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1.  Differential Expression of 26S Proteasome Subunits and Functional Activity during Neonatal Development 
Biomolecules  2014;4(3):812-826.
Proteasomes regulate many essential cellular processes by degrading intracellular proteins. While aging is known to be associated with dysfunction of the proteasome, there are few reports detailing activity and function of proteasomes in the early stages of life. To elucidate the function and development of mammalian proteasomes, 26S proteasomes were affinity-purified from rat intestine, spleen and liver. The developmental expression of core, regulatory and immunoproteasome subunits was analyzed by immunoblotting and reverse-transcriptase PCR of mRNA subunits, and proteasome catalytic function was determined by fluorogenic enzymatic assays. The expression of core (β2, β5, α7 and β1) and regulatory (Rpt5) subunits was found to be present at low levels at birth and increased over time particularly at weaning. In contrast, while gradual developmental progression of proteasome structure was also seen with the immunoproteasome subunits (β1i, β5i, and β2i), these were not present at birth. Our studies demonstrate a developmental pattern to 26S proteasome activity and subunit expression, with low levels of core proteasome components and absence of immunoproteasomes at birth followed by increases at later developmental stages. This correlates with findings from other studies of a developmental hyporesponsiveness of the adaptive immune system to allow establishment of microbial colonization immediately after birth.
PMCID: PMC4192673  PMID: 25177858
proteasome; immunoproteasome; expression; catalytic; weaning
2.  Antivirulence Activity of the Human Gut Metabolome 
mBio  2014;5(4):e01183-14.
The mammalian gut contains a complex assembly of commensal microbes termed microbiota. Although much has been learned about the role of these microbes in health, the mechanisms underlying these functions are ill defined. We have recently shown that the mammalian gut contains thousands of small molecules, most of which are currently unidentified. Therefore, we hypothesized that these molecules function as chemical cues used by hosts and microbes during their interactions in health and disease. Thus, a search was initiated to identify molecules produced by the microbiota that are sensed by pathogens. We found that a secreted molecule produced by clostridia acts as a strong repressor of Salmonella virulence, obliterating expression of the Salmonella pathogenicity island 1 as well as host cell invasion. It has been known for decades that the microbiota protects its hosts from invading pathogens, and these data suggest that chemical sensing may be involved in this phenomenon. Further investigations should reveal the exact biological role of this molecule as well as its therapeutic potential.
Microbes can communicate through the production and sensing of small molecules. Within the complex ecosystem formed by commensal microbes living in and on the human body, it is likely that these molecular messages are used extensively during the interactions between different microbial species as well as with host cells. Deciphering such a molecular dialect will be fundamental to our understanding of host-microbe interactions in health and disease and may prove useful for the design of new therapeutic strategies that target these mechanisms of communication.
PMCID: PMC4128352  PMID: 25073640
3.  The influence of power dynamics and trust on multidisciplinary collaboration: a qualitative case study of type 2 diabetes mellitus 
Ongoing care for chronic conditions such as diabetes is best provided by a range of health professionals working together. There are challenges in achieving this where collaboration crosses organisational and sector boundaries. The aim of this article is to explore the influence of power dynamics and trust on collaboration between health professionals involved in the management of diabetes and their impact on patient experiences.
A qualitative case study conducted in a rural city in Australia. Forty five health service providers from nineteen organisations (including fee-for-service practices and block funded public sector services) and eight patients from two services were purposively recruited. Data was collected through semi-structured interviews that were audio-taped and transcribed. A thematic analysis approach was used using a two-level coding scheme and cross-case comparisons.
Three themes emerged in relation to power dynamics between health professionals: their use of power to protect their autonomy, power dynamics between private and public sector providers, and reducing their dependency on other health professionals to maintain their power. Despite the intention of government policies to support more shared decision-making, there is little evidence that this is happening. The major trust themes related to role perceptions, demonstrated competence, and the importance of good communication for the development of trust over time. The interaction between trust and role perceptions went beyond understanding each other's roles and professional identity. The level of trust related to the acceptance of each other's roles. The delivery of primary and community-based health services that crosses organisational boundaries adds a layer of complexity to interprofessional relationships. The roles of and role boundaries between and within professional groups and services are changing. The uncertainty and vulnerability associated with these changes has affected the level of trust and mistrust.
Collaboration across organisational boundaries remains challenging. Power dynamics and trust affect the strategic choices made by each health professional about whether to collaborate, with whom, and to what level. These decisions directly influenced patient experiences. Unlike the difficulties in shifting the balance of power in interprofessional relationships, trust and respect can be fostered through a mix of interventions aimed at building personal relationships and establishing agreed rules that govern collaborative care and that are perceived as fair.
PMCID: PMC3376040  PMID: 22413897
4.  Integrated primary health care in Australia 
To fulfil its role of coordinating health care, primary health care needs to be well integrated, internally and with other health and related services. In Australia, primary health care services are divided between public and private sectors, are responsible to different levels of government and work under a variety of funding arrangements, with no overarching policy to provide a common frame of reference for their activities.
Description of policy
Over the past decade, coordination of service provision has been improved by changes to the funding of private medical and allied health services for chronic conditions, by the development in some states of voluntary networks of services and by local initiatives, although these have had little impact on coordination of planning. Integrated primary health care centres are being established nationally and in some states, but these are too recent for their impact to be assessed. Reforms being considered by the federal government include bringing primary health care under one level of government with a national primary health care policy, establishing regional organisations to coordinate health planning, trialling voluntary registration of patients with general practices and reforming funding systems. If adopted, these could greatly improve integration within primary health care.
Careful change management and realistic expectations will be needed. Also other challenges remain, in particular the need for developing a more population and community oriented primary health care.
PMCID: PMC2787230  PMID: 19956377
primary health care; health policy; integration; Australia
5.  Developments in Australian general practice 2000–2002: what did these contribute to a well functioning and comprehensive Primary Health Care System? 
In recent years, national and state/territory governments have undertaken an increasing number of initiatives to strengthen general practice and improve its links with the rest of the primary health care sector. This paper reviews how far these initiatives were contributing to a well functioning and comprehensive primary health care system during the period 2000–2002, using a normative model of primary health care and data from a descriptive study to evaluate progress.
There was a significant number of programs, at both state/territory and national level. Most focused on individual care, particularly for chronic disease, rather than population health approaches. There was little evidence of integration across programs: each tended to be based in and focus on a single jurisdiction, and build capacity chiefly within the services funded through that jurisdiction. As a result, the overall effect was patchy, with similar difficulties being noted across all jurisdictions and little gain in overall system capacity for effective primary health care.
Efforts to develop more effective primary health care need a more balanced approach to reform, with a better balance across the different elements of primary health care and greater integration across programs and jurisdictions. One way ahead is to form a single funding agency, as in the UK and New Zealand, and so remove the need to work across jurisdictions and manage their competing interests. A second, perhaps less politically challenging starting point, is to create an agreed framework for primary health care within which a collective vision for primary health care can be developed, based on population health needs, and the responsibilities of different sectors services can be negotiated. Either of these approaches would be assisted by a more systematic and comprehensive program of research and evaluation for primary health care.
PMCID: PMC1379649  PMID: 16412243

Results 1-5 (5)