College of Medicine and Public Health

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https://hdl.handle.net/2328/26052

The College of Medicine and Public Health deliver clinical, population and lab based research, integrated teaching programs and high quality clinical services.

Our teaching footprint reaches out from our world class teaching hospital at the Flinders Medical Centre in South Australia to multiple rural clinical locations all the way to Darwin in the Northern Territory.

We promote research in health services, systems improvements, public and population health, improved clinical care and laboratory and precision medicine.

This approach has seen us investigate everything from community health problems to the smallest of molecules that influence human disease.

Our research and teaching equips the next generation of leaders and innovators with the skill, commitment and vision to protect vulnerable communities and truly advance health outcomes. It’s at the heart of everything we do.

It’s about improving the health and wellbeing for everyone in society.

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    A comparison of LKB1/AMPK/mTOR metabolic axis response to global ischaemia in brain, heart, liver and kidney in a rat model of cardiac arrest
    (BioMed Central, 2018-06-19) Majd, Shohreh ; Power, John Henry ; Chataway, Timothy Kennion ; Grantham, Hugh Jonathon
    Abstract Background Cellular energy failure in high metabolic rate organs is one of the underlying causes for many disorders such as neurodegenerative diseases, cardiomyopathies, liver and renal failures. In the past decade, numerous studies have discovered the cellular axis of LKB1/AMPK/mTOR as an essential modulator of cell homeostasis in response to energy stress. Through regulating adaptive mechanisms, this axis adjusts the energy availability to its demand by a systematized control on metabolism. Energy stress, however, could be sensed at different levels in various tissues, leading to applying different strategies in response to hypoxic insults. Methods Here the immediate strategies of high metabolic rate organs to time-dependent short episodes of ischaemia were studied by using a rat model (n = 6/group) of cardiac arrest (CA) (15 and 30 s, 1, 2, 4 and 8 min CA). Using western blot analysis, we examined the responses of LKB1/AMPK/mTOR pathway in brain, heart, liver and kidney from 15 s up to 8 min of global ischaemia. The ratio of ADP/ATP was assessed in all ischemic and control groups, using ApoSENSOR bioluminescent assay kit. Results Brain, followed by kidney showed the early dephosphorylation response in AMPK (Thr172) and LKB1 (Ser431); in the absence of ATP decline (ADP/ATP elevation). Dephosphorylation of AMPK was followed by rephosphorylation and hyperphosphorylation, which was associated with a significant ATP decline. While heart’s activity of AMPK and LKB1 remained at the same level during short episodes of ischaemia, liver’s LKB1 was dephosphorylated after 2 min. AMPK response to ischaemia in liver was mainly based on an early alternative and a late constant hyperphosphorylation. No significant changes was observed in mTOR activity in all groups. Conclusion Together our results suggest that early AMPK dephosphorylation followed by late hyperphosphorylation is the strategy of brain and kidney in response to ischaemia. While the liver seemed to get benefit of its AMPK system in early ischameia, possibly to stabilize ATP, the level of LKB1/AMPK activity in heart remained unchanged in short ischaemic episodes up to 8 min. Further researches must be conducted to elucidate the molecular mechanism underlying LKB1/AMPK response to oxygen supply.
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    A narrative account of implementation lessons learnt from the dissemination of an up-scaled state-wide child obesity management program in Australia: PEACH™ (Parenting, Eating and Activity for Child Health) Queensland
    (BioMed Central, 2018-03-13) Croyden, Debbie L ; Vidgen, Helen A ; Esdaile, Emma ; Hernandez, Emely ; Magarey, Anthea Margaret ; Moores, Carly J ; Daniels, Lynne Allison
    Background: PEACH QLD translated the PEACH Program, designed to manage overweight/obesity in primary school-aged children, from efficacious RCT and small scale community trial to a larger state-wide program. This paper describes the lessons learnt when upscaling to universal health coverage. Methods: The 6-month, family-focussed program was delivered in Queensland, Australia from 2013 to 2016. Its implementation was planned by researchers who developed the program and conducted the RCT, and experienced project managers and practitioners across the health continuum. The intervention targeted parents as the agents of change and was delivered via parent-only group sessions. Concurrently, children attended fun, non-competitive activity sessions. Sessions were delivered by facilitators who received standardised training and were employed by a range of service providers. Participants were referred by health professionals or self-referred in response to extensive promotion and marketing. A pilot phase and a quality improvement framework were planned to respond to emerging challenges. Results: Implementation challenges included engagement of the health system; participant recruitment; and engagement. A total of 1513 children (1216 families) enrolled, with 1122 children (919 families) in the face-to-face program (105 groups in 50 unique venues) and 391 children (297 families) in PEACH Online. Self-referral generated 68% of enrolments. Unexpected, concurrent and, far-reaching public health system changes contributed to poor program uptake by the sector (only 56 [53%] groups delivered by publicly-funded health organisations) requiring substantial modification of the original implementation plan. Process evaluation during the pilot phase and an ongoing quality improvement framework informed program adaptations that included changing from fortnightly to weekly sessions aligned with school terms, revision of parent materials, modification of eligibility criteria to include healthy weight children and provision of services privately. Comparisons between pilot versus state-wide waves showed comparable prevalence of families not attending any sessions (25% vs 28%) but improved number of sessions attended (median?=?5 vs 7) and completion rates (43% vs 56%). Conclusions: Translating programs developed in the research context to enable implementation at scale is complex and presents substantial challenges. Planning must ensure there is flexibility to accommodate and proactively manage the system changes that are inevitable over time
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    A qualitative study about the gendered experiences of motherhood and perinatal mortality in mountain villages of Nepal: implications for improving perinatal survival
    (BioMed Central, 2018-05-15) Paudel, Mohan ; Javanparast, Sara ; Dasvarma, Gouranga Lal ; Newman, Lareen Ann
    Abstract Background We aim to examine the gendered contexts of poor perinatal survival in the remote mountain villages of Nepal. The study setting comprised two remote mountain villages from a mid-western mountain district of Nepal that ranks lowest on the Human Development Index (0.304), and is reported as having the lowest child survival rates in the country. Methods The findings are taken from a larger study of perinatal survival in remote mountain villages of Nepal, conducted through a qualitative methodological approach within a framework of social constructionist and critical theoretical perspectives. Data were collected through in-depth interviews with 42 women and their families, plus a range of healthcare providers (nurses/auxiliary nurses, female health volunteers, support staff, Auxiliary Health Worker and a traditional healer) and other stakeholders from February to June, 2015. Data were analysed with a comprehensive coding process utilising the thematic analysis technique. Results The social construction of gender is one of the key factors influencing poor perinatal survival in the villages in this study. The key emerging themes from the qualitative data are: (1) Gendered social construct and vulnerability for poor perinatal survival: child marriages, son preference and repeated child bearing; (2) Pregnancy and childbirth in intra-familial dynamics of relationships and power; and (3) Perception of birth as a polluted event: birth in Gotha (cowshed) and giving birth alone. Conclusions Motherhood among women of a low social position is central to women and their babies experiencing vulnerabilities related to perinatal survival in the mountain villages. Gendered constructions along the continuum from pre-pregnancy to postnatal (girl settlement, a daughter-in-law, ritual pollution about mother and child) create challenges to ensuring perinatal survival in these villages. It is imperative that policies and programmes consider such a context to develop effective working strategies for sustained reduction of future perinatal deaths.
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    Aberrant detection of phenotypic markers in chronic lymphocytic leukemia (CLL) lymphocytes following cryopreservation
    (Elsevier, 2018) Thurgood, Lauren Alexandra ; Lower, Karen Marie ; Kuss, Bryone Jean
    The cryopreservation of peripheral blood mononuclear cells (PBMCs) is a routine research laboratory process, enabling long-term storage of primary patient blood samples. Retrospective analysis of these samples has the potential to identify markers which may associate with prognosis and response to treatment. In order to draw valid biological conclusions from this type of analysis, it is essential to ensure that any observed changes are directly related to the pathology of the disease rather than the preservation process itself. Therefore, we have investigated 15 cell surface markers which are relevant to chronic lymphocytic leukemia (CLL) on matched fresh and thawed samples to determine the effect of cryopreservation on their detection. We found that the number of CLL cells positive for the markers CD22, CD40, CD49d, CD54, CD69 and CXCR3 was significantly decreased following cryopreservation. In addition, the MFI of 10 of the 15 markers significantly changed following cryopreservation. These findings demonstrate that care must be taken when interpreting this type of analysis on thawed samples.
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    Ablation of Sphingosine 1-Phosphate Receptor Subtype 3 Impairs Hippocampal Neuron Excitability In vitro and Spatial Working Memory In vivo
    (Frontiers Media S.A., 2016-11-07) Weth-Malsch, Daniela ; Langeslag, Michiel ; Beroukas, Dimitra ; Zangrandi, Luca ; Kastenberger, Iris ; Quarta, Serena ; Malsch, Philipp ; Kalpachidou, Theodora ; Schwarzer, Christoph ; Proia, Richard L ; Haberberger, Rainer Viktor ; Kress, Michaela
    Understanding the role of the bioactive lipid mediator sphingosine 1-phosphate (S1P) within the central nervous system has recently gained more and more attention, as it has been connected to major diseases such as multiple sclerosis and Alzheimer's disease. Even though much data about the functions of the five S1P receptors has been collected for other organ systems, we still lack a complete understanding for their specific roles, in particular within the brain. Therefore, it was the aim of this study to further elucidate the role of S1P receptor subtype 3 (S1P3) in vivo and in vitro with a special focus on the hippocampus. Using an S1P3 knock-out mouse model we applied a range of behavioral tests, performed expression studies, and whole cell patch clamp recordings in acute hippocampal slices. We were able to show that S1P3 deficient mice display a significant spatial working memory deficit within the T-maze test, but not in anxiety related tests. Furthermore, S1p3 mRNA was expressed throughout the hippocampal formation. Principal neurons in area CA3 lacking S1P3 showed significantly increased interspike intervals and a significantly decreased input resistance. Upon stimulation with S1P CA3 principal neurons from both wildtype and S1P−/−3 mice displayed significantly increased evoked EPSC amplitudes and decay times, whereas rise times remained unchanged. These results suggest a specific involvement of S1P3 for the establishment of spatial working memory and neuronal excitability within the hippocampus.
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    The acceptability of participating in data linkage research: research with older Australians
    (Wiley, 2018-06-12) Harrison, Stephanie L ; Milte, Rachel ; Bradley, Clare Eileen ; Inacio, Maria C S ; Crotty, Maria
    Australians are increasingly concerned about the privacy of their data, but the biggest concerns relate to online services and identification fraud. Australians may be supportive of research that uses linked data; however, there have been conflicting findings as to whether formal consent from individuals should be sought, and the views of the older population have not been elicited specifically. A previous survey suggested half of Australians would expect consent to be sought for the use of de‐identified health information for research purposes, but the respondents were not specifically asked if they would expect an opt‐in or opt‐out approach to consent. The objectives of the current study were to determine if older Australians would find it acceptable to be part of the proposed registry and to explore different methods of consent.
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    Acceptability of Videoconference Technology for the Delivery of Continuing Education to Rural Pharmacists
    (Journal of Pharmacy Practice and Research, 2006) McNamara, Kevin Peter
    Videoconference technology is a valuable tool for the delivery of carefully structured CE sessions in rural and remote areas with an appropriate information technology infrastructure.
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    Acetylated Triterpene Glycosides and Their Biological Activity from Holothuroidea Reported in the Past Six Decades
    (MDPI, 2016-08) Bahrami, Yadollah ; Franco, Christopher Milton
    Sea cucumbers have been valued for many centuries as a tonic and functional food, dietary delicacies and important ingredients of traditional medicine in many Asian countries. An assortment of bioactive compounds has been described in sea cucumbers. The most important and abundant secondary metabolites from sea cucumbers are triterpene glycosides (saponins). Due to the wide range of their potential biological activities, these natural compounds have gained attention and this has led to their emergence as high value compounds with extended application in nutraceutical, cosmeceutical, medicinal and pharmaceutical products. They are characterized by bearing a wide spectrum of structures, such as sulfated, non-sulfated and acetylated glycosides. Over 700 triterpene glycosides have been reported from the Holothuroidea in which more than 145 are decorated with an acetoxy group having 38 different aglycones. The majority of sea cucumber triterpene glycosides are of the holostane type containing a C18 (20) lactone group and either D7(8) or D9(11) double bond in their genins. The acetoxy group is mainly connected to the C-16, C-22, C-23 and/or C-25 of their aglycone. Apparently, the presence of an acetoxy group, particularly at C-16 of the aglycone, plays a significant role in the bioactivity; including induction of caspase, apoptosis, cytotoxicity, anticancer, antifungal and antibacterial activities of these compounds. This manuscript highlights the structure of acetylated saponins, their biological activity, and their structure-activity relationships.
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    Achondroplasia with SRY-positive 46, XX disorder of sex development: an extremely rare association
    (Bioscientifica, 2018-07) Du, Yang Timothy ; Rutter, Angus ; Ho, Jul
    A 40-year-old man with achondroplasia presented with symptoms of hypogonadism, low libido and gynaecomastia. He was found to have hypergonadotropic hypogonadism, and karyotype and fluorescent in situ hybridisation analysis showed SRY-positive 46, XX disorder of sex development (DSD). He was tested to have the common activating mutation of the FGFR3 gene implicated in achondroplasia, indicating that he had the two rare conditions independently, with an extremely low incidence of 1 in 400 million. This, to the best of our knowledge, is the first report of an individual having these two rare conditions concurrently. This case highlights that individuals with achondroplasia should have normal sexual development, and in those presenting with incomplete sexual maturation or symptoms of hypogonadism should prompt further evaluation. We also propose a plausible link between achondroplasia and 46, XX DSD through the intricate interactions between the SRY, SOX9 and FGFR9 gene pathways.
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    Activation of ALDH1A1 in MDA-MB-468 breast cancer cells that over-express CYP2J2 protects against paclitaxel-dependent cell death mediated by reactive oxygen species
    (Elsevier, 2017-07-27) Allison, Sarah E ; Chen, Yongjuan ; Petrovic, Nenad ; Zhang, Jian ; Bourget, Kirsi ; Mackenzie, Peter Ian ; Murray, Michael
    Cytochrome P450 2J2 (CYP2J2) expression is elevated in breast and other tumours, and is known to be protective against cytotoxic agents that may be used in cancer chemotherapy. This study evaluated the mechanisms by which MDA-MB-468 breast cancer cells that stably expressed CYP2J2 (MDA-2J2 cells) were protected against killing by the anti-cancer agent paclitaxel. Compared to control cells caspase-3/7 activation by paclitaxel was lower in MDA-2J2 cells, while cell proliferation and colony formation following paclitaxel treatment were increased. Basal lipid peroxidation was lower in MDA-2J2 cells than in control cells, and the paclitaxel-mediated increase in peroxidation was attenuated. The mitochondrial complex III inhibitor antimycin A modulated basal and paclitaxel-activated reactive oxygen species (ROS) formation in control cells; paclitaxel-activated ROS production was also modulated by the NADPH oxidase inhibitor diphenyleneiodonium. Paclitaxel increased the formation of protein adducts by the reactive aldehyde 4-hydroxynonenal that is produced by lipid peroxidation; adduct formation was attenuated in MDA-2J2 cells. ALDH1A1 expression and activity was strongly upregulated in MDA-2J2 cells that was attributed to CYP2J2-derived 14,15-epoxyeicosatrienoic acid (14,15-EET); the 8,9- and 11,12-EET regioisomers did not activate ALDH1A1 expression. Silencing of ALDH1A1 restored the sensitivity of MDA-2J2 cells to paclitaxel, as indicated by a more pronounced decrease in proliferation, and greater increases in caspase activity and formation of ROS to levels comparable with control cells. Similar findings were observed with doxorubicin, sorafenib and staurosporine, that also promoted ROS-mediated cell death that was attenuated in MDA-2J2 cells and reversed by ALDH1A1 gene silencing. These findings implicate ALDH1A1 as an important gene that is activated in MDA-MB-468-derived cells that contain high levels of CYP2J2. ALDH1A1 modulates the production of ROS by anti-cancer agents such as paclitaxel and diminishes their efficacy. Future approaches could adapt this information to facilitate the targeting of ALDH1A1 to promote the efficacy of ROS-generating cytotoxic agents and enhance the treatment of breast cancer.
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    Acute Interstitial Nephritis Associated with Sofosbuvir and Daclatasvir
    (American College of Gastroenterology, 2017-07) Ashraf, Taha ; Majoni, Sandawana William
    Although new heptatis C virus treatments have increased efficacy and improved safety profiles, they also come with risk. We describe a 66-year-old white man with Child-Pugh A cirrhosis secondary to heptatis C virus genotype 3, who suffered from an acute kidney injury after treatment with sofosbuvir and daclatasvir. Kidney biopsy demonstrated evidence of acute tubular interstitial nephritis consistent with a drug reaction. A trial of steroid therapy was effective, and his creatinine continues to improve significantly. Our case is the first report in the literature that highlights potentially serious interstitial nephritis associated with sofosbuvir and daclatasvir use.
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    Additive and subtractive resilience strategies as enablers of biographical reinvention: a qualitative study of ex-smokers and never-smokers
    (Elsevier, 2011) Ward, Paul Russell ; Muller, Robert ; Tsourtos, George ; Hersh, Deborah ; Lawn, Sharon Joy ; Winefield, Anthony H ; Coveney, John David
    The notion of developing resilience is becoming increasingly important as a way of responding to the social determinants of poor health, particularly in disadvantaged groups. It is hypothesized that resilient individuals and communities are able to ‘bounce back’ from the adversities they face. This paper explores the processes involved in building resilience as an outcome in relation to both quitting smoking and never smoking. The study involved 93 qualitative, oral-history interviews with participants from population groups with high and enduring smoking rates in Adelaide, Australia, and was essentially interested in how some people in these groups managed to quit or never start smoking in the face of adversities, in comparison to a group of smokers. Our key findings relate to what we call additive and subtractive resilience strategies, which focus on the practices, roles and activities that individuals either ‘took on’ or ‘left behind’ in order to quit smoking or remain abstinent. The theoretical lenses we use to understand these resilience strategies relate to biographical reinforcement and biographical reinvention, which situate the resilience strategies in a broader ‘project of the self’, often in relation to attempting to develop ‘healthy bodies’ and ‘healthy biographies’.
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    Adherence to antibiotic guidelines and reported penicillin allergy: pooled cohort data on prescribing and allergy documentation from two English National Health Service (NHS) trusts
    (BMJ Publishing group, 2019-03-01) Phillips, Cameron J ; Gilchrist, Mark ; Cooke, Fiona J ; Franklin, Bryony D ; Enoch, David A ; Murphy, Michael E ; Santos, Reem ; Brannigan, Eimear T ; Holmes, Alison
    Objective To investigate documentation of antimicrobial allergy and to determine prescribing adherence to local antibiotic guidelines for inpatients with and without reported penicillin allergy treated for infection in a National Health Service (NHS) context. Setting Data were collected at two English hospital NHS trusts over two time-periods: June 2016 and February 2017. Design Cohort study. Trust 1 data were sourced from prospective point prevalence surveys. Trust 2 data were extracted retrospectively from an electronic report. Participants Inpatients treated for urinary tract infection (UTI), community-acquired pneumonia (CAP), hospital-acquired pneumonia (HAP) and skin and soft tissue infection (SSTI). Data on allergy were collected, and antibiotic selection assessed for adherence to trust guidelines with differences between groups presented as adjusted ORs. Results A total of 1497 patients were included, with 2645 antibiotics orders. Patients were treated for CAP (n=495; 33.1%), UTI (407; 27.2%), HAP (330; 22%) and SSTI (265; 17.7%). There were 240 (16%) patients with penicillin allergy. Penicillin allergy was recorded as allergy (n=52; 21.7%), side effect (27; 11.3%) and no documentation (161; 67.1%). Overall, 2184 (82.6%) antibiotic orders were guideline-adherent. Adherence was greatest for those labelled penicillin allergy (453 of 517; 87.6%) versus no allergy (1731 of 2128; 81.3%) (OR 0.52 (95% CI 0.37 to 0.73) p<0.001). Guideline-adherence for CAP was higher if penicillin allergy (151 of 163; 92.6%) versus no allergy (582 of 810; 71.9%) (OR 0.20 (95% CI 0.10 to 0.37) p<0.001). There was no difference in adherence between those with and without penicillin allergy for UTI, HAP or SSTI treatment. Conclusions A relatively high proportion of patients had a penicillin allergy and two thirds of these had no description of their allergy, which has important implications for patient safety. Patients with penicillin allergy treated for CAP, received more guideline adherent antibiotics than those without allergy. Future studies investigating the clinical impact of penicillin allergy should include data on adherence to antibiotic guidelines.
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    Adherence, Compliance, and Health Risk Factor Changes following Short-Term Physical Activity Interventions
    (Hindawi, 2015-08-25) Norton, Lynda ; Norton, Kevin ; Lewis, Nicole
    Background. Low physical activity (PA) levels are associated with poor health risk factor profiles. Intervention strategies to increase PA and quantify the rate and magnitude of change in risk factors are important. Methods. Interventions were conducted over 40 days to increase PA in 736 insufficiently active (ud_less_than150 min/wk PA) participants using either a pedometer or instructor-led group protocol. There were a further 135 active participants as controls. Major cardiovascular and metabolic risk factors, including fitness parameters, were measured before and after intervention. Results. Adherence to the interventions was higher for the group versus pedometer participants (87.1% versus 79.8%) and compliance rates for achieving sufficient levels of PA (≥150 min/wk) were also higher for the group participants (95.8% versus 77.6%). Total weekly PA patterns increased by 300 and 435 minutes, for the pedometer and group participants, respectively. Improvements were found for waist girth, total cholesterol, aerobic fitness, and flexibility relative to controls. The change in vigorous PA, but not moderate PA, was a significant predictor of the change in eight of 11 risk factor variables measured. Conclusions. Rapid and dramatic increases in PA among previously insufficiently active adults can result in important health benefits.
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    Adjunctive granulocyte colony-stimulating factor for treatment of septic shock due to melioidosis
    ( 2004) Stephens, Dianne Patricia ; Anstey, Nicholas Mark ; Cheng, Allen C ; Currie, Bart John
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    Adult Non-Cystic Fibrosis Bronchiectasis Is Characterised by Airway Luminal Th17 Pathway Activation
    (Public Library of Science, 2015) Chen, Alice ; Martin, Megan L ; Lourie, R ; Rogers, Geraint B ; Burr, Lucy D ; Hasnain, Sumaira Z ; Bowler, Simon D ; McGuckin, Michael A ; Serisier, D
    BACKGROUND: Non-cystic fibrosis (CF) bronchiectasis is characterised by chronic airway infection and neutrophilic inflammation, which we hypothesised would be associated with Th17 pathway activation. METHODS: Th17 pathway cytokines were quantified in bronchoalveolar lavage fluid (BALF), and gene expression of IL-17A, IL-1β, IL-8 and IL-23 determined from endobronchial biopsies (EBx) in 41 stable bronchiectasis subjects and 20 healthy controls. Relationships between IL-17A levels and infection status, important clinical measures and subsequent Pseudomonas aeruginosa infection were determined. RESULTS: BALF levels of all Th17 cytokines (median (IQR) pg/mL) were significantly higher in bronchiectasis than control subjects, including IL-17A (1.73 (1.19, 3.23) vs. 0.27 (0.24, 0.35), 95% CI 1.05 to 2.21, p<0.0001) and IL-23 (9.48 (4.79, 15.75) vs. 0.70 (0.43, 1.79), 95% CI 4.68 to 11.21, p<0.0001). However, BALF IL-17A levels were not associated with clinical measures or airway microbiology, nor predictive of subsequent P. aeruginosa infection. Furthermore, gene expression of IL-17A in bronchiectasis EBx did not differ from control. In contrast, gene expression (relative to medians of controls) in bronchiectasis EBx was significantly higher than control for IL1β (4.12 (1.24, 8.05) vs 1 (0.13, 2.95), 95% CI 0.05 to 4.07, p = 0.04) and IL-8 (3.75 (1.64, 11.27) vs 1 (0.54, 3.89), 95% CI 0.32 to 4.87, p = 0.02) and BALF IL-8 and IL-1α levels showed significant relationships with clinical measures and airway microbiology. P. aeruginosa infection was associated with increased levels of IL-8 while Haemophilus influenzae was associated with increased IL-1α. CONCLUSIONS AND CLINICAL RELEVANCE: Established adult non-CF bronchiectasis is characterised by luminal Th17 pathway activation, however this pathway may be relatively less important than activation of non-antigen-specific innate neutrophilic immunity.
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    Advax, a Delta Inulin Microparticle, Potentiates In-built Adjuvant Property of Co-administered Vaccines
    (Elsevier, 2017-02-15) Hayashi, Masayuki ; Aoshi, Taiki ; Haseda, Yasunari ; Kobiyamaa, Kouji ; Wijaya, Edward ; Nakatsu, Noriyuki ; Igarashi, Yoshinobu ; Standley, Daron M ; Yamada, Hiroshi ; Honda-Okubo, Yoshikazu ; Hara, Hiromitsu ; Saito, Takashi ; Takai, Toshiyuki ; Coban, Cevayir ; Petrovsky, Nikolai ; Ishii, Ken J
    Advax, a delta inulin-derived microparticle, has been developed as an adjuvant for several vaccines. However, its immunological characteristics and potential mechanism of action are yet to be elucidated. Here, we show that Advax behaves as a type-2 adjuvant when combined with influenza split vaccine, a T helper (Th)2-type antigen, but behaves as a type-1 adjuvant when combined with influenza inactivated whole virion (WV), a Th1-type antigen. In addition, an adjuvant effect was not observed when Advax-adjuvanted WV vaccine was used to immunize toll-like receptor (TLR) 7 knockout mice which are unable to respond to RNA contained in WV antigen. Similarly, no adjuvant effect was seen when Advax was combined with endotoxin-free ovalbumin, a neutral Th0-type antigen. An adjuvant effect was also not seen in tumor necrosis factor (TNF)-α knockout mice, and the adjuvant effect required the presences of dendritic cells (DCs) and phagocytic macrophages. Therefore, unlike other adjuvants, Advax potentiates the intrinsic or in-built adjuvant property of co-administered antigens. Hence, Advax is a unique class of adjuvant which can potentiate the intrinsic adjuvant feature of the vaccine antigens through a yet to be determined mechanism.
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    Age-related impairment of esophagogastric junction relaxation and bolus flow time
    (Baishideng Publishing Group Inc, 2017-04-21) Cock, Charles ; Besanko, Laura K ; Burgstad, Carly M ; Thompson, Alison ; Kritas, Stamatiki ; Heddle, Robert John ; Fraser, Robert J L ; Omari, Taher
    AIM To investigate the functional effects of abnormal esophagogastric (EGJ) measurements in asymptomatic healthy volunteers over eighty years of age. METHODS Data from 30 young controls (11 M, mean age 37 ± 11 years) and 15 aged subjects (9 M, 85 ± 4 years) were compared for novel metrics of EGJ-function: EGJ-contractile integral (EGJ-CI), “total” EGJ-CI and bolus flow time (BFT). Data were acquired using a 3.2 mm, 25 pressure (1 cm spacing) and 12 impedance segment (2 cm) solid-state catheter (Unisensor and MMS Solar GI system) across the EGJ. Five swallows each of 5 mL liquid (L) and viscous (V) bolus were analyzed. Mean values were compared using Student’s t test for normally distributed data or Mann Whitney U-test when non-normally distributed. A P value < 0.05 was considered significant. RESULTS EGJ-CI at rest was similar for older subjects compared to controls. “Total” EGJ-CI, measured during liquid swallowing, was increased in older individuals when compared to young controls (O 39 ± 7 mmHg.cm vs C 18 ± 3 mmHg.cm; P = 0.006). For both liquid and viscous bolus consistencies, IRP4 was increased (L: 11.9 ± 2.3 mmHg vs 5.9 ± 1.0 mmHg, P = 0.019 and V: 14.3 ± 2.4 mmHg vs 7.3 ± 0.8 mmHg; P = 0.02) and BFT was reduced (L: 1.7 ± 0.3 s vs 3.8 ± 0.2 s and V: 1.9 ± 0.3 s vs 3.8 ± 0.2 s; P < 0.001 for both) in older subjects, when compared to young. A matrix of bolus flow and presence above the EGJ indicated reductions in bolus flow at the EGJ occurred due to both impaired bolus transport through the esophageal body (i.e., the bolus never reached the EGJ) and increased flow resistance at the EGJ (i.e., the bolus retained just above the EGJ). CONCLUSION Bolus flow through the EGJ is reduced in asymptomatic older individuals. Both ineffective esophageal bolus transport and increased EGJ resistance contribute to impaired bolus flow.
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    Aged care clinical mentoring model of change in nursing homes in China: study protocol for a cluster randomized controlled trial
    (BMC, 2018-10-25) Feng, Hui ; Li, Hui ; Xiao, Lily Dongxia ; Ullah, Shahid ; Mao, Pan ; Yang, Yunxia ; Hu, Hengyu ; Zhao, Yinan
    Background: Residents living in nursing homes usually have complex healthcare needs and require a comprehensive care approach to identifying and meeting their care needs. Suboptimal quality of care is reported in nursing homes and is associated with the poor health and well-being of the residents, the burden on acute care hospitals and the high costs of healthcare for the government. The aim of this study is to test the hypothesis that an Aged Care Clinical Mentoring Model will create and sustain evidence-based quality improvement in priority areas and will be cost-effective in nursing homes in Hunan Province, China. Methods: A cluster randomized controlled trial will be applied to the study. Fourteen nursing homes will be randomly allocated to either the intervention group (n=7) or the control group (n=7). Forty staff will be recruited from each nursing home and the estimated sample size will be 280 staff in each group. The intervention includes a structured, evidence-based quality improvement education program for staff to facilitate knowledge translation in evidence-based quality improvement targeting urinary incontinence, pressure injury and falls prevention. The primary outcomes are nursing homes' capacity to create and sustain quality improvement, staff perceptions of person-centered care, self-reported quality of care by residents and selected quality indicators at 12 months follow-up adjusted for baseline value. Secondary outcomes are residents' quality of life, residents' unplanned admissions to acute care hospitals, quality of care reported by staff, staff job satisfaction and staff intention to leave adjusted for baseline value. A mixed linear regression model will be adopted to compare the significant differences between groups over a 12-month period. Discussion: Although the Aged Care Clinical Mentoring Model has been tested as an effective model to bring positive changes in nursing homes in a high-income country, factors affecting the adaptation of the model in nursing homes in low- and middle-income countries are unknown. The carefully planned intervention protocol enables the project team to consider enablers and barriers when adapting the Model. Therefore, strategies and resources will be in place to manage challenges while demonstrating best practice in this study.
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    Agents of change: establishing quality improvement collaboratives to improve adherence to Australian clinical guidelines for dementia care
    (BMC, 2018-09-24) Cations, Monica ; Crotty, Maria ; Fitzgerald, Janna A ; Kurrle, Susan E ; Cameron, Ian D ; Whitehead, Craig Hamilton ; Thompson, Jane ; Kaambwa, Billingsley ; Hayes, Kate ; de la Perrelle, Lenore ; Radisic, Gorjana ; Laver, Kate
    Background Dissemination of clinical practice guidelines alone is insufficient to create meaningful change in clinical practice. Quality improvement collaborative models have potential to address the evidence-practice gap in dementia care because they capitalise on known knowledge translation enablers and incorporate optimal approaches to implementation. Non-pharmacological interventions focused on promoting independence are effective and favoured by people with dementia and their carers but are not routinely implemented. The objective of this translational project is to assess the impact of quality improvement collaboratives (QICs) on adherence to non-pharmacological recommendations from the Clinical Practice Guidelines for Dementia in Australia. Methods This project will employ an interrupted time-series design with process evaluation to assess the impact, uptake, feasibility, accessibility, cost, and sustainability of the QICs over 18 months. Thirty clinicians from across Australia will be invited to join the QICs to build their capacity in leading innovation in dementia care. Clinicians will participate in a training program and be supported to develop and implement a quality improvement project unique to their service context using plan-do-study-act cycles. Regular online meetings with their peers in the QIC will facilitate benchmarking and problem-solving. Clinicians will describe their practice via monthly checklists, and guideline adherence will be determined against a set of defined criteria. Phone interviews with up to 180 client dyads will be used to assess satisfaction with care and client outcomes. Clinician interviews and field note data will be used to explore implementation and costs. Involvement of people with dementia and carers will be embedded in the study design, conduct, and reporting, in addition to clinical and industry expertise. Discussion The quality of dementia care in Australia is largely dependent on the clinician involved and the extent to which they apply best available evidence in their practice. This study will determine the elements of this multifaceted implementation strategy that contributed to guideline adherence and client outcomes. The findings will inform future translational approaches to improving care and outcomes for people with dementia and their carers.