Medicine (Western Health) - Research Publications

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    Osteocalcin and its forms respond similarly to exercise in males and females
    Hiam, D ; Landen, S ; Jacques, M ; Voisin, S ; Alvarez-Romero, J ; Byrnes, E ; Chubb, P ; Levinger, I ; Eynon, N (ELSEVIER SCIENCE INC, 2021-03-01)
    INTRODUCTION: Acute exercise increases osteocalcin (OC), a marker of bone turnover, and in particular the undercarboxylated form (ucOC). Males and females differ in baseline levels of total OC and it is thought the hormonal milieu may be driving these differences. Males and females adapt differently to the same exercise intervention, however it is unclear whether the exercise effects on OC are also sex-specific. We tested whether the responses of OC and its forms to acute High Intensity Interval Exercise (HIIE) and High Intensity Interval Training (HIIT) differed between males and females. Secondly, we examined whether sex hormones vary with OC forms within sexes to understand if these are driving factor in any potential sex differences. METHODS: Total OC (tOC), undercarboxylated OC (ucOC), and carboxylated OC (cOC) were measured in serum of 96 healthy participants from the Gene SMART cohort (74 males and 22 females) at rest, immediately after, and 3 h after a single bout of HIIE, and at rest, 48 h after completing a four week HIIT intervention. Baseline testosterone and estradiol were also measured for a subset of the cohort (Males = 38, Females = 20). Linear mixed models were used to a) uncover the sex-specific effects of acute exercise and short-term training on OC forms and b) to examine whether the sex hormones were associated with OC levels. RESULTS: At baseline, males had higher levels of tOC, cOC, and ucOC than females (q < 0.01). In both sexes tOC, and ucOC increased to the same extent after acute HIIE. At baseline, in males only, higher testosterone was associated with higher ucOC (β = 3.37; q < 0.046). Finally, tOC and ucOC did not change following 4 weeks of HIIT. CONCLUSION/DISCUSSION: While there were no long-term changes in OC and its forms. tOC and ucOC were transiently enhanced after a bout of HIIE similarly in both sexes. This may be important in metabolic signalling in skeletal muscle and bone suggesting that regular exercise is needed to maintain these benefits. Overall, these data suggest that the sex differences in exercise adaptations do not extend to the bone turnover marker, OC.
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    The effects of acute exercise on bone turnover markers in middle-aged and older adults: A systematic review
    Smith, C ; Tacey, A ; Mesinovic, J ; Scott, D ; Lin, X ; Brennan-Speranza, TC ; Lewis, JR ; Duque, G ; Levinger, I (ELSEVIER SCIENCE INC, 2021-02-01)
    BACKGROUND: Bone turnover is the cellular machinery responsible for bone integrity and strength and, in the clinical setting, it is assessed using bone turnover markers (BTMs). Acute exercise can induce mechanical stress on bone which is needed for bone remodelling, but to date, there are conflicting results in regards to the effects of varying mechanical stimuli on BTMs. OBJECTIVES: This systematic review examines the effects of acute aerobic, resistance and impact exercises on BTMs in middle and older-aged adults and examines whether the responses are determined by the exercise mode, intensity, age and sex. METHODS: We searched PubMed, SCOPUS, Web of Science and EMBASE up to 22nd April 2020. Eligibility criteria included randomised controlled trials (RCTs) and single-arm studies that included middle-aged (50 to 65 years) and older adults (>65 years) and, a single-bout, acute-exercise (aerobic, resistance, impact) intervention with measurement of BTMs. PROSPERO registration number CRD42020145359. RESULTS: Thirteen studies were included; 8 in middle-aged (n = 275, 212 women/63 men, mean age = 57.9 ± 1.5 years) and 5 in older adults (n = 93, 50 women/43 men, mean age = 68.2 ± 2.2 years). Eleven studies included aerobic exercise (AE, 7 middle-aged/4 older adults), and two included resistance exercise (RE, both middle-aged). AE significantly increased C-terminal telopeptide (CTX), alkaline phosphatase (ALP) and bone-ALP in middle-aged and older adults. AE also significantly increased total osteocalcin (tOC) in middle-aged men and Procollagen I Carboxyterminal Propeptide and Cross-Linked Carboxyterminal Telopeptide of Type I Collagen in older women. RE alone decreased ALP in older adults. In middle-aged adults, RE with impact had no effect on tOC or BALP, but significantly decreased CTX. Impact (jumping) exercise alone increased Procollagen Type 1 N Propeptide and tOC in middle-aged women. CONCLUSION: Acute exercise is an effective tool to modify BTMs, however, the response appears to be exercise modality-, intensity-, age- and sex-specific. There is further need for higher quality and larger RCTs in this area.
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    Progressive Resistance Training for Concomitant Increases in Muscle Strength and Bone Mineral Density in Older Adults: A Systematic Review and Meta-Analysis
    O'Bryan, SJ ; Giuliano, C ; Woessner, MN ; Vogrin, S ; Smith, C ; Duque, G ; Levinger, I (ADIS INT LTD, 2022-05-24)
    BACKGROUND: Older adults experience considerable muscle and bone loss that are closely interconnected. The efficacy of progressive resistance training programs to concurrently reverse/slow the age-related decline in muscle strength and bone mineral density (BMD) in older adults remains unclear. OBJECTIVES: We aimed to quantify concomitant changes in lower-body muscle strength and BMD in older adults following a progressive resistance training program and to determine how these changes are influenced by mode (resistance only vs. combined resistance and weight-bearing exercises), frequency, volume, load, and program length. METHODS: MEDLINE/PubMed and Embase databases were searched for articles published in English before 1 June, 2021. Randomized controlled trials reporting changes in leg press or knee extension one repetition maximum and femur/hip or lumbar spine BMD following progressive resistance training in men and/or women ≥ 65 years of age were included. A random-effects meta-analysis and meta-regression determined the effects of resistance training and the individual training characteristics on the percent change (∆%) in muscle strength (standardized mean difference) and BMD (mean difference). The quality of the evidence was assessed using the Cochrane risk-of-bias tool (version 2.0) and Grading of Recommendation, Assessment, Development, and Evaluation (GRADE) criteria. RESULTS: Seven hundred and eighty studies were identified and 14 were included. Progressive resistance training increased muscle strength (∆ standardized mean difference = 1.1%; 95% confidence interval 0.73, 1.47; p ≤ 0.001) and femur/hip BMD (∆ mean difference = 2.77%; 95% confidence interval 0.44, 5.10; p = 0.02), but not BMD of the lumbar spine (∆ mean difference = 1.60%; 95% confidence interval - 1.44, 4.63; p = 0.30). The certainty for improvement was greater for muscle strength compared with BMD, evidenced by less heterogeneity (I2 = 78.1% vs 98.6%) and a higher overall quality of evidence. No training characteristic significantly affected both outcomes (p > 0.05), although concomitant increases in strength and BMD were favored by higher training frequencies, increases in strength were favored by resistance only and higher volumes, and increases in BMD were favored by combined resistance plus weight-bearing exercises, lower volumes, and higher loads. CONCLUSIONS: Progressive resistance training programs concomitantly increase lower-limb muscle strength and femur/hip bone mineral density in older adults, with greater certainty for strength improvement. Thus, to maximize the efficacy of progressive resistance training programs to concurrently prevent muscle and bone loss in older adults, it is recommended to incorporate training characteristics more likely to improve BMD.
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    Digital self-management interventions for osteoarthritis: a systematic scoping review of intervention characteristics, adherence and attrition
    Patten, RK ; Tacey, A ; Pile, R ; Parker, A ; De Gori, M ; Tran, P ; McKenna, MJ ; Lane, R ; Apostolopoulos, V ; Said, CM ; Levinger, I ; Woessner, MN (BMC, 2022-03-31)
    BACKGROUND: Osteoarthritis (OA) is a chronic, progressive condition that can be effectively managed via conservative treatments including exercise, weight management and education. Offering these treatments contemporaneously and digitally may increase adherence and engagement due to the flexibility and cost-effectiveness of digital program delivery. The objective of this review was to summarise the characteristics of current digital self-management interventions for individuals with OA and synthesise adherence and attrition outcomes. METHODS: Electronic databases were searched for randomised controlled trials utilising digital self-management interventions in individuals with OA. Two reviewers independently screened the search results and extracted data relating to study characteristics, intervention characteristics, and adherence and dropout rates. RESULTS: Eleven studies were included in this review. Intervention length ranged from 6 weeks to 9 months. All interventions were designed for individuals with OA and mostwere multi-component and were constructed around physical activity. The reporting of intervention adherence varied greatly between studies and limited the ability to form conclusions regarding the impact of intervention characteristics. However, of the seven studies that quantified adherence, six reported adherence > 70%. Seven of the included studies reported attrition rates < 20%, with contact and support from researchers not appearing to influence adherence or attrition. CONCLUSIONS: Holistic digital interventions designed for a targeted condition are a promising approach for promoting high adherence and reducing attrition. Future studies should explore how adherence of digital interventions compares to face-to-face interventions and determine potential influencers of adherence.
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    The mitochondrial profile in women with polycystic ovary syndrome: impact of exercise.
    Malamouli, M ; Levinger, I ; McAinch, AJ ; Trewin, AJ ; Rodgers, RJ ; Moreno-Asso, A (Bioscientifica, 2022-03-01)
    Polycystic ovary syndrome (PCOS) is a common endocrine disorder affecting pre-menopausal women and involves metabolic dysregulation. Despite the high prevalence of insulin resistance, the existence of mitochondrial dysregulation and its role in the pathogenesis of PCOS is not clear. Exercise is recommended as the first-line therapy for women with PCOS. In particular, high-intensity interval training (HIIT) is known to improve metabolic health and enhance mitochondrial characteristics. In this narrative review, the existing knowledge of mitochondrial characteristics in skeletal muscle and adipose tissue of women with PCOS and the effect of exercise interventions in ameliorating metabolic and mitochondrial health in these women are discussed. Even though the evidence on mitochondrial dysfunction in PCOS is limited, some studies point to aberrant mitochondrial functions mostly in skeletal muscle, while there is very little research in adipose tissue. Although most exercise intervention studies in PCOS report improvements in metabolic health, they show diverse and inconclusive findings in relation to mitochondrial characteristics. A limitation of the current study is the lack of comprehensive mitochondrial analyses and the diversity in exercise modalities, with only one study investigating the impact of HIIT alone. Therefore, further comprehensive large-scale exercise intervention studies are required to understand the association between metabolic dysfunction and aberrant mitochondrial profile, and the molecular mechanisms underlying the exercise-induced metabolic adaptations in women with PCOS.
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    A Brief, Daily, Online Mental Health and Well-being Intervention for University Staff During the COVID-19 Pandemic: Program Description and Outcomes Using a Mixed Methods Design.
    Parker, A ; Dash, S ; Bourke, M ; Patten, R ; Craike, M ; Baldwin, P ; Hosking, W ; Levinger, I ; Apostolopoulos, V ; de Courten, M ; Sharples, J ; Naslund, M ; Stavropoulos, V ; Woessner, M ; Sonn, C ; Stansen, C ; Pascoe, M (JMIR Publications Inc., 2022-02-25)
    BACKGROUND: The unprecedented changes and isolation measures to contain COVID-19 have had multiple psychological and social impacts, with implications for professional and personal functioning. Evidence-informed interventions that can be rapidly implemented under pandemic conditions to support mental health during such times are urgently needed. OBJECTIVE: The aim of this study was to determine the acceptability and preliminary outcomes of a daily online mental health promotion program for tertiary education staff during the COVID-19 pandemic. METHODS: The "Victoria University (VU) Elevenses" program was delivered as an uncontrolled intervention at Victoria University (VU) in the western metropolitan region of Melbourne, Australia. In April 2020, an email invitation was sent to all academic and professional staff inviting them to: (1) participate in the program and (2) opt-in to the research component. The "VU Elevenses" program provided 10-15-minute microinterventions comprising lifestyle and well-being strategies to promote mental health via an online meeting platform at 11 AM each weekday. A mixed methods approach was used to evaluate the program, combining structured questionnaires with semistructured interviews to investigate the experiences of staff who participated in the program. RESULTS: Between 16 and 90 participants provided weekly program feedback. A total of 106 university staff opted into the longitudinal research component and 10 staff participated in the interviews. Participants reported high levels of satisfaction with sessions and perceived benefits for mental health. Approximately one quarter of participants reported moderate to severe symptoms of depression, anxiety, and stress at baseline, with significant reductions in these symptoms in the first 7 weeks of the program, corresponding with easing in mandatory isolation ("lockdown") restrictions. Symptoms of depression, anxiety, and stress all increased when lockdown measures were reintroduced, but not to the same levels as found during the initial lockdown period. Overall changes in depression and anxiety from baseline to the end of the program were explained by changes in COVID-19-related distress, whereas changes in self-compassion explained changes in stress. CONCLUSIONS: We show that it is feasible and acceptable to develop and deliver a program of brief interventions in a timely manner, using a simple and accessible online platform. Although participation in the program was initially associated with reduced symptoms of depression, anxiety, and stress, participants' mental health worsened with the reintroduction of a "lockdown" period. However, as symptoms of depression, anxiety, and stress did not return to levels observed at the start of the VU Elevenses program, participation in the uncontrolled intervention may have offered a protective benefit against the impact of the second significant lockdown period.
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    Lipocalin-2 Variants and Their Relationship With Cardio-Renal Risk Factors
    Li, D ; Li, H ; Bauer, C ; Hu, Y ; Lewis, JR ; Xu, A ; Levinger, I ; Wang, Y (FRONTIERS MEDIA SA, 2021-12-06)
    OBJECTIVES: To investigate the serum, plasma and urine levels of lipocalin-2 (LCN2) variants in healthy humans and their associations with risk factors for cardiometabolic (CMD) and chronic kidney (CKD) diseases. METHODS: Fifty-nine males and 41 females participated in the study. Blood and urine were collected following an overnight fasting. LCN2 variants were analyzed using validated in-house ELISA kits. Heart rate, blood pressure, lipids profile, glucose, adiponectin, high-sensitivity C-reactive protein (hsCRP), creatinine, cystatin C, and biomarkers for kidney function were assessed. RESULTS: The levels of hLcn2, C87A and R81E in serum and urine, but not plasma, were significantly higher in men than women. Increased levels of LCN2 variants, as well as their relative ratios, in serum and plasma were positively associated with body mass index, blood pressure, triglyceride and hsCRP (P<0.05). No significant correlations were found between these measures and hLcn2, C87A or R81E in urine. However, LCN2 variants in urine, but not plasma or serum, were correlated with biomarkers of kidney function (P<0.05). CONCLUSIONS: Both the serum and plasma levels of LCN2 variants, as well as their ratios are associated with increased cardiometabolic risk, whereas those in urine are correlated with renal dysfunction. LCN2 variants represent promising biomarkers for CMD and CKD.
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    Neuropeptide Y1 receptor antagonism protects beta-cells and improves glycemic control in type 2 diabetes
    Yang, C-H ; Ann-Onda, D ; Lin, X ; Fynch, S ; Nadarajah, S ; Pappas, EG ; Liu, X ; Scott, JW ; Oakhill, JS ; Galic, S ; Shi, Y ; Moreno-Asso, A ; Smith, C ; Loudovaris, T ; Levinger, I ; Eizirik, DL ; Laybutt, DR ; Herzog, H ; Thomas, HE ; Loh, K (ELSEVIER, 2021-12-31)
    OBJECTIVES: Loss of functional β-cell mass is a key factor contributing to poor glycemic control in advanced type 2 diabetes (T2D). We have previously reported that the inhibition of the neuropeptide Y1 receptor improves the islet transplantation outcome in type 1 diabetes (T1D). The aim of this study was to identify the pathophysiological role of the neuropeptide Y (NPY) system in human T2D and further evaluate the therapeutic potential of using the Y1 receptor antagonist BIBO3304 to improve β-cell function and survival in T2D. METHODS: The gene expression of the NPY system in human islets from nondiabetic subjects and subjects with T2D was determined and correlated with the stimulation index. The glucose-lowering and β-cell-protective effects of BIBO3304, a selective orally bioavailable Y1 receptor antagonist, in high-fat diet (HFD)/multiple low-dose streptozotocin (STZ)-induced and genetically obese (db/db) T2D mouse models were assessed. RESULTS: In this study, we identified a more than 2-fold increase in NPY1R and its ligand, NPY mRNA expression in human islets from subjects with T2D, which was significantly associated with reduced insulin secretion. Consistently, the pharmacological inhibition of Y1 receptors by BIBO3304 significantly protected β cells from dysfunction and death under multiple diabetogenic conditions in islets. In a preclinical study, we demonstrated that the inhibition of Y1 receptors by BIBO3304 led to reduced adiposity and enhanced insulin action in the skeletal muscle. Importantly, the Y1 receptor antagonist BIBO3304 treatment also improved β-cell function and preserved functional β-cell mass, thereby resulting in better glycemic control in both HFD/multiple low-dose STZ-induced and db/db T2D mice. CONCLUSIONS: Our results revealed a novel causal link between increased islet NPY-Y1 receptor gene expression and β-cell dysfunction and failure in human T2D, contributing to the understanding of the pathophysiology of T2D. Furthermore, our results demonstrate that the inhibition of the Y1 receptor by BIBO3304 represents a potential β-cell-protective therapy for improving functional β-cell mass and glycemic control in T2D.
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    Predictors of Referral to Cardiac Rehabilitation in Patients following Hospitalisation with Heart Failure: A Multivariate Regression Analysis
    Giuliano, C ; Vicendese, D ; Vogrin, S ; Lane, R ; Driscoll, A ; Dinh, D ; Palmer, K ; Levinger, I ; Neil, C (MDPI, 2022-03-01)
    BACKGROUND: This exploratory observational case-control study investigated the rate of referral to cardiac rehabilitation (CR) among patients hospitalised with heart failure (HF) and identified factors associated with referral. METHODS: Patients hospitalised with HF as identified by the Victorian Cardiac Outcomes Registry HF study were included. Factors found to be univariately associated with referral were selected for multivariate logistic regression. RESULTS: Among 1281 patients (mean age: 76.9 years; 32.8% HFrEF and 33.9% HfpEF), 125 (9.8%) were referred to CR. Patients referred were younger (73.6 (2.7, 81.5) vs. 80.2 (71.1, 86.5) p < 0.001) and were more likely to be men (72%, p < 0.001). Factors associated with referral included inpatient percutaneous coronary intervention (OR, 3.31; 95% CI, 1.04-10.48; p = 0.04), an aetiology of ischaemic or rhythm-related cardiomyopathy, and anticoagulants prescribed on discharge. Factors that lowered the likelihood of referral included older age, female, receiving inpatient oxygen therapy, and the presence of chronic obstructive pulmonary disease (COPD) or anaemia. CONCLUSIONS: The rate of referral to CR following hospitalisation with HF is low. Shortfalls are particularly evident among females, older patients, and in those with COPD or anaemia. Future studies should focus on improving referral processes and translating proven strategies that increase referrals to CR into practice.
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    Higher Levels of Circulating Osteoprogenitor Cells Are Associated With Higher Bone Mineral Density and Lean Mass in Older Adults: A Cross-Sectional Study
    Feehan, J ; Smith, C ; Tripodi, N ; Degabrielle, E ; Al Saedi, A ; Vogrin, S ; Duque, G ; Levinger, I (WILEY, 2021-10-17)