An exploration of healthcare providers' experiences and perspectives of Traditional and complementary medicine usage and disclosure by Indigenous cancer patients.

BACKGROUND: Traditional and complementary medicines (T&CM) are any form of medicine, practice, treatment, product, technology, knowledge system or ceremony outside of conventional medical practice that aims to prevent and/or treat illness and/or promote well-being. Alongside conventional cancer treatments, T&CM usage is increasing; with 19% of indigenous Australians with cancer reporting using T&CM. There is limited evidence surrounding T&CM use and disclosure by indigenous patients. Our aim was to explore healthcare providers' views about usage, disclosure/non-disclosure of T&CM by Indigenous cancer patients. METHODS: Semi-structured, in-depth interviews with 18 healthcare providers, including three indigenous providers, at a large urban hospital providing care to Indigenous cancer patients were conducted to explore providers' experiences and attitudes towards T&CM use by Indigenous cancer patients. An interpretive phenomenological approach was used to thematically analyse the data. RESULTS: Analysis revealed six themes: concern about risk; no 'real' benefits; perception of T&CM and conventional medicine as antithetical; barriers to disclosure; 'patients' choice' a double-edged sword; and providers' lack of knowledge about T&CM. Healthcare providers perceived discord between T&CM and conventional medicine. Most lacked knowledge of T&CM, and had concerns around negative-interactions with conventional treatments. They considered T&CM outside their role, citing this as reasoning for their lack of knowledge. Indigenous healthcare providers had greater understanding and openness towards T&CM. CONCLUSIONS: Given the potential usage of T&CM by Indigenous cancer patients, providers need a more comprehensive understanding of T&CM in order to inform discussion and facilitate effective disclosure on this topic. If indigenous Australians with cancer feel that cancer care providers are unreceptive to discussing T&CM, patient care risks being compromised; particularly given the potential for negative interactions between T&CM and conventional cancer treatments. Fostering health care interactions where indigenous patients feel comfortable to discuss T&CM usage should be a priority for all cancer care services.

Rationale and methods for a cross-sectional study of mental health and wellbeing following river flooding in rural Australia, using a community-academic partnership approach.

BACKGROUND: Climate change is associated with greater frequency, duration, intensity and unpredictability of certain weather-related events, including floods. Floods harm mental health. There is limited understanding of the mental health and well-being effects from river flooding, particularly over the longer term and in rural contexts. This paper describes the rationale, aims, objectives, study design and socio-demographic characteristics of the sample for a study measuring associations between flood experience and mental health and wellbeing of residents (particularly those most likely to be negatively impacted and hard to reach) in rural NSW Australia 6 months following a devastating flood in 2017. To our knowledge, the study is the first of its kind within Australia in a rural community and is an important initiative given the likelihood of an increasing frequency of severe flooding in Australia given climate change. METHODS: A conceptual framework (The Flood Impact Framework) drawing on social ecological approaches was developed by the research team. It was based on the literature and feedback from the community. The Framework describes putative relationships between flood exposure and mental health and wellbeing outcomes. Within a community-academic partnership approach, a cross-sectional survey was then undertaken to quantify and further explore these relationships. RESULTS: The cross-sectional survey was conducted online (including on mobile phone) and on paper between September and November 2017 and recruited 2530 respondents. Of those, 2180 provided complete demographic data, among whom 69% were women, 91% were aged 25-74, 4% identified as Aboriginal and/or Torres Strait Islander, 9% were farmers and 33% were business owners. CONCLUSIONS: The study recruited a wide range of respondents and the partnership facilitated the community's engagement with the design and implementation of the study. The study will provide a basis for a follow-up study, that will aim to improve the understanding of mental health and wellbeing effects over the longer term. It will provide an important and original contribution to understanding river flooding and mental health in rural Australia, a topic that will grow in importance in the context of human-induced climate change, and identify critical opportunities to strengthen services, emergency planning and resilience to future flooding.

Exploring traditional and complementary medicine use by Indigenous Australian women undergoing gynaecological cancer investigations.

BACKGROUND: Indigenous Australian women experience worse gynaecological cancer outcomes than non-Indigenous women. While traditional and complementary medicine (T&CM) is increasingly used by cancer patients alongside conventional treatments, little is known about T&CM use by Indigenous women. This study aimed to explore the beliefs, attitudes and experiences related to T&CM use and disclosure among Indigenous women undergoing gynaecological cancer investigations. METHODS: A mixed-methods design explored T&CM use among Indigenous women who presented for gynaecological cancer investigation at an urban Queensland hospital (September 2016 and January 2018). RESULTS: Fourteen women participated. The reported use (86%) and perceived value of T&CM was high among the participants, however, women reported major challenges in communicating with healthcare providers about T&CM, commonly associated with trust and rapport. CONCLUSIONS: These findings highlight the need for strategies to facilitate culturally-appropriate doctor-patient communication around T&CM to foster trust and transparency in gynaecological cancer care for Indigenous women.

Long-Term Dietary Nitrate Supplementation Does Not Prevent Development of the Metabolic Syndrome in Mice Fed a High-Fat Diet.

BACKGROUND: Nitric oxide (NO) is an important vascular signaling molecule that plays a role in vascular homeostasis. A reduction in NO bioavailability is thought to contribute to endothelial dysfunction, an early risk factor for both cardiovascular disease and type 2 diabetes. Dietary nitrate, through the nitrate-nitrite-NO pathway, may provide an alternate source of NO when the endogenous eNOS system is compromised. In addition to a role in the vascular system, NO may also play a role in the metabolic syndrome including obesity and glucose tolerance. AIM: To investigate the effect of long-term dietary nitrate supplementation on development of the metabolic syndrome in mice fed a high-fat diet. METHODS: Following 1 week of acclimatisation, male (6-8 weeks) C57BL6 mice were randomly assigned to the following groups (10/group) for 12 weeks: (i) normal chow + NaCl (1 mmol/kg/day), (ii) normal chow + NaNO3 (1 mmol/kg/day), (iii) high-fat diet + NaCl (1 mmol/kg/day), and (iv) high-fat diet + NaNO3 (1 mmol/kg/day). Body weight and food consumption were monitored weekly. A subset of mice (5/group) underwent running wheel assessment. At the end of the treatment period, all mice underwent fasting glucose tolerance testing. Caecum contents, serum, and tissues (liver, skeletal muscle, white and brown adipose, and kidney) were collected, frozen, and stored at -80°C until analysis. RESULTS: Consumption of the high-fat diet resulted in significantly greater weight gain that was not affected by dietary nitrate. Mice on the high-fat diet also had impaired glucose tolerance that was not affected by dietary nitrate. There was no difference in adipose tissue expression of thermogenic proteins or energy expenditure as assessed by the running wheel activity. Mice on the high-fat diet and those receiving dietary nitrate had reduced caecum concentrations of both butyrate and propionate. CONCLUSIONS: Dietary nitrate does not prevent development of the metabolic syndrome in mice fed a high-fat diet. This may be due, in part due, to reductions in the concentration of important short-chain fatty acids.

Green coffee polyphenols do not attenuate features of the metabolic syndrome and improve endothelial function in mice fed a high fat diet.

We have investigated the effects of the major polyphenol in coffee, chlorogenic acid (CGA), on obesity, glucose intolerance, insulin resistance, systemic oxidative stress and endothelial dysfunction in a mouse model of the metabolic syndrome. Thirty C57BL6 mice were randomly divided into (n=10/group) (i) normal diet (ND), (ii) high fat diet (HFD), or (iii) high fat diet supplemented with 0.5% w/w green coffee bean extract (GCE) rich in chlorogenic acid (HFD+GCE). The high fat diet consisted of 28% fat and all animals were maintained on their diets for 12 weeks. The mice fed a HFD and HFD+GCE displayed symptoms of the metabolic syndrome compared to their normal fed counterparts, although no endothelial dysfunction was detected in the abdominal aortas after 12 weeks. GCE did not attenuate HFD-induced obesity, glucose intolerance, insulin resistance or systemic oxidative stress. Furthermore, GCE did not protect against ex vivo oxidant (hypochlorous acid)-induced endothelial dysfunction.

Interleukin-6-deficient mice develop hepatic inflammation and systemic insulin resistance.

AIMS/HYPOTHESIS: The role of IL-6 in the development of obesity and hepatic insulin resistance is unclear and still the subject of controversy. We aimed to determine whether global deletion of Il6 in mice (Il6 (-/-)) results in standard chow-induced and high-fat diet (HFD)-induced obesity, hepatosteatosis, inflammation and insulin resistance. METHODS: Male, 8-week-old Il6 (-/-) and littermate control mice were fed a standard chow or HFD for 12 weeks and phenotyped accordingly. RESULTS: Il6 (-/-) mice displayed obesity, hepatosteatosis, liver inflammation and insulin resistance when compared with control mice on a standard chow diet. When fed a HFD, the Il6 (-/-) and control mice had marked, equivalent gains in body weight, fat mass and ectopic lipid deposition in the liver relative to chow-fed animals. Despite this normalisation, the greater liver inflammation, damage and insulin resistance observed in chow-fed Il6 (-/-) mice relative to control persisted when both were fed the HFD. Microarray analysis from livers of mice fed a HFD revealed that genes associated with oxidative phosphorylation, the electron transport chain and tricarboxylic acid cycle were uniformly decreased in Il6 (-/-) relative to control mice. This coincided with reduced maximal activity of the mitochondrial enzyme ß-hydroxyacyl-CoA-dehydrogenase and decreased levels of mitochondrial respiratory chain proteins. CONCLUSIONS/INTERPRETATION: Our data suggest that IL-6 deficiency exacerbates HFD-induced hepatic insulin resistance and inflammation, a process that appears to be related to defects in mitochondrial metabolism.

Brain-derived neurotrophic factor is produced by skeletal muscle cells in response to contraction and enhances fat oxidation via activation of AMP-activated protein kinase.

AIMS/HYPOTHESIS: Brain-derived neurotrophic factor (BDNF) is produced in skeletal muscle, but its functional significance is unknown. We aimed to determine the signalling processes and metabolic actions of BDNF. METHODS: We first examined whether exercise induced BDNF expression in humans. Next, C2C12 skeletal muscle cells were electrically stimulated to mimic contraction. L6 myotubes and isolated rat extensor digitorum longus muscles were treated with BDNF and phosphorylation of the proteins AMP-activated protein kinase (AMPK) (Thr(172)) and acetyl coenzyme A carboxylase beta (ACCbeta) (Ser(79)) were analysed, as was fatty acid oxidation (FAO). Finally, we electroporated a Bdnf vector into the tibialis cranialis muscle of mice. RESULTS: BDNF mRNA and protein expression were increased in human skeletal muscle after exercise, but muscle-derived BDNF appeared not to be released into the circulation. Bdnf mRNA and protein expression was increased in muscle cells that were electrically stimulated. BDNF increased phosphorylation of AMPK and ACCbeta and enhanced FAO both in vitro and ex vivo. The effect of BDNF on FAO was AMPK-dependent, since the increase in FAO was abrogated in cells infected with an AMPK dominant negative adenovirus or treated with Compound C, an inhibitor of AMPK. Electroporation of a Bdnf expression vector into the tibialis cranialis muscle resulted in increased BDNF protein production and tropomyosin-related kinase B (TrkB(Tyr706/707)) and extracellular signal-regulated protein kinase (p44/42 Thr(202)/Tyr(204)) phosphorylation in these muscles. In addition, phosphorylation of ACCbeta was markedly elevated in the Bdnf electroporated muscles. CONCLUSIONS/INTERPRETATION: These data identify BDNF as a contraction-inducible protein in skeletal muscle that is capable of enhancing lipid oxidation in skeletal muscle via activation of AMPK.

National Hospital Management Portal (NHMP): a framework for e-health implementation.

Health information represents the main basis for health decision-making process and there have been some efforts to increase access to health information in developing countries. However, most of these efforts are based on the internet which has minimal penetration especially in the rural and sub-urban part of developing countries. In this work, a platform for medical record acquisition via the ubiquitous 2.5G/3G wireless communications technologies is presented. The National Hospital Management Portal (NHMP) platform has a central database at each specific country's national hospital which could be updated/accessed from hosts at health centres, clinics, medical laboratories, teaching hospitals, private hospitals and specialist hospitals across the country. With this, doctors can have access to patients' medical records more easily, get immediate access to test results from laboratories, deliver prescription directly to pharmacists. If a particular treatment can be provided to a patient more effectively in another country, NHMP makes it simpler to organise and carry out such treatment abroad.

PCDD/Fs and PCBs in seafood species from Moreton Bay, Queensland, Australia.

Previous studies have identified elevated levels of polychlorinated dibenzo-p-dioxins (PCDDs) in sediments and megafauna (dugongs and green turtles) in the marine environment of southeast Queensland, Australia. Little information exists, however, regarding the levels of PCDDs, polychlorinated dibenzofurans (PCDFs) and related polychlorinated biphenyls (PCBs) in seafood from this area. This study aims to establish baseline information on PCDD/F and PCB contamination in a range of seafood species from Moreton Bay and to investigate contaminant variability due to harvesting season, size, habitat location and trophic level. In addition, different seafood extraction methods were tested to evaluate their impact on lipid yields and contaminant concentration. Overall, the median TEQ(DF&PCB) levels in seafood from Moreton Bay were elevated compared to background levels in Australian marine/estuarine and retail fish. However, TEQ(DF&PCB) levels of most seafood analysed were below the respective EU maximum limits. High inter- and intraspecies variability was observed, which could be partially attributed to differences in trophic level, season harvested and habitat location.

Flame retardants (PBDEs) in marine turtles, dugongs and seafood from Queensland, Australia.

Polybrominated diphenyl ethers (PBDEs) are used as flame retardants in numerous products. These compounds have been found to enter the marine environment where they have the potential to bioaccumulate in biota. Limited information is currently available concerning the levels of PBDEs in Australian marine wildlife. This study presents baseline information on PBDE levels in a variety of marine species from Queensland, Australia and considers the influence of species-specific factors on contaminant levels and tissue distribution in marine turtles. Overall, the PBDE levels measured in this study are relatively low compared to marine biota from the northern hemisphere, indicating low level input into the marine system of Queensland. This is in general agreement with global estimates which suggest low PBDE usage in Australia. Previous studies, however, have found relatively high PBDE levels in Australian human milk and sera. This discrepancy in contamination trends between terrestrial and marine biota suggests that future transport of PBDEs may occur to the marine system in Australia.

A locus affecting immunoglobulin isotype selection (Igis1) maps to the MHC region in C57BL, BALB/c and NOD mice.

We have previously shown that H2b mice with B10 or BALB genetic backgrounds have higher basal levels of IgG2a than H2k and H2d congenic strains and, hence, have low IgG1/IgG2a ratios, which is consistent with a T1 cytokine milieu. The phenotypic marker of the high IgG2a levels, denoted immunoglobulin isotype-1 (Igis1) was provisionally mapped telomeric of IEbeta using MHC recombinant mice. In addition, data from B10.A(2R), B10.A(1R) and B10.A(18R) mice indicated that Igis1 may lie in a 27 kb region between G7b (Sm-X5) and G7c. In the present study we confirm that Igis1 is in the H2 region using BALB and B10 congenic F2 mice. H2bb F2 mice had higher IgG2a levels than the H2dd parental strains. H2bd F1 and F2 mice on the B10 background produced IgG2a levels comparable with the H2bb parental strain, indicating that the b allele was dominant. In contrast, the H2bd F1 and F2 mice on the BALB background produced IgG2a levels between those of the H2bb and H2dd parental strains, indicating codominance of the b and d alleles. This suggests that a background gene influences regulation of IgG2a levels by Igis1. Non-obese diabetic (NOD) mice (KdIAg7IEnu11Db), which can develop type 1 diabetes, had higher levels of IgG2a than NOD-H2d congenic mice. Thus, Igis1 affects isotype selection in the presence of non-MHC diabetes genes. As type 1 diabetes is associated with T1 responses, Igis1 may affect susceptibility to this condition.

The H2(b) haplotype modifies the production of pro-inflammatory cytokines: implications for immunopathology.

Congenic strains of mice which differ only in their H2 haplotype were used to examine the effects of MHC genes on production of pro-inflammatory cytokines, as we have shown previously that H2(b) mice produce low levels of T cell cytokines compared to congenic H2(k) and H2(d) mice. RNase protection assays were used to assess cytokine mRNA and cytokine protein was assessed by ELISA or bioassay. Concanavalin A or phorbol myristate acetate/calcium ionophore/anti-CD3 stimulation of spleen cells from H2(b) congenic mice induced less IL-1, IL-2, IFN-gamma and MIF mRNA and/or protein than the equivalent cells from H2(d) mice. However, following stimulation with lipopolysaccharide or phorbol myristate acetate/calcium ionophore, peritoneal cells from H2(b) mice synthesised significantly more IL-1 beta, TNF-alpha, TNFR and IFN-gamma protein and IFN-gamma mRNA than cells from congenic H2(k) or H2(d) mice. These differences were evident in congenic C57BL/10 and/or BALB/c strains. We suggest that the low IL-1 production in H2(b) spleen cultures is secondary to lower T cell activation. Evidence that the H2(b) haplotype carries an immunoregulatory allele which affects cytokine production warrants further investigation.

A novel locus affecting serum levels of IgG2a maps to the murine H2 region.

The effects of genes in the murine H2 region on basal immunoglobulin levels were investigated and ratios of IgG1/IgG2a were calculated, as low ratios indicate a Th1 cytokine mileu. H2b mice with B10 or BALB genetic backgrounds had higher levels of IgG2a than H2k and H2d congenic strains, and hence had low IgG1/IgG2a ratios. B10 (H2b) mice generally had high levels of IgG2b, IgG3, IgA and IgM, but this outcome was more variable. The high IgG2a phenotype was denoted Igis1 (Immunoglobulin isotype-1) and mapped telomeric of IEbeta using B10.A(4R) mice (high IgG2a) and B10.A(3R) and B10.A(5R) mice (low IgG2a). Further mapping in B10.A(2R), B10.A(1R) and B10.A(18R) mice placed Igis1 in the 27kb region between G7c and G7e.

Lymphocytes from H2 mice produce lower levels of several cytokines than congenic H2 or H2 mice.

Inbred mice of congenic strains that differ only in their H2 haplotype were used to examine the effects of MHC genes on production of cytokines. Spleen and lymph node cells were stimulated with mitogens in vitro, and cytokine protein was assessed by ELISA and/or bioassays. Cells from H2b mice synthesized less IL-3, IL-4, IL-5, TNF and IL-10 (less clearly) than the equivalent cells from H2k or H2d mice. Production of IL-6 by H2b spleen and lymph node cells was lower than that by cells from H2d mice. In addition, lower lymphoproliferative responses were observed in lymph node cultures from H2b mice. These effects were evident in congenic B10 and BALB strains. B10 H2b mice stimulated in vivo with anti-CD3 had lower levels of IFN-gamma and IL-5 protein in their serum compared with equivalent H2k and H2d mice. Because class I- or II-mediated antigen presentation was not required in our model, an immunoregulatory gene in the central MHC is implicated. Preliminary studies of MHC recombinant mice suggested that the gene or genes responsible lie telomeric of IEbeta. Evidence that the H2b haplotype carries an immunoregulatory allele with a small but consistent effect on cytokine production warrants further investigation.

Morphological features of Murray Valley encephalitis virus infection in the central nervous system of Swiss mice.

We have examined the histological and ultrastructural features of CNS infection with Murray Valley encephalitis (MVE) virus in mice inoculated with a virulent parental strain (BH3479). Light microscopic examination revealed neuronal necrosis in the olfactory bulb and hippocampus of MVE-infected brains by 5 days post-infection (pi). Electron microscopy of these regions showed endoplasmic reticulum membrane proliferation, and tubular and spherical structures in the cisternae of the endoplasmic reticulum, Golgi complex and nuclear envelope. At seven to eight days pi, infected neurones exhibited chromatin condensation and extrusion, nuclear fragmentation, loss of segments of the nuclear envelope, reduced surface contact with adjacent cells and loss of cytoplasmic organelles. This cell injury was particularly noticeable in the proximal CA3 and distal CA1 regions of the hippocampus. The inflammatory cell profile consisted of macrophages, lymphocytes and especially neutrophils, and many of these inflammatory cells were apoptotic. High mortality rates in the BH3479-infected population of mice correlated with the intense polymorphonuclear and mononuclear leucocyte inflammatory infiltrate in the CNS.

Parallel stimulation of glucose and Mg(2+) accumulation by insulin in rat hearts and cardiac ventricular myocytes.

The stimulation of beta-adrenoceptors in cardiac cells results in a rapid loss of cellular Mg(2+). Because insulin physiologically counteracts several of the cellular effects mediated by the activation of beta-adrenoceptors and the elevation of cytosolic cAMP levels, we investigated whether insulin administration could prevent Mg(2+) mobilization from rat hearts and ventricular myocytes. Rat hearts were perfused in a retrograde Langendorff system, and the changes in extracellular Mg(2+) were measured by atomic absorbance spectrophotometry. Pretreatment of the hearts with 6 nmol/L insulin completely prevented the Mg(2+) extrusion induced by the beta-adrenergic agonist isoproterenol. Furthermore, the administration of insulin per se induced an accumulation of Mg(2+) by the heart. This accumulation was small but detectable in the presence of 25 to 35 micromol/L [Mg(2+)](o) and increased in proportion to [Mg(2+)](o). Insulin-mediated Mg(2+) accumulation was not observed in hearts perfused with a medium devoid of glucose or with a medium containing the inhibitors of glucose transport, cytochalasin B and phloretin. Insulin-stimulated [(3)H]2-deoxyglucose accumulation was measured in collagenase-dispersed cardiac ventricular myocytes in the presence of varying levels of [Mg(2+)](o). Glucose transport was not observed below 25 micromol/L [Mg(2+)](o), and it also increased in proportion to [Mg(2+)](o). Taken together, these results indicate the presence of a major uptake of Mg(2+) into cardiac cells that is stimulated by insulin and may require the insulin-induced operation of a glucose transporter. Hence, extracellular and/or intracellular Mg(2+) may modulate glucose transport and/or utilization.

The severity of murray valley encephalitis in mice is linked to neutrophil infiltration and inducible nitric oxide synthase activity in the central nervous system.

A study of immunopathology in the central nervous system (CNS) during infection with a virulent strain of Murray Valley encephalitis virus (MVE) in weanling Swiss mice following peripheral inoculation is presented. It has previously been shown that virus enters the murine CNS 4 days after peripheral inoculation, spreads to the anterior olfactory nucleus, the pyriform cortex, and the hippocampal formation at 5 days postinfection (p.i.), and then spreads throughout the cerebral cortex, caudate putamen, thalamus, and brain stem between 6 and 9 days p.i. (P. C. McMinn, L. Dalgarno, and R. C. Weir, Virology 220:414-423, 1996). Here we show that the encephalitis which develops in MVE-infected mice from 5 days p.i. is associated with the development of a neutrophil inflammatory response in perivascular regions and in the CNS parenchyma. Infiltration of neutrophils into the CNS was preceded by increased expression of tumor necrosis factor alpha and the neutrophil-attracting chemokine N51/KC within the CNS. Depletion of neutrophils with a cytotoxic monoclonal antibody (RB6-8C5) resulted in prolonged survival and decreased mortality in MVE-infected mice. In addition, neutrophil infiltration and disease onset correlated with expression of the enzyme-inducible nitric oxide synthase (iNOS) within the CNS. Inhibition of iNOS by aminoguanidine resulted in prolonged survival and decreased mortality in MVE-infected mice. This study provides strong support for the hypothesis that Murray Valley encephalitis is primarily an immunopathological disease.