Medicine (RMH) - Research Publications
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ItemNo Preview AvailableRegulation of the endosomal SNARE protein syntaxin 7 by colony-stimulating factor 1 in macrophages(AMER SOC MICROBIOLOGY, 2008-10)Colony-stimulating factor 1 (CSF-1) is the main growth factor controlling the development of macrophages from myeloid progenitor cells. However, CSF-1 also regulates some of the key effector functions of macrophages (e.g., phagocytosis and cytokine secretion). The endosomal SNARE protein syntaxin 7 (Stx7) regulates vesicle trafficking events involved in phagocytosis and cytokine secretion. Therefore, we investigated the ability of CSF-1 to regulate Stx7. CSF-1 upregulated Stx7 expression in primary mouse macrophages; it also upregulated expression of its SNARE partners Vti1b and VAMP8 but not Stx8. Additionally, CSF-1 induced the rapid serine phosphorylation of Stx7 and enhanced its binding to Vti1b, Stx8, and VAMP8. Bioinformatics analysis and results from experiments with kinase inhibitors suggested the CSF-1-induced phosphorylation of Stx7 was mediated by protein kinase C and Akt in response to phosphatidylinositol 3-kinase activation. Based on mutagenesis studies, CSF-1 appeared to increase the binding of Stx7 to its SNARE partners by inducing the phosphorylation of serine residues in the Habc domain and/or "linker" region of Stx7. Thus, CSF-1 is a key regulator of Stx7 expression and function in macrophages. Furthermore, the effects of CSF-1 on Stx7 may provide a mechanism for the regulation of macrophage effector functions by CSF-1.
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ItemNo Preview AvailableGata-3 Negatively Regulates the Tumor-Initiating Capacity of Mammary Luminal Progenitor Cells and Targets the Putative Tumor Suppressor Caspase-14(AMER SOC MICROBIOLOGY, 2011-11)The transcription factor Gata-3 is a definitive marker of luminal breast cancers and a key regulator of mammary morphogenesis. Here we have explored a role for Gata-3 in tumor initiation and the underlying cellular mechanisms using a mouse model of "luminal-like" cancer. Loss of a single Gata-3 allele markedly accelerated tumor progression in mice carrying the mouse mammary tumor virus promoter-driven polyomavirus middle T antigen (MMTV-PyMT mice), while overexpression of Gata-3 curtailed tumorigenesis. Through the identification of two distinct luminal progenitor cells in the mammary gland, we demonstrate that Gata-3 haplo-insufficiency increases the tumor-initiating capacity of these progenitors but not the stem cell-enriched population. Overexpression of a conditional Gata-3 transgene in the PyMT model promoted cellular differentiation and led to reduced tumor-initiating capacity as well as diminished angiogenesis. Transcript profiling studies identified caspase-14 as a novel downstream target of Gata-3, in keeping with its roles in differentiation and tumorigenesis. A strong association was evident between GATA-3 and caspase-14 expression in preinvasive ductal carcinoma in situ samples, where GATA-3 also displayed prognostic significance. Overall, these studies identify GATA-3 as an important regulator of tumor initiation through its ability to promote the differentiation of committed luminal progenitor cells.
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ItemMinimum technical standards and recommendations for traumatic brain injury specialist rehabilitation teams in sudden-onset disasters (for Disaster Rehabilitation Committee special session) (Abstract)(Elsevier BV, 2018-07)Introduction/Background: Sudden-onset disasters (SODs) result in increased number of survivors with complex and long-term disabling injuries, including traumatic brain injury (TBI) that warrants comprehensive specialist rehabilitation. This presentation highlights the minimum technical standards required for specialised TBI rehabilitation teams and their integration into WHO Emergency Medical Teams (EMTs) to facilitate comprehensive management of TBI survivors in disaster settings. Material and method: A team of medical rehabilitation physicians from the Royal Melbourne Hospital conducted a comprehensive review of literature for TBI management, based on the WHO core-guidelines for ‘Minimum technical standards and recommendations for rehabilitation for EMTs’. These were endorsed by a specialist TBI expert panel in the Asia-Pacific region. Results: Comprehensive rehabilitation programs improve functional outcomes and quality of life of TBI survivors. It is recommended that specialised TBI care teams need to be embedded into EMTs for disaster response and management for early diagnosis, management and social reintegration. This guidance documents the minimum standards for deployment of TBI specialist rehabilitation teams in the context of SODs, including: skill requirements, team configuration and profile, professional competencies for management of TBI and complications, list of required equipment and consumables, information management/dissemination. Conclusion: TBI rehabilitation should commence from the early response phase in SODs by accredited rehabilitation professionals to minimise complications and disability. Integration of specialised TBI rehabilitation professionals into EMTs for disaster response will improve functional outcomes of survivors.
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ItemHealth services : knowledge, use and satisfaction of Afghan, Iranian and Iraqi settlers in Australia(Radcliffe Publishing, 2007)This paper reports the findings of a study examining the knowledge of, use of and satisfaction with local primary healthcare services reported by new arrivals to Australia from Iran, Iraq and Afghanistan. The study sample consisted of a purposive sample of 98 new settlers from the selected countries and used a semi-structured questionnaire and focus groups to attain information. Key findings were that friends and family were the greatest sources of health provider information and there was a lack of both more general health information and understanding of the health system. While study participants were able to access primary healthcare services and were generally satisfied, several major operational deficiencies were reported. General practitioners (GPs) were the major health providers for these groups. Health-seeking behaviours were strongly influenced by the country of birth in comparison with the other examined factors, and experiences of health service encounters also varied greatly between countries of birth. The facility’s proximity to the participant’s home was a strong influence in the selection of health services. The researchers recommend that a network of appropriately supported and staffed community health centres and/ or GP clinics is needed in areas where there are high concentrations of refugees and immigrants.
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ItemDetermining Expected Research Skills of Medical Students on Graduation: a Systematic Review(Springer, 2020-12)BACKGROUND: Global interest in research skills in undergraduate medical education is growing. There is no consensus regarding expected research skills of medical students on graduation. We conducted a systematic review to determine the aims and intended learning outcomes (ILOs) of mandatory research components of undergraduate medical curricula incorporating the teaching, assessment, and evaluation methods of these programs. METHODS: Using the PRISMA protocol, MEDLINE and ERIC databases were searched with keywords related to "medical student research programs" for relevant articles published up until February 2020. Thematic analysis was conducted according to student experience/reactions, mentoring/career development, and knowledge/skill development. RESULTS: Of 4880 citations, 41 studies from 30 institutions met the inclusion criteria. Programs were project-based in 24 (80%) and coursework only-based in 6 (20%). Program aims/ILOs were stated in 24 programs (80%). Twenty-seven different aims/ILOs were identified: 19 focused on knowledge/skill development, 4 on experience/reactions, and 4 on mentoring/career development. Project-based programs aimed to provide an in-depth research experience, foster/increase research skills, and critically appraise scientific literature. Coursework-based programs aimed to foster/apply analytical skills for decision-making in healthcare and critically appraise scientific literature. Reporting of interventions was often incomplete, short term, and single institution. There was poor alignment between aims, teaching, assessment, and evaluation methods in most. CONCLUSIONS: The diversity of teaching programs highlights challenges in defining core competencies in research skills for medical graduates. Incomplete reporting limits the evidence for effective research skills education; we recommend those designing and reporting educational interventions adopt recognized educational reporting criteria when describing their findings. Whether students learn by "doing", "proposing to do", or "critiquing", good curriculum design requires constructive alignment between teaching, assessment, and evaluation methods, aims, and outcomes. Peer-reviewed publications and presentations only evaluate one aspect of the student research experience.
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ItemNo Preview AvailableFinancial sustainability planning for immunization services in Cambodia(OXFORD UNIV PRESS, 2006-07)The expanded programme of immunization was established in Cambodia in 1986. In 2002, 67% of eligible children were immunized, despite significant health sector and macro-economic financial constraints. A financial sustainability planning process for immunization was introduced in 2002, in order to mobilize national and international resources in support of the achievement of child health objectives. The aim of this paper is to outline this process, describe its early impact as an advocacy tool and recommend additional strategies for mobilizing additional resources for health. The methods of financial sustainability planning are described, including the advocacy strategies that were applied. Analysis of financial sustainability planning results indicates rising programme costs associated with new vaccine introduction and new technologies. Despite this, the national programme has demonstrated important early successes in using financial sustainability planning to advocate for increased mobilization of national and international sources of funding for immunization. The national immunization programme nevertheless faces formidable system and financial challenges in the coming years associated with rising costs, potentially diminishing sources of international assistance, and the developing role of sub-national authorities in programme management and financing.
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ItemMalaria prevention in the expatriate and long-term traveller(Therapeutic Guidelines Limited, 2002-01-01)The prevention of malaria in expatriates and long-term travellers is complex. The traveller's doctor needs to consider the destination, the nature of the travel, the effectiveness and potential adverse effects of antimalarial medication, and the general health of the traveller. A preventative regimen can be devised combining several strategies including mosquito avoidance measures, chemoprophylaxis, emergency standby treatment and rapid self-diagnosis of malaria.
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ItemHealth services utilisation and barriers for settlers from the Horn of Africa(WILEY, 2007-08)OBJECTIVE: To examine health services use and barriers for recently arrived immigrants from the Horn of Africa. METHOD: A cross-sectional study conducted in Melbourne, Australia, with a convenience sample of newly arrived immigrants (n=126) from Somalia (n=67), Ethiopia (n=24), Eritrea (n=26) and Sudan (n=6). RESULTS: GPs were the major health providers for participants, yet 22 (17%) respondents had not yet accessed health services in Australia. Thirty-three (26%) participants reported having had an unmet health concern for which they would have liked to seek advice. The most commonly identified barriers to health care and recommendations for improving services were associated with communication. CONCLUSIONS: This study illustrates unmet health needs among new arrivals and a need for linguistically appropriate information about the use of Australia's health system. IMPLICATIONS: The findings support increased use of professional interpreting services and support for new arrivals in making initial contact with the health system.
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ItemNo Preview AvailableAnemia, iron deficiency, meat consumption, and hookworm infection in women of reproductive age in northwest Vietnam(AMER SOC TROP MED & HYGIENE, 2008-03)Iron deficiency anemia poses an important public health problem for women of reproductive age living in developing countries. We assessed the prevalence of iron deficiency and anemia and associated risk factors in a community-based sample of women living in a rural province of northwest Vietnam. A cross-sectional survey, comprised of written questionnaires and laboratory analysis of hemoglobin (Hb), ferritin, transferrin receptor, and stool hookworm egg count, was undertaken, and the soluble transferrin receptor/log ferritin index was calculated. Of 349 non-pregnant women, 37.53% were anemic (Hb < 12 g/dL), and 23.10% were iron deficient (ferritin < 15 ng/L). Hookworm infection was present in 78.15% of women, although heavy infection was uncommon (6.29%). Iron deficiency was more prevalent in anemic than non-anemic women (38.21% versus 14.08%, P < 0.001). Consumption of meat at least three times a week was more common in non-anemic women (51.15% versus 66.67%, P = 0.042). Mean ferritin was lower in anemic women (18.99 versus 35.66 ng/mL, P < 0.001). There was no evidence of a difference in prevalence (15.20% versus 17.23%, P = 0.629) or intensity (171.07 versus 129.93 eggs/g, P = 0.412) of hookworm infection between anemic and non-anemic women. Although intensity of hookworm infection and meat consumption were associated with indices of iron deficiency in a multiple regression model, their relationship with hemoglobin was not significant. Anemia, iron deficiency, and hookworm infection were prevalent in this population. Intake of meat was more clearly associated with hemoglobin and iron indices than hookworm. An approach to addressing iron deficiency in this population should emphasize both iron supplementation and deworming.
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ItemNo Preview AvailableComparison of QuantiFERON-TB Gold In-Tube Test and Tuberculin Skin Test for Identification of Latent Mycobacterium tuberculosis Infection in Healthcare Staff and Association Between Positive Test Results and Known Risk Factors for Infection(CAMBRIDGE UNIV PRESS, 2009-03)OBJECTIVE: We compared a whole-blood interferon-gamma release assay (QuantiFERON-TB Gold In-Tube test, hereafter "QFT-in tube test") with a tuberculin skin test (TST) to determine which test more accurately identified latent Mycobacterium tuberculosis infection in healthcare staff. METHODS: A total of 481 hospital staff members were recruited from 5 hospitals in Melbourne, Australia. They provided information about demographic variables and tuberculosis (TB) risk factors (ie, birth or travel in a country with a high prevalence of TB, working in an occupation likely to involve contact with M. tuberculosis or individuals with TB, or being a household contact of an individual with a proven case of pulmonary TB). The QFT-in tube test and the TST were administered in accordance with standardized protocols. Concordance between the test results and positive risk factors was analyzed using the kappa statistic, the McNemar test, and logistic regression. RESULTS: A total of 358 participants had both a TST result and a QFT-in tube test result available for comparison. There were fewer positive QFT-in tube test results than positive TST results (6.7% vs. 33.0%; P<.001). Agreement between the tests was poor (71%; kappa=0.16). A positive QFT-in tube test result was associated with birth in a country with a high prevalence of TB, the number of years an individual had lived in a country with a high prevalence of TB (ie, the effect of each additional year, treated as a continuous variable), and high-risk occupational contact. A positive TST result was associated with older age, receipt of bacille Calmette-Guérin (BCG) vaccination, and working in an occupation that involved patient contact. Receipt of BCG vaccination was most strongly associated with discordant results in instances in which the TST result was positive and the QFT-in tube test result was negative. CONCLUSION: In a population of healthcare staff with a low prevalence of TB and a significant rate of BCG vaccination, a positive QFT-in tube test result was associated with the presence of known risk factors for TB exposure, whereas a positive TST result was more strongly associated with a prior history of BCG vaccination.