ECMO : the clinician’s view

Background: Extra corporeal membrane oxygenation (ECMO) is a complex rescue therapy used to provide cardiac and/or respiratory support for critically ill patients who have failed maximal conventional medical management. ECMO is based on a modified cardiopulmonary bypass (CPB) circuit, and can provide cardiopulmonary support for up-to several months. It can be used in a veno venous configuration for isolated respiratory failure, (VV-ECMO), or in a veno arterial configuration (VA-ECMO) where support is necessary for cardiac +/- respiratory failure. The ECMO circuit consists of five main components: large bore cannulae (access cannulae) for drainage of the venous system, and return cannulae to either the venous (in VV-ECMO) or arterial (in VA ECMO) system. An oxygenator, with a vast surface area of hollow filaments, allows addition of oxygen and removal of carbon dioxide; a centrifugal blood pump allows propulsion of blood through the circuit at upto 10 L/minute; a control module and a thermoregulatory unit, which allows for exact temperature control of the extra corporeal blood. Methods: The first successful use of ECMO for ARDS in adults occurred in 1972, and its use has become more commonplace over the last 30 years, supported by the improvement in design and biocompatibility of the equipment, which has reduced the morbidity associated with this modality. Whilst the use of ECMO in neonatal population has been supported by numerous studies, the evidence upon which ECMO was integrated into adult practice was substantially less robust. Results: Recent data, including the CESAR study (Conventional Ventilatory Support versus Extra corporeal membrane oxygenation for Severe Respiratory failure) has added a degree of evidence to the role of ECMO in such a patient population. The CESAR study analysed 180 patients, and confirmed that ECMO was associated with an improved rate of survival. More recently, ECMO has been utilized in numerous situations within the critical care area, including support in high-risk percutaneous interventions in cardiac catheter lab; the operating room, emergency department, as well in specialized inter-hospital retrieval services. The increased understanding of the risk:benefit profile of ECMO, along with a reduction in morbidity associated with its use will doubtless lead to a substantial rise in the utilisation of this modality. As with all extra-corporeal circuits, ECMO opposes the basic premises of the mammalian inflammation and coagulation cascade where blood comes into foreign circulation, both these cascades are activated. Anti-coagulation is readily dealt with through use of agents such as heparin, but the inflammatory excess, whilst less macroscopically obvious, continues un-abated. Platelet consumption and neutrophil activation occur rapidly, and the clinician is faced with balancing the need of anticoagulation for the circuit, against haemostasis in an acutely bleeding patient. Alterations in pharmacokinetics may result in inadequate levels of disease modifying therapeutics, such as antibiotics, hence paradoxically delaying recovery from conditions such as pneumonia. Key elements of nutrition and the innate immune system maysimilarly be affected. Summary: This presentation will discuss the basic features of ECMO to the nonspecialist, and review the clinical conundrum faced by the team treating these most complex cases.

Perceived barriers to healthy lifestyle activities in midlife and older Australian women with type 2 diabetes

Purpose: Type 2 diabetes is a leading cause of morbidity and mortality in midlife and older Australian women with known modifiable risk factors for type 2 diabetes including smoking, nutrition, physical activity and obesity. In Australia little research has been done to investigate the perceived barriers to healthy lifestyle activities in midlife and older women with type 2 diabetes. The primary aim of this study was to explore the level and type of perceived barriers to health promotion activities. The secondary aim was to explore the relationship of perceived barriers to smoking behaviour, fruit and vegetable intake, physical activity, and body mass index. Methods: The study was a cross sectional survey of women, aged over 45 with type 2 diabetes, attending metropolitan community health clinics (N = 41). Data was collected from self-report questionnaire and analysed using descriptive and inferential statistics. Results: Women in the study had average total barriers scores similar to those reported in the literature for women with a range of physical disabilities and illnesses. The leading barriers for this group of women were: lack of interest, concern about safety, too tired, lack of money and feeling what they do does not help. There was no association between total barriers scores and body mass index, physical activity, fruit and vegetable intake or socio-demographic variables. Conclusion: This study contributes to understanding the perceptions of midlife and older women with type 2 diabetes about the level and type of barriers to healthy lifestyle activities that they experience. Evidence from this study can be applied to inform health promotion for lifestyle risk factor reduction in women with type 2 diabetes.

Can a “Blue Sky” return to Indian megacities?

Deterioration of air quality in Indian megacities (Delhi, Mumbai or Kolkata) is much more significant than that observed in the megacities of developed countries. Densely packed high-rise buildings restrict the self-cleaning capabilities of Indian megacities. Also, the ever growing number of on-road vehicles, resuspension of the dust, and anthropogenic activities exacerbate the levels of ambient air pollution, which is in turn breathed by urban dwellers. Pollution levels exceeding the standards on a regular basis often result in a notable increase in morbidity and mortality. This article discusses the challenges faced by Indian megacities in their quest for sustainable growth, without compromising the air quality and urban way of life.

Making more sustainable urban environments by responding to neurodiversity in later life

The ageing population is increasing worldwide, as are a range of chronic diseases, conditions, and physical and cognitive disabilities associated with later life. The older population is also neurologically diverse, with unique and specific challenges around mobility and engagement with the urban environment. Older people tend to interact less with cities and neighbourhoods, putting them at risk of further illnesses and co-morbidities associated with being less physically and socially active. Empirical evidence has shown that reduced access to healthcare services, health-related resources and social interaction opportunities is associated with increases in morbidity and premature mortality. While it is crucial to respond to the needs of this ageing population, there is insufficient evidence for interventions regarding their experiences of public space from the vantage point of neurodiversity. This paper provides a conceptual and methodological framework to investigate relationships between the sensory and cognitive abilities of older people, and their use and negotiation of the urban environment. The paper will refer to a case example of the city of Logan, an urban area in Queensland, Australia, where current urban development provides opportunities for the design of spaces that take experiences of neurodiversity into account. The framework will inform the development of principles for urban design for increasingly neurologically diverse populations.

Evaluating the effectiveness of heat warning systems : a systematic review of epidemiological evidence

Objectives To review the existing research on the effectiveness of heat warning systems (HWSs) in saving lives and reducing harm. Methods A systematic search of major databases was conducted, using “heat, heatwave, high temperature, hot temperature, OR hot climate” AND “warning system”. Results Fifteen articles were retrieved. Six studies asserted that fewer people died of excessive heat after HWS implementation. HWS was associated with reduction in ambulance use. One study estimated the benefits of HWS to be 468millionforsaving117livescomparedto210,000 costs of running the system. Eight studies showed that mere availability of HWS did not lead to behavioral changes. Perceived threat of heat dangers to self/others was the main factor related to heeding warnings and taking proper actions. However, costs and barriers associated with taking protective actions, such as costs of running air conditioners, were of significant concern particularly to the poor. Conclusions Research in this area is limited. Prospective designs applying health behavior theories should establish whether HWS can produce the health benefits they are purported to achieve by identifying the target vulnerable groups.

Are heat warning systems effective?

Heatwaves are associated with significant health risks particularly among vulnerable groups. To minimize these risks, heat warning systems have been implemented. The question therefore is how effective these systems are in saving lives and reducing heat-related harm. We systematically searched and reviewed 15 studies which examined this. Six studies asserted that fewer people died of excessive heat after the implementation of heat warning systems. Demand for ambulance decreased following the implementation of these systems. One study also estimated the costs of running heat warning systems at US$210,000 compared to the US$468 million benefits of saving 117 lives. The remaining eight studies investigated people?s response to heat warning systems and taking appropriate actions against heat harms. Perceived threat of heat dangers emerged as the main factor related to heeding the warnings and taking proper actions. However, barriers, such as costs of running air-conditioners, were of significant concern, particularly to the poor. The weight of the evidence suggests that heat warning systems are effective in reducing mortality and, potentially, morbidity. However, their effectiveness may be mediated by cognitive, emotive and socio-demographic characteristics. More research is urgently required into the cost-effectiveness of heat warning systems? measures and improving the utilization of the services.

Modulation of LPS-induced chorioamnionitis by ureaplasma parvum in sheep chorioamnionitis in sheep

ABSTRACT Objective: Ureaplasma parvum colonization in the setting of polymicrobial flora is common in women with chorioamnionitis, and is a risk factor for preterm delivery and neonatal morbidity. We hypothesized that ureaplasma colonization of amniotic fluid will modulate chorioamnionitis induced by E.coli lipopolysaccharide (LPS). Methods: Sheep received intra-amniotic (IA) injections of media (control) or live ureaplasma either 7 or 70d before delivery. Another group received IA LPS 2d before delivery. To test for interactions, U.parvum exposed animals were challenged with IA LPS, and delivered 2d later. All animals were delivered preterm at 125±1 day gestation. Results: Both IA ureaplasmas and LPS induced leukocyte infiltration of chorioamnion. LPS greatly increased the expression of pro-inflammatory cytokines and myeloperoxidase in leukocytes, while ureaplasmas alone caused modest responses. Interestingly, 7d but not 70d ureaplasma exposure significantly downregulated LPS induced pro-inflammatory cytokines and myeloperoxidase expression in the chorioamnion. Conclusion: U.parvum can suppress LPS induced experimental chorioamnionitis.

Young women's drinking experiences in public drinking venues

Alcohol-related mortality and morbidity represents a substantial financial burden to communities across the world. In Australia, conservative estimates place the societal cost (2004-2005) for alcohol abuse at approximately 15.3 billion dollar annually (Collins & Lapsley, 2008). Research has found that adolescence and young adulthood is a peak period for heavy episodic alcohol consumption, with over a third of all people aged 14-19 years having been at risk for acute alcohol-related harm at least once in the prior 12 months (Australian Institute of Health and Welfare [AIHW], (2008). While excessive alcohol consumption has, for a long time, been seen as a male problem; there has been a gradual shift towards a social acceptance of female drinking which has resulted in a diminishing gap in drinking quantity and style between men and women (Roche & Deehan, 2002). There is substantial evidence that women are at higher risk than men for detrimental physical, medical, social and psychological effects of at-risk alcohol consumption (Epstein, et al., 2007). Research outlining the epidemiology of women’s substance use emphasises the need for further examination into influences that may be gender specific and culturally defined (Matheson, 2008; Measham & Ostergaard, 2009). As such, there is a need to utilise female perspectives in examining alcohol consumption and alcohol related problems in order to reflect a more balanced and competent version of drinking in today’s culture (Allamani, 2008). Currently a number of reasons are offered to explain the observed trends including reduction in traditional sanctions and social norms against women drinking, financial emancipation, cultural shift and targeted advertising to name a few. However, there is yet comparatively little research examining drinking by young women in order to understand this ‘new’ drinking pattern. Most research into alcohol use and subsequent intervention and prevention campaigns have been based on male perceptions and constructs of drinking. While such approaches have provided important information regarding the quantity and frequency of alcohol consumption by women, they do not address the important question of why. To understand the why, research needs to explore the difference between males and females in the meaning of the behaviour and the place that drinking holds to them.

Evaluation in health outcomes research : linking theories, methodologies and practice in health promotion.

Health outcomes research has developed as a means of evaluating the effectiveness of health care interventions and as an approach to informing resource allocation. The use of a health outcomes approach in health promotion has made increasing demands on evaluation methodologies to demonstrate program effectiveness. However, criticism of the contribution of health promotion to outcomes research has made several assumptions about the use of qualitative methodologies and the content of program objectives largely derived from a biomedical approach. In contrast to the measurement of biomedical interventions in clinical health care, health promotion practice involves social phenomena, wide-reaching cultural, psychological, political and ideological problems and issues. The integration of methodologies of health promotion evaluation will inform further conceptualisation of the health outcomes approach with the differentiation of three types of outcomes: health development outcomes; social health outcomes; and biomedical health outcomes. It is concluded that this differentiation moves away from dualist concepts that advocate the replacement of goals and targets with regional and locally based approaches. Rather, the future direction for health promotion evaluation needs to employ a framework that elaborates multiple methodologies and approaches necessary for establishing what relationships exist between morbidity, mortality, health advancement and equity.

The contribution of psychosocial factors to socioeconomic differences in food purchasing

In developed countries the relationship between socioeconomic position (SEP) and health is unequivocal. Those who are socioeconomically disadvantaged are known to experience higher morbidity and mortality from a range of chronic diet-related conditions compared to those of higher SEP. Socioeconomic inequalities in diet are well established. Compared to their more advantaged counterparts, those of low SEP are consistently found to consume diets less consistent with dietary guidelines (i.e. higher in fat, salt and sugar and lower in fibre, fruit and vegetables). Although the reasons for dietary inequalities remain unclear, understanding how such differences arise is important for the development of strategies to reduce health inequalities. Both environmental (e.g. proximity of supermarkets, price, and availability of foods) and psychosocial (e.g. taste preference, nutrition knowledge) influences are proposed to account for inequalities in food choices. Although in the United States (US), United Kingdom (UK), and parts of Australia, environmental factors are associated with socioeconomic differences in food choices, these factors do not completely account for the observed inequalities. Internationally, this context has prompted calls for further exploration of the role of psychological and social factors in relation to inequalities in food choices. It is this task that forms the primary goal of this PhD research. In the small body of research examining the contribution of psychosocial factors to inequalities in food choices, studies have focussed on food cost concerns, nutrition knowledge or health concerns. These factors are generally found to be influential. However, since a range of psychosocial factors are known determinants of food choices in the general population, it is likely that a range of factors also contribute to inequalities in food choices. Identification of additional psychosocial factors of relevance to inequalities in food choices would provide new opportunities for health promotion, including the adaption of existing strategies. The methodological features of previous research have also hindered the advancement of knowledge in this area and a lack of qualitative studies has resulted in a dearth of descriptive information on this topic. This PhD investigation extends previous research by assessing a range of psychosocial factors in relation to inequalities in food choices using both quantitative and qualitative techniques. Secondary data analyses were undertaken using data obtained from two Brisbane-based studies, the Brisbane Food Study (N=1003, conducted in 2000), and the Sixty Families Study (N=60, conducted in 1998). Both studies involved main household food purchasers completing an interviewer-administered survey within their own home. Data pertaining to food-purchasing, and psychosocial, socioeconomic and demographic characteristics were collected in each study. The mutual goals of both the qualitative and quantitative phases of this investigation were to assess socioeconomic differences in food purchasing and to identify psychosocial factors relevant to any observed differences. The quantitative methods then additionally considered whether the associations examined differed according to the socioeconomic indicator used (i.e. income or education). The qualitative analyses made a unique contribution to this project by generating detailed descriptions of socioeconomic differences in psychosocial factors. Those with lower levels of income and education were found to make food purchasing choices less consistent with dietary guidelines compared to those of high SEP. The psychosocial factors identified as relevant to food-purchasing inequalities were: taste preferences, health concerns, health beliefs, nutrition knowledge, nutrition concerns, weight concerns, nutrition label use, and several other values and beliefs unique to particular socioeconomic groups. Factors more tenuously or inconsistently related to socioeconomic differences in food purchasing were cost concerns, and perceived adequacy of the family diet. Evidence was displayed in both the quantitative and qualitative analyses to suggest that psychosocial factors contribute to inequalities in food purchasing in a collective manner. The quantitative analyses revealed that considerable overlap in the socioeconomic variation in food purchasing was accounted for by key psychosocial factors of importance, including taste preference, nutrition concerns, nutrition knowledge, and health concerns. Consistent with these findings, the qualitative transcripts demonstrated the interplay between such influential psychosocial factors in determining food-purchasing choices. The qualitative analyses found socioeconomic differences in the prioritisation of psychosocial factors in relation to food choices. This is suggestive of complex cultural factors that distinguish advantaged and disadvantaged groups and result in socioeconomically distinct schemas related to health and food choices. Compared to those of high SEP, those of lower SEP were less likely to indicate that health concerns, nutrition concerns, or food labels influenced food choices, and exhibited lower levels of nutrition knowledge. In the absence of health or nutrition-related concerns, taste preferences tended to dominate the food purchasing choices of those of low SEP. Overall, while cost concerns did not appear to be a main determinant of socioeconomic differences in food purchasing, this factor had a dominant influence on the food choices of some of the most disadvantaged respondents included in this research. The findings of this study have several implications for health promotion. The integrated operation of psychosocial factors on food purchasing inequalities indicates that multiple psychosocial factors may be appropriate to target in health promotion. It also seems possible that the inter-relatedness of psychosocial factors would allow health promotion targeting a single psychosocial factor to have a flow-on affect in terms of altering other influential psychosocial factors. This research also suggests that current mass marketing approaches to health promotion may not be effective across all socioeconomic groups due to differences in the priorities and main factors of influence in food purchasing decisions across groups. In addition to the practical recommendations for health promotion, this investigation, through the critique of previous research, and through the substantive study findings, has highlighted important methodological considerations for future research. Of particular note are the recommendations pertaining to the selection of socioeconomic indicators, measurement of relevant constructs, consideration of confounders, and development of an analytical approach. Addressing inequalities in health has been noted as a main objective by many health authorities and governments internationally. It is envisaged that the substantive and methodological findings of this thesis will make a useful contribution towards this important goal.

The individual and interactive relationship between long chain omega-3 polyunsaturated fatty acids and physical activity as predictors of cognition in cognitively impaired and non-impaired older adults

Alterations in cognitive function are characteristic of the aging process in humans and other animals. However, the nature of these age related changes in cognition is complex and is likely to be influenced by interactions between genetic predispositions and environmental factors resulting in dynamic fluctuations within and between individuals. These inter and intra-individual fluctuations are evident in both so-called normal cognitive aging and at the onset of cognitive pathology. Mild Cognitive Impairment (MCI), thought to be a prodromal phase of dementia, represents perhaps the final opportunity to mitigate cognitive declines that may lead to terminal conditions such as dementia. The prognosis for people with MCI is mixed with the evidence suggesting that many will remain stable within 10-years of diagnosis, many will improve, and many will transition to dementia. If the characteristics of people who do not progress to dementia from MCI can be identified and replicated in others it may be possible to reduce or delay dementia onset, thus reducing a growing personal and public health burden. Furthermore, if MCI onset can be prevented or delayed, the burden of cognitive decline in aging populations worldwide may be reduced. A cognitive domain that is sensitive to the effects of advancing age, and declines in which have been shown to presage the onset of dementia in MCI patients, is executive function. Moreover, environmental factors such as diet and physical activity have been shown to affect performance on tests of executive function. For example, improvements in executive function have been demonstrated as a result of increased aerobic and anaerobic physical activity and, although the evidence is not as strong, findings from dietary interventions suggest certain nutrients may preserve or improve executive functions in old age. These encouraging findings have been demonstrated in older adults with MCI and their non-impaired peers. However, there are some gaps in the literature that need to be addressed. For example, little is known about the effect on cognition of an interaction between diet and physical activity. Both are important contributors to health and wellbeing, and a growing body of evidence attests to their importance in mental and cognitive health in aging individuals. Yet physical activity and diet are rarely considered together in the context of cognitive function. There is also little known about potential underlying biological mechanisms that might explain the physical activity/diet/cognition relationship. The first aim of this program of research was to examine the individual and interactive role of physical activity and diet, specifically long chain polyunsaturated fatty acid consumption(LCn3) as predictors of MCI status. The second aim is to examine executive function in MCI in the context of the individual and interactive effects of physical activity and LCn3.. A third aim was to explore the role of immune and endocrine system biomarkers as possible mediators in the relationship between LCn3, physical activity and cognition. Study 1a was a cross-sectional analysis of MCI status as a function of erythrocyte proportions of an interaction between physical activity and LCn3. The marine based LCn3s eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) have both received support in the literature as having cognitive benefits, although comparisons of the relative benefits of EPA or DHA, particularly in relation to the aetiology of MCI, are rare. Furthermore, a limited amount of research has examined the cognitive benefits of physical activity in terms of MCI onset. No studies have examined the potential interactive benefits of physical activity and either EPA or DHA. Eighty-four male and female adults aged 65 to 87 years, 50 with MCI and 34 without, participated in Study 1a. A logistic binary regression was conducted with MCI status as a dependent variable, and the individual and interactive relationships between physical activity and either EPA or DHA as predictors. Physical activity was measured using a questionnaire and specific physical activity categories were weighted according to the metabolic equivalents (METs) of each activity to create a physical activity intensity index (PAI). A significant relationship was identified between MCI outcome and the interaction between the PAI and EPA; participants with a higher PAI and higher erythrocyte proportions of EPA were more likely to be classified as non-MCI than their less active peers with less EPA. Study 1b was a randomised control trial using the participants from Study 1a who were identified with MCI. Given the importance of executive function as a determinant of progression to more severe forms of cognitive impairment and dementia, Study 1b aimed to examine the individual and interactive effect of physical activity and supplementation with either EPA or DHA on executive function in a sample of older adults with MCI. Fifty male and female participants were randomly allocated to supplementation groups to receive 6-months of supplementation with EPA, or DHA, or linoleic acid (LA), a long chain polyunsaturated omega-6 fatty acid not known for its cognitive enhancing properties. Physical activity was measured using the PAI from Study 1a at baseline and follow-up. Executive function was measured using five tests thought to measure different executive function domains. Erythrocyte proportions of EPA and DHA were higher at follow-up; however, PAI was not significantly different. There was also a significant improvement in three of the five executive function tests at follow-up. However, regression analyses revealed that none of the variance in executive function at follow-up was predicted by EPA, DHA, PAI, the EPA by PAI interaction, or the DHA by PAI interaction. The absence of an effect may be due to a small sample resulting in limited power to find an effect, the lack of change in physical activity over time in terms of volume and/or intensity, or a combination of both reduced power and no change in physical activity. Study 2a was a cross-sectional study using cognitively unimpaired older adults to examine the individual and interactive effects of LCn3 and PAI on executive function. Several possible explanations for the absence of an effect were identified. From this consideration of alternative explanations it was hypothesised that post-onset interventions with LCn3 either alone or in interation with self-reported physical activity may not be beneficial in MCI. Thus executive function responses to the individual and interactive effects of physical activity and LCn3 were examined in a sample of older male and female adults without cognitive impairment (n = 50). A further aim of study 2a was to operationalise executive function using principal components analysis (PCA) of several executive function tests. This approach was used firstly as a data reduction technique to overcome the task impurity problem, and secondly to examine the executive function structure of the sample for evidence of de-differentiation. Two executive function components were identified as a result of the PCA (EF 1 and EF 2). However, EPA, DHA, the PAI, or the EPA by PAI or DHA by PAI interactions did not account for any variance in the executive function components in subsequent hierarchical multiple regressions. Study 2b was an exploratory correlational study designed to explore the possibility that immune and endocrine system biomarkers may act as mediators of the relationship between LCn3, PAI, the interaction between LCn3 and PAI, and executive functions. Insulin-like growth factor-1 (IGF-1), an endocrine system growth hormone, and interleukin-6 (IL-6) an immune system cytokine involved in the acute inflammatory response, have both been shown to affect cognition including executive functions. Moreover, IGF-1 and IL-6 have been shown to be antithetical in so far as chronically increased IL-6 has been associated with reduced IGF-1 levels, a relationship that has been linked to age related morbidity. Further, physical activity and LCn3 have been shown to modulate levels of both IGF-1 and IL-6. Thus, it is possible that the cognitive enhancing effects of LCn3, physical activity or their interaction are mediated by changes in the balance between IL-6 and IGF-1. Partial and non-parametric correlations were conducted in a subsample of participants from Study 2a (n = 13) to explore these relationships. Correlations of interest did not reach significance; however, the coefficients were quite large for several relationships suggesting studies with larger samples may be warranted. In summary, the current program of research found some evidence supporting an interaction between EPA, not DHA, and higher energy expenditure via physical activity in differentiating between older adults with and without MCI. However, a RCT examining executive function in older adults with MCI found no support for increasing EPA or DHA while maintaining current levels of energy expenditure. Furthermore, a cross-sectional study examining executive function in older adults without MCI found no support for better executive function performance as a function of increased EPA or DHA consumption, greater energy expenditure via physical activity or an interaction between physical activity and either EPA or DHA. Finally, an examination of endocrine and immune system biomarkers revealed promising relationships in terms of executive function in non-MCI older adults particularly with respect to LCn3 and physical activity. Taken together, these findings demonstrate a potential benefit of increasing physical activity and LCn3 consumption, particularly EPA, in mitigating the risk of developing MCI. In contrast, no support was found for a benefit to executive function as a result of increased physical activity, LCn3 consumption or an interaction between physical activity and LCn3, in participants with and without MCI. These results are discussed with reference to previous findings in the literature including possible limitations and opportunities for future research.

Designing a continuum of quality external cause of injury information in Queensland : from ambulance to hospital

This study is the first to employ an epidemiological framework to evaluate the ‘fit-for-purpose’ of ICD-10-AM external cause of injury codes, ambulance and hospital clinical documentation for injury surveillance. Importantly, this thesis develops an evidence-based platform to guide future improvements in routine data collections used to inform the design of effective injury prevention strategies. Quantification of the impact of ambulance clinical records on the overall information quality of Queensland hospital morbidity data collections for injury causal information is a unique and notable contribution of this study.

Plasma metabolomics reveals biomarkers of the atherosclerosis

Atherosclerotic cardiovascular disease remains the leading cause of morbidity and mortality in industrialized societies. The lack of metabolite biomarkers has impeded the clinical diagnosis of atherosclerosis so far. In this study, stable atherosclerosis patients (n=16) and age- and sex-matched non-atherosclerosis healthy subjects (n=28) were recruited from the local community (Harbin, P. R. China). The plasma was collected from each study subject and was subjected to metabolomics analysis by GC/MS. Pattern recognition analyses (principal components analysis, orthogonal partial least-squares discriminate analysis, and hierarchical clustering analysis) commonly demonstrated plasma metabolome, which was significantly different from atherosclerotic and non-atherosclerotic subjects. The development of atherosclerosis-induced metabolic perturbations of fatty acids, such as palmitate, stearate, and 1-monolinoleoylglycerol, was confirmed consistent with previous publication, showing that palmitate significantly contributes to atherosclerosis development via targeting apoptosis and inflammation pathways. Altogether, this study demonstrated that the development of atherosclerosis directly perturbed fatty acid metabolism, especially that of palmitate, which was confirmed as a phenotypic biomarker for clinical diagnosis of atherosclerosis.

Molecular characterisation and expression analysis of interferon gamma in response to natural chlamydia infection in the koala, phascolarctos cinereus

Interferon gamma (IFNγ) is a key Th1 cytokine, with a principal role in the immune response against intracellular organisms such as Chlamydia. Along with being responsible for significant morbidity in human populations, Chlamydia is also responsible for wide spread infection and disease in many animal hosts, with reports that many Australian koala subpopulations are endemically infected. An understanding of the role played by IFNγ in koala chlamydial diseases is important for the establishment of better prophylactic and therapeutic approaches against chlamydial infection in this host. A limited number of IFNγ sequences have been published from marsupials and no immune reagents to measure expression have been developed. Through preliminary analysis of the koala transcriptome, we have identified the full coding sequence of the koala IFNγ gene. Transcripts were identified in spleen and lymph node tissue samples. Phylogenetic analysis demonstrated that koala IFNγ is closely related to other marsupial IFNγ sequences and more distantly related to eutherian mammals. To begin to characterise the role of this important cytokine in the koala's response to chlamydial infection, we developed a quantitative real time PCR assay and applied it to a small cohort of koalas with and without active chlamydial disease, revealing significant differences in expression patterns between the groups. Description of the IFNγ sequence from the koala will not only assist in understanding this species' response to its most important pathogen but will also provide further insight into the evolution of the marsupial immune system

Effect of induced airway inflammation in asthma : the expression of trefoil factors, secretoglobins and genes involved in histone acetylation

Asthma is an incapacitating disease of the respiratory system, which causes extensive morbidity and mortality worldwide. Asthma affects more than 300 million people globally(Masoli et al. 2004). In Australia, it affects 10.2% of the population (Masoli et al. 2004) and causes 60,000 people to be hospitalised annually. Health care expenditure due to asthma in Australia was $606 million in 2004–2005. There are four primary biological factors that function in the initiation and exacerbation of asthma. Airway inflammation is important as it is often the first response to an airway insult, initiating the three other components: bronchoconstriction, mucus hyper-secretion and hyper-reactivity. The mediators involved in asthma are still not well understood, and current anti-inflammatory corticosteroid treatments are not effective with all asthmatics. As there is currently no cure for asthma, and airway inflammation is the primary component of the disease, it is important that we understand and investigate the mediators of airway inflammation to look for a potential cure and to produce better therapeutics to treat the inflammation. Trefoil factors (TFFs) and secretoglobins (SCGBs) are small secreted proteins involved in the mediation of inflammation and epithelial restitution. TFFs are pro-inflammatory and SCGBs anti-inflammatory by nature. The hypothesis of this study is that in response to induced acute airway inflammation, the expression of TFF1 and TFF3 will increase and expression of SCGB1A1 and SCGB3A2 will decrease in non-asthmatics (N-A), asthmatics medicating with bronchodilators (A-BD) and asthmatics medicating with corticosteroids (A-ST). When comparing the three groups, we expect to see higher expression of the TFFs in the A-BD group compared to the N-A and A-ST groups, indicating that inflammation is mediated by TFFs in asthma and that corticosteroid medication controls their expression as part of the control of inflammation. We expect to see the opposite with SCGBs, with a greater decrease in the A-BD group compared to the other two groups, suggesting that the A-BD group has the least anti-inflammatory activity in response to inflammatory insult. Epigenetic modification plays a role in the regulation of genes that initiate disease states such as inflammatory conditions and cancers. Histone acetylation is one such modification, which involves the acetylation of histones in chromatin by histone acetyltransferases (HATs). This increases the transcription of genes involved with inflammation or enrols histone deacetylases (HDACs) to down-regulate the transcription of inflammatory genes. These HATs and HDACs work in a homeostatic fashion; however, in the event of inflammation, increased HAT activity can stimulate further inflammation, which is believed to be the mechanism involved in some inflammatory diseases. This study hypothesises that in response to inflammation, the expression of HDACs (HDAC1-5) will decrease and the expression of HATs (NCOA1-3, HAT-1 and CREBBP) will increase in all groups. When comparing the expression between the groups, it was expected that a greater decrease in HDACs and a greater increase in HATs will be seen in the A-BD group compared to the other two groups. This would identify histone acetylation as a mechanism involved in the inflammatory condition of asthma and indicate that corticosteroids may treat the inflammation in asthma at least in part by controlling histone acetylation. The aim of the project was to compare the expression of inflammatory genes TFF1, TFF3, SCGB1A1 and SCGB3A2, as well as to compare the gene expression of HDAC1-5, NCOA1-3, HAT-1 and CREBBP within and between N-A (n=15), A-BD (n=15) and A-ST (n=15) groups in response to inflammation. This was performed by collecting airway cells and proteins by sputum induction in three sessions. The sessions were coordinated into an initial baseline collection (SI-1), followed by a second session at least one week later (SI-2) and a third session, six hours after SI-2 to collect a sample containing the resultant acute inflammation caused in SI-2 (SI-3). Analysis of the SI-1 and SI-2 samples in all three groups had high amounts of variability between samples. The samples were taken at least one weak apart and the environmental stimuli on each participant outside of the testing sessions could not be controlled. For this reason, the SI-1 samples were not used for analysis; instead SI-2 and SI-3 samples were compared as they were same-day collections, reducing the probability of differences being due to anything other than the sputum induction. The gene expressions of the TFFs, SCGBs, HDACs and HATs were analysed using real-time PCR. Western blot analysis was performed to analyse the protein concentrations of the TFFs and SCGBs in secreted fractions of the sputum collection. Both the secreted and intracellular protein fractions collected from the sputum inductions for pre- and post-inflammation (SI-2, SI-3) samples of the N-A and A-BD groups were analysed using a proteomic method called iTRAQ. This allowed the comparison of the change in protein expression as a result of airway inflammation in each group. This technique was used as a discovery method to identify novel proteins that are modulated by induced acute airway inflammation. Any proteins of interest would then be further validated and used for future research. Inflammation was achieved in the SI-3 samples of the N-A group with a 21% unit increase in % neutrophils compared to SI-2 (p=0.01). The N-A group had a marked 5.5-fold decrease in HDAC1 gene expression in SI-3 compared to SI-2 (p=0.03). No differences were seen in any of the TFFs, SCGBs or any of the rest of the HDACs and HATs. Western blot data did not display any significant changes in the protein levels of the TFFs and SCGBs analysed. However, non-significant analysis of the data displayed increases in TFF1 and TFF3, and decreases in SCGB1A1 and SCGB3A2 for the majority of SI-3 samples compared to SI-2. The A-BD group also presented a marked increase in neutrophils in the SI-3 samples compared to SI-2 (27% unit increase, p=0.04). The A-BD group had a significant increase in TFF3 and SCGB1A1 gene expression concomitant with induced acute airway inflammation. A 7.3-fold increase in TFF3 (p=0.05) in SI-3 indicated that TFF3 is linked to inflammation in asthmatics. A 2.8-fold increase in SCGB1A1 (p=0.03) indicated that this gene is also up-regulated, suggesting that this SCGB is expressed to try to combat induced acute airway inflammation. No significant changes were seen in any of the other genes analysed. Western blot data did not display any significant changes in the protein levels of the TFFs and SCGBs analysed. However, non-significant analysis of the data displayed an increase in TFF1 and TFF3, and a decrease in SCGB1A1 and SCGB3A2 in SI-3, similar to that seen in the N-A group. The A-ST group was different from the A-BD group, characterised by the use of inhaled corticosteroid medication to treat asthma symptoms. Inhaled corticosteroids are known to treat asthma symptoms through the control of inflammation. Therefore, it was expected that corticosteroid medication would also control the expression of TFFs, SCGBs, HATs and HDACs. Gene expression results only identified a 7.6-fold decrease in HDAC2 expression in SI-3 (p=0.001), which is proposed to be due to the up-regulation of HDAC2 protein that is known to be a function of corticosteroid use. Western blot data did not display any significant changes in the protein levels of the TFFs and SCGBs analysed. The gene expression in SI-2 and SI-3 in each group was compared. When comparing the A-BD group to the N-A group, a 9-fold increase in TFF3 (p=0.008) and a 34-fold increase in SCGB1A1 (p=0.03) were seen in the SI-3 samples. Comparisons of the A-ST group to the N-A group had an increased expression in SI-2 samples for HDAC5 (3.6-fold, p=0.04), NCOA2 (8.5-fold, p=0.04), NCOA3 (17-fold, p=0.01), HAT-1 (36-fold, p=0.003) and CREBBP (13-fold, p=0.001). The SI-3 samples in the A-ST group compared to the N-A group had increased expression for HDAC1 (6.4-fold, p=0.04), HDAC5 (5.2-fold, p=0.008), NCOA2 (9.6-fold, p=0.03), NCOA3 (16-fold, p=0.06), HAT-1 (41-fold, p<0.001) and CREBBP (31-fold, p=0.001). Comparisons of the A-ST group to the A-BD group had SI-2 increases in HDAC1 (3.8-fold, p=0.03), NCOA3 (4.5-fold, p=0.03), HAT-1 (5.3-fold, p=0.01) and CREBBP (23-fold, p=0.001), while SI-3 comparisons saw a decrease in HDAC2 (41-fold, p=0.008) and increases in HAT-1 (4.3-fold, p=0.003) and CREBBP (40-fold, p=0.001). Results showed that TFF3 and SCGB1A1 expression is higher in asthmatics than non-asthmatics and that histone acetylation is more active in the A-ST group than either the N-A or A-BD group, which suggests that histone acetylation activity may be positively correlated with asthma severity. The iTRAQ proteomic analysis of the secreted protein samples identified the SCGB1A1 protein and found it to be decreased in both the N-A and A-BD groups post-inflammation, but significantly so only in the A-BD group. Although no significant results were obtained from the western blot data, both groups displayed a decrease in SCGB1A1 concentration in SI-3 samples, suggesting a correlation with the proteomic data. Only 31 peptides were identified from the secreted samples. The intracellular iTRAQ analysis successfully identified 664 peptides, eight of which had differential expression in association with induced acute airway inflammation. Significant increases were seen in the A-BD group in SI-3 compared to SI-2 than in the N-A group in chloride intracellular channel protein 1, keratin-19, eosinophil cationic protein, calnexin, peroxiredoxin-5, and ATP-synthase delta subunit, while decreases were seen in cystatin-A and mucin-5AC. The iTRAQ analysis was only a discovery measure and further validation must be performed. In summary, the expression of TFFs and SCGBs differed between non-asthmatics and asthmatics. It is clear that TFF3 is active in the airway inflammation associated with asthma as indicated by an increase associated with inflammation in the A-BD group compared to the N-A group. Results for HDAC and HAT genes showed high HAT expression in the A-ST group compared to the N-A and A-BD groups, suggesting that histone acetyltransferases may be responsible for the characteristic unregulated inflammatory symptoms of asthmatics taking corticosteroids. Interestingly, corticosteroid medication did not seem to silence the expression of the analysed HAT genes, which indicates that corticosteroids may not control inflammation by direct regulation of HATs, but instead by competition, most probably with HDAC2 protein. As a discovery tool, iTRAQ is a potent method to both identify and compare the concentration of proteins between samples. The method is a powerful first step into the identification of novel proteins that are regulated in response to different treatments.