Alternative models of cardiac rehabilitation : a systematic review

The traditional hospital-based model of cardiac rehabilitation faces substantial challenges, such as cost and accessibility. These challenges have led to the development of alternative models of cardiac rehabilitation in recent years. The aim of this study was to identify and critique evidence for the effectiveness of these alternative models. A total of 22 databases were searched to identify quantitative studies or systematic reviews of quantitative studies regarding the effectiveness of alternative models of cardiac rehabilitation. Included studies were appraised using a Critical Appraisal Skills Programme tool and the National Health and Medical Research Council's designations for Level of Evidence. The 83 included articles described interventions in the following broad categories of alternative models of care: multifactorial individualized telehealth, internet based, telehealth focused on exercise, telehealth focused on recovery, community- or home-based, and complementary therapies. Multifactorial individualized telehealth and community- or home-based cardiac rehabilitation are effective alternative models of cardiac rehabilitation, as they have produced similar reductions in cardiovascular disease risk factors compared with hospital-based programmes. While further research is required to address the paucity of data available regarding the effectiveness of alternative models of cardiac rehabilitation in rural, remote, and culturally and linguistically diverse populations, our review indicates there is no need to rely on hospital-based strategies alone to deliver effective cardiac rehabilitation. Local healthcare systems should strive to integrate alternative models of cardiac rehabilitation, such as brief telehealth interventions tailored to individual's risk factor profiles as well as community- or home-based programmes, in order to ensure there are choices available for patients that best fit their needs, risk factor profile, and preferences.

What should I say?: Qualitative findings on dilemmas in palliative care nursing

The nursing literature suggests that talking and listening to patients about issues associated with death and dying, is both important and difficult, and may be improved with training. This discussion presents the results of recent nursing research to confirm, and elaborate on, this theme. In this research participants touched on many central issues in communicating with patients that included articulating a sense of discomfort and inadequacy about the whole process, detailing the innumerable blocks to open communication [e.g., interference, denial, unrealistic optimism, resistance, collusion and anger] and sharing their sense of success and failure. The insights of nurses who participated in this research testify to the ongoing need to prioritize the development of nursing skills and support in this challenging but important area.

A study of post diagnosis breast cancer concerns for women living in rural and remote Queensland. Part I : Personal concerns

The findings presented in this paper are part of a research project designed to provide a preliminary indication of the support needs of postdiagnosis women with breast cancer in remote and isolated areas in Queensland. This discussion will present data that focuses on the women’s expressed personal concerns. For participants in this research a diagnosis of breast cancer involves a confrontation with their own mortality and the possibility of a reduced life span. This is a definite life crisis, creating shock and needing considerable adjustment. Along with these generic issues the participants also articulated significant issues in relation to their experience as women in a rural setting. These concerns centred around worries about how their partner and families cope during their absences for treatment, the additional burden on the family of having to cope with running the property or farm during the participant’s absence or illness, added financial strain brought about by the cost of travel for treatment, maintenance of properties during absences, and problems created by time off from properties or self-employment. These findings accord with other reports of health and welfare services for rural Australian and the generic literature on psycho-oncology studies of breast cancer.

Exercise-based cardiac rehabilitation for the 21st century

Exercise-based cardiac rehabilitation (CR) is efficacious in reducing mortality and hospital admissions; however it remains inaccessible to large proportions of the patient population. Removal of attendance barriers for hospital or centre-based CR has seen the promotion of home-based CR. Delivery of safe and appropriately prescribed exercise in the home was first documented 25 years ago, with the utilisation of fixed land-line telecommunications to monitor ECG. The advent of miniature ECG sensors, in conjunction with smartphones, now enables CR to be delivered with greater flexibility with regard to location, time and format, while retaining the capacity for real-time patient monitoring. A range of new systems allow other signals including speed, location, pulse oximetry, and respiration to be monitored and these may have application in CR. There is compelling evidence that telemonitored-based CR is an effective alternative to traditional CR practice. The long-standing barrier of access to centre-based CR, combined with new delivery platforms, raises the question of when telemonitored-based CR could replace conventional approaches as the standard practice.

Investigations Into the Significance of Lysine Residues in IGF-I

This PhD thesis presents novel and original research in the field of Insulin-like Growth Factor-I (or IGF-I) biology. IGF-I plays an essential role in promoting normal human growth and development; it also represents both a target and treatment for various diseases. This thesis provides interesting insights into previously uncharacterised mechanisms of action that underlie IGF-I biology. Such findings may lead to improved and novel treatments across a broad range of medical conditions.

A combined environmental scanning electron microscopy and Raman microscopy study of methanol oxidation on silver(I) oxide

The techniques of environmental scanning electron microscopy (ESEM) and Raman microscopy have been used to respectively elucidate the morphological changes and nature of the adsorbed species on silver(I) oxide powder, during methanol oxidation conditions. Heating Ag2O in either water vapour or oxygen resulted firstly in the decomposition of silver(I) oxide to polycrystalline silver at 578 K followed by sintering of the particles at higher temperature. Raman spectroscopy revealed the presence of subsurface oxygen and hydroxyl species in addition to surface hydroxyl groups after interaction with water vapour. Similar species were identified following exposure to oxygen in an ambient atmosphere. This behaviour indicated that the polycrystalline silver formed from Ag2O decomposition was substantially more reactive than silver produced by electrochemical methods. The interaction of water at elevated temperatures subsequent to heating silver(I) oxide in oxygen resulted in a significantly enhanced concentration of subsurface hydroxyl species. The reaction of methanol with Ag2O at high temperatures was interesting in that an inhibition in silver grain growth was noted. Substantial structural modification of the silver(I) oxide material was induced by catalytic etching in a methanol/air mixture. In particular, "pin-hole" formation was observed to occur at temperatures in excess of 773 K, and it was also recorded that these "pin- holes" coalesced to form large-scale defects under typical industrial reaction conditions. Raman spectroscopy revealed that the working surface consisted mainly of subsurface oxygen and surface Ag=O species. The relative lack of sub-surface hydroxyl species suggested that it was the desorption of such moieties which was the cause of the "pin-hole" formation.

Encapsulation of transition metal species into zeolites and molecular sieves as redox catalysts: Part I-preparation and characterisation of nanosized TiO2, CdO and ZnO semiconductor particles anchored in NaY zeolite

In this paper, we report the preparation and characterisation of nanometer-sized TiO2, CdO, and ZnO semiconductor particles trapped in zeolite NaY. Preparation of these particles was carried out via the traditional ion exchange method and subsequent calcination procedure. It was found that the smaller cations, i.e., Cd2+ and Zn2+ could be readily introduced into the SI′ and SII′ sites located in the sodalite cages, through ion exchange; while this is not the case for the larger Ti species, i.e., Ti monomer [TiO]2+ or dimer [Ti2O3]2+ which were predominantly dispersed on the external surface of zeolite NaY. The subsequent calcination procedure promoted these Ti species to migrate into the internal surface of the supercages. These semiconductor particles confined in NaY zeolite host exhibited a significant blue shift in the UV-VIS absorption spectra, in contrast to the respective bulk semiconductor materials, due to the quantum size effect (QSE). The particle sizes calculated from the UV-VIS optical absorption spectra using the effective mass approximation model are in good agreement with the atomic absorption data.

In vitro functional characterisation of IGF-I : VN-induced breast cancer progression

Members of the insulin-like growth factor (IGF) family have been shown to play critical roles in normal growth and development, as well as in tumour biology. The IGF system is complex and the biological effects of the IGFs are determined by their diverse interactions between many molecules, including their interactions with extracellular matrix (ECM) proteins. Recent studies have demonstrated that IGFs associate with the ECM protein vitronectin (VN) through IGF-binding proteins (IGFBP) and that this interaction modulates IGF-stimulated biological functions, namely cell migration and cell survival through the cooperative involvement of the type-I IGF receptor (IGF-1R) and VN-binding integrins. Since IGFs play important roles in the transformation and progression of breast cancer and VN has been found to be over-expressed at the leading edge of breast tumours, this project aimed to describe the effects of IGF-I:VN interactions on breast cell function. This was undertaken to dissect the molecular mechanisms underlying IGF-I:VN-induced responses and to design inhibitors to block the effects of such interactions. The studies described herein demonstrate that the increase in migration of MCF-7 breast cancer cells in response to the IGF-I:IGFBP-5:VN complex is accompanied by differential expression of genes known to be involved in migration, invasion and/or survival, including Tissue-factor (TF), Stratifin (SFN), Ephrin-B2, Sharp-2 and PAI-1. This „migration gene signature‟ was confirmed using real-time PCR analysis. Substitution of the native IGF-I within the IGF-I:IGFBP:VN complex with the IGF-I analogue, \[L24]\[A31]-IGF-I, which has a reduced affinity for the IGF-1R, failed to stimulate cell migration and interestingly, also failed to induce the differential gene expression. This supports the involvement of the IGF-1R in mediating these changes in gene expression. Furthermore, lentiviral shRNA-mediated stable knockdown of TF and SFN completely abrogated the increased cell migration induced by IGF-I:IGFBP:VN complexes in MCF-7 cells. Indeed, when these cells were grown in 3D Matrigel™ cultures a decrease in the overall size of the 3D spheroids in response to the IGF-I:IGFBP:VN complexes was observed compared to the parental MCF-7 cells. This suggests that TF and SFN have a role in complex-stimulated cell survival. Moreover, signalling studies performed on cells with the reduced expression of either TF or SFN had a decreased IGF-1R activation, suggesting the involvement of signalling pathways downstream of IGF-1R in TF- and/or SFN-mediated cell migration and cell survival. Taken together, these studies provide evidence for a common mechanism activated downstream of the IGF-1R that induces the expression of the „migration gene signature‟ in response to the IGF-I:IGFBP:VN complex that confers breast cancer cells the propensity to migrate and survive. Given the functional significance of the interdependence of ECM and growth factor (GF) interactions in stimulating processes key to breast cancer progression, this project aimed at developing strategies to prevent such growth factor:ECM interactions in an effort to inhibit the downstream functional effects. This may result in the reduction in the levels of ECM-bound IGF-I present in close proximity to the cells, thereby leading to a reduction in the stimulation of IGF-1R present on the cell surface. Indeed, the inhibition of IGF-I-mediated effects through the disruption of its association with ECM would not alter the physiological levels of IGF-I and potentially only exert effects in situations where abnormal over expression of ECM proteins are found; namely carcinomas and hyperproliferative diseases. In summary, this PhD project has identified novel, innovative and realistic strategies that can be used in vitro to inhibit the functions exerted by the IGF-I:IGFBP:VN multiprotein complexes critical for cancer progression, with a potential to be translated into in vivo investigations. Furthermore, TF and SFN were found to mediate IGF-I:IGFBP:VN-induced effects, thereby revealing their potential to be used as therapeutic targets or as predictive biomarkers for the efficacy of IGF-1R targeting therapies in breast cancer patients. In addition to its therapeutic and clinical scope, this PhD project has significantly contributed to the understanding of the role of the IGF system in breast tumour biology by providing valuable new information on the mechanistic events underpinning IGF-I:VN-mediated effects on breast cell functions. Furthermore, this is the first instance where favourable binding sites for IGF-II, IGFBP-3 and IGFBP-5 on VN have been identified. Taken together, this study has functionally characterised the interactions between IGF-I and VN and through innovative strategies has provided a platform for the development of novel therapies targeting these interactions and their downstream effects.

Indigenous health: Embracing and enacting the spirit of change. Opening keynote address

In speaking at the Cardiac Society this morning, I am conscious of this year’s 60th Anniversary. It is 60 years since motivated and impassioned people travelled to form the organisation that became the Cardiac Society. They started an organisation and a movement of sorts which was joined by many others over the years and which brings us to this room on this morning. This started in 1952. What were you doing in 1952? Where you just born and for some of you were? Others here were not born and may be your parents hadn’t even met yet. I want you to gain a sense of this time, of 60 years ago.

"If they say go faster or something I'll probably go faster" - peer influence upon the risky driving behaviour of young novice drivers

Purpose Young novice drivers are at considerable risk of injury on the road, and their behaviour appears vulnerable to the social influence of their friends. Research was undertaken to identify the nature and mechanisms of peer influence upon novice driver (16-25 years) behaviour to inform the design of more effective young driver countermeasures. Methods. Peer influence was explored in small group interviews (n = 21) and three surveys (n1 = 761, n2 = 1170, n3 = 390) as part of a larger Queensland-wide study. Surveys two and three were part of a six-month longitudinal study. Results Peer influence was reported from the pre-Licence to the Provisional (intermediate) periods. Young novice drivers who experienced or expected social punishments including ‘being told off’ for risky driving reported less riskiness. Conversely young novice drivers who experienced or expected social rewards such as being ‘cheered on’ by their friends – who were also more risky drivers – reported more risky driving including crashes and offences. Conclusions Peers appear influential in the risky behaviour of young novice drivers, and influence occurs through social mechanisms of reinforcement and sanction. Interventions enhancing positive influence and curtailing negative influence may improve road safety outcomes not only for young novice drivers, but for all persons who share the road with them. Among the interventions warranting further development and evaluation are programs to encourage the modelling of safe driving behaviour and attitudes by young drivers; and minimisation of social reinforcement and promotion of social sanctions for risky driving behaviour in particular.

'I want to educate school age children' : producing early childhood teacher professional identities

The Australian Government’s current workforce reforms in early childhood education and care (ECEC) include a major shift in qualification requirements. The new requirement is that university four-year degree-qualified teachers are employed in before-school contexts, including child care. Ironically, recent research studies show that, in Australia, the very preservice teachers who are enrolled in these degree programs have a reluctance to work in childcare. This article reports on part of a larger study which is inquiring into how early childhood teacher professional identities are discursively produced, and provides a partial mapping of the literature. One preservice teacher’s comment provides the starting point, and the paper locates some the discourses that are accessible to preservice teachers as they prepare for the early years workforce. An awareness of the discursive field provides a sound background for preparing early childhood teachers. A challenge for the field is to consider which discourses are dominant, and how they potentially work to privilege work in some ECEC contexts over others.

Investigation of Association between PFO complicated by cryptogenic stroke and a common variant of the cardiac transcription factor GATA4

Patent foramen ovale (PFO) is associated with clinical conditions including cryptogenic stroke, migraine and varicose veins. Data from studies in humans and mouse suggest that PFO and the secundum form of atrial septal defect (ASDII) exist in an anatomical continuum of septal dysmorphogenesis with a common genetic basis. Mutations in multiple members of the evolutionarily conserved cardiac transcription factor network, including GATA4, cause or predispose to ASDII and PFO. Here, we assessed whether the most prevalent variant of the GATA4 gene, S377G, was significantly associated with PFO or ASD. Our analysis of world indigenous populations showed that GATA4 S377G was largely Caucasian-specific, and so subjects were restricted to those of Caucasian descent. To select for patients with larger PFO, we limited our analysis to those with cryptogenic stroke in which PFO was a subsequent finding. In an initial study of Australian subjects, we observed a weak association between GATA4 S377G and PFO/Stroke relative to Caucasian controls in whom ASD and PFO had been excluded (OR = 2.16; p = 0.02). However, in a follow up study of German Caucasians no association was found with either PFO or ASD. Analysis of combined Australian and German data confirmed the lack of a significant association. Thus, the common GATA4 variant S377G is likely to be relatively benign in terms of its participation in CHD and PFO/Stroke.

Lysine residues of IGF-I are substrates for transglutaminases and modulate downstream IGF-I signalling

Numerous studies have reported associations between IGF-I and other extra cellular matrix (ECM) proteins, including fibronectin (FN), integrins, IGF-binding proteins (IGFBPs) and through IGFBPs, with vitronectin (VN). Nevertheless, the precise nature and mechanisms of these interactions are still being characterised. In this paper, we discuss transglutaminases (TGases) as a constituent of the ECM and provide evidence for the first time that IGF-I is a lysine (K)-donor substrate to TGases. When IGF-I was incubated with an alpha-2 plasmin inhibitor-derived Q peptide in the presence of tissue transglutaminase (TG2), an IGF-I:Q peptide cross-linked species was detected using Western immunoblotting and confirmed by mass spectrometry. Similar findings were observed in the presence of Factor XIIIa (FXIIIa) TGase. To identify the precise location of this K-donor TGase site/s on IGF-I, all the three IGF-I K-sites, individually and collectively (K27, K65 and K68), were substituted to arginine (R) using site-directed mutagenesis. Incubation of these K→R IGF-I analogues with Q peptide in the presence of TG2 or FXIIIa resulted in the absence of cross-linking in IGF-I analogues bearing arginine substitution at site 68. This established that K68 within the IGF-I D-domain was the principal K-donor site to TGases. We further annotated the functional significance of these K→R IGF-I analogues on IGF-I mediated actions. IGF-I analogues with K→R substitution within the D-domain at K65 and K68 hindered migration of MCF-7 breast carcinoma cells and correspondingly reduced PI3-K/AKT activation. Therefore, this study also provides first insights into a possible functional role of the previously uncharacterised IGF-I D-domain.

PEGylation of lysine residues reduces the pro-migratory activity of IGF-I

Background: The insulin-like growth factor (IGF) system is composed of ligands and receptors which regulate cell proliferation, survival, differentiation and migration. Some functions are regulated via intracellular signaling cascades, others by involvement of the extracellular milieu, including binding proteins and other extracellular matrix proteins. However, understanding of their functions and the exact nature of these interactions remains incomplete. Methods: IGF-I was PEGylated at its lysine sites - K27, K65 and K68. Binding of PEG-IGF-I to the IGFBPs was analyzed using BIAcore and its ability to activate the IGF-IR was assessed using IGF-IR phosphorylation assay. Furthermore, functional consequences of PEGylating the lysine residues of IGF-I was investigated using cell viability and cell migration assays. In addition, particular downstream signaling pathways regularly implicated in these mechanisms were also dissected using phospho-AKT and phospho-ERK1/2 assays. Results: In this study, IGF-I specifically PEGylated at lysine 27 (PEG-K27), 65 (PEG-K65) or 68 (PEG-K68) were employed. Receptor phosphorylation was only reduced by 2-fold with PEG-K65 and PEG-K68 over all the time points tested, and as observed in two cell types, 3T3 fibroblasts and MCF-7 breast cancer cells. PEGylation at K27 resulted in a much larger effect, with more than 10-fold lower activation for 3T3 fibroblasts and a ~3 fold reduced IGF-IR activation for MCF-7 breast cancer cells over 15 minutes. In addition, all PEG-IGF-I variants demonstrated a ten-fold reduction in the association rate to IGF binding proteins (IGFBPs). Functionally, all PEG variants completely lost their ability to induce cell migration in the presence of IGFBP-3/vitronectin (VN) complexes as compared to IGF-I; in contrast, cell viability was fully preserved. Further investigations into the downstream signaling pathways revealed that the PI3-K/AKT pathway was preferentially affected upon treatment with the PEG-IGF-I variants compared to the MAPK/ERK pathway. Conclusion: PEGylation of IGF-I has an impact on cell migration but not cell viability. General significance: PEG-IGF-I may differentially modulate IGF-I mediated functions that are dependent on its interaction with its receptor as well as key extracellular proteins such as VN and IGFBPs.

Mutations in cardiac T-Box Factor gene TBX20 are associated with diverse cardiac pathologies, including defects of septation and valvulogenesis and cardiomyopathy

The T-box family transcription factor gene TBX20 acts in a conserved regulatory network, guiding heart formation and patterning in diverse species. Mouse Tbx20 is expressed in cardiac progenitor cells, differentiating cardiomyocytes, and developing valvular tissue, and its deletion or RNA interference-mediated knockdown is catastrophic for heart development. TBX20 interacts physically, functionally, and genetically with other cardiac transcription factors, including NKX2-5, GATA4, and TBX5, mutations of which cause congenital heart disease (CHD). Here, we report nonsense (Q195X) and missense (I152M) germline mutations within the T-box DNA-binding domain of human TBX20 that were associated with a family history of CHD and a complex spectrum of developmental anomalies, including defects in septation, chamber growth, and valvulogenesis. Biophysical characterization of wild-type and mutant proteins indicated how the missense mutation disrupts the structure and function of the TBX20 T-box. Dilated cardiomyopathy was a feature of the TBX20 mutant phenotype in humans and mice, suggesting that mutations in developmental transcription factors can provide a sensitized template for adult-onset heart disease. Our findings are the first to link TBX20 mutations to human pathology. They provide insights into how mutation of different genes in an interactive regulatory circuit lead to diverse clinical phenotypes, with implications for diagnosis, genetic screening, and patient follow-up.