A cross-sectional health literacy profile of Australian regional adults using the Health Literacy Questionnaire©.

OBJECTIVE: Health literacy is the resources and abilities required to make and enact health decisions. This study aimed to describe the health literacy of a diverse cross-section of adults in regional Victoria. METHODS: Participants were recruited from two primary care clinics differing in socioeconomic scope and through non-clinical recruitment via the town's largest football club. Health Literacy Questionnaire© measured nine distinct scales, and comprehensive demographic data were also collected. Effect-sizes and regression were used for health literacy comparison between groups. RESULTS: In this sample of 351 adults, health literacy strengths were observed in Scale 1: 'Feeling understood and supported by healthcare providers' (mean 3.29/4 ±0.5) and Scale 9: 'Understanding health information well enough to know what to do' (mean 4.10/5 ±0.6). Challenging areas were Scale 5: 'Appraising health information' (mean 2.88/4 ±0.5) and Scale 7: 'Navigating the healthcare system' (mean 3.84/5 ±0.6). After adjustment, living alone predicted lower scores across most scales. CONCLUSIONS: This study showed greater health literacy barriers experienced by certain groups, particularly those who live alone and those who weren't clinically recruited. IMPLICATIONS FOR PUBLIC HEALTH: These findings have implications for further research into addressing health literacy barriers in marginalised individuals and non-clinical settings. Results from this study may inform interventions which address identified barriers.

Cytotoxic effects of aptamer-doxorubicin conjugates in an ovarian cancer cell line.

Despite medical advances in treatment strategies over the past 30-years, epithelial ovarian cancer (EOC) continues to be defined by poor patient survival rates and aggressive, drug resistant relapse. Traditional approaches to cancer chemotherapy are typically limited by severe off-target effects on healthy tissue and aggressive drug-resistant recurrence. Recent shifts towards targeted therapies offer the possibility of circumventing the obstacles experienced by these treatments. While antibodies are the pioneering agents in such targeted therapies, several intrinsic characteristics of antibodies limits their clinical translation and efficacy. In contrast, oligonucleotide chemical antibodies, known as aptamers, are ideal for this application given their small size and lack of immunogenicity. This study explored the efficacy of a DNA aptamer, designed to target a well-established cancer biomarker, EpCAM, to deliver a chemotherapeutic drug. The results from this study support evidence that EpCAM aptamers can bind to epithelial ovarian cancer; and offers a valid alternative as a targeting ligand with tuneable specificity and sensitivity. It also supports the growing body of evidence that aptamers show great potential for application-specific, post-SELEX engineering through rational modifications. Through in vitro assays, these aptamers demonstrated cytotoxicity in both monolayer and tumoursphere assays, as well as in tumourigenic enriching assays. Further experimentation based on the results achieved in this project might aid in the development of novel cancer therapeutics and guide the novel designs of drugs for targeted drug delivery.

Physical activity knowledge, attitudes and behaviours of pre-clinical medical students attending an Australian university.

BACKGROUND: Through the provision of advice and counselling, general practitioners (GPs) play an important part in promoting physical activity (PA). Lack of knowledge is a key barrier to engaging in such practice. Little is known about the knowledge and attitudes of current medical students and their preparedness to engage in PA promoting practice in the future. This study aimed to investigate the PA knowledge, attitudes and behaviours of medical students attending an Australian university. METHODS: A sample of 107 pre-clinical medical students from an Australian university completed an online survey. Questions asked about age, sex and past-week PA behaviour (using the International Physical Activity Questionnaire-Short form) as well as understanding of key PA messages and perceptions of the role of a GP, confidence to engage in PA promoting practices and satisfaction with current medical school training (responses were on 5-point Likert scale). Descriptive statistics (proportions, means) were used to summarise demographic and attitudinal measures. RESULTS: Almost all students (92%) were categorised as being moderately or highly active in the past-week. Knowledge of key PA messages was moderate (3.6 ± 0.9), however understanding of key messages about the dose of PA varied (ranging from 0% to 80.4% agreement). GPs were regarded as having a role to play in promoting PA; with high agreement that discussing the benefits of PA is a part of the role of a GP (4.7 ± 0.5). There was only moderate agreement that participants had received training in the health benefits of PA (3.1 ± 1.0) and in PA counselling (3.2 ± 1.0). Students indicated lower levels of satisfaction with this training (2.5 ± 0.9). CONCLUSIONS: Students in this study were typically physically active, had positive attitudes toward PA and felt that it was the role of the GP to engage in PA promoting practices. Students understood key PA messages, and while they reportedly received some training in providing PA counselling, they were somewhat dissatisfied with this training.

ADAMTS-15 Has a Tumor Suppressor Role in Prostate Cancer.

Extracellular matrix remodeling has emerged as an important factor in many cancers. Proteoglycans, including versican (VCAN), are regulated via cleavage by the proteolytic actions of A Disintegrin-like And Metalloproteinase domain with Thrombospondin-1 motif (ADAMTS) family members. Alterations in the balance between Proteoglycans and ADAMTS enzymes have been proposed to contribute to cancer progression. Here, we analyzed the expression of ADAMTS-15 in human prostate cancer, and investigated the effects of enforced expression in prostate cancer cell lines. ADAMTS-15 was found to be expressed in human prostate cancer biopsies with evidence of co-localization with VCAN and its bioactive cleavage fragment versikine. Enforced expression of ADAMTS-15, but not a catalytically-inactive version, decreased cell proliferation and migration of the 'castrate-resistant' PC3 prostate cancer cell line in vitro, with survival increased. Analysis of 'androgen-responsive' LNCaP prostate cancer cells in vivo in NOD/SCID mice revealed that ADAMTS-15 expression caused slower growing tumors, which resulted in increased survival. This was not observed in castrated mice or with cells expressing catalytically-inactive ADAMTS-15. Collectively, this research identifies the enzymatic function of ADAMTS-15 as having a tumor suppressor role in prostate cancer, possibly in concert with androgens, and that VCAN represents a likely key substrate, highlighting potential new options for the clinic.

Defining a new model of interdisciplinary cancer cachexia care in regional Victoria, Australia.

PURPOSE: Cachexia is a wasting condition affecting approximately 50% of cancer patients, associated with decreased quality of life and survival. Barwon Health's Cachexia and Nutrition Support Service provides person-centred interdisciplinary care to assist the management of cachexia symptoms. This study describes a novel and effective service model established in a regional cachexia clinic and the patient population it serves. METHODS: A descriptive, retrospective longitudinal study was conducted of records from patients attending Barwon Health between 2008 and 2013 (n = 175), alongside the description of service refinement over this time. Patients with ≥ 2 attendance dates were assessed for anthropometric measures, follow-up intervals, and muscle function outcomes to describe patient trajectory during clinic involvement. RESULTS: This is the first detailed description of a successful interdisciplinary clinic specific to cancer cachexia management, where patients are seen outside established 8- to 12-week structured programs which prevail in other cachexia clinics. Seventy-five patients (43%) attended one appointment only, with almost half of these (n = 33) first attending within 60 days of death. Of the 99 patients with two or more appointments, 49% displayed positive outcomes with > 2-kg weight gain between two consecutive appointments, and > 50% improved functional strength between two consecutive appointments. CONCLUSIONS: The majority of patients attending clinic multiple times maintained or increased weight and functional status during their involvement with the service. However, successes of care provision were muted by high attrition, primarily due to delayed referral and expected high mortality within the study cohort. Planned future analyses with greater patient numbers and cancer stratification will establish cachectic populations most likely to benefit from this novel mode of interdisciplinary care. The Cachexia and Nutrition Support Service provides an effective and efficient service model for the provision of specialist cachexia care to community-dwelling patients in regional Australia.

Competent with patients and populations: integrating public health into a medical program.

BACKGROUND: As the global burden of chronic disease grows, and infectious disease threats loom large, the need for medical graduates with expertise in public health medicine (PHM) is growing. A recurrent challenge is integrating this broad knowledge into crowded medical curricula and making PHM relevant. This study describes the process of integrating public health content into an Australian graduate entry medical course. METHODS: A redesign of the PHM curriculum at Deakin University School of Medicine was conducted in 2014 to make the curriculum practice-based and solution-oriented. Central to the redesign was the development of a curriculum map. RESULTS: Public health is now taught from a practice-based framework adapted from the World Health Organization emphasizing skills aligned with the Australasian Faculty of Public Health Medicine domains that prepare students for specialisation. Learning outcomes are structured to build depth and application in student knowledge. Mapping the curriculum provided the ability to measure alignment of learning outcomes with course, university and accrediting body outcomes. Regular feedback from students indicates engagement has improved along with perceived relevance to future careers. CONCLUSIONS: Doctors with public health skills are increasingly sought after in Australia, particularly in rural areas. Deakin graduates are well placed to meet this demand.

The extracellular matrix in cancer progression: Role of hyalectan proteoglycans and ADAMTS enzymes.

Remodelling of the extracellular matrix (ECM) has emerged as a key factor in cancer progression. Proteoglycans, including versican and other hyalectans, represent major structural elements of the ECM where they interact with other important molecules, including the glycosaminoglycan hyaluronan and the CD44 cell surface receptor. The hyalectan proteoglycans are regulated through cleavage by the proteolytic actions of A Disintegrin-like And Metalloproteinase domain with Thrombospondin-1 motif (ADAMTS) family members. Alteration in the balance between hyalectan proteoglycans and ADAMTS enzymes has been proposed to be a crucial factor in cancer progression either in a positive or negative manner depending on the context. Further complexity arises due to the formation of bioactive cleavage products, such as versikine, which may also play a role, and non-enzymatic functions for ADAMTS proteins. This research is providing fresh insights into cancer biology and opportunities for the development of new diagnostic and treatment strategies.

Visualization of HIV-1 interactions with penile and foreskin epithelia: clues for female-to-male HIV transmission.

To gain insight into female-to-male HIV sexual transmission and how male circumcision protects against this mode of transmission, we visualized HIV-1 interactions with foreskin and penile tissues in ex vivo tissue culture and in vivo rhesus macaque models utilizing epifluorescent microscopy. 12 foreskin and 14 cadaveric penile specimens were cultured with R5-tropic photoactivatable (PA)-GFP HIV-1 for 4 or 24 hours. Tissue cryosections were immunofluorescently imaged for epithelial and immune cell markers. Images were analyzed for total virions, proportion of penetrators, depth of virion penetration, as well as immune cell counts and depths in the tissue. We visualized individual PA virions breaching penile epithelial surfaces in the explant and macaque model. Using kernel density estimated probabilities of localizing a virion or immune cell at certain tissue depths revealed that interactions between virions and cells were more likely to occur in the inner foreskin or glans penis (from local or cadaveric donors, respectively). Using statistical models to account for repeated measures and zero-inflated datasets, we found no difference in total virions visualized at 4 hours between inner and outer foreskins from local donors. At 24 hours, there were more virions in inner as compared to outer foreskin (0.0495 +/- 0.0154 and 0.0171 +/- 0.0038 virions/image, p = 0.001). In the cadaveric specimens, we observed more virions in inner foreskin (0.0507 +/- 0.0079 virions/image) than glans tissue (0.0167 +/- 0.0033 virions/image, p<0.001), but a greater proportion was seen penetrating uncircumcised glans tissue (0.0458 +/- 0.0188 vs. 0.0151 +/- 0.0100 virions/image, p = 0.099) and to significantly greater mean depths (29.162 +/- 3.908 vs. 12.466 +/- 2.985 µm). Our in vivo macaque model confirmed that virions can breach penile squamous epithelia in a living model. In summary, these results suggest that the inner foreskin and glans epithelia may be important sites for HIV transmission in uncircumcised men.

Short-chain fatty acids increase expression and secretion of stromal cell-derived factor-1 in mouse and human pre-adipocytes.

OBJECTIVE: Stromal cell-derived factor-1 (SDF-1) is expressed in pre-adipocytes but its role is unknown. We investigated butyrate (a histone deacetylase inhibitor--HDACi) and other short-chain fatty acids (SCFA) in the regulation of SDF-1. We further investigated whether effects of SCFA were signalled through G protein-coupled receptors FFA2 and FFA3. DESIGN AND RESULTS: SDF-1 mRNA expression and protein secretion were studied in 3T3-L1 cells and human pre-adipocytes. SDF-1 was abundant, with mRNA and protein levels increased by butyrate. This was replicated with acetate and propionate, but not with trichostatin or valproate. Trichostatin inhibited SDF-1 secretion. Pertussis toxin blocked stimulation by butyrate. The order of potency of SCFA in stimulating SDF-1 (C3 > C4 > C2) is consistent with action through FFA3. Silencing the FFA3 gene abolished butyrate-stimulated SDF-1 expression and secretion. FFA3 was expressed in both pre-adipocytes and adipocytes, while FFA2 was expressed in adipocytes only. SDF-1 expression was low in murine macrophage J774.2 cells, while the SDF-1 receptor CXCR4 was absent from 3T3-L1 cells but abundant in J774.2 macrophages. In human pre-adipocytes, FFA3 was also expressed and SCFA increased SDF-1 secretion. CONCLUSIONS: SDF-1 and CXCR4 may mediate the interaction between adipose stromal cells and macrophages. Effects of SCFA are mediated through FFA3, but not histone deacetylase inhibition.

The effect of physical activity on psychological distress, cortisol and obesity: results of the Farming Fit intervention program.

BACKGROUND: Rural and regional Australians have a higher likelihood of mental illness throughout their lifetime than people living in major cities, although the underlying reasons are not yet well defined. Additionally, rural populations experience more lifestyle associated co-morbidities including obesity, diabetes and cardiovascular disease. Research conducted by the National Centre for Farmer Health between 2004 and 2009 revealed a positive correlation between obesity and psychological distress among the farming community. Chronic stress is known to overstimulate the regulation of the hypothalamic-pituitary-adrenal (HPA) axis and cortisol secretion which are associated with abdominal adiposity. Increasing physical activity may normalise cortisol secretion and thereby positively impact both physical and mental health. This paper assesses the effects of increasing physical activity on obesity, health behaviors and mental health in Victorian farming men and women. METHODS: Farming Fit was a six month quasi-experimental (convenience sample) longitudinal design control-intervention study. Overweight or obese (BMI ≥25 kg/m2) farm men (n = 43) and women (n = 29) were recruited with demographic, health behaviors, anthropometric, blood pressure and biochemistry data collected at baseline and at a six months. Salivary cortisol and depression anxiety stress scale results were collected at baseline, three and six months. The intervention group (n = 37) received a personalized exercise program and regular phone coaching to promote physical activity. RESULTS: The intervention group showed significant reductions in body weight and waist circumference. Results indicated that following the six month exercise program, the intervention group were 2.64 ± 0.65 kg lighter (p < 0.001), had reduced waist circumference by 2.01 ± 0.86 cm (p = 0.02) and BMI by 0.97 ± 0.22 kg/m2 (p < 0.001) relative to the control group. CONCLUSION: Increasing physical activity altered measures of obesity in farm men and women but did not affect mental health measures or cortisol secretion levels. TRIAL REGISTRATION: ACTRN12610000827033.

Defining the interaction of HIV-1 with the mucosal barriers of the female reproductive tract.

Worldwide, HIV-1 infects millions of people annually, the majority of whom are women. To establish infection in the female reproductive tract (FRT), HIV-1 in male ejaculate must overcome numerous innate and adaptive immune factors, traverse the genital epithelium, and establish infection in underlying CD4(+) target cells. How the virus achieves this remains poorly defined. By utilizing a new technique, we define how HIV-1 interacts with different tissues of the FRT using human cervical explants and in vivo exposure in the rhesus macaque vaginal transmission model. Despite previous claims of the squamous epithelium being an efficient barrier to virus entry, we reveal that HIV-1 can penetrate both intact columnar and squamous epithelial barriers to depths where the virus can encounter potential target cells. In the squamous epithelium, we identify virus entry occurring through diffusive percolation, penetrating areas where cell junctions are absent. In the columnar epithelium, we illustrate that virus does not transverse barriers as well as previously thought due to mucus impediment. We also show a statistically significant correlation between the viral load of inocula and the ability of HIV-1 to pervade the squamous barrier. Overall, our results suggest a diffusive percolation mechanism for the initial events of HIV-1 entry. With these data, we also mathematically extrapolate the number of HIV-1 particles that penetrate the mucosa per coital act, providing a biological description of the mechanism for HIV-1 transmission during the acute and chronic stages of infection.

Cardiovascular risk factors and psychological distress in Australian farming communities.

OBJECTIVE: To examine the prevalence of cardiovascular disease (CVD) risk factors, psychological distress and associations between physical and mental health parameters within a cohort of the Australian farming community. DESIGN: Cross-sectional descriptive study. SETTING: Farming communities across Australia. PARTICIPANTS: Data of men (n = 957) and women (n = 835) farmers from 97 locations across Australia were stratified into categories based on National Cholesterol Education Program guidelines. MAIN OUTCOME MEASURE(S): Prevalence of and interrelationship between overweight, obesity, dyslipidaemia, hypertension, diabetes risk and psychological distress. RESULTS: There was a higher prevalence of overweight (42.5%, 95% confidence interval (CI), 34.2-50.8), obesity (21.8%, 95% CI, 18.3-25.3), abdominal adiposity (38.4% 95% CI, 24.5-52.5), hypertension (54.0%, 95% CI, 34.4-73.5) and diabetes risk (25.3%, 95% CI, 17.7-36.7) in the farming cohort compared with national data. There was also a positive significant association between the prevalence of psychological distress and obesity, abdominal adiposity, body fat percentage and metabolic syndrome in older (age ≥ 50 years) participants. CONCLUSIONS: This study group of farming men and women exhibited an increased prevalence of CVD risk factors and co-morbidities. The findings indicate a positive association between psychological distress and risk for developing CVD, particularly in the older farmers. If the younger cohort were to maintain elevated rates of psychological distress, then it is foreseeable that the next generation of farmers could experience poorer physical health than their predecessors.

Chest pain in rural communities; balancing decisions and distance.

OBJECTIVE: This pilot study examines the prevalence of cardiac risk factors in a cohort of agricultural workers, assesses their knowledge of local emergency health services and investigates their decision-making abilities with regard to when and how they would seek help when experiencing chest pain. METHODS: Farm men and women were recruited from 20 rural Victorian sites and underwent health assessments for total cholesterol, blood glucose, weight, height and blood pressure. Participants completed a survey to determine their knowledge of chest pain treatment, local emergency services and likely response to chest pain. RESULTS: Cardiac risk factors within this cohort of 186 adult farming men and women were common, with 61% of men (58/95, 95% confidence interval [CI] 51-70) and 74% of women (68/91, 95% CI 65-83) either overweight or obese. When asked to name their nearest ED, 10% of participants (19/184, 95% CI 7-16) nominated health services or towns where no ED exists. Furthermore, 67% of respondents (123/185, 95% CI 59-73) believed it was safe to travel to hospital by car while potentially having a myocardial infarction. CONCLUSIONS: This cohort of agricultural workers were at considerable risk of experiencing acute coronary events, but many would make decisions about when and how to seek medical help for chest pain that are at odds with published community guidelines. These results highlight the need for education to improve knowledge of local emergency services and address behavioural barriers to accessing care.

Reducing psychological distress and obesity in Australian farmers by promoting physical activity.

BACKGROUND: Studies have confirmed that the rate of mental illness is no higher in rural Australians than that of urban Australians. However, the rate of poor mental health outcomes, and in particular suicide, is significantly raised in rural populations. This is thought to be due to lack of early diagnosis, health service access, the distance-decay effect, poor physical health determinants and access to firearms. Research conducted by the National Centre for Farmer Health between 2004 and 2009 reveals that there is a correlation between obesity and psychological distress among the farming community where suicide rates are recognised as high. Chronic stress overstimulates the regulation of the hypothalamic-pituitary-adrenal (HPA) axis that is associated with abdominal obesity. Increasing physical activity may block negative thoughts, increase social contact, positively influence brain chemistry and improve both physical and mental health. This paper describes the design of the Farming Fit study that aims to identify the effect of physical activity on psychological distress, obesity and health behaviours such as diet patterns and smoking in farm men and women. METHODS/DESIGN: For this quasi-experimental (convenience sample) control-intervention study, overweight (Body Mass Index ≥25 kg/m(2)) farm men and women will be recruited from Sustainable Farm Families™ (SFF) programs held across Victoria, Australia. Baseline demographic data, health data, depression anxiety stress scale (DASS) scores, dietary information, physical activity data, anthropometric data, blood pressure and biochemical analysis of plasma and salivary cortisol levels will be collected. The intervention group will receive an exercise program and regular phone coaching in order to increase their physical activity. Analysis will evaluate the impact of the intervention by longitudinal data (baseline and post intervention) comparison of intervention and control groups. DISCUSSION: This study is designed to examine the effect of physical activity on psychological health and other co-morbidities such as obesity, impaired glucose tolerance, hypertension and dyslipidaemia within a high-risk cohort. The outcomes of this research will be relevant to further research and service delivery programs, in particular those tailored to rural communities. TRIAL REGISTRATION: ACTRN12610000827033.

Farming fit? Dispelling the Australian agrarian myth.

BACKGROUND: Rural Australians face a higher mental health and lifestyle disease burden (obesity, diabetes and cardiovascular disease) than their urban counterparts. Our ongoing research reveals that the Australian farming community has even poorer physical and mental health outcomes than rural averages. In particular, farm men and women have high rates of overweightness, obesity, abdominal adiposity, high blood pressure and psychological distress when compared against Australian averages. Within our farming cohort we observed a significant association between psychological distress and obesity, abdominal adiposity and body fat percentage in the farming population. PRESENTATION OF HYPOTHESIS: This paper presents a hypothesis based on preliminary data obtained from an ongoing study that could potentially explain the complex correlation between obesity, psychological distress and physical activity among a farming population. We posit that spasmodic physical activity, changing farm practices and climate variability induce prolonged stress in farmers. This increases systemic cortisol that, in turn, promotes abdominal adiposity and weight gain. TESTING THE HYPOTHESIS: The hypothesis will be tested by anthropometric, biochemical and psychological analysis matched against systemic cortisol levels and the physical activity of the subjects. IMPLICATIONS OF THE HYPOTHESIS TESTED: Previous studies indicate that farming populations have elevated rates of psychological distress and high rates of suicide. Australian farmers have recently experienced challenging climatic conditions including prolonged drought, floods and cyclones. Through our interactions and through the media it is not uncommon for farmers to describe the effect of this long-term stress with feelings of 'defeat'. By gaining a greater understanding of the role cortisol and physical activity have on mental and physical health we may positively impact the current rates of psychological distress in farmers. TRIAL REGISTRATION: ACTRN12610000827033.

Potential HIV-1 target cells in the human penis.

OBJECTIVES: To study the distribution of HIV-1 receptors and degree of keratinization in the human penis. DESIGN: Formalin-fixed penises were obtained from nine uncircumcised cadavers. Foreskins were obtained from 21 healthy adult men undergoing elective circumcision for social reasons. Uncircumcised penises were obtained within 24 h of death from eight men. All tissues were stained for keratin and HIV-1 receptors. METHODS: Penises from nine formalin fixed cadavers aged 64-80 years were obtained from the Department of Anatomy, University of Melbourne. Foreskins were obtained from 21 men aged 18-64 years following circumcision performed at either the Freemason's or Mercy Private Hospitals, Melbourne, Australia. Fresh penile necropsy specimens from eight uncircumcised men aged 23-63 years were obtained from the Victorian Institute of Forensic Medicine, Melbourne. The degree of keratinization was scored, and the distribution of HIV-1 susceptible cells was mapped in the glans penis, penile urethra, urethral meatus, frenulum and foreskin. RESULTS: Cells with HIV-1 receptors were present in all penile epithelia, but Langerhans' cells were most superficial in the inner foreskin and frenulum. The inner foreskin had a significantly thinner keratin layer (1.8 +/- 0.1 units), than the outer foreskin (3.3 +/- 0.1), or glans penis (3.3 +/- 0.2), P < 0.05. CONCLUSIONS: Superficial Langerhans' cells on the inner aspect of the foreskin and frenulum are poorly protected by keratin and thus could play an important role in primary male infection. These findings provide a possible anatomical explanation for the epidemiologically observed protective effect of male circumcision.

Sperm immobilizing properties of lemon juice.

The aim of this study was to evaluate the sperm-immobilizing properties of lemon juice to determine if they are consistent with its traditional contraceptive use. It was found that lemon juice supernatant (LJS) has high osmolality (550-60 mOsm) and low pH (2.2-2.6) and that addition of LJS to semen to give a final concentration of 20% v/v reduced the pH from around 8.4 to 4.1. This acidification was associated with irreversible cessation of all sperm movements within 1 minute. In conclusion, lemon juice should be further evaluated for acceptability, safety, and efficacy as a topical vaginal contraceptive agent.