Search tips
Search criteria

Results 1-25 (65)

Clipboard (0)

Select a Filter Below

Year of Publication
more »
Research indicates that responses to stress are sexually dimorphic, particularly in regard to learning and memory processes: while males display impaired cognitive performance and hippocampal CA3 pyramidal cell dendritic remodeling following chronic stress, females exhibit enhanced performance and no remodeling. Leu-enkephalin, an endogenous opioid peptide found in the hippocampal mossy fiber pathway, plays a critical role in mediating synaptic plasticity at the mossy fiber-CA3 pyramidal cell synapse. Estrogen is known to influence the expression of leu-enkephalin in the mossy fibers of females, with leu-enkephalin levels being highest at proestrus and estrus, when estrogen levels are elevated. Since stress is also known to alter the expression of leu-enkephalin in various brain regions, this study was designed to determine whether acute or chronic stress had an effect on mossy fiber leu-enkephalin levels in females or males, through the application of correlated quantitative light and electron microscopic immunocytochemistry. Both acute and chronic stress eliminated the estrogen-dependence of leu-enkephalin levels across the estrous cycle in females, but had no effect on male levels. However, following acute stress leu-enkephalin levels in females were consistently lowered to values comparable to the lowest control values, while following chronic stress they were consistently elevated to values comparable to the highest control values. Ultrastructural changes in leu-enkephalin labeled dense core vesicles paralleled light microscopic observations, with acute stress inducing a decrease in leu-enkephalin labeled dense core vesicles, and chronic stress inducing an increase in leu-enkephalin labeled dense-core vesicles in females. These findings suggest that alterations in leu-enkephalin levels following stress could play an important role in the sex-specific responses that females display in learning processes, including those important in addiction.
PMCID: PMC4225781  PMID: 24275289
Stress; hippocampus; female; leu-enkephalin; estrogen; immunohistochemistry; opioids; sex differences; estrogens; chronic stress; acute stress; addiction
2.  Jamie's Ministry of Food: Quasi-Experimental Evaluation of Immediate and Sustained Impacts of a Cooking Skills Program in Australia 
PLoS ONE  2014;9(12):e114673.
To evaluate the immediate and sustained effectiveness of the first Jamie's Ministry of Food Program in Australia on individuals' cooking confidence and positive cooking/eating behaviours.
A quasi- experimental repeated measures design was used incorporating a wait-list control group. A questionnaire was developed and administered at baseline (T1), immediately post program (T2) and 6 months post completion (T3) for participants allocated to the intervention group, while wait -list controls completed it 10 weeks prior to program commencement (T1) and just before program commencement (T2). The questionnaire measured: participants' confidence to cook, the frequency of cooking from basic ingredients, and consumption of vegetables, vegetables with the main meal, fruit, ready-made meals and takeaway. Analysis used a linear mixed model approach for repeated measures using all available data to determine mean differences within and between groups over time.
All adult participants (≥18 years) who registered and subsequently participated in the program in Ipswich, Queensland, between late November 2011- December 2013, were invited to participate.
In the intervention group: 694 completed T1, 383 completed T1 and T2 and 214 completed T1, T2 and T3 assessments. In the wait-list group: 237 completed T1 and 149 completed T1 and T2 assessments. Statistically significant increases within the intervention group (P<0.001) and significant group*time interaction effects (P<0.001) were found in all cooking confidence measures between T1 and T2 as well as cooking from basic ingredients, frequency of eating vegetables with the main meal and daily vegetable intake (0.52 serves/day increase). Statistically significant increases at T2 were sustained at 6 months post program in the intervention group.
Jamie's Ministry of Food Program, Australia improved individuals' cooking confidence and cooking/eating behaviours contributing to a healthier diet and is a promising community-based strategy to influence diet quality.
PMCID: PMC4267737  PMID: 25514531
3.  Understanding evidence: a statewide survey to explore evidence-informed public health decision-making in a local government setting 
The value placed on types of evidence within decision-making contexts is highly dependent on individuals, the organizations in which the work and the systems and sectors they operate in. Decision-making processes too are highly contextual. Understanding the values placed on evidence and processes guiding decision-making is crucial to designing strategies to support evidence-informed decision-making (EIDM). This paper describes how evidence is used to inform local government (LG) public health decisions.
The study used mixed methods including a cross-sectional survey and interviews. The Evidence-Informed Decision-Making Tool (EvIDenT) survey was designed to assess three key domains likely to impact on EIDM: access, confidence, and organizational culture. Other elements included the usefulness and influence of sources of evidence (people/groups and resources), skills and barriers, and facilitators to EIDM. Forty-five LGs from Victoria, Australia agreed to participate in the survey and up to four people from each organization were invited to complete the survey (n = 175). To further explore definitions of evidence and generate experiential data on EIDM practice, key informant interviews were conducted with a range of LG employees working in areas relevant to public health.
In total, 135 responses were received (75% response rate) and 13 interviews were conducted. Analysis revealed varying levels of access, confidence and organizational culture to support EIDM. Significant relationships were found between domains: confidence, culture and access to research evidence. Some forms of evidence (e.g. community views) appeared to be used more commonly and at the expense of others (e.g. research evidence). Overall, a mixture of evidence (but more internal than external evidence) was influential in public health decision-making in councils. By comparison, a mixture of evidence (but more external than internal evidence) was deemed to be useful in public health decision-making.
This study makes an important contribution to understanding how evidence is used within the public health LG context.
Trial registration
Electronic supplementary material
The online version of this article (doi:10.1186/s13012-014-0188-7) contains supplementary material, which is available to authorized users.
PMCID: PMC4314798  PMID: 25496505
4.  Structure of Haze Forming Proteins in White Wines: Vitis vinifera Thaumatin-Like Proteins 
PLoS ONE  2014;9(12):e113757.
Grape thaumatin-like proteins (TLPs) play roles in plant-pathogen interactions and can cause protein haze in white wine unless removed prior to bottling. Different isoforms of TLPs have different hazing potential and aggregation behavior. Here we present the elucidation of the molecular structures of three grape TLPs that display different hazing potential. The three TLPs have very similar structures despite belonging to two different classes (F2/4JRU is a thaumatin-like protein while I/4L5H and H2/4MBT are VVTL1), and having different unfolding temperatures (56 vs. 62°C), with protein F2/4JRU being heat unstable and forming haze, while I/4L5H does not. These differences in properties are attributable to the conformation of a single loop and the amino acid composition of its flanking regions.
PMCID: PMC4252030  PMID: 25463627
5.  Fair relationships and policies to support family day care educators’ mental health: a qualitative study 
BMC Public Health  2014;14(1):1214.
High quality child care is a population health investment that relies on the capacity of providers. The mental health and wellbeing of child care educators is fundamental to care quality and turnover, yet sector views on the relationship between working conditions and mental health and wellbeing are scarce. This paper examines child care educators’ and sector key informants’ perspectives on how working in family day care influences educator’s mental health and wellbeing.
Semi-structured telephone interviews were conducted with Australian family day care educators (n = 16) and key informants (n = 18) comprised of representatives from family day care schemes, government and other relevant organisations regarding the relationship between working conditions and educator mental health. Thematic analysis referenced the assumptions and concepts of critical inquiry and used social exchange theory.
Educators and key informants reported that educators’ mental health was affected by the quality of their relationships with government, family day care schemes, and the parents and children using their services. These social relationships created and contributed to working conditions that were believed to promote or diminish educators’ mental health. High quality relationships featured fair exchanges of educator work for key resources of social support and respect; adequate income; professional services; and information. Crucially, how exchanges influenced educator wellbeing was largely contingent on government policies that reflect the values and inequities present in society.
Making policies and relationships between educators, government and family day care schemes fairer would contribute strongly to the protection and promotion of educator mental health and wellbeing, and in turn contribute to workforce stability and care quality.
PMCID: PMC4256732  PMID: 25420621
Child care; Mental health; Occupational health; Policy; Child care provider
6.  Stress differentially alters mu opioid receptor density and trafficking in parvalbumin-containing interneurons in the female and male rat hippocampus 
Synapse (New York, N.Y.)  2013;67(11):757-772.
Stress differentially affects hippocampal dependent learning relevant to addiction and morphology in male and female rats. Mu opioid receptors (MORs), which are located in parvalbumin (PARV)-containing GABAergic interneurons and are trafficked in response to changes in the hormonal environment, play a critical role in promoting principal cell excitability and long-term potentiation. Here, we compared the effects of acute and chronic immobilization stress (AIS and CIS) on MOR trafficking in PARV-containing neurons in the hilus of the dentate gyrus in female and male rats using dual label immuno-electron microscopy. Following AIS, the density of MOR silver-intensified gold particles (SIGs) in the cytoplasm of PARV-labeled dendrites was significantly reduced in females (estrus stage). Conversely, AIS significantly increased the proportion of cytoplasmic MOR SIGs in PARV-labeled dendrites in male rats. CIS significantly reduced the number of PARV-labeled neurons in the dentate hilus of males but not females. However, MOR/PARV-labeled dendrites and terminals were significantly smaller in CIS females, but not males, compared to controls. Following CIS, the density of cytoplasmic MOR SIGs increased in PARV-labeled dendrites and terminals in females. Moreover, the proportion of near-plasmalemmal MOR SIGs relative to total decreased in large PARV-labeled dendrites in females. After CIS, no changes in the density or trafficking of MOR SIGs were seen in PARV-labeled dendrites or terminals in males. These data show that AIS and CIS differentially affect available MOR pools in PARV-containing interneurons in female and male rats. Furthermore, they suggest that CIS could affect principal cell excitability in a manner that maintains learning processes in females but not males.
PMCID: PMC3778032  PMID: 23720407
opioids; sex differences; estrogens; chronic stress; acute stress
7.  Sex and estrogen receptor expression influence opioid peptide levels in the mouse hippocampal mossy fiber pathway 
Neuroscience letters  2013;552:10.1016/j.neulet.2013.07.048.
The opioid peptides, dynorphin (DYN) and enkephalin (L-ENK) are contained in the hippocampal mossy fiber pathway where they modulate synaptic plasticity. In rats, the levels of DYN and L-ENK immunoreactivity (-ir) are increased when estrogen levels are elevated (Torres-Reveron et al. 2008 and 2009). Here, we used quantitative immunocytochemistry to examine whether opioid levels are similarly regulated in wildtype (WT) mice over the estrous cycle, and how these compared to males. Moreover, using estrogen receptor (ER) alpha and beta knockout mice (AERKO and BERKO, respectively), the present study examined the role of ERs in rapid, membrane-initiated (6 hr), or slower, nucleus-initiated (48 hr) estradiol effects on mossy fiber opioid levels. Unlike rats, the levels of DYN and L-ENK-ir did not change over the estrous cycle. However, compared to males, females had higher levels of DYN-ir in CA3a and L-ENK-ir in CA3b. In WT and BERKO ovariectomized (OVX) mice, neither DYN- nor L-ENK-ir changed following 6 or 48 hrs estradiol benzoate (EB) administration. However, DYN-ir significantly increased 48 hours after EB in the dentate gyrus (DG) and CA3b of AERKO mice only. These findings suggest that cyclic hormone levels regulate neither DYN nor L-ENK levels in the mouse mossy fiber pathway as they do in the rat. This may be due to species-specific differences in the mossy fiber pathway. However, in the mouse, DYN levels are regulated by exogenous EB in the absence of ERα possibly via an ERβ-mediated pathway requiring new gene transcription.
PMCID: PMC3857632  PMID: 23933204
opioids; dentate gyrus; CA3 region; synaptic plasticity
8.  Lessons from obesity prevention for the prevention of mental disorders: the primordial prevention approach 
BMC Psychiatry  2014;14(1):254.
Emerging evidence supports a relationship between risk factors for obesity and the genesis of the common mental disorders, depression and anxiety. This suggests common mental disorders should be considered as a form of non-communicable disease, preventable through the modification of lifestyle behaviours, particularly diet and physical activity.
Obesity prevention research since the 1970’s represents a considerable body of knowledge regarding strategies to modify diet and physical activity and so there may be clear lessons from obesity prevention that apply to the prevention of mental disorders. For obesity, as for common mental disorders, adolescence represents a key period of vulnerability. In this paper we briefly discuss relationships between modifiable lifestyle risk factors and mental health, lifestyle risk factor interventions in obesity prevention research, the current state of mental health prevention, and the implications of current applications of systems thinking in obesity prevention research for lifestyle interventions.
We propose a potential focus for future mental health promotion interventions and emphasise the importance of lessons available from other lifestyle modification intervention programmes.
PMCID: PMC4172880  PMID: 25204469
Obesity prevention; Common mental disorders; Prevention; Intervention design; Complex intervention; Systems
9.  The effect of gender and age on the association between weight status and health-related quality of life in Australian adolescents 
BMC Public Health  2014;14(1):898.
Evidence suggests an inverse relationship between excess weight and health-related quality of life (HRQoL) in children and adolescents, however little is known about whether this association is moderated by variables such as gender and age. This study aimed to investigate these relationships.
Participants were secondary school students (818 females, 52% and 765 males, 48%) from 23 secondary schools in Victoria, Australia. Age ranged from 11.0 to 19.6 years (mean age 14.5 years). The adolescent version of the Assessment of Quality of Life (AQoL) Instrument (AQoL-6D) which is a self-reported measure of adolescent quality of life was administered and anthropometric measures (height and weight) were taken. Assessment of weight status was categorized using the Body Mass Index (BMI).
HRQoL was associated with gender and age, but not weight status or socio-economic status; with males and younger adolescents having higher HRQoL scores than their female and older adolescent counterparts (both p < 0.05). There was also a significant interaction of weight status by gender whereby overweight females had poorer HRQoL (-.06 units) relative to healthy weight females (p < 0.05).
This study contributes to the evidence base around factors associated with adolescent HRQoL and reveals that gender and age are important correlates of HRQoL in an Australian adolescent population. This knowledge is critical to inform the design of health promotion initiatives so they can be tailored to be gender- and age-specific.
Trial registration
Australian Clinical Trials Registration Number 12609000892213.
PMCID: PMC4158070  PMID: 25183192
Health-related quality of life; Weight status; Age; Gender; Adolescents; Obesity
10.  A qualitative study of the factors that influence mothers when choosing drinks for their young children 
BMC Research Notes  2014;7:430.
The consumption of sweetened beverages is a known common risk factor for the development of obesity and dental caries in children and children consume sweet drinks frequently and in large volumes from an early age. The aim of this study was to examine factors that influence mothers when choosing drinks for their children.
Semi-structured interviews (n = 32) were conducted with a purposive sample of mothers of young children from Victoria’s Barwon South Western Region (selected from a larger cohort study to include families consuming different types of water, and different socioeconomic status and size). Inductive thematic analysis was conducted on transcribed interviews.
Several themes emerged as influencing child drink choice. Child age: Water was the main beverage for the youngest child however it was seen as more acceptable to give older children sweetened beverages. Child preference and temperament: influencing when and if sweet drinks were given; Family influences such as grandparents increased children’s consumption of sweet drinks, often providing children drinks such as fruit juice and soft drinks regardless of maternal disapproval. The Setting: children were more likely to be offered sweetened drinks either as a reward or treat for good behaviour or when out shopping, out for dinner or at parties.
Limiting intake of sweet drinks is considered an important step for child general and oral health. However, the choice of drinks for children has influences from social, environmental and behavioural domains, indicating that a multi-strategy approach is required to bring about this change.
PMCID: PMC4097085  PMID: 24997015
11.  The influences of reproductive status and acute stress on the levels of phosphorylated delta opioid receptor immunoreactivity in rat hippocampus☆ 
Brain research  2013;1518:71-81.
In the hippocampus, ovarian hormones and sex can alter the trafficking of delta opioid receptors (DORs) and the proportion of DORs that colocalize with the stress hormone, corticotropin releasing factor. Here, we assessed the effects of acute immobilization stress (AIS) and sex on the phosphorylation of DORs in the rat hippocampus. We first localized an antibody to phosphorylated DOR (pDOR) at the SER363 carboxy-terminal residue, and demonstrated its response to an opioid agonist. By light microscopy, pDOR-immunoreactivity (ir) was located predominantly in CA2/CA3a pyramidal cell apical dendrites and in interneurons in CA1-3 stratum oriens and the dentate hilus. By electron microscopy, pDOR-ir primarily was located in somata and dendrites, associated with endomembranes, or in dendritic spines. pDOR-ir was less frequently found in mossy fibers terminals. Quantitative light microscopy revealed a significant increase in pDOR-ir in the CA2/CA3a region of male rats 1 h following an injection of the opioid agonist morphine (20 mg/kg, I.P). To look at the effects of stress on pDOR, we compared pDOR-ir in males and cycling females after AIS. The level of pDOR-ir in stratum radiatum of CA2/CA3a was increased in control estrus (elevated estrogen and progesterone) females compared to proestrus and diestrus females and males. However, immediately following 30 min of AIS, no significant differences in pDOR levels were seen across estrous cycle phase or sex. These findings suggest that hippocampal levels of phosphorylated DORs vary with estrous cycle phase and that acute stress may dampen the differential effects of hormones on DOR activation in females.
PMCID: PMC3764923  PMID: 23583481
Opioids; Sex differences; Estrogens; CA2 region of the hippocampus; Pyramidal cells; Mossy fiber pathway
12.  Parent-reported measures of child health and wellbeing in same-sex parent families: a cross-sectional survey 
BMC Public Health  2014;14:635.
It has been suggested that children with same-sex attracted parents score well in psychosocial aspects of their health, however questions remain about the impact of stigma on these children. Research to date has focused on lesbian parents and has been limited by small sample sizes. This study aims to describe the physical, mental and social wellbeing of Australian children with same-sex attracted parents, and the impact that stigma has on them.
A cross-sectional survey, the Australian Study of Child Health in Same-Sex Families, was distributed in 2012 to a convenience sample of 390 parents from Australia who self-identified as same-sex attracted and had children aged 0-17 years. Parent-reported, multidimensional measures of child health and wellbeing and the relationship to perceived stigma were measured.
315 parents completed the survey (completion rate = 81%) representing 500 children. 80% of children had a female index parent while 18% had a male index parent. Children in same-sex parent families had higher scores on measures of general behavior, general health and family cohesion compared to population normative data (β = 2.93, 95% CI = 0.35 to 5.52, P = .03; β = 5.60, 95% CI = 2.69 to 8.52, P = <.001; and β = 6.01, 95% CI = 2.84 to 9.17, P = <.001 respectively). There were no significant differences between the two groups for all other scale scores. Physical activity, mental health, and family cohesion were all negatively associated with increased stigma (β = -3.03, 95% CI = -5.86 to -0.21, P = .04; β = -10.45, 95% CI = -18.48 to -2.42, P = .01; and β = -9.82, 95% CI = -17.86 to -1.78, P = .02 respectively) and the presence of emotional symptoms was positively associated with increased stigma (β =0.94, 95% CI = 0.08 to 1.81, P = .03).
Australian children with same-sex attracted parents score higher than population samples on a number of parent-reported measures of child health. Perceived stigma is negatively associated with mental health. Through improved awareness of stigma these findings play an important role in health policy, improving child health outcomes.
PMCID: PMC4082299  PMID: 24952766
Child health; Stigma; Sexuality; Parenting
13.  Deletion of the NMDA-NR1 receptor subunit gene in the mouse nucleus accumbens attenuates apomorphine-induced dopamine D1 receptor trafficking and acoustic startle behavior 
Synapse (New York, N.Y.)  2013;67(6):265-279.
The nucleus accumbens (Acb) contains subpopulations of neurons defined by their receptor content and potential involvement in sensorimotor gating and other behaviors that are dysfunctional in schizophrenia. In Acb neurons, the NMDA NR1 (NR1) subunit is co-expressed not only with the dopamine D1 receptor (D1R), but also with the μ-opioid receptor (μ-OR), which mediates certain behaviors that are adversely impacted by schizophrenia. The NMDA-NR1 subunit has been suggested to play a role in the D1R trafficking and behavioral dysfunctions resulting from systemic administration of apomorphine, a D1R and dopamine D2 receptor agonist that impacts prepulse inhibition (PPI) to auditory-evoked startle (AS). Together, this evidence suggests that the NMDA receptor may regulate D1R trafficking in Acb neurons, including those expressing μ-OR, in animals exposed to auditory startle and apomorphine. We tested this hypothesis by combining spatial-temporal gene deletion technology, dual labeling immunocytochemistry, and behavioral analysis. Deleting NR1 in Acb neurons prevented the increase in the dendritic density of plasma membrane D1Rs in single D1R and dual (D1R and μ-OR) labeled dendrites in the Acb in response to apomorphine and AS. Deleting NR1 also attenuated the decrease in AS induced by apomorphine. In the absence of apomorphine and startle, deletion of Acb NR1 diminished social interaction, without affecting novel object recognition, or open field activity. These results suggest that NR1 expression in the Acb is essential for apomorphine-induced D1R surface trafficking and reduction in AS, but also plays an independent role in controling social behaviors that are impaired in multiple psychiatric disorders.
PMCID: PMC3894854  PMID: 23345061
auditory startle; mu-opioid receptor; prepulse-inhibition; sociability; substance abuse
14.  An unusual dimeric small heat shock protein provides insight into the mechanism of this class of chaperones 
Journal of molecular biology  2013;425(10):1683-1696.
Small heat shock proteins (sHSPs) are virtually ubiquitous stress proteins that are also found in many normal tissues and accumulate in diseases of protein folding. They generally act as ATP-independent chaperones to bind and stabilize denaturing proteins that can be later reactivated by ATP-dependent Hsp70/DnaK, but the mechanism of substrate capture by sHSPs remains poorly understood. A majority of sHSPs form large oligomers, a property that has been linked to their effective chaperone action. We describe AtHsp18.5 from Arabidopsis thaliana, demonstrating it is dimeric and exhibits robust chaperone activity, adding support to the model that suboligomeric sHSP forms are a substrate binding species. Notably, like oligomeric sHSPs, when bound to substrate AtHsp18.5 assembles into large complexes, indicating reformation of sHSP oligomeric contacts are not required for assembly of sHSP-substrate complexes. Monomers of AtHsp18.5 freely exchange between dimers, but fail to coassemble in vitro with dodecameric plant cytosolic sHSPs, suggesting AtHsp18.5 does not interact by coassembly with these other sHSPs in vivo. Data from controlled proteolysis and hydrogen-deuterium exchange coupled with mass spectrometry show that the N- and C-termini of AtHsp18.5 are highly accessible and lack stable secondary structure, most likely a requirement for substrate interaction. Chaperone activity of a series of AtHsp18.5 truncation mutants confirm that the N-terminal arm is required for substrate protection and that different substrates interact differently with the N-terminal arm. In total, these data imply that the core α-crystallin domain of the sHSPs is a platform for flexible arms that capture substrates to maintain their solubility.
PMCID: PMC3646915  PMID: 23416558
chaperone; α-crystallin domain; protein flexibility; subunit exchange; hydrogen deuterium exchange; mass spectrometry of protein complexes
15.  An exploratory trial implementing a community-based child oral health promotion intervention for Australian families from refugee and migrant backgrounds: a protocol paper for Teeth Tales 
BMJ Open  2014;4(3):e004260.
Inequalities are evident in early childhood caries rates with the socially disadvantaged experiencing greater burden of disease. This study builds on formative qualitative research, conducted in the Moreland/Hume local government areas of Melbourne, Victoria 2006–2009, in response to community concerns for oral health of children from refugee and migrant backgrounds. Development of the community-based intervention described here extends the partnership approach to cogeneration of contemporary evidence with continued and meaningful involvement of investigators, community, cultural and government partners. This trial aims to establish a model for child oral health promotion for culturally diverse communities in Australia.
Methods and analysis
This is an exploratory trial implementing a community-based child oral health promotion intervention for Australian families from refugee and migrant backgrounds. Families from an Iraqi, Lebanese or Pakistani background with children aged 1–4 years, residing in metropolitan Melbourne, were invited to participate in the trial by peer educators from their respective communities using snowball and purposive sampling techniques. Target sample size was 600. Moreland, a culturally diverse, inner-urban metropolitan area of Melbourne, was chosen as the intervention site. The intervention comprised peer educator led community oral health education sessions and reorienting of dental health and family services through cultural Competency Organisational Review (CORe).
Ethics and dissemination
Ethics approval for this trial was granted by the University of Melbourne Human Research Ethics Committee and the Department of Education and Early Childhood Development Research Committee. Study progress and output will be disseminated via periodic newsletters, peer-reviewed research papers, reports, community seminars and at National and International conferences.
Trial registration number
Australian New Zealand Clinical Trials Registry (ACTRN12611000532909).
PMCID: PMC3963385  PMID: 24622949
16.  Distribution of angiotensin type 1a receptor containing cells in the brains of bacterial artificial chromosome transgenic mice 
Neuroscience  2012;226:489-509.
In the central nervous system, angiotensin II (AngII) binds to angiotensin type 1 receptors (AT1R) to affect autonomic and endocrine functions as well as learning and memory. However, understanding the function of cells containing AT1Rs has been restricted by limited availability of specific antisera, difficulties discriminating AT1 receptor-immunoreactive cells in many brain regions and, the identification of AT1R-containing neurons for physiological and molecular studies. Here, we demonstrate that an Agtr1a bacterial artificial chromosome (BAC) transgenic mouse line that expresses type A AT1Rs (AT1aRs) identified by enhanced green fluorescent protein (EGFP) overcomes these shortcomings. Throughout the brain, AT1aR-EGFP was detected in the nuclei and cytoplasm of cells, most of which were neurons. EGFP often extended into dendritic processes and could be identified either natively or with immunolabeling of EGFP. The distribution of AT1aR-EGFP cells in brain closely corresponded to that reported for AngII binding and AT1aR protein and mRNA. In particular, AT1aR-EGFP cells were in autonomic regions (e.g., hypothalamic paraventricular nucleus, central nucleus of the amygdala, parabrachial nucleus, nuclei of the solitary tract and rostral ventrolateral medulla) and in regions involved in electrolyte and fluid balance (i.e., subfornical organ) and learning and memory (i.e., cerebral cortex and hippocampus). Additionally, dual label electron microscopic studies in select brain areas demonstrate that cells containing AT1aR-EGFP colocalize with AT1R-immunoreactivity. Assessment of AngII-induced free radical production in isolated EGFP cells demonstrated feasibility of studies investigating AT1aR signaling ex vivo. These findings support the utility of Agtr1a BAC transgenic reporter mice for future studies understanding the role of AT1 receptor containing cells in brain function.
PMCID: PMC3505886  PMID: 22922351
autonomic nuclei; hypothalamus; subfornical organ; amygdala; nucleus of the solitary tract; rostral ventrolateral medulla
17.  Beyond Bushfires: Community, Resilience and Recovery - a longitudinal mixed method study of the medium to long term impacts of bushfires on mental health and social connectedness 
BMC Public Health  2013;13:1036.
Natural disasters represent an increasing threat both in terms of incidence and severity as a result of climate change. Although much is known about individual responses to disasters, much less is known about the social and contextual response and how this interacts with individual trajectories in terms of mental health, wellbeing and social connectedness. The 2009 bushfires in Victoria, Australia caused much loss of life, property destruction, and community disturbance. In order to progress future preparedness, response and recovery, it is crucial to measure and understand the impact of disasters at both individual and community levels.
This study aims to profile the range of mental health, wellbeing and social impacts of the Victorian 2009 bushfires over time using multiple methodologies and involving multiple community partners. A diversity of communities including bushfire affected and unaffected will be involved in the study and will include current and former residents (at the time of the Feb 2009 fires). Participants will be surveyed in 2012, 2014 and, funding permitting, in 2016 to map the predictors and outcomes of mental health, wellbeing and social functioning. Ongoing community visits, as well as interviews and focus group discussions in 2013 and 2014, will provide both contextual information and evidence of changing individual and community experiences in the medium to long term post disaster. The study will include adults, adolescents and children over the age of 5.
Conducting the study over five years and focussing on the role of social networks will provide new insights into the interplay between individual and community factors and their influence on recovery from natural disaster over time. The study findings will thereby expand understanding of long term disaster recovery needs for individuals and communities.
PMCID: PMC3818325  PMID: 24180339
Disasters; Social networks; Mental health; Epidemiologic methods; Qualitative research; Community-based participatory research
18.  Testing the PRISMA-Equity 2012 Reporting Guideline: the Perspectives of Systematic Review Authors 
PLoS ONE  2013;8(10):e75122.
Reporting guidelines can be used to encourage standardised and comprehensive reporting of health research. In light of the global commitment to health equity, we have previously developed and published a reporting guideline for equity-focused systematic reviews (PRISMA-E 2012). The objectives of this study were to explore the utility of the equity extension items included in PRISMA-E 2012 from a systematic review author perspective, including facilitators and barriers to its use. This will assist in designing dissemination and knowledge translation strategies. We conducted a survey of systematic review authors to expose them to the new items in PRISMA-E 2012, establish the extent to which they had historically addressed those items in their own reviews, and gather feedback on the usefulness of the new items. Data were analysed using Microsoft Excel 2008 and Stata (version 11.2 for Mac). Of 151 respondents completing the survey, 18.5% (95% CI: 12.7% to 25.7%) had not heard of the PRISMA statement before, although 83.4% (95% CI: 77.5% to 89.3%) indicated that they plan to use PRISMA-E 2012 in the future, depending on the focus of their review. Most (68.9%; 95% CI: 60.8% to 76.2%) thought that using PRISMA-E 2012 would lead them to conduct their reviews differently. Important facilitators to using PRISMA-E 2012 identified by respondents were journal endorsement and incorporation of the elements of the guideline into systematic review software. Barriers identified were lack of time, word limits and the availability of equity data in primary research. This study has been the first to ‘road-test’ the new PRISMA-E 2012 reporting guideline and the findings are encouraging. They confirm the acceptability and potential utility of the guideline to assist review authors in reporting on equity in their reviews. The uptake and impact of PRISMA-E 2012 over time on design, conduct and reporting of primary research and systematic reviews should continue to be examined.
PMCID: PMC3794945  PMID: 24130684
19.  Knowledge translation strategies to improve the use of evidence in public health decision making in local government: intervention design and implementation plan 
Knowledge translation strategies are an approach to increase the use of evidence within policy and practice decision-making contexts. In clinical and health service contexts, knowledge translation strategies have focused on individual behavior change, however the multi-system context of public health requires a multi-level, multi-strategy approach. This paper describes the design of and implementation plan for a knowledge translation intervention for public health decision making in local government.
Four preliminary research studies contributed findings to the design of the intervention: a systematic review of knowledge translation intervention effectiveness research, a scoping study of knowledge translation perspectives and relevant theory literature, a survey of the local government public health workforce, and a study of the use of evidence-informed decision-making for public health in local government. A logic model was then developed to represent the putative pathways between intervention inputs, processes, and outcomes operating between individual-, organizational-, and system-level strategies. This formed the basis of the intervention plan.
The systematic and scoping reviews identified that effective and promising strategies to increase access to research evidence require an integrated intervention of skill development, access to a knowledge broker, resources and tools for evidence-informed decision making, and networking for information sharing. Interviews and survey analysis suggested that the intervention needs to operate at individual and organizational levels, comprising workforce development, access to evidence, and regular contact with a knowledge broker to increase access to intervention evidence; develop skills in appraisal and integration of evidence; strengthen networks; and explore organizational factors to build organizational cultures receptive to embedding evidence in practice. The logic model incorporated these inputs and strategies with a set of outcomes to measure the intervention’s effectiveness based on the theoretical frameworks, evaluation studies, and decision-maker experiences.
Documenting the design of and implementation plan for this knowledge translation intervention provides a transparent, theoretical, and practical approach to a complex intervention. It provides significant insights into how practitioners might engage with evidence in public health decision making. While this intervention model was designed for the local government context, it is likely to be applicable and generalizable across sectors and settings.
Trial registration
Australia New Zealand Clinical Trials Register ACTRN12609000953235.
PMCID: PMC3853093  PMID: 24107358
Knowledge translation; Evidence; Public health; Decision-making
20.  Membrane trafficking of NADPH oxidase p47phox in paraventricular hypothalamic neurons parallels local free radical production in angiotensin II slow-pressor hypertension 
Nicotinamide adenine dinucleotide phosphate (NADPH) oxidase-generated reactive oxygen species (ROS) are highly implicated in the development of angiotensin II (AngII)-dependent hypertension mediated in part through the hypothalamic paraventricular nucleus (PVN). This region contains vasopressin and non-vasopressin neurons that are responsive to cardiovascular dysregulation, however it is not known if ROS is generated by one or both cell-types in response to “slow pressor” infusion of AngII. We addressed this question using ROS imaging and electron microscopic dual labeling for vasopressin and p47phox, a cytoplasmic NADPH oxidase subunit requiring mobilization to membranes for the initiation of ROS production. C57BL/6 mice or vasopressin-enhanced green fluorescent protein (VP-eGFP) mice were infused systemically with saline or AngII (600 ng/kg/min; s.c.) for two weeks during which they slowly developed hypertension. Ultrastructural analysis of the PVN demonstrated p47phox immunolabeling in many glial and neuronal profiles, most of which were postsynaptic dendrites. Compared with saline, AngII recipient mice had a significant increase in p47phox immunolabeling on endomembranes just beneath the plasmalemmal surface (+42.1±11.3%; p<0.05) in non-vasopressin dendrites. In contrast, AngII infusion decreased p47phox immunolabeling on the plasma membrane (−35.5±16.5%; p<0.05) in vasopressin dendrites. Isolated non-VP-eGFP neurons from the PVN of AngII-infused mice also showed an increase in baseline ROS production not seen in VP-eGFP neurons. Our results suggest that chronic low dose AngII may offset the homeostatic control of blood pressure by differentially affecting membrane assembly of NADPH oxidase and ROS production in vasopressin and non-vasopressin neurons located within the PVN.
PMCID: PMC3616374  PMID: 23467347
cardiovascular regulation; vasopressin; reactive oxygen species; electron microscopy
21.  Health equity: evidence synthesis and knowledge translation methods 
Systematic Reviews  2013;2:43.
At the Rio Summit in 2011 on Social Determinants of Health, the global community recognized a pressing need to take action on reducing health inequities. This requires an improved evidence base on the effects of national and international policies on health inequities. Although systematic reviews are recognized as an important source for evidence-informed policy, they have been criticized for failing to assess effects on health equity.
This article summarizes guidance on both conducting systematic reviews with a focus on health equity and on methods to translate their findings to different audiences. This guidance was developed based on a series of methodology meetings, previous guidance, a recently developed reporting guideline for equity-focused systematic reviews (PRISMA-Equity 2012) and a systematic review of methods to assess health equity in systematic reviews.
We make ten recommendations for conducting equity-focused systematic reviews; and five considerations for knowledge translation. Illustrative examples of equity-focused reviews are provided where these methods have been used.
Implementation of the recommendations in this article is one step toward monitoring the impact of national and international policies and programs on health equity, as recommended by the 2011 World Conference on Social Determinants of Health.
PMCID: PMC3702469  PMID: 23799964
Health Equity; Evidence Synthesis; Knowledge Translation; Systematic Reviews
22.  Evolutionarily Assembled cis-Regulatory Module at a Human Ciliopathy Locus 
Science (New York, N.Y.)  2012;335(6071):966-969.
Neighboring genes are often coordinately expressed within cis-regulatory modules, but evidence that nonparalogous genes share functions in mammals is lacking. Here, we report that mutation of either TMEM138 or TMEM216 causes a phenotypically indistinguishable human ciliopathy, Joubert syndrome. Despite a lack of sequence homology, the genes are aligned in a head-to-tail configuration and joined by chromosomal rearrangement at the amphibian-to-reptile evolutionary transition. Expression of the two genes is mediated by a conserved regulatory element in the noncoding intergenic region. Coordinated expression is important for their interdependent cellular role in vesicular transport to primary cilia. Hence, during vertebrate evolution of genes involved in ciliogenesis, nonparalogous genes were arranged to a functional gene cluster with shared regulatory elements.
PMCID: PMC3671610  PMID: 22282472
23.  Methods for the evaluation of the Jamie Oliver Ministry of Food program, Australia 
BMC Public Health  2013;13:411.
Community-based programs aimed at improving cooking skills, cooking confidence and individual eating behaviours have grown in number over the past two decades. Whilst some evidence exists to support their effectiveness, only small behavioural changes have been reported and limitations in study design may have impacted on results.
This paper describes the first evaluation of the Jamie Oliver Ministry of Food Program (JMoF) Australia, in Ipswich, Queensland. JMoF Australia is a community-based cooking skills program open to the general public consisting of 1.5 hour classes weekly over a 10 week period, based on the program of the same name originating in the United Kingdom.
A mixed methods study design is proposed. Given the programmatic implementation of JMoF in Ipswich, the quantitative study is a non-randomised, pre-post design comparing participants undergoing the program with a wait-list control group. There will be two primary outcome measures: (i) change in cooking confidence (self-efficacy) and (ii) change in self-reported mean vegetable intake (serves per day). Secondary outcome measures will include change in individual cooking and eating behaviours and psycho-social measures such as social connectedness and self-esteem. Repeated measures will be collected at baseline, program completion (10 weeks) and 6 months follow up from program completion. A sample of 250 participants per group will be recruited for the evaluation to detect a mean change of 0.5 serves a day of vegetables at 80% power (0.5% significance level). Data analysis will assess the magnitude of change of these variables both within and between groups and use sub group analysis to explore the relationships between socio-demographic characteristics and outcomes.
The qualitative study will be a longitudinal design consisting of semi-structured interviews with approximately 10-15 participants conducted at successive time points. An inductive thematic analysis will be conducted to explore social, attitudinal and behavioural changes experienced by program participants.
This evaluation will contribute to the evidence of whether cooking programs work in terms of improving health and wellbeing and the underlying mechanisms which may lead to positive behaviour change.
Trial registration
Australian and New Zealand Trial registration number: ACTRN12611001209987.
PMCID: PMC3655061  PMID: 23631683
24.  Ovarian steroids alter mu opioid receptor trafficking in hippocampal parvalbumin GABAergic interneurons 
Experimental neurology  2009;219(1):319-327.
The endogenous hippocampal opioid systems are implicated in learning associated with drug use. Recently, we showed that ovarian hormones regulate enkephalin levels in the mossy fiber pathway. This pathway overlaps with parvalbumin (PARV)-basket interneurons that contain the enkephalin-activated mu opioid receptors (MORs) and are important for controlling the “temporal timing” of granule cells. Here, we evaluated the influence of ovarian steroid on the trafficking of MORs in PARV interneurons. Two groups of female rats were analyzed: cycling rats in proestrus (relatively high estrogens) or diestrus; and ovariectomized rats euthanized 6, 24 or 72 hr after estradiol benzoate (10μg, s.c.) administration. Dorsal hippocampal sections were dually immunolabeled for MORs and PARV and examined by light and electron microscopy. As in males, in females MOR-immunoreactivity (-ir) was in numerous PARV-labeled perikarya, dendrites and terminals in the dentate hilar region. Variation in ovarian steroid levels altered the subcellular distribution of MORs in PARV-labeled dendrites but not terminals. In normal cycling rats, MOR-gold particles on the plasma membrane of small PARV-labeled dendrites (area < 1μm2) had higher density in proestrus rats than in diestrus rats. Likewise, in ovariectomized rats MORs showed higher density on the plasma membrane of small PARV-labeled dendrites 72 hrs after estradiol exposure. The number of PARV-labeled cells was not affected by estrous cycle phase or estrogen levels. These results demonstrate that estrogen levels positively regulate the availability of MORs on GABAergic interneurons in the dentate gyrus, suggesting cooperative interaction between opioids and estrogens in modulating principal cell excitability.
PMCID: PMC3593250  PMID: 19505458
estrogen; estrous cycle; ovariectomy; hippocampus; endogenous opioids
25.  Estrogen effects on the brain: actions beyond the hypothalamus via novel mechanisms 
Behavioral neuroscience  2012;126(1):4-16.
From its origins in how the brain controls the endocrine system via the hypothalamus and pituitary gland, neuroendocrinology has evolved into a science that now includes hormone action on many aspects of brain function. These actions involve the whole central nervous system and not just the hypothalamus. Advances in our understanding of cellular and molecular actions of steroid hormones have gone beyond the important cell nuclear actions of steroid hormone receptors to include signaling pathways that intersect with other mediators such as neurotransmitters and neuromodulators. This has, in turn, broadened the search for and identification of steroid receptors to include non-nuclear sites in synapses, dendrites, mitochondria and glial cells, as well as cell nuclei. The study of estrogen receptors and estrogen actions on processes related to cognition, mood, autonomic regulation, pain and neuroprotection, among other functions, has led the way in this new view of hormone actions on the brain. In this review we summarize past and current work in our laboratory on this topic. This exciting and growing field involving many laboratories continues to reshape our ideas and approaches to neuroendocrinology both at the bench and the bedside.
PMCID: PMC3480182  PMID: 22289042
estrogens; progesterone; rapid non-genomic actions; hippocampus; cognition; mood; autonomic regulation

Results 1-25 (65)