiatry. 2018;16(1):90-9.
2. Firth J, Solmi M, Wootten RE, Vancampfort D, Schuch FB, Hoare E, et al. A meta-review of “lifestyle psychiatry”: the role of exercise, smoking, diet and sleep in the prevention and treatment of mental disorders. World Psychiatry. 2020;19:360-80.

Hajara Aslam, Mojtaba Lotfaliany, Dan So, Kirsten Berding, Michael Berk, Tetyana Rocks, Meghan Hockey, Felice N Jacka, Wolfgang Marx, John F. Cryan, Heidi M Staudacher

Background

Dietary fibres hold potential to influence depressive and anxiety outcomes by modulating the microbiota-gut-brain axis. Evidence for the effects of fibres on depressive and anxiety outcomes remains unclear.

Methods

A systematic literature review and meta-analysis was conducted including observational studies and randomised controlled trials (RCTs). Eligible studies were identified through a systematic search conducted across PubMed, EMBASE, CENTRAL, CINAHL and PsychINFO. Meta-analyses via random effects models were performed to examine the 1) association between fibre intake and depressive and anxiety outcomes in observational studies, 2) effect of fibre intervention on depressive and anxiety outcomes compared with placebo in RCTs.

Results

A total of 181,405 participants were included in 23 observational studies. In cross-sectional studies, an inverse association was observed between fibre intake and depressive (Cohen’s d effect size (d): -0.11; 95% CI: −0.16, −0.05) and anxiety (d: −0.25; 95% CI: −0.38, −0.12) outcomes. In longitudinal studies there was an inverse association between fibre intake and depressive outcomes (d: -0.07; 95% CI: −0.11, −0.04). In total, 740 participants were included in 10 RCTs, all of which used fibre supplements. No difference was found between fibre supplementation and placebo for depressive (d: −0.47; 95% CI: −1.26, 0.31) or anxiety (d: −0.30; 95% CI: −0.67, 0.07) outcomes. Although observational data suggest a potential benefit for higher fibre intake for depressive and anxiety outcomes, evidence from current RCTs do not support fibre supplementation for improving depressive or anxiety outcomes. Further research, in clinical populations and using a broad range of fibres is needed.

Key words: dietary fibre, prebiotics, depression, anxiety, gut microbiota

Tabinda Jabeen¹, Wolfgang Marx¹, Samantha Dawson¹, Claire Young¹, Debbie Ashtree¹, Robyn Wootton^2,3, Elizabeth Gamage¹, Emma Todd¹, Melissa Lane¹, Adrienne O’Neil¹

Affiliations

1. Food & Mood Centre, IMPACT, School of Medicine, Deakin University, Geelong, Australia.
2. School of Psychological Science, University of Bristol, Bristol, UK.
3. Nic Waals Institute. Lovisenberg Diaconal Hospital. Oslo, Norway.

Background

Observational studies have demonstrated a bidirectional association between depression and cardiometabolic diseases^{1, 2}. However, the temporality of this relationship remains unclear, and there is a risk of reverse causation. Mendelian randomisation can help minimise reverse causality and confounding in observational studies, by using measured genetic variants to examine the potential causal relationship between depression and cardiometabolic diseases³. We aim to investigate whether Mendelian randomisation studies can elucidate this bidirectional relationship.

Methods

The review will be reported according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. MEDLINE, EMBASE, PsycINFO and CINAHL databases will be used to search for relevant studies, using key words related to mental health, cardiometabolic diseases and Mendelian randomisation. Study screening and data extraction will be done in duplicate using pre-determined criteria. Risk of bias assessment will be done using the Newcastle-Ottawa Scale (NOS)⁴ and the Q-genie tool⁵. We will conduct a random-effects meta-analysis to determine the association of depression with cardiometabolic disease, including exploring potential sources of heterogeneity (I²>75%) and subgroup analyses, where possible. To assess publication bias Egger’s test will be used⁶.

Results

This review will be pre-registered on PROSPERO. Preliminary results will be presented at the IMPACT showcase.

Discussion

This review will help clarify the potential causal relationship between depression and cardiometabolic diseases. Addressing this gap has important implications for health care systems and policy in Australia and beyond and can help identify new prevention strategies for cardiometabolic disease in high-risk populations.

References

1. Rotella F, Mannucci E. Depression as a risk factor for diabetes: a meta-analysis of longitudinal studies. The Journal of clinical psychiatry. 2013;74(1):4231.
2. Rotella F, Mannucci E. Diabetes mellitus as a risk factor for depression. A meta-analysis of longitudinal studies. Diabetes research and clinical practice. 2013;99(2):98-104.
3. Bowden J, Holmes MV. Meta‐analysis and Mendelian randomization: A review. Research synthesis methods. 2019;10(4):486-96.
4. Wells GA, Shea B, O’Connell D, Peterson J, Welch V, Losos M, et al. The Newcastle-Ottawa Scale (NOS) for assessing the quality of nonrandomised studies in meta-analyses 2000 [https://www.ohri.ca/programs/clinical_epidemiology/oxford.asp].
5. Sohani ZN, Meyre D, de Souza RJ, Joseph PG, Gandhi M, Dennis BB, et al. Assessing the quality of published genetic association studies in meta-analyses: the quality of genetic studies (Q-Genie) tool. Bmc Genetics. 2015;16(1):1-8.
6. Egger M, Smith GD, Schneider M, Minder C. Bias in meta-analysis detected by a simple, graphical test. Bmj. 1997;315(7109):629-34.

Elizabeth Gamage¹, Rebecca Orr¹, Nikolaj Travica¹, Melissa M. Lane¹, Thusharika Dissanayaka¹, Jee Hyun Kim¹, Giuseppe Grosso², Justyna Godos², Wolfgang Marx¹

Affiliations

1. Food & Mood Centre, Institute for Mental and Physical Health and Clinical Translation (IMPACT), School of Medicine, Deakin University, Geelong, Victoria, 3220, Australia
2. Department of Biomedical and Biotechnological Sciences, University of Catania, Catania, Italy

Background

Numerous animal and human observational and interventional studies have assessed the relationship between polyphenol intakes and depressive-like behaviours, depressive risk, and depressive symptoms. However, overall, the results from these different study designs, each offering unique insights, are yet to be synthesised.

To improve our understanding of polyphenol consumption as a potential prevention and treatment strategy for depression and to guide future research, the aim of this review was to synthesise the available evidence from animal and human studies.

Methods

A systematic literature search of five electronic databases (Pubmed, EMBASE, The Cochrane Library (Cochrane Database of Systematic Reviews, Cochrane Central Register of Controlled Trials (CENTRAL), Cochrane Methodology Register), CINAHL, PsycINFO) was conducted. Animal studies, observational studies, interventional studies, and systematic reviews and meta-analyses of observational and interventional studies were included.

Results

We included 164 animal studies, as well as 16 observational and 44 interventional human studies assessing the associations of polyphenol intake with depressive-like behaviours, depressive risk, and depressive symptoms, respectively. In animal models, polyphenol exposure largely alleviated depressive-like behaviours. However, the evidence from human studies was less clear, with some studies reporting an inverse relationship of depression risk or depressive symptoms with the intake of certain individual polyphenols (e.g., curcumin), and polyphenol-rich foods (e.g., tea), while others reported no association or effect (e.g., daidzein).

Conclusion

While polyphenol exposure appears to alleviate depressive-like behaviours in animal models, its role as a prevention and treatment strategy for depressive outcomes in humans remains to be determined.

Lara K. Radovic¹, Tetyana Rocks¹, Wolfgang Marx¹, & Adrienne O’Neil¹

Affiliations

1. Deakin University, IMPACT (the Institute for Mental and Physical Health and Clinical Translation), Food & Mood Centre, Geelong, VIC, Australia

Background

Lifestyle treatments are shown to be efficacious in reducing depressive symptoms¹, but their effectiveness in real-life health settings is unknown. Our aim is to identify essential characteristics for the implementation of lifestyle programs by using a process evaluation of CALM, a non-inferiority trial that recruited participants with psychological distress and randomised them to a lifestyle or psychotherapy program for 8 weeks.

Methods

The outcomes collected for the evaluation to date all speak to the implementability of the lifestyle intervention, and include participant feedback (overall and sessional), facilitator observations, and fidelity ratings. Non-parametric tests were conducted to identify differences in patient feedback between groups, while thematic analysis was employed to categorize differences between facilitator observations. Parametric tests were used to show any differences in adherence.

Results

Participant feedback was similar between groups, with the main difference being that those receiving psychotherapy found it significantly easier to use the skills they learned in the program. Facilitators of the psychotherapy groups observed more varied engagement, fatigue, and spontaneous discussion than those leading the lifestyle groups, who noted more stable engagement and a higher focus on content and time management. Both groups had participants that supported each other and were more engaged in smaller groups. There were no significant differences in fidelity between the two treatment streams.

Conclusion  

To date, the process evaluation of the CALM trial suggests comparable participant satisfaction with lifestyle and psychotherapy programs, with differences in group dynamics and content accessibility that may inform how lifestyle programs can be employed.

Reference

Marx, W., Manger, S., O’Neil, A., et al. (2022). World Federations for the Society of Biological Psychiatry & Australasian Society of Lifestyle Medicine guidelines for lifestyle-based mental health care. World Journal of Biological Psychiatry.

Samantha Dawson,¹ Laura Alston,² Claire Young,¹ Amy Loughman,¹ Luba Sominski,³ Poshmaal Dhar,³ Megan Turner,¹ Peter Vuillermin,³ Felice Jacka¹

Affiliations

1. Food & Mood Centre, IMPACT, Deakin University, Geelong, Australia
2. School of Medicine, Deakin University, Geelong, Australia
3. IMPACT, Deakin University, Geelong, Australia

Background

We hypothesise that targeting prenatal diet-by-microbiome pathways will be effective in improving prenatal diet quality,¹ and mental health-related outcomes in children.^{2, 3} Our new Bugs & Bumps smartphone app teaches women to ‘eat for their gut bugs’ and is based on our face-to-face intervention that improved prenatal diet quality.¹

Our ECR team has received MRFF funding to conduct an RCT study to test whether Bugs & Bumps: 1) improves diet quality, 2) alters gut microbiota and inflammatory markers, and 3) improves socio-emotional and neurocognitive outcomes in children compared to an app focused on the Australian Dietary Guidelines (ADG). This abstract details our study with the aim of initiating collaborations.

Methods

Our RCT study is powered on diet quality as the primary outcome, and will recruit a total of 120 Geelong-based women from pregnancy clinics. Participation is from gestation week 26 until children are 18 months old. At week 26, after baseline data and stool sample collection, women will be randomised to receive Bugs & Bumps or an ADG-focused app throughout pregnancy. Maternal follow-up is at 36 weeks, and involves data and sample collection (blood, urine, stool, and vaginal swab). Infant follow-up occurs at birth, 9, 12 and 18 months where health, diet, and socio-emotional and neurocognitive outcomes and stool samples will be collected.

Results

This presentation will detail the study and highlight opportunities for collaboration and contribution.

Conclusion  

This study will provide efficacy data on the potential for diet-by-microbiome pathways to promote better mental health-related outcomes in children.

References

1. Dawson SL, et al. Targeting the perinatal diet to modulate the gut microbiota increases dietary variety and prebiotic and probiotic food intakes: results from a randomised controlled trial. Public Health Nutr. 2021;24(5):1129-41.

2. Dawson SL, et al. Maternal prenatal gut microbiota composition predicts child behaviour. EBioMedicine. 2021;68:103400.

3. Dawson SL, Finlay-Jones A, Ball L, Rocks T, Jacka F. Supporting Maternal and Child Mental Health Through Dietary Changes Focused on the Gut Microbiota. Psychiatr Ann. 2022;52(2):51-5.

Deborah N Ashtree¹, Rebecca Orr¹, Melissa M Lane¹, Felice N Jacka^1,2,3,*, Adrienne O’Neil¹*

Affiliations

1. Food & Mood Centre, The Institute for Mental and Physical Health and Clinical Translation (IMPACT), School of Medicine, Deakin University, Geelong, VIC, Australia.
2. Centre for Adolescent Health, Murdoch Children's Research Institute, Parkville, VIC, Australia.
3. College of Public Health, Medical & Veterinary Sciences, James Cook University, Townsville, QLD, Australia.

*Co-senior authors

Background

The Global Burden of Disease study (GBD) provides critical evidence for local, regional, and global public health strategies by collecting risk-outcome data for dietary exposures and physical health outcomes. However, the GBD currently lacks such data for common mental disorder (CMD) outcomes. Therefore, we cannot yet quantify the potential reduction in CMD burden by eliminating these risk factors globally. 

The Global burden of disease Lifestyle And mental Disorder Taskforce (GLAD; established 2022) will collaborate with the GBD and global experts to quantify this diet-CMD risk relationship.

Methods

To be considered by the GBD Committee, we are following four stages:

1. Systematically search and recruit relevant studies.
2. Determine Taskforce priorities at an international symposium (October 2022; 88 members from 14 countries).
3. Estimate study-level diet-CMD associations using GBD-approved, harmonised data analysis protocols.
4. Meta-analyse evidence for diet and CMDs, using GBD methods.

Results

Our search identified 48 relevant studies; of which 31 (n=455,000) have enrolled in GLAD (Australasia n=12, Italy n=2, The Netherlands n=3, Norway n=1, Spain n=3, UK n=8, and multi-country n=2). Stage 3 results are anticipated from December 2023. Stage 4 results are expected by December 2024.

Conclusion

GLAD will quantify the contribution of diet to CMDs at the population level; providing the GBD with necessary evidence to integrate diet as a risk factor for CMDs and evaluate the potential reduction in CMD burden by targeting poor diet. This has the potential to inform priority setting and public health policy decisions at the regional and global level.

Melissa M Lane¹, Elizabeth Gamage¹, Nikolaj Travica¹, Thusharika Dissanayaka¹, Deborah N Ashtree¹, Sarah Gauci¹, Mojtaba Lotfaliany¹, Adrienne O’Neil¹, Felice N Jacka^{1, 2, 3, 4} and Wolfgang Marx¹

Affiliations

1. Deakin University, IMPACT (the Institute for Mental and Physical Health and Clinical Translation), Food & Mood Centre, School of Medicine, Barwon Health, Geelong, Australia
2. Centre for Adolescent Health, Murdoch Children’s Research Institute, VIC; Australia
3. James Cook University, QLD; Australia

Background

Since previous meta-analyses, which were limited only to depression and by a small number of studies available for inclusion at the time of publication, several additional studies have been published assessing the link between ultra-processed food consumption and depression as well as other mental disorders.

Methods

We aimed to build on existing reviews and clarify the associations between consumption of ultra-processed food and mental disorders by conducting an updated synthesis and meta-analysis of the contemporary evidence base.

Results

Seventeen observational studies were included (N=385,541); 15 cross-sectional and two prospective. Greater ultra-processed food consumption was cross-sectionally associated with higher odds of the prevalence of depressive and anxiety symptoms, both when these outcomes were assessed together (common mental disorder symptoms odds ratio: 1.53, 95%CI 1.43 to 1.63) and separately (depressive symptoms odds ratio: 1.44, 95%CI 1.14 to 1.82; and, anxiety symptoms odds ratio: 1.48, 95%CI 1.37 to 1.59). Furthermore, a meta-analysis of prospective cohort studies demonstrated associations between greater ultra-processed food intake and an increased risk of incident depressive outcomes (hazard ratio: 1.22, 95%CI 1.16 to 1.28).

Conclusion

While we found evidence for associations of ultra-processed food consumption with the prevalence and incidence of adverse mental health, further rigorously designed prospective and experimental studies are needed to better understand directionality and causal pathways.

Amna Siddiqui¹, Faiza Basheer^1,2, Amardeep Dhillon^1,2

Affiliation

1. School of Medicine, Deakin University, Geelong, VIC, Australia
2. Institute of Mental and Physical Health and Clinical Translation, Deakin University, Geelong, VIC, Australia

Background  

Colorectal cancer (CRC) causes over 900,000 deaths each year, primarily due to our inability to prevent and treat metastatic forms of the disease. While CRCs that are detected early can be successfully treated, outcomes for patients with metastatic disease remain extremely poor. Such advanced disease is present in approximately 25% of patients at initial diagnosis and develops in about half of all CRC patients. To metastasize, CRC cells that leave the primary site must overcome several physiological barriers to successfully colonize distant organs. The mechanisms by which some CRC cells successfully complete these complex processes are not well understood. Therefore, elucidating mechanisms facilitating metastatic colonisation has the potential to uncover new avenues to treat metastatic CRC.

The current gold-standard for studying metastasis are models where human cancer cells or patient-derived xenografts are transplanted into immune-compromised mice. Despite the undoubted value of these models, they do not allow easy non-invasive visualization of tumour rendering them unviable for clinical practice. To overcome these challenges, researchers have generated novel zebrafish cancer models, including optically-clear lines that facilitate in vivo tracking of tumor cells in real time.

Methods  

To establish a model to better understand CRC metastasis and identify potential targets for treating metastatic CRCs, we developed a novel optically-clear immuno-compromised zebrafish model (Casper/Il2rgc.a-/-) lacking T and NK cells. In contrast to standard zebrafish embryonic xenotransplantation assays where animals develop immunity from 7 days post-fertilisation (dpf), Casper/Il2rgc.a-/- embryos are immune-deficient until 21 dpf, thus providing a broader window to evaluate the fate of xenotransplanted cancer cells.

Results

Xenotransplantation of various human CRC cell lines into Casper/Il2rgc.a-/-embryos revealed that over time, some small metastatic lesions progressed to form larger lesions, suggesting that this model facilitates studies into the later stages of metastasis.

Conclusion  

Embryos from Casper/Il2rgc.a-/- zebrafish provide a novel xenotransplantation model for studying cancer metastasis and testing anti-cancer therapies.

Kira Hughes^1,2,3, Angel Torriero⁴, Dwan Price^1,2,3,5, Matthew Symonds⁶, Cenk Suphioglu^1,2,3,5

Affiliation

1. NeuroAllergy Research Laboratory (NARL), School of Life and Environmental Sciences, Faculty of Science, Engineering and Built Environment, Deakin University, 221 Burwood Highway, Burwood, VIC 3125, Australia
2. Deakin AIRwatch Pollen and Spore Counting and Forecasting Facility, Deakin University, Burwood, VIC 3125, Australia
3. Institute for Mental and Physical Health and Clinical Translation (IMPACT), Deakin University, 75 Pigdons Road, Waurn Ponds, VIC 3216, Australia
4. School of Life and Environmental Sciences, Faculty of Science, Engineering and Built Environment, Deakin University, 221 Burwood Highway, Burwood, VIC 3125, Australia
5. NeuroAllergy Research Laboratory (NARL), School of Life and Environmental Sciences, Faculty of Science, Engineering and Built Environment, Deakin University, 75 Pigdons Road, Waurn Ponds, VIC 3216, Australia
6. Centre for Integrative Ecology, School of Life and Environmental Sciences, Faculty of Science, Engineering and Built Environment, Deakin University, 221 Burwood Highway, Burwood, VIC 3125, Australia

Background

Hirst-type traps are the most common sampling machines implemented at aeroallergen monitoring stations worldwide¹. While Hirst-type traps can effectively collect airborne particulates over a long time, limitations arise from these lengthy and labour-intensive collection times, and can be error prone by an inexperienced counter. Current sampling can be significantly improved by developing "real-time" automatic monitoring methods to assist researchers with detecting sudden fluctuations in aeroallergen concentrations over shorter periods and provide valuable data for ETSA forecasts as thunderstorm asthma events are unfolding. One example of "real-time" automated sampling is biological immunosensors (biosensors), which are based on reactions between antigens and antibodies, coupled with electrical or chemical components, to produce an analytical signal². The formation of antibody-antigen complexes can be measured with a level of high sensitivity to determine the presence or concentration of specific molecules².

Methods

Mass-sensitive biosensors were developed to detect allergens Lol p 5/Phl p 1 and Alt a 1 found in prominent allergenic pollen and fungi, respectively. 1:3 11-MUA and 9-MNL thiols were modified via NHS/EDC activation to enable antibody attachment.

Results

Antibody-antigen complexes were successfully formed in a simulation chamber under controlled conditions. The development of these biosensors are the first of its kind, as none had yet been built to detect pollen or fungal spore allergens.

Conclusion  

This research demonstrates that biosensors may become a viable alternative to conventional methods for monitoring airborne allergens in "real-time". Future studies should focus on testing biosensors in field conditions to validate their real-world usage.

Reference

1. Hirst JM. An Automatic Volumetric Spore Trap. Annals of Applied Biology. 1952;39(2):257-265. doi:https://doi.org/10.1111/j.1744-7348.1952.tb00904.x
2. Ju H, Lai G, Yan F. 1 - Introduction. In: Ju H, Lai G, Yan F, eds. Immunosensing for Detection of Protein Biomarkers. Elsevier; 2017:1-30.

Dr. Jasmin Akter¹, A/Prof. Sarah Auburn², Prof. Ric Price², Prof. Olivo Miotto³, Dr. Rashidul Haque¹, Dr. Cristina Ariani⁴ and Prof. Alyssa E. Barry⁵

Affiliation

1. Infectious Diseases Division, International Centre for Diarrhoeal Diseases Research, Bangladesh (icddr,b), Dhaka, Bangladesh.
2. Menzies School of Health Research, Darwin, Australia.
3. Nuffield Department of Medicine, Oxford University, Oxford, UK
4. Wellcome Sanger Institute, Hinxton, Cambridge, UK
5. Centre for Innovation in Infectious Diseases and Immunology Research (CIIDIR), IMPACT and School of Medicine, Deakin University, Geelong, Victoria, Australia

Abstract

Bangladesh has achieved an 80% reduction in malaria cases over the last decade, but these gains are threatened by the rapid spread of Plasmodium falciparum resistance to the frontline artemisinin and partner drugs in the Greater Mekong Subregion (GMS). Over 90% of malaria cases occur in the Chittagong Hill Tracts (CHT) districts, bordering Myanmar. To date, there is no evidence of artemisinin resistance in the CHT; however, large influx of refugees fleeing Myanmar into Bangladesh warrants dedicated surveillance. The National Malarial Elimination Programme (NMEP) currently receives data on antimalarial drug efficacy from clinical surveys in select locations; however, the high financial cost and logistical complexities constrain their frequency and ability to detect emerging resistance in other locations. My proposed research program aligns closely with and extend the activities of the NMEP and leading malaria genomics researchers to establish amplicon sequencing as a sustainable, high-throughput molecular surveillance platform to monitor antimalarial drug resistance and transmission dynamics. The resulting data will provide early warning signals to prevent widespread resistance to artemisinin and partner drugs in the CHT. The study will generate genomic data on antimalarial drug resistance and parasite genetic relatedness in the CHT and establish capacity for processing the data that leverages on existing informatics pipelines. The statistical outputs will inform the NMEP with clear intelligence on where to upscale antimalarial interventions, conduct clinical surveys of drug efficacy, and to change drug policy if high levels of resistance are detected.

Esrin Aydin (Hons)^1,2, Dr. Serap Azizoglu², Dr. Moneisha Gokhale², Dr. Luke Chong² and AsPr.Cenk Suphioglu¹

Affiliation

1. NeuroAllergy Research Lab (NARL), School of Life and Environmental Sciences, Deakin University, Waurn Ponds, Australia
2. School of Medicine, Deakin University, Waurn Ponds, Australia

Background

Ocular allergy (OA) is a localised subset of allergy characterised by ocular surface itchiness, redness and inflammation. Inflammation and eye-rubbing, due to allergy-associated itchiness, are common in OA sufferers and may trigger changes to the ocular surface biochemistry. The primary aim of this study is to assess the differences in human tear proteome between OA sufferers and healthy controls during peak allergy season in Victoria, Australia.

Methods

31 participants (21 OA sufferers, 10 healthy controls) aged 18-45 were recruited for this study. Participants were completed symptom and quality of life questionnaires. Tear samples were collected using a non-invasive microcapillary flow technique. Extracted proteins were run on an Orbitrap Mass Spectrometer and were matched to a DIA library. Data was analysed using software MaxQuant, Perseus, FunRich and IBM SPSS.

Results

877 proteins were quantified in tear samples of OA sufferers and healthy controls, of which 23 showed a significant difference in expression between groups (p<0.05). 9 proteins showed increased expression in OA sufferers versus healthy controls, and 14 were decreased. Decreased proteins in OA sufferers related to cell structure, inflammatory and antimicrobial regulation. OA sufferers were shown to have increased expression of proteins relating to inflammation, immunity, and cellular development.

Conclusion  

Tear protein quantification showed dysregulation of proteins involved in inflammation, immunity, and cellular structures. Proteins relating to cellular structure may suggest a possible link between OA-associated itch and the subsequent ocular surface damage via eye-rubbing, while inflammatory and immune protein changes highlight potential diagnostic and therapeutic biomarkers of OA.

Gaddu GK¹, Basheer F^1,2, Dhillon AS^1,2

Affiliation

1. School of Medicines, Deakin University, Waurn Ponds, VIC, Australia
2. Institute of Mental Health and Clinical Translation Deakin University Waurn Ponds

Abstract

DNA and proteins packaged in the cell nucleus are affected by histone acetylation, which affects chromatin organization and gene expression. The acetylation of core histones has been associated with chromatin opening and closing, gene transcription, DNA damage repair, and chromosome decondensation in mitosis and meiosis. Lysine residues are acetylated by tightly regulated histone lysine acetyltransferases (KATs) and deacetylases. There is an increasing body of research indicating that dysregulation of KATs and aberrant lysine acetylation is linked to tumorigenesis in cancer and poor prognosis, presenting an opportunity for finding new therapeutic targets in this area. Kat5 is a histone acetyltransferase family member and regulates DNA damage response by acetylating histones and remodelling of the chromatin.

My research is focussed on investigating the effects of acute deletion of kat5 using CRISPR/Cas9 mediated deletion in zebrafish and its potential role in tumorigenesis. Zebrafish have been increasingly used as an animal model to better understand the genetics and biology of vertebrate development. I found that mutation of kat5 is associated with multiple developmental issues and disease such as survival, lymphoma, oophoritis, seminoma, spinal deformity, spindle cell tumour, neurodegenerative disorders, and facial malformation. Characterization of key mechanisms causing these defects and performing further studies will pave the better understanding of role of kat5 in zebrafish development and cancer studies.

Kaushalya Perera¹, Clifford Liongue^1,2, Alister Ward^1,2.

Affiliation

1. School of Medicine, Deakin University, Geelong, VIC, Australia
2. Institute for Mental and Physical Health and Clinical Translation, Deakin University, Geelong, VIC, Australia

Background

Zebrafish has emerged as an invaluable model for studying haematopoiesis and haematopoietic diseases. There is a strong conservation of their haematopoietic cells and the key genes they express to mammals. Their genome is highly accessible to genetic modification, and they can be manipulated to examine disease pathogenesis and potential therapeutic agents. There is a growing body of literature around zebrafish immune cells, including macrophages, neutrophils, and T and B lymphocytes that have demonstrated their importance in regulating immune responses to pathogens and cancer. However, thus far less attention has been given to Natural Killer (NK) cells whose identity, ontogeny and specific roles in zebrafish remain unknown. This study seeks to address this knowledge gap by identifying and developing marker genes to investigate NK cell biology in zebrafish.

Methods

Based on available transcriptomic and molecular studies, this study analyses various NK cell-related genes using Reverse Transcriptase Polymerase Chain Reaction (RT-PCR) and high-resolution whole mount in situ hybridization (WISH) to evaluate their specific expression in the zebrafish NK cell lineage.

Results

The study presents different NK cell-specific genes to be expressed throughout zebrafish embryonic development. The expressions of these genes were significantly reduced in the IL-2Rγc knockout fish which lack NK cells compared to wildtypes. Importantly, the study shows that zebrafish NK cells reside in zebrafish thymus which also accommodates T lymphocytes.

Conclusion

Together, the study provides new evidence of zebrafish NK cells and establishes cellular markers that can be used to identify NK cells in zebrafish.

Reference  

Gore, A. V., Pillay, L. M., Venero Galanternik, M. & Weinstein, B. M. 2018. The zebrafish: A fintastic model for hematopoietic development and disease. Wiley interdisciplinary reviews. Developmental biology, 7, e312-e312.

Christina Dizdarevic^1*, Joyanta Modak¹, Mrittika Chowdury¹ and Tania de Koning-Ward¹

Affiliation

1. Institute for Mental and Physical Health and Clinical Translation (IMPACT), School of Medicine, Deakin University, Waurn Ponds VIC 3216

Background

Malaria is caused by protozoan parasites of the Plasmodium genus, of which P. falciparum is the most lethal. Plasmodium parasites invade and remodel erythrocytes to grow and obtain essential nutrients. One organelle implicated in invasion, parasite establishment within erythrocytes, and remodelling is the rhoptry. To date, only 30 Plasmodium rhoptry proteins have been identified using empirical approaches. Elucidating the rhoptry proteome will be crucial to understanding the roles of rhoptry proteins in mediating host-parasite interactions.

Methods  

Novel techniques in proteomics, like proximity labelling, can identify proteins localising to a particular cellular region. In proximity labelling, a labelling enzyme is fused to a gene to label nearby proteins. One such enzyme, TurboID, biotinylates proximal proteins by catalysing their covalent attachment to biotin-AMP. Proximity labelling studies in P. falciparum are limited.

Results

The aim of the study was to identify the rhoptry proteome by fusing TurboID to proteins localising to different regions in the rhoptry. This body of work demonstrates the development of TurboID-fused PfCERLI, which localises to the rhoptry cytoplasmic face, and TurboID-fused PbRON3, a rhoptry bulb-localising protein. Mass spectrometry revealed 129 proximal proteins significantly enriched in CERLI-TurboID-expressing parasites, 14 of which are known rhoptry proteins. The most significantly enriched proteins localise to apical cellular compartments or to membranous structures, and include proteins involved in vesicle-mediated transport.

Conclusion  

Identification of rhoptry proteins provides the basis for understanding their trafficking through the secretory pathway and evaluation of their potential as novel therapeutic targets, which are desperately required due to rising drug resistance of parasites.

Ereeny Mikhail, MOptom ^1,2,3, Mohammadreza Mohebbi, PhD ⁴, Moneisha Gokhale, PhD ^2,3, Serap Azizoglu, PhD ^2,3, Khyber Alam, PhD ⁵, and Cenk Suphioglu, PhD ^1,3

Affiliation

1. NeuroAllergy Research Laboratory (NARL), School of Life and Environmental Sciences, Deakin University, Waurn Ponds, Geelong, Victoria, 3216, Australia.
2. Deakin Optometry, School of Medicine, Deakin University, Waurn Ponds, Geelong, Victoria, 3216, Australia.
3. Institute for Mental and Physical Health and Clinical Translation (IMPACT), Deakin University, Waurn Ponds, Victoria, 3216, Australia.
4. Biostatistics Unit, Faculty of Health, Deakin University, Geelong, Victoria, 3216, Australia.
5. Health and Medical Sciences, Department of Optometry, University of Western Australia,

Background

Current research has revealed a lack of consensus in health practitioner diagnostic, treatment, and collaborative care approaches to Ocular Allergy (OA). However, the exact gaps have not been determined. Thus, the ‘Survey on Ocular Allergy for Health Practitioners (SOAHP)’ study was conducted to better understand the current gaps in the knowledge and practices of relevant health practitioners in OA. However, as SOAHP was a closed-ended survey study, this did not capture all aspects of health practitioner involvement in OA. Thus, interviews were conducted to gain a greater understanding of health practitioner attitudes, perspectives, experiences and influences surrounding OA. The secondary aim was to create a collaborative care model on OA.

Methods

Semi-structured in-depth interviews were conducted on 35 health practitioners which included 5 Allergists/Immunologists, 3 General Practitioners, 2 Ophthalmologists, 21 Optometrists and 4 Pharmacists. A qualitative descriptive approach was taken. Data was analysed using the Reflexive Thematic Analysis by Braun and Clarke.

Results

This qualitative study derived five themes from the data which included Attitudes towards OA, Current Practice Patterns in OA, Interdisciplinary Collaborations in OA, Barriers to Diagnosis and Management of OA, and Enablers to Diagnosis and Management of OA patients.

Conclusion

It was found that health practitioners viewed OA as a routine, and non-sight threatening condition regardless of the known effects. However, although viewed in a simple light, there were multiple barriers identified including a lack of a clear diagnostic method, no framework for treatments, and no collaborative care model. Thus, most participants requested multiple enablers to alleviate such barriers. Finally, a collaborative care model on OA was created through the results from SOAHP and this interview-based study.

Andrew Wiesa¹, Sean McGee¹, Rasika Samarasinghe¹

Affiliation

1. Deakin University School of Medicine

Background

Pediatric glioblastoma (pGBM) is an aggressive brain tumor with limited survival, and traditional treatments for adult GBM are often ineffective in children. The distinctive biology of pGBM demands specialized therapies. While the shift towards increased glycolysis and lactate production (Warburg effect) is well-studied in adult GBM, this metabolic dysregulation in pGBM is largely unexplored.

Methods

We aimed to compare glucose metabolism in pediatric GBM (SF188), adult GBM (T98G), and non-cancerous cells (CT003 and HEK293) in both monolayer and 3D spheroids, hypothesizing that the cancers demonstrate dysregulated metabolism. The metabolic phenotype, including oxidative and glycolytic flux, was assessed using the Seahorse XF analyzer, with all data normalized to protein concentration (BCA).

Results

The pGBM and T98G cells showed significantly higher oxygen consumption (OCR) rates of 2.7 ± 0.21 and 4.5 ± 0.24 pmol/min/µg protein, respectively, and increased extracellular acidification rates (ECAR) of 0.98 ± 0.04 and 1.4 ± 0.04 mpH/min/µg protein, respectively. These values were considerably higher compared to the non-cancerous CT003 and HEK cell lines, with OCR of 0.91 ± 0.11 and 0.91 ± 0.13 pmol/min/µg protein, and ECAR of 0.30 ± 0.02 and 0.1 ± 0.02 mpH/min/µg protein, respectively (n=4 ± SEM).

Conclusion  

Our study identifies that adult and pGBM cells have heightened glycolytic and aerobic metabolism, reflecting increased energy capacity, especially in 3D models and monolayers. pGBM metabolism aligns with the Warburg effect, differing from adult GBM, requiring unique research strategies. Future work will explore elevated glycolysis in pGBM, its role in proliferation and survival, and potential therapeutic targeting.

Joyanta K Modak ^1,2 andTania F de Koning-Ward^1,2

Affiliation

1. School of Medicine, Deakin University, Geelong, Australia
2. The Institute for Mental and Physical Health and Clinical Translation, Deakin University, Geelong, Australia

Background

Malaria is caused by infection with Plasmodium parasites, with ~400,000 deaths and >200 million cases each year. There is no efficacious licensed vaccine and thus anti-malaria drugs are critical for treating malaria. Due to major problems with resistance to current anti-malarials, new strategies to combat Plasmodium are desperately needed. This project aims to identify the role of thioredoxin (TRX2) in P. falciparum, a component of the parasite’s protein export machinery (PTEX), in trafficking cysteine rich proteins such as PfEMP1 (the major virulence factor) to the host cell surface and its contribution to parasite survival.

Methods

To determine the role of TRX2 in parasite survival, a transgenic parasite line PfTRX2-HAglmS was created using CRISPR/Cas9 technique, enabling knockdown of HA-tagged TRX2 expression with glucosamine. The effect of TRX2 knockdown on parasites growth was tested by growing them with and without glucosamine. The comparative growth analysis was performed using student’s t-test. to identify the role TRX2 in trafficking PfEMP1 to the host cell surface, immunofluorescence assay (IFA) was performed by probing parasites smears with ATS antibody.

Results

Diagnostic PCR results indicated successful creation of PfTRX2-HAglmS transgenic parasites line. Western blot analysis showed that glucosamine treatment reduced more than 85% TRX2 protein expression. Knockdown of TRX2 protein resulted in significant reduction of parasites growth (50%). In addition, IFA results revealed significant defects in PfEMP1 protein export to the erythrocytes membrane when TRX2 protein expression was depleted.

Conclusion

Using molecular and biochemical techniques, it has been shown that TRX2 is important for optimal growth of P. falciparum and export of PfEMP1 protein to the host cell surface.

Poshmaal Dhar^1#, Luba Sominsky^1,2, Martin O’Hely¹, Samantha Dawson¹, Fiona Collier¹, Mimi LK. Tang^3,4, Toby Mansell³, David Burgner^3,4, Craig Smith¹, Natalie Hyde¹, Katherine Downing⁵, Kylie D Hesketh⁵, Anne-Louise Ponsonby^3,6, Peter Vuillermin^1,2, the Barwon Infant Study Investigator Group*.

Affiliation

1. Deakin University, Institute for Mental and Physical Health and Clinical Translation (IMPACT), School of Medicine, Geelong, VIC, Australia
2. Barwon Health, Geelong, Victoria, Australia
3. Murdoch Children’s Research Institute, Royal Children’s Hospital, Parkville, Victoria, Australia
4. Department of Paediatrics, University of Melbourne, Parkville, VIC, Australia.
5. Institute for Physical Activity and Nutrition, School of Exercise and Nutrition Sciences, Deakin University, Geelong, VIC, Australia
6. The Florey Institute of Neuroscience and Mental Health, University of Melbourne, Parkville, Victoria, Australia

# Centre for Innovation in Infectious Disease and Immunology Research (CIIDIR), IMPACT, Deakin University

Background

Physical activity (PA) during pregnancy has numerous benefits, partly mediated via its effect on the immune system. However, this evidence is inconsistent. We estimated the effect of PA during pregnancy on systemic inflammatory markers in mothers recruited in the Barwon Infant Study.

Methods

Participants reported their previous week's PA at their 28-week antenatal appointment. Women were grouped into low, moderate and high PA categories based on duration and frequency of walking, moderate- or vigorous-intensity PA. Women reporting moderate levels of PA, which is consistent with current recommendations, served as the comparison group. Markers of systemic inflammation, high sensitivity C-reactive protein (hsCRP) and glycoprotein acetyls (GlycA), and cytokines were measured at 28 weeks gestation. Regression analyses adjusted for maternal smoking, gestational diabetes mellitus, pre-pregnancy BMI and household size were performed.

Results

Compared to women in the moderate group (n = 371, 42%) women reporting low PA (n = 436, 50%) had a 10.1% higher hsCRP (95% CI (3.7%, 16.6%), p<0.01) while women in high PA (n = 76, 9%) had a 14% higher hsCRP (95% CI (3.1%, 24.8%), p=0.01). Women in high PA category had higher interleukin (IL)-4 (q=0.03) and IL-9 (q=0.03) levels compared to those in moderate category. Each vigorous MET-minute/week was associated with lower GlycA (p = 0.03).

Conclusion  

Low and high PA is associated with higher systemic inflammation and high PA affects T cell-associated cytokines during pregnancy. As excessive inflammation is a risk factor for pregnancy-related complications, studies are now required to assess impact of this on clinical outcomes.

Satendra K. Jaysawal^1,2, Rocky Chowdhury^1,2, Rajindra Napit^1,2, Haben Melke^1,2, Jasmine Catague^1,2, Shweta Patel^1,2, Cuong Pham³, Lingxue Kong⁴, Wei Duan^1,2

Affiliation

1. School of Medicine, Deakin University, Geelong, Australia
2. Institute of Mental and Physical Health and Clinical Translation (IMPACT), Deakin University, Geelong, Australia
3. Molecular Imaging and Theranostics Laboratory, Baker Heart and Diabetes Institute, Melbourne, Australia
4. Institute for Frontier Materials, Deakin University, Geelong, Australia

Email: sjaysawal@deakin.edu.au

Background

PD-L1 (Programmed death ligand-1) is a crucial protein that contributes to immune cell tolerance by acting as an immune checkpoint ligand of the co-inhibitory receptor PD-1. However, when PD-L1 binds to T-cells, it suppresses their growth and proliferation, promoting cancer cell growth. PD-L1 on the surface of small extracellular vesicles (sEVs) that are derived from tumour cells, thus, can facilitate drug resistance by binding to PD-L1 antibodies upon treatment, reducing their effectiveness. Therefore, a quantitative detection system is necessary to identify and capture PD-L1 positive sEVs in the liquid samples. This project aims to develop an aptamer that specifically targets PD-L1 positive sEVs, enhancing the efficacy of therapies.

Methods

The aim is to identify the most promising aptamers candidate for further engineering and development of effective liquid biopsy. In this study, potential aptamers targeting PD-L1 peptide were selected using SELEX, followed by primary screening and engineering. Also, these aptamers have been characterized. The techniques of choice were ELISA and flow cytometry for this study.

Results

Twenty-nine candidate aptamers were obtained from SELEX where PD-L1-24-apt and PD-L1-29-apt showed promising binding to the PD-L1 protein. PD-L1-24-apt and PD-L1-29-apt affinity were 310 nM and 286 nM respectively. Moreover, these aptamers have shown substantial selective binding to the native structure of PD-L1 protein anchored in the cell surface.

Conclusions

Final aptamers selected will have fast on-rate and slow off-rate and will be able to establish aptamer-based capture of PD-L1 positive sEVs through liquid biopsy. However, further verification is required to confirm aptamers efficacy.

Bing-Ru Wu¹, Claire E Emson¹, Jess Pedrina¹, John Stambas¹

Affiliation

1. School of Medicine, Faculty of Health, Deakin University, Waurn Ponds, Australia 

Background

Single-cell RNA sequencing (scRNA-seq) is a technique that combines next-generation sequencing (NGS) and single-cell technology to facilitate quantitative characterization of cell heterogeneity following virus infection. Our laboratory has previously identified the importance of extracellular matrix enzymes in viral immunity as the absence of one such enzyme, ADAMTS5, a member of ADisintegrin and Metalloproteinase with Thrombospondin motifs (ADAMTS) family leads to delayed virus clearance and sub-optimal virus-specific CD8 T cell migration following influenza virus infection [1]. Another enzyme if interest is ADAMT7, a protein associated with inflammatory responses in rheumatoid arthritis. Its contribution to influenza pathogenesis is not yet characterized [2].

Methods

In order to establish and compare the transcriptome baseline between ADAMT7 knock-out (KO) and WT mice at the single cell level, a BD Rhapsody™ Whole Transcriptome Analysis protocol was established. cDNA libraries from both strains of mice were constructed from 20,000 splenocytes in accordance with the BD Rhapsody™ Express methodology (a single cell capture system) and sequencing was performed using an Illumina NovaSeq 6000. Data processing was conducted using the Seven bridge platform (cloud computing) and Seurat package in R programming.

Results

A total of 19 cell subsets were identified from WT and KO mice. KO mice exhibited exclusive cell subsets that included CD177+ neutrophils, germinal centre and marginal zone B cells. There were also higher frequencies of erythrocytes, monocytes, red pulp macrophages and activated B cells when compared with WT mice.

Conclusion  

These results suggest that expression of ADAMTS7 may impact influenza immunopathogenesis through differential cell subsets and further investigation using in vivo mouse models is required.

Reference

1. McMahon, M., et al., ADAMTS5 Is a Critical Regulator of Virus-Specific T Cell Immunity. PLoS Biol, 2016. 14(11): p. e1002580.
2. Liu, C.J., et al., ADAMTS-7: a metalloproteinase that directly binds to and degrades cartilage oligomeric matrix protein. FASEB J, 2006. 20(7): p. 988-90.

Khadizatul Kubra¹, Faiza Basheer^1,2 and Amardeep S. Dhillon^1,2

Affiliation

1. School of Medicine, Deakin University, Waurn Ponds, Victoria 3216, Australia.
2. Institute for Mental Health and Clinical Translation, Deakin University, Waurn Ponds, Victoria 3216, Australia.

Background

Tp53 plays a very significant role in maintaining the genomic integrity of multicellular organism by preventing mutation of the genome and oncogenic transformation under any stressful condition. More than 50% of all human cancers have disrupted tp53 function. However, to date the effect of tp53 mutation in developing cancers, their overall progression and metastatic nature of the cancers is not well studied. Therefore, to understand tp53 knockout effect in vivo, we have generated tp53 mutant zebrafish and characterized them.

Methods

CRISPR/CAS9 technique has been used to create tp53 mutation in zebrafish. Regular monitoring and histopathological test have been conducted to identify zebrafish cancer spectrum. Adult xenotransplantation has been performed to generate syngeneic zebrafish cancer model and observe the metastatic nature of the cancers.

Results

tp53mutant (tp53 ^-/-) zebrafish autonomously developed cancers, mainly anaplastic sarcoma along with a good number of hemangiosarcoma and few rhabdomyosarcomas. By 4 months, the onset of tumour was observed while 66% of homozygous tp53 ^-/-animals developed tumour by 27 weeks. Xenotransplantation of two largely developed cancer, anaplastic and hemangio-sarcomas in both immune competent and compromised zebrafish showed that both are transplantable and metastatic in nature where immune cells might play different role in metastasis and tumour engraftment.

Conclusion

tp53 knockout zebrafish allowed us to study two deadly cancers anaplastic sarcoma and hemangiosarcoma. The transplantable nature of the cancers has allowed to have the cancer model faster for further dissecting as well as to understand the role of immune cells in cancer microenvironment.

References

1. Kastenhuber ER, Lowe SW. Putting p53 in context. Cell. 2017 Sep 7;170(6):1062-78.
2. Ignatius MS, Hayes MN, Moore FE, Tang Q, Garcia SP, Blackburn PR, Baxi K, Wang L, Jin A, Ramakrishnan A, Reeder S. tp53 deficiency causes a wide tumour spectrum and increases embryonal rhabdomyosarcoma metastasis in zebrafish. Elife. 2018 Sep 7;7:e37202.

Mitchell Trickey¹*, Natalie Counihan¹, Joyanta Modak¹ & Tania de Koning-Ward¹

Affiliation

1. School of Medicine, Deakin University

Abstract

Malaria is one of the leading infectious diseases in the world and is caused by protozoan parasites of the species Plasmodium. Plasmodium parasites infecting humans have developed resistance to all antimalarial drugs, and it is therefore critical for new therapeutics to be developed. New permeation pathways (NPPs) have been validated as a crucial modification of the host erythrocyte, facilitating nutrient acquisition, and are therefore an attractive therapeutic target. Understanding the channel’s structure is critical for targeted drug design. RhopH1/clag genes have previously been implicated in NPP formation (Nguitragool et al. 2011). Rodent malaria species Plasmodium berghei could be used to investigate clag’s contribution to NPPs if it can be shown functionality remains the same across species.

However, there is currently no method available for assessing NPP functionality in a rodent model.

Firstly, this study aimed to develop an osmotic lysis assay to determine NPP functionality in infected rodent erythrocytes. A series of compounds were screened on infected erythrocytes for their ability to selectively cause lysis, guanidinium-hydrochloride was found to exclusively lyse infected erythrocytes. Subsequently, NPP inhibitors and synchronous population assays showed lysis was mediated by the NPPs.

Next, the P. berghei clag gene was modified such that it expressed P. falciparum c-terminal region to reveal if clag gene functionality is conserved across the two species. Transgenic parasites were generated, proposing the conservation of clag gene across species. This work shows that clag genes can be studied in rodent model P. berghei with a higher confidence of relatability to P. falciparum parasite function.

Nguitragool, W, Bokhari, AAB, Pillai, AD, Rayavara, K, Sharma, P, Turpin, B, Aravind, L & Desai, SA 2011, 'Malaria parasite clag3 genes determine channel-mediated nutrient uptake by infected red blood cells', Cell, vol. 145, no. 5, pp. 665-77.

Yen Ting Wong¹, Michael A Tayeb², Timothy C Stone³, Laurence B Lovat³, Andrew E Teschendorff^4,5, Rafal Iwasiow², Jeffrey M Craig^1,6,7

Affiliations

1. IMPACT Strategic Research Centre, School of Medicine, Barwon Health, Geelong, Vic, Australia
2. DNA Genotek Inc., Ottawa, ON, Canada
3. Division of Surgery & Interventional Science, UCL, London WC1E 6BT, UK
4. CAS Key Laboratory of Computational Biology, CAS-MPG Partner Institute for Computational Biology, Shanghai Institutes for Biological Sciences, 320 Yue Yang Road, Shanghai 200031, PR China.
5. UCL Cancer Institute, 72 Huntley Street, University College London, London WC1E 6BT, UK.
6. Murdoch Children’s Research Institute, Department of Paediatrics, The University of Melbourne, Royal Children's Hospital, Melbourne, Vic., Australia.
7. Corresponding author jeffrey.craig@deakin.edu.au

Background

Saliva and buccal samples are popular for epigenome wide association studies (EWAS) due to their ease of collection compared and their ability to sample a different cell lineage compared to blood. As these samples contain a mix of white blood cells and buccal epithelial cells that can vary within a population, this cellular heterogeneity may confound EWAS. This has been addressed by including cellular heterogeneity obtained through cytology at the time of collection or by using cellular deconvolution algorithms built on epigenetic data from specific cell types. However, to our knowledge, the two methods have not yet been compared.

Results

Here we show that the two methods are highly correlated in saliva and buccal samples (R = 0.84, P <0.0001) by comparing data generated from cytological staining and Infinium MethylationEPIC arrays and the EpiDISH deconvolution algorithm from buccal and saliva samples collected from twenty adults. In addition, by using an expanded dataset from both sample types, we confirmed our previous finding that age has strong, non-linear negative correlation with epithelial cell proportion in both sample types. However, children and adults showed a large within-population variation in cellular heterogeneity.

Conclusion

Our results validate the use of the EpiDISH algorithm in estimating the effect of cellular heterogeneity in EWAS and showed DNA methylation generally underestimates the epithelial cell content obtained from cytology.

Shiva Ganjali¹, Mojtaba Lotfaliany¹, Andrew Tonkin², Mark Nelson^{2, 3}, Christopher Reid², John McNeil², Rory Wolfe², Enayet Chowdhury⁴, Robyn Woods², Michael Berk¹, Mohammadreza Mohebbi^{1, 5}

Affiliations

1. IMPACT—the Institute for Mental and Physical Health and Clinical Translation, School of Medicine, Faculty of Health, Deakin University, Geelong, VIC, Australia
2. School of Public Health and Preventive Medicine, Monash University, Melbourne, Vic, Australia
3. Menzies Institute for Medical Research, University of Tasmania, Hobart, Tas, Australia
4. School of Public Health, Curtin University, Perth, WA, Australia
5. Biostatistics unit, Faculty of Health, Deakin University, Geelong, Vic, Australia

Background

Owing to the rapid growth in the population of older adults, who are at an increased risk of developing cardiovascular disease (CVD), it is essential to have a CVD risk prediction model that is inclusive of the aged, in order to prevent and manage CVD burden in terms of mortality, morbidity, disability, functional decline, and healthcare cost, in this population. However, the old CVD risk prediction models were developed in middle-aged populations, and their usefulness in the aged population remains unclear. So, this study for the first time aimed to validate some established CVD risk prediction models including ACC/AHA, Framingham, Globorisk, SCORE2-OP, and Predict1 based on the Australian and the United States community-dwellers older adults.

Methods

Data from ASPREE (ASPirin in Reducing Events in the Elderly) cohort, which is a large-scale longitudinal, prospective study, are considered for CVD risk prediction. Models’ performance of prediction function was assessed by discrimination (Harrell's C index and time-dependent ROC curves) and calibration (Calibration plots) assessments.

Results

All the original models showed poor discrimination (c-indexes range, 0.58-0.61 for males, and 0.61-0.66 for females, and AUC range, 0.60-0.64) as well as clearly miscalibration, with over-prediction. However, by updating, the models’ discrimination (c-indexes range, 0.62-0.66 for males, and 0.67-0.70 for females, and AUC range, 0.66-0.69) and calibration power were notably improved.

Conclusion

These CVD risk prediction models indicated low performance in predicting CVD event in older adults and need to be updated to use in clinical practice for the aged population.

Reference

1. Australian Bureau of Statistics 2020, Causes of Death 2019, cat. no. 3303.0, October
2. SCORE2-OP working group and ESC Cardiovascular risk collaboration. European Heart Journal. 2021.

Md Rashadul Islam¹, Yen Ting Wong¹, Tim Silk², Jeffrey Craig¹

Affiliations

1. The Institute for Mental and Physical Health and Clinical Translation (IMPACT),  School of Medicine, Faculty of Health, Deakin University, Geelong Waurn Ponds Campus, Locked Bag 2000, Geelong, VIC 3220
2. Faculty of Health, School of Psychology, Melbourne Burwood Campus, Deakin University, 221 Burwood Highway, Burwood Victoria 3125

Background

Poor neurocognitive outcomes significantly burden children, their families and healthcare systems. However, little is still known about the interactions among genetic and early ;life environmental processes that influence variation in cognition, behaviour and brain structure and function.

Methods

Our proposed study aimed to quantify the associations between DNA methylation state using Infinium Methylation EPIC array (850K) in buccal (cheek swab) samples at birth and the full-scale IQ, average cortical thickness and average cortical surface area at the age of 11 years from the Peri/postnatal Epigenetic Twins Study (PETS) cohort using twins as individuals and within pair differences models. We also aimed to identify whether the association of DNA methylation at birth with cognitive outcome and brain morphology at 11 years are stable in when DNA methylation is measured at 18 months, six years and 11 years.

Results

We expect that differentially methylated CpG sites will be significantly associated with full-scale IQ, cortical thickness and cortical surface area with false discovery (FDR) <0.05 and top CpGs ranked by p-value will be enriched in genes associated with neurocognitive development and the top ranked CpGs observed in associations between DNA methylation at birth and those outcomes at 11 years will be present at 18 months, 6 years and 11 years of age.

Conclusion

This proposed study will allow us to investigate the developmental stability of epigenetic effects over time and assess how early life events and epigenetic states associate with functional and structural differences in neurodevelopmental outcomes in mid-childhood.

Yen Wong^a, Martha Lappas^b,c, Jeffrey Craig^a, Mark Ziemann ^d, Ratana Lim^b,c, Caitlyn Nguyen-Ngo^b,c, Priya Sumithran^e,f

Affiliations

a. Deakin University, School of Medicine, IMPACT, Institute for innovation in Physical and Mental health and Clinical Translation, Geelong, Australia.

b. University of Melbourne, Department of Obstetrics and Gynaecology, Melbourne, Australia

c. Mercy Hospital for Women, Melbourne, Australia

d. Deakin University, Geelong, Australia, School of Life and Environmental Sciences

e. University of Melbourne, Department of Medicine (St Vincent's), Melbourne, Australia

f. Department of Endocrinology, Austin Health, Melbourne, Australia

Objective

Excessive gestational weight gain is associated with the risk of diabetes in later life for both mothers and offspring. To shed light on the mechanisms behind the association of gestational weight gain and maternal obesity, we aimed to study the association between gestational weight gain, DNA methylation and gene expression of genes associated with body weight regulation and inflammation in adipose tissue from women without pre-existing obesity, at birth.

Methods

Omental adipose tissue was obtained from 25 women aged 25-40 with a healthy singleton pregnancy and a pre-pregnancy BMI of 18.5-25 kg/m². DNA methylation and gene expression were analysed within the LEP, TNF, NPY, POMC and SOCS3 genes using bisulfite amplicon sequencing and quantitative real-time RT-PCR, respectively.

Results

We found no evidence for an association at any CpGs from any amplicon at FDR <0.05. However, all 31 CpGs analysed within LEP exhibited a negative association with GWG, including six at P<0.05. Permutation testing showed that this relationship was unlikely to arise from random chance. Average DNA methylation across the whole LEP amplicon was negatively correlated with GWG, with a gradient of 0.79% DNA methylation decrease per kilo of GWG. The NPY amplicon had a gradient of 0.71% DNA methylation decrease per kilo of GWG, despite individual CpGs showing a mix of positive and negative correlations. Levels of messenger RNA showed a low negative correlation with DNA methylation at both LEP and NPY.

Conclusions

We present preliminary evidence that gestational weight gain is negatively correlated with DNA methylation in omental tissues in LEP and NPY. Such knowledge, if replicated, will shed light on the mechanisms that link gestational weight gain and maternal obesity.

Ditty Ann Johns¹, Shae Quirk^1,2, Julie Pasco^1,2, Natalie Hyde^1,2,Lana J Williams^1,2

Affiliations

1. Deakin University, IMPACT – The Institute for Mental and Physical Health and Clinical Translation, School of Medicine, Geelong VIC Australia
2. Barwon Health, Geelong VIC Australia

Background

Attention deficit hyperactivity disorder (ADHD) is a neuropsychiatric condition prevalent in both the child and adult populations. With the growing awareness of the importance of the pre-conception period, and considering the diverse etiological background in ADHD including a combination of biomedical, psychological and social factors (1), it is essential to understand how parental mental health and related factors operating during preconception years affect offspring ADHD. Thus, we aim to systematically review the available evidence on associations between parental mental health conditions and/or use of psychotropic medications and the risk of offspring ADHD.

Methods

Studies will be eligible if they are: i) population- or clinically-based cohort studies; ii) examine preconception parental mental health conditions and/or use of psychotropic medications; and iii) offspring ADHD. Relevant peer-reviewed literature will be identified via electronic searching of research databases (Embase, PubMed, OVID, CINAHL, Medline). Reference lists of eligible articles will be hand searched and grey literature may be considered. The included studies will undergo critical appraisal using standardised critical appraisal checklist developed by JBI.

Results

A preliminary search strategy developed by listing and mapping keywords was implemented for Medline Complete via the EBSCOHost platform yielding 1,511 potentially relevant studies. Following the screening process, a descriptive synthesis will be conducted, and the key findings presented. This will include characteristics of the included studies, critical appraisal scores, and summary of findings (presented in text and visually). If appropriate, a meta-analysis will also be conducted.

Conclusion

To the best of our knowledge this will be the first systematic review to collate and critically appraise the existing evidence investigating parental mental health conditions during the preconception years and its association with offspring ADHD.

Reference

1. Nigg JT, Sibley MH, Thapar A, Karalunas SL. Development of ADHD: Etiology, heterogeneity, and early life course. Annual review of developmental psychology. 2020;2:559-83.

Allegra Chajinsi Gaza¹, Dr Yen Ting Wong¹,Prof Jeffrey Craig¹

Affiliations

1. Institute of Mental and Physical Health and Clinical Translation, Deakin University, Waurn Ponds, Australia

Background

Bowel cancer is the abnormal growth of cells in the lining of the colon and rectum. It is a significant public health concern and the most common cancer in Australia, with 103 deaths per week. Early detection is therefore crucial and currently, a colonoscopy is the gold standard procedure for detecting possible underlying bowel cancer. However, the procedure can be very expensive, invasive, cumbersome and cause infection, bleeding, or bowel perforation. In response, new forms of non-invasive screening have been implemented like the immunochemical faecal occult blood test (iFOBT). However, they solely detect blood in faeces, to identify haemoglobin, resulting in high specificity but low sensitivity in detecting early-stage cancers which commonly exhibit no bleeding. Only 1 in 20 individuals with positive iFOBT result have bowel cancer after their required colonoscopy. The false positive rates (~ 96%), cause unnecessary invasive actions and stress. Cells from early-stage and asymptomatic advanced cancer, however, can shed and be released in stool. A more sensitive screening tool, especially for early-stage cancer would save more lives and unnecessary stress for many.

Our research project aims to develop a new cell-based bowel cancer screening tool to increase accuracy, reduce false positives by analysing the cells instead of just detecting blood. So far, our research team has successfully isolated human cells from healthy stool, and isolated HT-29 colon cancer cells spiked in healthy stool.

Methods

We will recruit iFOBT positive and negative participants’ and collect stool samples (n=20) and perform a series of physical isolation methods to extract a pure population of human cells. We will then analyse the cells through cytological and immunocytochemical techniques.

Conclusion

Ultimately, we expect to better patient outcomes and early detection of bowel cancer through a novel cell-based method with higher sensitivity and more efficiency.

George, Victoria^1,2, Craig, Jeffrey¹, Wong, Yen Ting¹, McLachlan, Robert³, Barres, Romain², Preston, Jessica²

Affiliations

1. Deakin University, School of Medicine, IMPACT, Institute for innovation in Physical and Mental health and Clinical Translation, Geelong, Australia.
2. University of Copenhagen, Novo Nordisk Foundation, Centre for Basic Metabolic Research, Copenhagen, Denmark
3. Hudson Institute of Medical Research, Centre for Endocrinology and Metabolism, Melbourne, Australia

Email: georgevic@deakin.edu.au

Background

The global increase in obesity is largely attributed to the availability of processed foods and sedentary lifestyles. Concurrently, there is a growing prevalence of stress and mental health disorders. Both are linked with adverse health outcomes.

Animal studies have recently indicated that paternal diet, weight, and stress levels can impact offspring health, with epigenetic mechanisms being the proposed mediator. However, human research in this context is scant.

Methods

My research aims to bridge this gap by examining how modern dietary habits - a shift towards processed foods - might alter the sperm epigenome. I plan to recruit 25 twin pairs. Each twin will be randomly assigned to receive Diet A (unprocessed diet) or Diet B (processed diet) over a three-week period.

Furthermore, I aim to investigate the effect of stress across ones’ life on the sperm epigenome, via responses to validated stress questionnaires.

Semen collected at baseline and post intervention will be processed and motile sperm isolated to assess epigenetic state. The level of DNA methylation will be measured using Reduced Representation Bisulfite Sequencing (RRBS). Small non-coding RNA sequencing will be performed and sorted based on RNA categories (miRNA, piRNA, and tRNA).

Conclusion 

The findings from this research will contribute to our understanding of paternal epigenetic inheritance in humans and aid in formulating informed pre-conception dietary and lifestyle advice for prospective fathers, reducing the risk of adverse health outcomes in their offspring.

Luba Sominsky ^{a, b, *}, Martin O’Hely ^{b, c}, Katherine Drummond ^d, Sifan Cao ^b, Fiona Collier ^b, Poshmaal Dhar ^b, Amy Loughman ^b, Samantha Dawson ^b, Mimi LK. Tang ^{c, e, f}, Toby Mansell ^{c, e}, Richard Saffery ^c, David Burgner ^{c, e, f}, Anne-Louise Ponsonby ^d, Peter Vuillermin ^{a, b, c, *}, the Barwon Infant Study Investigator Group.

Affiliations

a. Barwon Health, Geelong, Victoria, Australia

b. Deakin University, IMPACT - the Institute for Mental and Physical Health and Clinical Translation, School of Medicine, Geelong, Victoria, Australia

c. Murdoch Children’s Research Institute, Royal Children’s Hospital, Parkville, Victoria, Australia

d. The Florey Institute of Neuroscience and Mental Health, University of Melbourne, Parkville, Victoria, Australia

e. The University of Melbourne, Parkville, Victoria, Australia

f. Royal Children’s Hospital, Melbourne, Victoria, Australia

Background

Inflammation is one of the key mechanisms of major depressive disorder. However, the evidence regarding the role of inflammation in perinatal depression is inconsistent. We investigated the association between pre-pregnancy obesity, a chronic inflammatory state, and perinatal depressive symptoms in a pre-birth cohort, the Barwon Infant Study. We also assessed if circulating inflammatory markers during pregnancy mediated this relationship.

Methods

Body mass index (BMI) was calculated in 883 women and depressive/stress symptoms assessed using the Edinburgh Postnatal Depression and Perceived Stress scales (EPDS/PSS) at 28 weeks gestation and 4 weeks postpartum. Circulating glycoprotein acetyls (GlycA), high-sensitivity C-reactive protein (hsCRP), and cytokines were measured at 28 weeks gestation. We analysed data using regression modelling and assessed mediation using nested counterfactual models.

Results

Women with pre-pregnancy obesity (BMI≥30 kg/m²) had greater antenatal EPDS and PSS scores, compared to healthy weight women (18.5-24.9 kg/m²). Compared to healthy weight women, GlycA, hsCRP, interleukin (IL)-1ra and IL-6 were higher in women with obesity, while eotaxin and IL-4 were lower. While IL-6 and eotaxin were negatively associated with EPDS/PSS scores, with no evidence for mediation, higher GlycA, was associated with higher EPDS/PSS scores and partially mediated the association between pre-pregnancy obesity and antenatal depression.

Conclusions

Our findings highlight the role of inflammation in maternal mental health, showing that pre-pregnancy obesity increases the risk of antenatal depression and GlycA, a novel biomarker of systemic inflammation, partially mediates this relationship. These findings have wide significance to those investigating the biological underpinnings of mental health disorders.

Aksha Dhawan¹, Himadri Bohidar¹, Palash Kumar Manna¹, Richard Williams², Fred Pfeffer², Craig Smith², Dinesh Kalyanasundaram³, Pushplata Singh^*1

Affiliations

1. TERI Deakin Nanobiotechnology Centre, TERI Gram, Gurugram, India
2. Deakin University, Faculty of Health, Australia
3. Centre for Biomedical Engineering, Indian Institute of Technology Delhi, New Delhi, India

E-mail: aksha.dhawan@teri.res.in, pushplata.singh@teri.res.in

Background

As the globe battles with environmental issues including climate change, pollution, and depleting natural resources, the need for sustainable development has never been more pressing. In this study, Polyhydroxybutyrate (PHB), a green biopolymer having the potential to replace non-biodegradable plastics and the biogenic nanohydroxyapatite (nHAP) were used as the sustainable raw materials to produce nanocomposite scaffold for bone tissue engineering.

Methods

In this work, micro and nano-sized composite fibrous scaffolds mimicking the extracellular matrix of bone were developed using sustainable raw materials i.e., biogenic PHB and nHAP. This study aimed to screen several in-house bacterial strains for their potential to produce PHB by Nile blue A staining, and the elite species was selected. PHB was extracted and characterized by various techniques like Transmission electron microscopy, Fourier transform-infrared spectroscopy, Gas chromatography-mass spectroscopy, and UV-visible spectrometry to confirm the structure and composition. Further, a nanocomposite fibrous scaffold using the bio-derived PHB and nHAP was fabricated by electrospinning and was characterized.

Results

The PHB was successfully identified by Nile blue A staining and TEM. Fourier transform infrared of the extracted PHB indicated the characteristic C=O peak. Gas chromatography-mass spectroscopy and UV-Visible spectroscopy confirmed the presence of PHB monomers. The physiochemical characterization such as Scanning electron microscopy, Fourier transform-infrared spectroscopy, and X-ray diffraction analysis of the PHB/nHAP confirmed the synthesis of nanofibers and the incorporation of the nHAP with good dispersion and with suitable porosity like that of cancellous bone.

Conclusion  

The polymeric nanocomposite composed of green biomaterials will aid in bone repair and will lead to the emergence of an eco-friendly environment in near future.

Caroline J Bushell¹ and Bryony A McNeill¹

Affiliations

1. Institute for Mental and Physical Health and Clinical Translation (IMPACT)

Background

Endothelial dysfunction is a key pathophysiological change that occurs in the initial stages of diabetic microvasculature complications. Hydrogen sulfide (H₂S), enzymatically produced by 3-Mercaptopyruvate sulfurtransferase (3-MST), is an important cell signaling molecule that exerts protective effects against diabetic endothelial dysfunction. Recently we demonstrated that the H₂S/3-MST pathway is impaired in endothelial cells exposed to hyperglycemic stress. The aim of this study was to determine whether supplementation with dihydrolipoic acid (DHLA), an essential 3-MST cofactor, can restore the function of the H₂S/3-MST pathway in endothelial cells exposed to hyperglycemic stress.

Methods

H₂S production capacity was determined in human primary endothelial cells (HUVECS) exposed to high glucose (25mmol/L) for 72 hours before supplementation with DHLA. Would healing assays were used to determine endothelial cell function. Both assays were performed with and without the selective 3-MST inhibitor HMPSNE. 3-MST gene and protein expression was also measured.

Results

DHLA increased H₂S production in a dose dependent manner in diabetic endothelial cells which was associated with improved endothelial wound healing. Inhibition of 3-MST by HMPSNE reduced H₂S production capacity, slowed wound healing, and increased 3-MST protein expression.

Conclusion  

The findings of this study demonstrate that DHLA supplementation has beneficial effects for endothelial function under high glucose conditions, which are dependent on the H₂S/3-MST pathway. These findings suggest that DHLA supplementation may have therapeutic applications for the treatment and prevention of diabetic microvascular complications by restoring H₂S/3-MST signalling.

Alex Eisner¹, Martin O’Hely^2,3,4

Affiliations

1. Florey Institute of Neuroscience and Mental Health, Melbourne
2. Impact Institute, School of Medicine, Deakin University, Geelong 
3. Murdoch Children’s Research Institute, Melbourne
4. Presenting author.

Background

There is a received wisdom that adjusting for a covariate which affects only the outcome constitutes over- adjustment and should be avoided, both on causal grounds (that there is no reduction in bias to be had by including it) and because it is well understood that the precision of an odds ratio estimate will be decreased upon making such an adjustment, although the opposite effect is seen in the setting of linear regression.

Methods

Here we present a simulation framework, implemented in webR, for exploring the consequences of adjusting for such an independent determinant in a variety of settings. We also calculate the asymptotic variance of a regression estimator using standard methods and bound it using well-known inequalities.

Results

We highlight two observations based on these explorations. Firstly, the unconditional odds ratio for a binary outcome on an exposure is generally not equal to a common odds ratio conditional on an independent determinant. Secondly we see that the precision of an estimate of the relative risk can be improved by adjusting for an independent determinant, and we show that the improvement is valid in general.

Conclusion

We believe the second of these points is novel and adds to a recent body of literature making a case that logarithmic regression, estimating relative risk, should be preferred to logistic regression.

Kate Phuong-Nguyen¹, Martin O’Hely^2,3, Sean L McGee¹, Kathryn Aston-Mourney¹, Malik Q Mahmood¹, and Leni R Rivera¹

Affiliations

1. School of Medicine, IMPACT – the Institute for Mental and Physical Health and Clinical Translation, Deakin University, Waurn Ponds, Australia
2. School of Medicine, IMPACT – the Institute for Mental and Physical Health and Clinical Translation, Deakin University, Barwon Health, Australia
3. Murdoch Children’s Research Institute, Royal Children's Hospital, The University of Melbourne, Melbourne, Australia

Background

Many individuals rapidly regain excess weight once they stop dieting. This phenomenon, commonly termed yoyo-dieting, is a pattern of losing weight and then regaining it, placing individuals at greater risk for metabolic complications and obesity. Evidence suggests that yoyo-dieting-induced obesity causes long-term alterations in the gut microbiome composition and metabolism. This study aimed to investigate how yoyo-dieting affects gut health and whether RS could be a promisingly effective weight management strategy.

Methods

Male and female C57BL/6 mice (n=48/sex, n=8/group) were allocated to six different diets for 20 weeks [control, high-fat (HFD), yoyo-diet (HFD interspaced with control every 5 weeks), control with RS, HFD with RS, and yoyo-diet with RS]. Metabolic measurements were performed, including body weight, glucose and insulin tolerance tests, tissue weights. Intestinal integrity was assessed in Ussing chambers. Microbial profiling was assessed using 16S rRNA sequencing.

Results

Male mice fed a HFD with RS had significantly lower weight gain, liver mass, adipose tissue, and insulin tolerance compared to mice fed a HFD alone. No significant differences in glucose tolerance and intestinal permeability were observed across all diets and between sexes. Males had significantly higher alpha diversity and a different microbiota profile compared to females. Mice fed diets with RS had significantly lower alpha diversity and a different microbiota profile compared to mice fed without RS.

Conclusion  

Different microbiome signatures and metabolic measurements were observed in male and female mice. In male mice consuming a HFD, RS improved metabolic measurements and shifted the microbiota profile to one similar to mice fed control diets.

P. Yang¹, A. Rifai¹, G. E. Boer¹, L. S. De Silva¹, D. Nisbet³ A Quigley², R Kapsa², R. Williams^1,*

Affiliations

1. School of Medicine, Deakin University, Waurn Ponds, VIC 3216, Australia
2. School of Engineering, RMIT Melbourne
3. Graeme Clark Institute, Department of Biomedical Engineering, The University of Melbourne

Background

When volumetric muscle injuries overwhelm self-repair systems, endogenous tissue restoration often malfunctions. ​(1)​ Biofabrication as a promising pathway is urgently needed to effectively regenerate damaged skeletal muscles. ​(2)​ The objective of biofabricated constructs is to intricately replicate muscle tissue with cellular interactions that ultimately restore tissue physiology. Naturally derived polysaccharide hydrogels are a promising material vector due to their outstanding biocompatibility, biodegradability and tunability. ​(3)​ The constraint of adopting polysaccharide hydrogels is the absence of fibrous, mechanical and bioactive cues, which considerably confine their ability to emulate the extracellular matrix (ECM) of muscle tissue. ​(3)​

Methods

We combine polysaccharide hydrogels with fluorenyl-9-methoxycarbonyl (Fmoc) self-assembling peptides (SAPs) that comprise ECM-protein-fibrous motifs to form uniquely adjustable mechanical, dynamic and physiological biocomposites. We investigate the mechanical and structural properties of these tailorable composited hydrogels via transmission electron microscopy (TEM), cryo-scanning electron microscopy (CryoSEM) and Small-Angle-Xray-Scattering (SAXS), the rheological characteristics using a parallel-plate rheometer, as well as printability test. We also examine the cytocompatibility of the designed bioinks in terms of cell viability, differentiation and migration behaviours.

Results

Our results show that the mechanics of biocomposites could be tuned by controlling the concentration and crosslinking of polysaccharides alone. We achieve a biofunctional stiffness range, bioactive micro- and nano-topography, mechanical and structural integrity and consistent nanofibrous assemblies by incorporated Fmoc-SAP polysaccharides networks.

Conclusion  

We demonstrate that the formulation of Fmoc-SAPs with polysaccharide hydrogels has the biomimetic ability to meet the requirements of muscle tissue and ameliorates bio-printability outcomes.

Reference

1. Ngan CGY, Quigley A, Williams RJ, O’Connell CD, Blanchard R, Boyd-Moss M, et al. Matured Myofibers in Bioprinted Constructs with In Vivo Vascularization and Innervation. Gels. 2021;7(4).
2. Firipis K, Nisbet DR, Franks SJ, Kapsa RMI, Pirogova E, Williams RJ, et al. Enhancing peptide biomaterials for biofabrication. Vol. 13, Polymers. 2021.
3. Firipis K, Boyd-Moss M, Long B, Dekiwadia C, Hoskin W, Pirogova E, et al. Tuneable hybrid hydrogels via complementary self-assembly of a bioactive peptide with a robust polysaccharide. ACS Biomaterials Science and Engineering

Zoe SJ Liu¹, Trang TT Truong¹, Chiara C Bortolasci¹, Briana Spolding¹, Bruna Panizzutti¹, Courtney Swinton¹, Jee Hyun Kim^1,2, Damian Hernandez¹, Srisaiyini Kidnapillai¹, Laura Gray¹, Michael Berk^1,2, Olivia M Dean^1,2,*, and Ken Walder^1,*

Affiliations

1. Deakin University, IMPACT, The Institute for Mental and Physical Health and Clinical Translation, School of Medicine, Geelong 3220, Australia
2. Florey Institute of Neuroscience and Mental Health, Parkville 3010, Australia

^* These authors contributed equally

Background

Baicalin is a flavone glycoside derived from flowering plants belonging to the Scutellaria genus. Previous studies have reported baicalin’s anti-inflammatory and neuroprotective properties in rodent models, indicating the potential of baicalin in neuropsychiatric disorders where these processes are implicated. However, it is unknown whether these effects can be reproduced in a human neuronal cell model.

Methods

We treated NT2-N cells (human neuronal-like cell model) with three different doses of baicalin (0.1, 1 and 5mM) or vehicle control (DMSO) for 24 hours. To determine the transcriptional effects of baicalin on NT2-N cells, RNA extraction, genome-wide mRNA expression profiles and gene set enrichment analysis (GSEA) were utilised. We also performed neurite outgrowth assays and mitochondrial flux bioanalysis (Seahorse) in NT2-N cells treated with baicalin or vehicle control.

Results

We found in NT2-N cells that baicalin positively affected neurite outgrowth and transcriptionally up-regulated genes in the tricarboxylic acid cycle and the glycolysis pathway. Similarly, flux bioanalysis showed increased oxygen consumption rate in baicalin-treated NT2-N cells, an indicator of enhanced mitochondrial function.

Conclusion  

Our findings have confirmed the mitochondria enhancing effects of baicalin in human neuronal-like cells, suggesting potential therapeutic application of baicalin in human neuropsychiatric disorders where these processes are operative.

Ayushi Priyam¹, Colin J. Barrow², Richard J. Williams¹

Affiliations

1. IMPACT, School of Medicine, Deakin University, Geelong, Victoria 3216, Australia.
2. Centre for Chemistry and Biotechnology, School of Life and Environmental Science, Deakin University, Geelong, Victoria 3216, Australia.

Background

In everyday life, chronic infectious wounds are of immense concern due to long term patient discomfort and multiple hospital visits. Patients suffering from chronic wounds also tend to acquire secondary infection that makes the whole wound care management challenging. There is also evidence of increasing cases of chronic infectious wounds like Buruli ulcer in Australia, particularly in regions of Victoria ^1,2. Existing antibiotic therapies are challenging. Long term treatment regimens are required, necessitating multiple dosing which have concerns around developing resistance and side-effects that can affect vital organs. This opens a scope to strategize the optimal application of antibiotics via direct delivery of drug formulations to the site of insult. Here, we present a strategy for seaweed derived functionalised hydrogels with nanoparticles and anti-inflammatory components can provide a relevant 3D platform for smart release of antibiotics.

Methods

Seaweed derived alginate and fucoidan were used to prepare hydrogels infused with nanohydroxyapatite particles. The hydrogel was integrated with rifampicin and tested against for antibacterial effects. A classical wound scratch assay was performed to analyse the cell migration activities in the presence of the functionalised hydrogel.

Results

The functionalised hydrogel shows accelerated cell migration in vitro and antibacterial effects.

Conclusion  

The bio-inspired functionalised hydrogels can be further explored for its wound closure ability and antibacterial effects against pathogenic bacteria including, MRSA and Mycobacterium ulcerans to provide sustainable solution against emerging chronic infectious wounds.

Reference

(1) Loftus, M. J.; Tay, E. L.; Globan, M.; Lavender, C. J.; Crouch, S. R.; Johnson, P. D.; Fyfe, J. A. Epidemiology of buruli ulcer infections, Victoria, Australia, 2011–2016. Emerging infectious diseases 2018, 24 (11), 1988.

(2) Muleta, A. J.; Lappan, R.; Stinear, T. P.; Greening, C. Understanding the transmission of Mycobacterium ulcerans: A step towards controlling Buruli ulcer. PLoS Neglected Tropical Diseases 2021, 15 (8), e0009678.

Damián Hernádez¹,Bruna Panizzutti¹, Megan Ellis¹, Zoe Liu¹, Courtney Swinton¹, Briana Spolding¹, Michael Berk^1,2,3, Ken Walder¹.

Affiliations

1. Deakin University, IMPACT, The Institute for Mental and Physical Health and Clinical Translation, School of Medicine, Geelong, Australia
2. Florey Institute of Neuroscience and Mental Health, Parkville, Australia
3. Orygen, The National Centre of Excellence in Youth Mental Health, Centre for Youth Mental Health, The Florey Institute for Neuroscience and Mental Health and the Department of Psychiatry, University of Melbourne, Parkville, Australia

Background

Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a debilitating chronic disease characterized by severe fatigue exacerbated by activity. Its pathophysiology remains poorly understood, hindering effective treatments. Although classified as a neurological disorder, other clinical manifestations, such as impaired muscle function, suggest additional cellular involvement. To address this gap, we established an induced pluripotent stem cell (iPSC) biobank derived from ME/CFS patients and healthy individuals.

We hypothesize that ME/CFS is associated with an energy imbalance, particularly in skeletal muscle cells. Our project aims to: 1) differentiate iPSCs into functional skeletal muscle cells from ME/CFS patients and healthy controls (8 iPSC lines per group), 2) analyse metabolic and transcriptomic differences between these cells, and 3) identify potential drug candidates for ME/CFS treatment.

Methods

Patient recruitment is completed, and iPSCs are currently being generated from peripheral blood mononuclear cells using episomal vectors, and characterized (pluripotency, genotyping and karyotyping). The muscle cell differentiation protocol has been established, with differentiated cells exhibiting skeletal muscle cell markers (Myosin Heavy Chain, Titin and Myogenin), morphology (elongated rod shape), and spontaneous contractions. Our analysis will involve next-generation sequencing, metabolomics, bioinformatics, and bioassays for mitochondrial function, oxidative stress, and inflammation.

Conclusion  

By using iPSC-derived skeletal muscle cells from ME/CFS participants, we will uncover novel insights into the cellular mechanisms underlying ME/CFS. Our findings may provide crucial information about energy imbalance in skeletal muscle cells, potentially leading to the identification of new therapeutic targets and repurposed drugs for ME/CFS treatment.

L.S. De Silva¹, P. Yang^1*, D.R. Nisbet^3,4* G.E. Boer^1*, A. Rifai ^1,2*, R. Williams ^1,3*

* Denotes equal contribution

Affiliations

1. IMPACT, School of Medicine, Deakin University, Waurn Ponds, VIC 3216, Australia
2. School of Engineering, RMIT University, Melbourne, VIC 3001, Australia
3. Biofab3D, Aikenhead Centre for medical Discovery, St Vincent’s Hospital Melbourne, Fitzroy, VIC 3065, Australia
4. Graeme Clark Institute, Department of Biomedical Engineering, The University of Melbourne, Victoria 3010 Australia

Abstract

A significant characteristic of the musculoskeletal system is the contiguous interface where the soft connective tissues such as cartilage, tendon and ligaments connect to the crystalline bone [1]. This transition is a unique zone that ensures the stability of the joints by creating support around the joints [2]. These soft to hard tissue interfaces are prone to injury and are limited by their ability to self-repair. Thus, increasing the chances of risk to damage and decreasing the functionality. Restoring such gradient interfaces remains a major challenge in interfacial tissue engineering (ITE) because of their complex and dynamic nature [3].

A novel hybrid hyaluronic acid (HA) and peptide-based hydrogel approach was taken to construct a biomimetic tissue scaffold of defined porosity, with growth factors were incorporated to functionalise the material, we then used extrusion based 3D bioprinting technique to fabricate the physical gradients. In this method, multipotent stem cells were embedded into the hydrogel, and a controlled biochemical stimulus promoted cell differentiation. The mechanical properties of the tissue scaffold are optimised to match the natural tissue to withstand forces until the remodelling process ends as the joints are exposed to different mechanical stresses regularly.

The properties of the hydrogels were tested using differential scanning calorimetry (DSC), Rheoology, Fourier transform infrared microscopy (FTIR), Cryo SEM and Atomic Force Microscopy (AFM). We demonstrate the synthesized novel bioink can bioprint tissue constructs with both physical and chemical gradients. The mechanical test results demonstrated that the synthesised hydrogels have certain structural properties that resemble the structure of the natural tissue. The biological evaluation of the hydrogels showed a gradient responsive control over cell fate, and measures of cell viability, cell attachment and cell proliferation. This research has recognised a potential novel bio-ink that can fabricate gradient tissue constructs that can mimic the host tissue while sustaining growth factor delivery to promote repair in tissue in the musculoskeletal interface.

References

[1] O. E. Armitage and M. L. Oyen, "Hard-Soft Tissue Interface Engineering," in Engineering Mineralized and Load Bearing Tissues, L. E. Bertassoni and P. G. Coelho Eds. Cham: Springer International Publishing, 2015, pp. 187-204.

[2] S. Patel et al., "Integrating soft and hard tissues via interface tissue engineering," (in eng), J Orthop Res, vol. 36, no. 4, pp. 1069-1077, Apr 2018, doi: 10.1002/jor.23810.

[3] L. Baldino, S. Cardea, N. Maffulli, and E. Reverchon, "Regeneration techniques for bone-to-tendon and muscle-to-tendon interfaces reconstruction," British Medical Bulletin, vol. 117, no. 1, pp. 25-37, 2016, doi: 10.1093/bmb/ldv056.

Aaqil Rifai¹ and Richard Williams^1,2

Affiliations

1. School of Medicine, Deakin University, Waurn Ponds, VIC 3216, Australia
2. Biofab3D, Aikenhead Centre for Medical Discovery, St Vincent’s Hospital Melbourne, Fitzroy, VIC 3065, Australia

Background

Osteoarthritis (OA) is a highly prevalent disease, affecting upwards of 1 in 8 adults worldwide and is projected to increase by 60% in the next two decades.¹ The treatment methods for OA are limited to removing or modifying existing cartilage. Fabricating, reproducing, and predicting cell to tissue formation are the key bottlenecks to translate to clinical applications.

Methods

Emerging tissue engineering approaches seek to address this challenge by utilising the cell’s own capacity to produce an extracellular matrix (ECM) (material surrounding cell) under the guidance of specific exogenous cues, i.e., both soluble factors and biophysical signals generated by cell-cell and cell-ECM interactions.^2,3 As such, we leverage the capacity of cells to self-organise and produce a tissue that has structural, morphological and functional properties comparable to the native tissue with functionalised peptide hydrogels.

Results

Here we show a new tissue engineering strategy to control the spatiotemporal behaviour of mouse bone stromal cells with self-assembled peptide hydrogels. As a result, these cells exhibit a specific gene expression profile that could map the gradient structure of the osteochondral interface.

Conclusion  

The findings suggest that the progenitor cells can differentiate in response to predefined physical conditions of hydrogels to enable the fusion and remodelling of structurally organised tissues in vitro. Successful implementation of this research will enable us to realise the potential impact of high-resolution micro and nanoscale devices, which could provide new therapies for treating degenerative diseases including OA.

References  

1. Bowden, J. L. et al., Nat. Rev. Rheumatol., 16(8), 434-447 (2020).

2. Burdis, R. and Kelly, D. J. Acta Biomater., 126, 1-14 (2021).

3. Wang, Y. et al., Adv. Func. Mater., 30(9), 1900390 (2020).

Demagi K. Herath¹, Jason M Hodge³, Lana J. Williams^1,2, Julie A. Pasco^1,2 and Rasika M. Samarasinghe^1,2

Affiliations

1. School of Medicine, Deakin University, Waurn Ponds, VIC, Australia
2. The Institute for Mental and Physical Health and Clinical Translation (IMPACT), Deakin University, Geelong, VIC, Australia 3. Barwon Health, Geelong, VIC, Australia

Background

A multitude of techniques exists for detection and quantification of DNA methylation (DNAm). Primarily, there are three approaches: a chemical reaction using sodium bisulfite, cleavage of DNA with restriction enzymes (REs), and affinity capture of methylated DNA. In addition, there are few bisulfite, RE and antibody-free techniques (Khodadadi et al., 2021). These approaches can be combined with broadly practiced techniques such as Polymerase Chain Reaction (PCR), sequencing or microarrays to determine the status of DNAm (Laird, 2010). All these techniques have benefits and limitations, however a universal technique that can be accessible by any basic molecular  biology  laboratory  requires  development,  careful  optimisation  and validation.

Methods

A literature search was conducted to identify the ideal technique for differential methylation analysis, using Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Database used was PubMed with several query terms and exclusion criteria to filter the search.

Quantitative methylation specific PCR (qMS-PCR) and High-Resolution Melting (HRM) curve analysis was optimised and tested using HEK293, MDA-MB-231, Caco- 2, T98G and FHs 74 Int cell lines for 15 genes. The technique was validated using patient samples and microarray data from the Geelong Osteoporosis Study (GOS).

Results

The literature search revealed that quantitative methylation specific polymerase chain reaction (qMS-PCR) was the most economical and user-friendly technique that can be performed with available of equipment, reagents, with less time. and expertise required for data analysis. This technique was developed, optimised, and validated as an economical and efficient procedure to determine the status of DNAm.

Conclusion

This study identified that qMS-PCR with HRM was an effective technique to determine the status of differential DNAm.

Reference

Khodadadi, E., Fahmideh, L., Khodadadi, E., Dao, S., Yousefi, M., Taghizadeh, S., Asgharzadeh, M., Yousefi, B., & Kafil, H. S. (2021). Current Advances in DNA Methylation Analysis Methods. BioMed research international, 2021, 8827516. https://doi.org/10.1155/2021/8827516

Laird P. W. (2010). Principles and challenges of genomewide DNA methylation

analysis. Nature reviews. Genetics, 11(3), 191–203. https://doi.org/10.1038/nrg2732

Dona Johns^1,2, Craig Smith^1,2, Richard Williams^1,2, Pavani Nadiminti³, Rasika Samarasinghe^1,2

Affiliations

1. Paediatric oncology and translational epigenetics lab, School of Medicine, Deakin University.
2. IMPACT, Deakin University.
3. La Trobe institute for agriculture & food (LIAF), La Trobe university

Background

Paediatric and adult astrocytoma are notably different. Understanding differentially methylated regions (DMRs) and their association with the aetiology of different diseases have improved prognosis of this lethal disease. We have tried to unravel the epigenetic modifications in Paediatric astrocytoma (pA) and signify the importance of studying these alterations which may have roles in predicting tumour progression.

Methods

A meta-analysis was done with 2513 studies. Methylation datasets were downloaded from NCBI and were analysed using an R- based differential methylation analysis tool, RnBeads. Differential methylation of CpG islands, CpG sites, promotors and genes were computed individually to correlate the effect of DMRs on DNA with respect to each other following which drug repurposing was done.

Results

Differential methylation analysis of CpG sites showed significant hyper-methylation at 211674 sites and significant hypo-methylation at 153807 sites. DMA of CpG islands showed significant hyper-methylation at 3980 sites and significant hypo-methylation at 16595 sites. DMA of promotors showed significant hyper-methylation at 13146 sites and significant hypo-methylation at 13690 sites. DMA of genes showed significant hyper-methylation at 6580 sites and significant hypo-methylation at 4187 sites (Samples having mean p value < 0.8, combined p value < 0.01 were considered hypermethylated and those having mean p value<0.2, combined p value < 0.01 were considered hypo methylated).

Conclusion

This study has identified significantly hyper and hypo methylated regions within the genome of patients with pA which are crucial in devising prognostic criteria and in studying the effects of epigenetic alterations in promoting tumour progression. We have also identified repurposed drugs based on these changes.

References

1. Capper, D., et al., DNA methylation-based classification of central nervous system tumours. Nature, 2018. 555(7697): p. 469-474

Megan Ellis¹, Bruna Panizzutti¹, Trang TT Truong¹, Zoe SJ Liu¹, Briana Spolding¹, Courtney Swinton¹, Damian Hernandez¹, Chiara Bortolasci¹, Olivia M Dean^1,2, Michael Berk^1,2,3, Sean McGee¹, Jee Hyun Kim^1,2, Ken Walder¹

Affiliations

1. Deakin University, IMPACT, The Institute for Mental and Physical Health and Clinical Translation, School of Medicine, Geelong, Australia
2. Florey Institute of Neuroscience and Mental Health, Parkville, Australia
3. Orygen, The National Centre of Excellence in Youth Mental Health, Centre for Youth Mental Health, The Florey Institute for Neuroscience and Mental Health and the Department of Psychiatry, University of Melbourne, Parkville, Australia

Background  

Previous studies have shown mitochondrial dysfunction in people with bipolar disorder. This study investigated how mitochondrial function and energy production changes throughout the cell differentiation process from induced pluripotent stem cells (iPSCs) to neural progenitor cells (NPCs) and the effects of lithium on mitochondrial function.

Methods  

Blood samples were collected from bipolar disorder (n=4) and healthy control participants (n=3). From these samples, peripheral blood mononuclear cells were isolated and reprogrammed using episomal vectors containing specific transcription factors to create iPSCs. These cells were then differentiated into NPCs. Both iPSCs and NPCs were then treated with lithium chloride (1mM) or vehicle as control. A mitochondrial bioenergetic profile was measured using a Seahorse XF24 Flux Analyser in the iPSCs and throughout differentiation into NPCs.

Results  

Results highlighted the effects of time and treatment on the bioenergetic profile. iPSCs predominantly utilized oxidative phosphorylation for energy production. As iPSCs differentiated into NPCs, energy generation shifted towards the glycolytic pathway. There was no significant difference in mitochondrial function between groups. However, lithium treatment exhibited an effect by increasing mitochondrial function in both groups. Further exploratory analysis of NPCs indicated enhanced mitochondrial function post-lithium treatment in bipolar disorder cell lines but not in control-derived lines.

Conclusions

Preliminary data implies that mitochondrial function and bioenergetics are affected by lithium treatment, suggesting a potential therapeutical mechanism of action. Further analysis with a larger sample size is required for conclusive evidence. Nonetheless, initial findings look promising towards pinpointing beneficial effects of lithium on mitochondrial function.

Trang TT Truong¹, Zoe SJ Liu¹, Bruna Panizzutti¹, Jee Hyun Kim^1,2, Olivia M Dean^1,2, Michael Berk^1,2,3, Ken Walder¹

Affiliations

1. Deakin University, IMPACT, The Institute for Mental and Physical Health and Clinical Translation, School of Medicine, Geelong, Australia
2. The Florey Institute of Neuroscience and Mental Health, Parkville, Australia
3. Orygen, the National Centre of Excellence in Youth Mental Health, Parkville, Australia

Background

Despite recent advances, drug discovery for schizophrenia remains challenging. Computational drug repurposing is a promising new methodology utilising expanding biomedical databases. Network analyses allow the comprehensive assessment of transcription factor regulatory effects via gene regulatory networks, reflecting transcription factor and target gene interactions by incorporating multiple lines of evidence.

Methods

We identified topological differences in the transcription factor-gene regulatory networks of schizophrenia cases versus unaffected controls using the PANDA algorithm. This incorporates binding motifs, protein interactions and gene co-expression data. The differential network was determined by comparing the strength of connections between the network associated with schizophrenia and the unaffected control network. The top positively differential transcription factors and negatively differential transcription factors were submitted to the CLUEreg tool of the GRAND database which utilises differential network signatures to find drugs that potentially target the disease’s gene signature.

Results

Using a large RNA-seq dataset of 532 post-mortem brain samples from CommonMind, we built co-expression gene regulatory networks for schizophrenia cases and unaffected control subjects with 15,831 genes and 413 transcription factors overlapping. From drug repurposing results, 18 drugs were highlighted as top candidates for repurposing to treat schizophrenia.

Conclusion  

Energy metabolism, immune response, cell adhesion, and thyroid hormone signalling are key pathways differentially regulated by transcription factors in schizophrenia cases compared to unaffected controls. Promising drug repurposing candidates, like rimonabant and kaempferol, show potential through these transcription factor-targeted pathways. Further preclinical and clinical investigations are needed to explore their mechanisms of action and efficacy in alleviating schizophrenia symptoms.

Gebreselassie Addisu Tilaye¹, Gareth Boer¹, Peiqi Yang¹, Andrew Wiesa¹, Aaqil Rifai^1,* and Richard Williams^1,*

Affiliations

1. Institute of Mental and Physical Health and Clinical Translation, School of Medicine, Deakin University, Waurn Ponds, Victoria, Australia
   * denotes equal last and corresponding authors

Abstract

Bone regeneration is a well-orchestrated physiological process that involves the recruitment of bone stromal cells to the injury site, the sustained release of growth factors and support from the extracellular matrix.

Here, we will discuss how a tissue engineering approach has been geared towards developing 3D scaffold to mimic the natural bone regeneration in vitro. We demonstrate that a functionalised multifactorial hydrogel can effectively direct the differentiation of bone stromal cells without the need for growth factors.

The natural components of ECM are mimicked through use of a biomimetic triumvirate. Hyaluronic acid is used as an inert yet hydrated support, the protein components are recapitulated with Self-assembled peptides containing signals representing laminin and fibronectin (IKVAV and RGD, respectively), and a method of controlling stiffness and mechanical properties via a covalent crosslinker (PEGDA). This yields a mechanically stable self-assembled hydrogel with nanostructure organization. These SAP-HA hydrogels are biocompatible and can effectively promotes bone stromal cells proliferation and differentiation.

We show, for the first time in such systems, dominant presentation of  the RGD-motif triggers cells towards chondrogenic lineage with elevated expression of collagen II (COLIIAI), whereas promoting the IKVAV-motif induces osteogenic lineage with the expression of collagen 1 (COLIAI). Within hours of seeding, bone stromal cells attach to the scaffold and start forming elaborate spindle shaped self-organization. Phenotype rescue using dorsomorphin have shown scaffold induced differentiation phenotype mimics BMP2 pathway.

The biomimetic material has been tested on three cell lines can be potentially used as for a engineerered stem cell graft for improved muscloskeletal tissue regeneration.

Bruna Panizzutti¹, Zoe Liu¹, Damián Hernández¹, Megan Ellis¹, Trang Truong¹, Chiara Bortolasci¹, Briana Spolding¹, Olivia Dean^1,2, Michael Berk^1,2,3, Ken Walder¹.

Affiliations

1. Deakin University, School of Medicine, IMPACT, Institute for Innovation in Physical and Mental Health and Clinical Translation, Geelong, 3220,  Australia.
2. Florey Institute for Neuroscience and Mental Health, University of Melbourne, Parkville, 3052, Australia
3. Orygen, The National Centre of Excellence in Youth Mental Health, Parkville, 3052, Australia

Background

Due to its episodic/cyclic nature, management of bipolar disorder (BD) is complex and reliant on medications from which many do not benefit. New treatment options for BD are urgently needed. We aim to identify off-patent drugs with known safety profiles that can rapidly translate to clinical practice to treat BD.

Methods

Sixteen research participants (8 BD and 8 matched (age, sex) healthy controls) were recruited for this study. Peripheral blood mononuclear cells isolated from blood samples were reprogrammed into induced pluripotent cells (iPSCs). iPSCs were differentiated into cortical networks (CNs), a mixture of neurons and astrocytes. CNs were harvested for RNA extraction and next-generation sequencing. The differentially expressed genes were used to run drug repurposing analyses completed using Connectivity Map (CMap, BROAD Institute) and LINCS2.

Results

The CMap analysis resulted in a list of compounds that could be repurposed for the treatment of bipolar disorder. Compounds with mechanisms of action associated with the pathophysiology of BD, like ACE inhibitors, acetylcholinesterase inhibitors, and calcium channel modulators (and many more), have been suggested as possible repurposing alternatives. The fact that drugs like lithium chloride and quetiapine are also on the list further validate your approach, as these are commonly prescribed for BD.

Conclusions

The hypothesis-generating data from the CMap analysis corroborates our idea that by using the stem cell-derived in vitro model, we can bypass a fundamental roadblock in therapy development in psychiatry: the lack of singular molecular targets.

Behnaz Azimi-Manavi¹, Amanda L Stuart¹, Julie A Pasco^1,2,3,4, Jason M Hodge^1,2, Kavindi Weerasinghe¹, Rasika M Samarasinghe¹, Lana J Williams^1,2

Affiliations

1. Deakin University, IMPACT – the Institute for Mental and Physical Health and Clinical Translation, School of Medicine, Barwon Health, Geelong, Australia
2. Barwon Health, Geelong, Australia
3. Department of Medicine-Western Health, The University of Melbourne, St Albans, Australia
4. Department of Epidemiology and Preventive Medicine, Monash University, Melbourne, Australia

Objective

It has been reported that antipsychotic use is associated with lower bone mineral density and bone quality. We aimed to determine whether antipsychotic use is associated with fracture risk in a population-based sample of adults living in the Barwon Statistical Division, south-eastern Australia.

Material and Methods

In this case-control study, 1,458 participants (51.8% women) with radiologically confirmed fracture between June 1^st 2012 and May 31^st 2013 (cases) were compared with 1,795 participants (46.5% women) without fracture (controls) for the same time period. Medication use, medical history and lifestyle factors were documented by self-report. Multivariable binary logistic regression was used to explore associations between antipsychotic use and fracture following adjustment for possible confounders.

Results

In women, antipsychotic use was identified for 20 of 755 (2.6%) cases and 10 of 834 (1.2%) controls (p=0.034) and in men, antipsychotic use was identified for 13 of 703 (1.8%) cases and 5 of 961 (0.5%) controls (p=0.010). Following adjustments, antipsychotic use was associated with a 3.0-fold increased risk of fracture in men and a 2.3-fold increased risk of fracture in women. Patterns persisted after exclusion of participants with non-fragility fractures and self-reported schizophrenia.

Conclusion  

These population-based data suggest antipsychotic use is associated with higher fracture risk in women and men. While future research exploring underlying mechanisms is needed, regular monitoring of bone health in antipsychotic users is suggested.

Acknowledgment  

The study is supported by the National Health and Medical Research Council (NHMRC), Australia (1162867, 628582, 251638, 299831). BAM is supported by a Deakin University Postgraduate Research Scholarship (DUPRS) and LJW by an NHMRC Emerging Leadership Fellowship (1174060). The authors thank Professor Graham Giles of the Cancer Epidemiology Centre of The Cancer Council Victoria, for permission to use the Dietary Questionnaire for Epidemiological Studies (Version 2), Melbourne: The Cancer Council Victoria 1996.

Emma West¹, Lana Williams¹, Julie Pasco^1,2,3,4

Affiliations

1. Deakin University, IMPACT – Institute for Mental and Physical Health and Clinical Translation, School of Medicine, Geelong, Australia
2. Barwon Health, Geelong, Australia
3. Department of Medicine-Western Health, The University of Melbourne, Australia
4. Department of Epidemiology and Preventative Medicine, Monash University, Australia

Background

Sarcopenia is characterised by an accelerated loss of skeletal muscle mass and function. It is associated with numerous adverse health outcomes however studies examining the relationship between sarcopenia and aspects of quality of life (QoL) are scarce.

Methods

This cross-sectional study involved 682 men and women (ages 60–96 years) from the Geelong Osteoporosis Study. Sarcopenia was defined according to the EWGSOP2 algorithm. Appendicular lean mass (ALM) was assessed using dual-energy X-ray absorptiometry. Handgrip strength (HGS) and the timed up-and-go (TUG) test were used to assess muscle function. The WHOQoL-BREF was used to assess QoL. Associations between sarcopenia and WHOQoL-BREF domains (physical, psychological, social relationships and environment) were investigated using multivariable logistic regression while testing for potential confounding.

Results

Fifty-seven participants (8.4%) had probable sarcopenia (low HGS strength), 12 (1.8%) had confirmed sarcopenia (low HGS and low ALM), and two had severe sarcopenia (low HGS, low ALM, and slow TUG). In crude analysis, probable sarcopenia was associated with low QoL across all four WHOQoL-BREF domains. After adjusting for sociodemographic and lifestyle variables probable sarcopenia was associated with poor psychological-related QoL [OR 2.11 (95% CI 1.13-3.92) p = 0.019]. No associations between confirmed sarcopenia and QoL were observed, likely due to a lack of statistical power.

Conclusion

Older adults with low HGS were more likely to have poor psychological-related QoL. Our findings reinforce the importance of muscle function for good QoL. Interventions to prevent or manage sarcopenia among older adults may contribute to better QoL for this population.

Jacob W Harland¹, Kimberly Cukier², Anna Lonie^2,3, Mark A Kotowicz^1,2,4, Julie A Pasco^1,2,4,5, and Kara L Holloway-Kew¹

Affiliations

1. Deakin University, IMPACT – Institute for Mental and Physical Health and Clinical Translation, Geelong, Australia.
2. University Hospital Geelong, Barwon Health, Geelong, Australia.
3. School of Medicine, Deakin University, Geelong, Australia.
4. Department of Medicine, The University of Melbourne – Western Campus, St Albans, Australia.
5. Department of Epidemiology and Preventive Medicine, Monash University, Melbourne, Australia.

Background

The group of individuals with diabetes are heterogenous and recently new, more homogenous subgroupings have been proposed (1). These are: mild age-related diabetes (MARD), mild obesity-related diabetes (MOD), severe insulin-resistant diabetes (SIRD), severe insulin-deficient diabetes (SIDD), and severe autoimmune diabetes (SAID). Little is known about how bone health varies between these groups. This study investigated these differences, comparing the subgroups and normoglycaemia.

Methods

Male participants (n=895, 20-97yr) were drawn from the Geelong Osteoporosis Study. Diabetes (n=105) was defined as fasting plasma glucose≥7.0mmol/L, self-report and/or use of antihyperglycaemic medication. Using hierarchical clustering, men with diabetes were categorised into the SAID subgroup (positive glutamic acid decarboxylase antibodies), k-means clustering was used to categorise the remaining men. The dual-energy x-ray absorptiometry was used to measure bone mineral density (BMD), lumbar spine scans were used to assess trabecular bone score (TBS). ANOVA and linear regression were used to identify differences in BMD and TBS. The SAID group was excluded from regression analyses due to low numbers.

Results

The groups analysed were normoglycaemia (n=790, age±SD 57.0±19.4yr) MARD (n=25, 80.2±4.5yr), MOD (n=30, 68.4±3.8yr), SIRD (n=31, 58.2±3.1yr), SIDD (n=16, 45.8±6.0yr), and SAID (n=3, 27.0±11.5yr). Femoral-neck BMD was lowest in the MARD group; this was not significant after adjusting for age. TBS was lower in all subgroups compared to normoglycaemia. The SIDD group remained lower (1.557(1.440-1.675)vs1.672(1.586-1.758),p=0.003) after adjusting for age and weight.

Conclusion

The SIDD group sustained a lower TBS after adjustment. These results may guide diabetes management strategies, focussing interventions on subgroups with poorer bone health.

References

1. Ahlqvist E, Storm P, Käräjämäki A, Martinell M, Dorkhan M, Carlsson A, Vikman P, Prasad RB, Aly DM, Almgren P, Wessman Y, Shaat N, Spégel P, Mulder H, Lindholm E, Melander O, Hansson O, Malmqvist U, Lernmark Å, Lahti K, Forsén T, Tuomi T, Rosengren AH, Groop L. Novel subgroups of adult-onset diabetes and their association with outcomes: a data-driven cluster analysis of six variables. Lancet Diabetes Endocrinol 2018;6:361-369

D. Kavindi Weerasinghe¹, Alister Ward¹, Clifford Lounge¹, Jason M. Hodge^{1, 2, 4}, Rasika M. Samarasinghe¹, Julie A. Pasco^{1, 2, 3}, Lana J. Williams ^{1, 2}

Affiliations

1. Deakin University, IMPACT (The Institute for Mental and Physical Health and Clinical Translation, School of Medicine, Barwon Health, Geelong, Australia)
2. Barwon Health, Geelong, Australia
3. Department of Medicine-Western Health, the University of Melbourne, St Albans, Australia

Background

Antipsychotics are the first line treatment in psychosis, with treatment often continued during pregnancy. To date there is no clear evidence on the effects of antipsychotics on fetal bone development. Therefore, we investigate the effects of antipsychotics on embryonic bone formation in-vivo using a zebrafish model.

Methods

The effect of first- (haloperidol; FGA), second- (olanzapine; SGA) and third- (aripiprazole; TGA) generation antipsychotics on zebrafish bone development was measured using alizarin red staining. Osteoblast development marker expression was measured using whole-mount in situ hybridization. Dopamine, serotonin and adrenergic receptor expression profiles were measured along with a marker of apoptosis (casp3a).

Results

Each antipsychotic reduced zebrafish bone formation in a dose-dependent manner, where haloperidol was the most potent inhibitor and olanzapine was the least potent inhibitor. Osteoblast genes expression was reduced with 10 µM of haloperidol and aripiprazole, whereas olanzapine reduced bone formation at 30 µM. There was no effect on casp3a expression, or dopamine or serotonin receptor expression upon antipsychotic exposure. However, higher concentration of olanzapine increased adrenergic receptor beta-2 expression, while lower concentrations had no effect.

Conclusion

Each antipsychotic reduced embryo bone development, with haloperidol being the most potent inhibitor. Haloperidol- and aripiprazole-induced bone loss was not due to apoptosis nor did antipsychotic exposure effect dopamine, serotonin or adrenergic receptor expression. Although, olanzapine-induced bone loss could be due to increased adrenergic receptor beta-2 expression. Further work into signalling pathways is needed to further understand the mechanisms involved in antipsychotic induced bone loss.

Aminu Suleiman¹, Mojtaba Lotfaliany Abrand Abadi^1,2, Lana J Williams¹, Richard Page^1,2, Stephen Gill^1,2, Anusha P Budehal¹, Julie A Pasco^1,2,3,4

Affiliations

1. IMPACT – the Institute for Mental and Physical Health and Clinical Translation, School of Medicine, Deakin University, Geelong, 3220 Australia
2. Barwon Health, Geelong, 3220 Australia
3. Department of Medicine-Western Health, The University of Melbourne, St Albans, 3021 Australia
4. Department of Epidemiology and Preventive Medicine, Monash University, Melbourne, 3004 Australia

Background

Chronic Osteoarthritis is a debilitating condition that can lead to the necessity of joint replacement surgery. This condition is characterized by severe pain, and, in some cases, loss of mobility. Thus, this study aimed to investigate the role of lifestyle as a key determinant associated with joint replacement.

Methods

Data from males participating in the Geelong Osteoporosis Study was linked with the Barwon Joint Registry (n=1539, 20-94 years). Height and weight were measured, and lifestyle factors were obtained via a questionnaire at baseline (2001-06). A preliminary analysis using Cox proportional hazards models was conducted by following men from baseline until JRS, death, or end of study (December 2022). The analysis was conducted using R statistical package.

Results

Eighty-one men (5.3%) underwent JRS during 15 years of follow-up. Hip replacement surgery was the prevailing procedure (71/81, 87.7%), followed by knee replacement surgery (6/81, 7.4%) and shoulder replacement surgery (4/81, 4.9%). Body mass index (BMI) and daily alcohol consumption were significantly associated with the increased risk of JRS (HR:1.04, CI:1.00, 1.08, HR:1.22, CI:1.07,1.38) after adjusting for smoking, dietary calcium intake and physical activity.

Conclusion

Higher BMI and daily alcohol consumption but not smoking, physical activity or dietary calcium intake appeared to be independently associated with increased risk for joint replacement surgery. Higher BMI and daily alcohol consumption are likely to be associated with the presence of osteoarthritis.

Bonnie Beasant¹, Mojtaba Lotfaliany¹, Monica Tembo², Scott McCoombe³, Vanessa Vaughan³, Julie A Pasco^{1, 4, 5}, Lana J Williams¹, Sarah M Hosking^{1, 2}

Affiliations

1. Deakin University, Institute for Mental and Physical Health and Clinical Translation (IMPACT)- Barwon Health, School of Medicine, Geelong, Victoria, Australia
2. School of Medicine, Deakin University, Geelong, Victoria, Australia
3. Medical School, The University of Western Australia, Perth, Western Australia, Australia
4. Department of Medicine -Western Health, The University of Melbourne, St. Albans, VIC, Australia
5. Department of Preventive Medicine, Monash University, Melbourne, VIC, Australia

Background

While health literacy has a confirmed association with several cardiovascular risk factors, its role in preventing a cardiovascular event has been largely unexplored. This study aimed to investigate how health literacy associates with 10-year predicted risk of a cardiovascular event.

Methods

Data were utilised from the Geelong Osteoporosis Study (GOS) 15-year follow up for 971 participants aged between 40 and 80 years. The Globorisk algorithm was used to predict 10-year risk of cardiovascular disease, providing a score between zero and 100%. The Health Literacy Questionnaire© (HLQ©) was used to measure participants’ health literacy across nine domains. Covariates considered in linear regression models were birth country, employment, education, socio-economic status and living alone.

Results

The median (IQR) Globorisk score was 0.014 (IQR 0.019, 0.070) indicating 4.1% risk of cardiovascular event. In adjusted models, the unit increases in three HLQ© scales were associated with lower predicted CVD risk: Scale 5: “Appraise health information” (mean difference -0.74, 95% CI -1.43, -0.05, p=0.03), Scale 8: “Ability to find good health information” (mean difference -0.95, 95% CI -1.61, -0.29, p=0.005) and Scale 9: “Understanding health information enough to know what to do” (mean difference -1.01, 95% CI -1.68, -0.33, p=0.003).

Conclusion  

This study demonstrated an inverse association between three domains of health literacy and 10-year risk of cardiovascular event in a sample of Australian men and women. Future studies could further explore this relationship especially among people who live alone.

Kara B Anderson¹, Pamela Rufus-Membere¹, Julie A Pasco^1,2,3,4, Mark A Kotowicz^1,2,3, Kara L Holloway-Kew¹

Affiliations

1. Deakin University, IMPACT – the Institute for Mental and Physical Health and Clinical Translation, School of Medicine, Geelong, Australia
2. Barwon Health, Geelong, Australia
3. Department of Medicine, The University of Melbourne – Western Health, St Albans, Australia
4. Department of Epidemiology and Preventative Medicine, Monash University, Prahran, Australia

Background

Bone material strength index (BMSi) quantifies bone strength in vivo at the mid tibia using impact microindentation (IMI). Anecdotal evidence suggests that within-participant variance in BMSi may be associated with individual level mean BMSi. This study aimed to investigate associations between mean and variance of IMI measures in a population-based study.

Methods

Participants were men (n=419) and women (n=32) from the Geelong Osteoporosis Study who underwent BMSi measurement using the OsteoProbe at recent follow-up phases (men 2016-2022; women 2022-2023). Median age was 63.6yr (IQR 52.5-71.6). BMSi standard deviation was skewed and therefore log transformed (referred to as log-SD). Linear regression models with log-SD as the dependent variable and mean BMSi as the independent variable adjusting for sex, age, height and weight were performed.

Results

In unadjusted models, a trend was observed whereby greater BMSi was associated with lower log-SD (β=-0.01, p=0.073). This association was sustained after adjustment, and an interaction between BMSi and age was observed (p=0.013). In those aged 63.6yr and over (median age), mean BMSi was inversely associated with log-SD (β=-0.01, p=0.010). Sex was not identified as an effect modifier. In younger participants, no BMSi-log-SD association observed (p=0.659).

Conclusion  

In older men and women, there is greater variance in low BMSi values. One potential reason for this observation may be the presence of an increased number of resorption pits in the cortical bone of older individuals. These data support a heightened fracture risk for men and women with low BMSi and poorer bone structure.

Kara L Holloway-Kew¹, Pamela G Rufus-Membere¹, Kara B Anderson¹, Jacob W Harland¹, Adolfo Diez-Perez², Mark A Kotowicz^1,3,4, Julie A Pasco^1,3,4,5

Affiliations

1. Deakin University, IMPACT – the Institute for Mental and Physical Health and Clinical Translation, School of Medicine, Geelong, Australia.
2. Barcelona- Department of Internal Medicine, Hospital del Mar-IMIM, Autonomous University of Barcelona and CIBERFES, Instituto Carlos III, Spain.
3. Barwon Health, Geelong, Australia.
4. Department of Medicine, The University of Melbourne – Western Health, St Albans, Australia.
5. Department of Epidemiology and Preventive Medicine, Monash University, Melbourne, Australia.

Background

Routine measurements of bone involve performing scans to determine how much bone is present. However, a relatively new technique called impact microindentation can assess the material properties of bone directly and provide an indication of bone strength. This technique produces a value called Bone Material Strength Index, or BMSi. It is not clear if there are differences in BMSi between men and women, and to date, sex differences have not been compared for individuals from the same population. Therefore, we compared BMSi values for men and women drawn from the same geographical location in Australia.

Methods

Participants (n=220) were from the Geelong Osteoporosis Study. BMSi was measured for participants at recent follow-up phases (women 2022-2023 and men 2016-2022). Women (n=55) were age matched to men (n=165) in a 1:3 ratio. A two-sample t test was used to determine intergroup differences in mean BMSi. Linear regression was also performed, adjusting for weight and height.

Results

Median (IQR) ages for men and women were 67.0 (61.7-71.5) and 67.4 (62.0-71.2) years (p=0.998). Men were heavier (81.0±10.9 vs 71.0±13.9 kg, p<0.001) and taller (173.9±6.4 vs 161.5±7.5 cm, p<0.001) than women.

Mean (±SD) BMSi for women (75.7±7.4) was lower than for men (82.8±6.8) (p<0.001). The difference persisted after adjustment for weight and height (mean±SE: 76.5±1.1 vs 82.5±0.6, p<0.001).

Conclusion  

BMSi was lower for women than men derived from the same population. This information is consistent with poorer bone health in women, and provides a baseline to perform longitudinal studies in the future.

Mohammadreza Mohebbi^1,2, Mehdi Noroozi¹, Michael Berk², Mojtaba Lotfaliany²

Affiliations

1. Faculty of Health, biostatistics Unit, Deakin University, Geelong, Vic, Australia
2. IMPACT—the Institute for Mental and Physical Health and Clinical Translation, School of Medicine, Faculty of Health, Deakin University, Geelong, Vic, Australia

Background

Alcohol intake is a potentially modifiable risk factor for depression. There are data suggesting that light to moderate consumption may be associated with a lower risk for depressive symptoms when compared with abstinence, with risk increasing again for heavier drinkers, resulting in a J-shaped relationship. However, the extent to which these protective effects are genuine causal relationships, as opposed to biased associations driven by methodological limitations, has not been established. We employed a marginal structural model (MSM) approach to investigate the J-shaped relationship between alcohol consumption and depression.

Methods

Community-dwelling, initially healthy individuals aged 70+ years (N = 19,114), were recruited from 2010 to 2014 through general practitioners (Australia) and clinic-based mailing lists (United States) and followed until June 2017 (median 4.7 years follow-up). The 10-item Center for Epidemiologic Studies Depression scale (CES-D10) was used to detect depressive symptoms. Alcohol drinking was stratified into abstinence, occasional consumption, moderate consumption, and above-guideline consumption according to current U.S. guidelines by incorporating frequency, volume, and heavy episodic drinking. Age, sex, race, ethnicity, education, smoking status, residential type, living arrangement, BMI, morbidities, or chronic conditions were considered as potential confounders. Subgroup analyses for men and women were performed. 

MSMs were used to fully adjust for measured confounders through a “marginal” approach and balance confounders and withdrawals across different levels of alcohol consumption.

Results

The model confirmed J-shaped relationship between alcohol and depression symptoms. Moderate drinkers had the lowest depression rate followed by occasional drinkers (OR:1.11; 95% CI [1.03-1.20]), and above the guideline drinkers (1.15; [1.06-1.24]), and abstinence from alcohol group had the highest rate of depression (1.19; [1.10-1.29].

Conclusion

Our findings contribute preliminary evidence that associations between moderate alcohol consumption and reduced risk for depression may reflect a causal linked. Further adjustment by considering the effect of healthier lifestyles known to be associated with light alcohol consumption including diet, physical activity, socioeconomic status, social networking, and social isolation on Australian sample (n=17,320) will be discussed. The collinearity of these factors has long been a pitfall for epidemiologic studies of the possible benefits of alcohol drinking.

Mia A Percival¹, Kara B Anderson¹, Julie A Pasco^1,2,3,4, Sarah M Hosking¹, Natalie K Hyde¹

Affiliations

1. Deakin University, Geelong, Victoria, Australia
2. Barwon Health, Geelong, Victoria, Australia
3. Department of Medicine-Western Health, The University of Melbourne, St Albans, Victoria, Australia
4. Department of Epidemiology and Preventative medicine, Monash University, Melbourne, Victoria, Australia

Background

There have been an abundance of studies reporting on maternal lifestyle during pregnancy and offspring health, with growing evidence examining the paternal origins of health and disease. This review aimed to systematically search extant literature regarding the relationship between paternal lifestyle and health exposures during early life, conception and pregnancy and offspring musculoskeletal, body composition and growth measures. This abstract focuses on offspring bone outcomes.

Methods 

A systematic search of the research databases MEDLINE, Embase, CINAHL and Cochrane Library was conducted and identified papers were reviewed for their eligibility by two independent reviewers. Searches were run from database inception until 1 March 2022. Findings were summarised descriptively.

Results

In total, 241 papers met inclusion for the review. There were 27,840 children reported in eight papers examining offspring bone health outcomes including bone mineral density (BMD), content (BMC) and area (BA). Seven were cohort studies and one was a cross-sectional study. There were nine paternal exposures examined and findings were mixed (Body mass index: no association with BMD, BMC or BA in full cohort, ↑ BMD in females. Age: mixed findings from two studies. Height: mixed findings from two studies. Bone measures: BA, BMC and BMD correlated with ↑ BA and BMC. BMD correlated with ↑ BMD. Education: ↓ BMD, BMC and BA. Smoking: mixed findings from two studies.)

Conclusion

Few studies report paternal determinants of offspring bone health, and existing papers provide conflicting evidence. More studies looking at associations such as paternal health behaviours are required.

Ashkan Pakzad¹, Shiva Ganjali², Mojtaba Lotfaliany², Mohammadreza Mohebbi³

Affiliations

1. School of Medicine, Deakin University, Geelong, Australia
2. The Institute for Mental and Physical Health and Clinical Translation (IMPACT), School of Medicine, Deakin University, Geelong, Australia
3. Biostatistics Unit, Deakin University, Geelong, Australia

Background

Depression among seniors is widespread yet inadequately addressed. Though previous studies have identified depression risk factors, intricate interplay between lifestyle and mental health complicates the identification of those most vulnerable. We compare modern machine learning techniques to model depression outcomes.

Methods

A literature review was conducted to identify health and lifestyle indicative risk factors of depression. Data available from ASPREE (ASPirin in Reducing Events in the Elderly) a large-scale cohort study with outcome of clinical depression was considered. Six popular machine learning algorithms including logistic regression, k-nearest neighbours (k-NN), random forest, gradient-boosted decision trees (GBDT), support vector machine and multi-layer perceptron neural networks were fit to classify depression outcome after three years. A grid search optimized hyperparameters via five-fold cross-validation. Best models were identified based on mean area-under-receiver-operator-curve (AUROC). Feature importance was evaluated. Least important features were gradually pruned while measuring performance to create a compact practical model.

Results

Individuals with 147 predictors of late-life depression were selected (n=12897; 54% female; 41% depressed after 3-years); preprocessing yielded 166 features. GBDT outperformed (AUROC 0.79; accuracy 0.73; precision 0.68; F1-score 0.68). Other models except kNN performed similarly. Compact GBDT matched performance (AUROC 0.78; accuracy 0.71; precision 0.65; F1-score 0.67) with 11 features.

Conclusion

Despite considering several depression predictors from the literature, few were found strongly indicative of depression. A compact machine learning model with only these important features performed similarly. This is valuable in creating

Najmeh Davoodian¹,*, Mojtaba Lotfaliany², Rachel R. Huxley³, Crystal Man Ying Lee⁴, Julie A. Pasco², Mohammadreza Mohebbi⁵

Affiliations

1. School of Medicine, Deakin University, Geelong, VIC, Australia
2. IMPACT – the Institute for Mental and Physical Health and Clinical Translation, School of Medicine, Deakin University, Geelong, VIC, Australia
3. Faculty of Health, Deakin University, Melbourne, VIC, Australia
4. School of Population Health, Curtin University, Perth, Western Australia
5. Biostatistics Unit, Faculty of Health, Deakin University, Geelong, VIC, Australia

Background 

Prediabetes, a subclinical precursor to diabetes that currently affects approximately 374 million adults worldwide, is a risk factor for the development of cardiovascular disease and stroke in addition to diabetes (1). Prediabetes can be reversed to normoglycaemia (2); hence, we aimed to quantify the role of the metabolic risk factors on prediabetes regression to normoglycaemia.

Methods

We used the Obesity, Diabetes, and Cardiovascular Disease Collaboration database for our individual participant data meta-analysis. This database includes 19 prospective cohort studies involving 113,296 adults across various ethnicities and age groups. We included individuals with prediabetes with at least one follow-up in the analysis. We utilized Discrete-Time Hidden Markov Models to estimate hazard ratios for prognostic factors of prediabetes regression in each cohort study. These estimations were then pooled in the random-effects meta-analysis model.

Results

We included 19,255 participants with prediabetes at baseline; median follow-up 9.8-year (IQR 5.8–12.3); 53% were women, mean age of 51 years for both sexes. Former smoking (hazard ratio 0.98, 95%CI 0.89-1.06), higher waist-to-hip ratio (0.86, 0.79-0.93), higher waist-to-height ratio (0.83, 075-0.92), higher value of waist-circumferences (0.87, 0.71-1.06), overweight (0.88, 0.81-0.96) and obesity (0.86, 0.71-1.04), high diastolic (0.93, 0.87-0.99) and systolic (0.96, 0.91-1.01) blood pressure, low serum HDL-cholesterol (0.87, 0.81-0.92) and high serum triglycerides (0.88, 0.81-0.96), were associated with the lower likelihood of an individuals with prediabetes achieve normoglycaemia.

Conclusions

The role of metabolic risk factors in prediabetes regression underscores the importance of lifestyle modification in the prediabetes state, not only to reduce T2DM development but also to attain normoglycaemia.

References

1. Almourani R, Chinnakotla B, Patel R, Kurukulasuriya LR, Sowers J. Diabetes and Cardiovascular Disease: an Update. Current Diabetes Reports. 2019;19(12):161.
2. Tabák AG, Herder C, Rathmann W, Brunner EJ, Kivimäki M. Prediabetes: a high-risk state for diabetes development. Lancet. 2012;379(9833):2279-90.

Jasmine R Cleminson^1,4, Julie A Pasco^2,3,4,5, Jason M Hodge^2,4,6, Rasika M Samarasinghe²,Lana J Williams^2,4

Affiliation

1. School of Medicine, IMPACT, Institute for Innovation in Physical and Mental Health and Clinical Translation, Deakin University, Geelong, Australia.
2. School of Medicine, IMPACT, Institute for Innovation in Physical and Mental Health and Clinical Translation, Deakin University, Geelong, Australia.
3. Department of Medicine-Western Health, Western Centre for Health Research & Education (WCHRE) Building, St Albans, Australia.
4. Barwon Health, University Hospital Geelong, Geelong, Australia.
5. Department of Epidemiology and Preventive Medicine, Monash University, Melbourne, Australia.

Background

Osteoporosis, a rapidly intensifying global health challenge, is intertwined with serotonin, a neurotransmitter influencing mood, appetite, and sleep. A deeper understanding of their relationship can offer insights into osteoporosis's pathophysiology and preventative strategies.

Method

Comprehensive PhD research investigated serotonin's relation to bone metabolism through a mixed-methods approach. Focusing on serotonin's association with bone metabolism influenced by diet, gut health, and psychopathology. Through the Geelong Osteoporosis Study (GOS) and a case-control study (PROFRAC), various aspects such as dietary tryptophan intake, serum lipopolysaccharide-binding protein (LBP) levels, anxiety, depressive symptoms, and antidepressant usage were analysed in relation to bone health indicators. Additionally, in vitro studies examined serotonin's impact on osteoclast formation and function.

Results  

The GOS revealed that in a population-based sample, high dietary tryptophan intake was linked to a more substantial bone mineral density (BMD) at the hip, although this association was attenuated by age. Another chapter found a connection between LBP and reduced mid-forearm BMD in heavier participants. The PROFRAC study underscored that depressive symptoms and antidepressant usage heightened fracture risk, especially in women. In vitro investigations denoted that serotonin promoted osteoclast resorption, and its synthesis impediment led to fusion and resorption alterations, indicating serotonin's significant role in osteoclast functions.

Conclusion

The studies collectively illuminate the multifaceted relationship between serotonin and bone health, providing a foundation for potential interventions in osteoporosis management and its prevention.

Pamela Rufus-Membere¹, Kara B Anderson¹, Kara L Holloway-Kew¹, Jacob Harland¹, Adolfo Diez-Perez², Mark A Kotowicz^1,3,4, Page, R,^3,5 Julie A Pasco^1,3,4,6

Affiliation

1. Deakin University, IMPACT- Institute for Mental and Physical Health and Clinical Translation, School of Medicine, Geelong Australia
2. Barcelona- Department of Internal Medicine, Hospital del Mar-IMIM, Autonomous University of Barcelona and CIBERFES, Instituto Carlos III, Spain
3. Barwon Health, Geelong, Australia
4. Department of Medicine-Western Health, The University of Melbourne, St. Albans, Australia.
5. Barwon Centre of Orthopaedic Research and Education (B-CORE), Geelong, Australia.
6. Department of Epidemiology and Preventive Medicine, Monash University, Melbourne, Australia.

Background

Impact microindentation (IMI) is a minimally invasive indentation technique that allows the assessment of bone material strength index (BMSi) in vivo, by measuring the depth of a micron-sized, spherical tip into cortical bone that is then indexed to the depth of the tip into a reference material. In this study, we aimed to assess the practicality of its application in women from the Geelong Osteoporosis Study.

Methods

Participants were 58 women aged 49-78yr from the Geelong Osteoporosis Study. Impact microindentation was performed in the mid-shaft of the right tibia using the OsteoProbe. Immediately following measurement, each participant was requested to rate on a Visual Analogue Scale [0-10] the level of discomfort anticipated and experienced, any initial reluctance towards the measurement and whether they were willing to repeat the measurement.

Results 

Of 58 potential participants who attended this assessment phase, 32 underwent IMI measurement. Reasons for non-measurement in 26 women were existing skin conditions (n=6), excessive soft tissue around mid-tibial region (n=16); four participants did not provide any reasons for declining. For 32 participants who had IMI performed, the expectation for pain when briefed about the procedure was low (2.07 ± 2.39), as was pain experienced during the measurement (0.91 ± 1.17). Participants were not reluctant to undergo the measurement (0.49 ± 1.17), and all indicated a willingness to repeat the measurement.

Conclusion

Results in this study quell such concerns that the minimally-invasive procedure might limit participant and patient involvement in research and/or clinical settings.

Behnaz Azimi-Manavi¹, Kayla B Corney¹, Mohammadreza Mohebbi¹, Shae E Quirk¹, Amanda L Stuart¹, Julie A Pasco^1,2,3,4, Jason M Hodge^1,2, Michael Berk^1,2,5,6,7, Lana J Williams^1,2

Affiliation

1. Deakin University, IMPACT – the Institute for Mental and Physical Health and Clinical Translation, School of Medicine, Barwon Health, Geelong, Australia
2. Barwon Health, Geelong, Australia
3. Department of Medicine-Western Health, The University of Melbourne, St Albans, Australia
4. Department of Epidemiology and Preventive Medicine, Monash University, Melbourne, Australia
5. Department of Psychiatry, The University of Melbourne, Parkville, Victoria, Australia
6. Florey Institute of Neuroscience and Mental Health, Parkville, Victoria, Australia
7. Orygen, The National Centre of Excellence in Youth Mental Health, Centre for Youth Mental Health, Parkville, Victoria, Australia

Objective

Schizophrenia is associated with increased risk of medical comorbidity, possibly including osteoporosis, which is a public health concern due to its significant social and health consequences. In this systematic review and meta-analysis, we aimed to determine whether schizophrenia is associated with bone fragility.

Material and Methods

The research question and inclusion/exclusion criteria were developed and presented according to the PECO (Population, Exposure, Comparison, Outcome) framework. Schizophrenia was identified from medical records, DSM-IV/5 or the ICD. The outcomes for this review were bone fragility [i.e., bone mineral density (BMD), fracture, bone turnover markers, bone quality]. A search strategy was developed and implemented for the electronic databases. A narrative synthesis was undertaken for all included studies; the results from eligible studies reporting on BMD and fracture were pooled using a random effects model to complete a meta-analysis. The conduct of the review and reporting of results adhered to PRISMA guidelines.

Results

Our search yielded 3,103 studies, of which 29 met the predetermined eligibility criteria. Thirty-seven reports from 29 studies constituted 17 studies investigating BMD, eight investigating fracture, three investigating bone quality and nine investigating bone turnover markers. The meta-analyses revealed that people with schizophrenia had lower BMD at the lumbar spine [standardised mean difference (SMD) -0.74, 95% CI -1.27, -0.20; Z=-2.71, p=0.01] and at the femoral neck (SMD -0.78, 95% CI -1.03, -0.53; Z=-6.18, p≤0.001). Also observed was a higher risk of fracture (OR 1.43, 95% CI 1.27, 1.61; Z=5.88, p≤0.001). Following adjustment for publication bias, the association between schizophrenia and femoral neck BMD (SMD -0.63, 95% CI -0.97, -0.29) and fracture (OR 1.32, 95% CI 1.28, 1.35) remained.

Conclusion  

This systematic review and meta-analysis provides evidence in support of bone fragility in people with schizophrenia. Further research is needed to evaluate the aetiology of bone fragility in this population.

Acknowledgment  

The authors want to acknowledge the help and support of Blair Kelly, Librarian at Deakin University.