Signature morphoelectric properties of diverse GABAergic interneurons in the human neocortex.

Human cortex transcriptomic studies have revealed a hierarchical organization of γ-aminobutyric acid-producing (GABAergic) neurons from subclasses to a high diversity of more granular types. Rapid GABAergic neuron viral genetic labeling plus Patch-seq (patch-clamp electrophysiology plus single-cell RNA sequencing) sampling in human brain slices was used to reliably target and analyze GABAergic neuron subclasses and individual transcriptomic types. This characterization elucidated transitions between PVALB and SST subclasses, revealed morphological heterogeneity within an abundant transcriptomic type, identified multiple spatially distinct types of the primate-specialized double bouquet cells (DBCs), and shed light on cellular differences between homologous mouse and human neocortical GABAergic neuron types. These results highlight the importance of multimodal phenotypic characterization for refinement of emerging transcriptomic cell type taxonomies and for understanding conserved and specialized cellular properties of human brain cell types.

A whole-brain monosynaptic input connectome to neuron classes in mouse visual cortex.

Identification of structural connections between neurons is a prerequisite to understanding brain function. Here we developed a pipeline to systematically map brain-wide monosynaptic input connections to genetically defined neuronal populations using an optimized rabies tracing system. We used mouse visual cortex as the exemplar system and revealed quantitative target-specific, layer-specific and cell-class-specific differences in its presynaptic connectomes. The retrograde connectivity indicates the presence of ventral and dorsal visual streams and further reveals topographically organized and continuously varying subnetworks mediated by different higher visual areas. The visual cortex hierarchy can be derived from intracortical feedforward and feedback pathways mediated by upper-layer and lower-layer input neurons. We also identify a new role for layer 6 neurons in mediating reciprocal interhemispheric connections. This study expands our knowledge of the visual system connectomes and demonstrates that the pipeline can be scaled up to dissect connectivity of different cell populations across the mouse brain.

Impact of the Make Healthy Normal mass media campaign (Phase 1) on knowledge, attitudes and behaviours: a cohort study.

OBJECTIVE: To determine the impact of the first phase of the Make Healthy Normal mass media campaign on NSW adults' active living and healthy eating knowledge, attitudes, intentions and behaviour. METHODS: Cohort design with NSW adults, followed up three times over 12 months, with n=939 participants completing all three waves. We used generalised linear mixed models to examine campaign awareness, knowledge, attitudes, intentions and behaviours over time. RESULTS: Campaign recognition built to a reasonable level (45% at Wave 3), although unprompted recall was low (9% at Wave 3). There were significant increases in knowledge of physical activity recommendations (46% to 50%), the health effects of obesity (52% to 64%), and weight loss benefits (53% to 65%), with stronger effects in campaign recognisers. Conversely, we found declines in self-efficacy and intention to increase physical activity (39% to 31%) and decrease soft drink consumption (31% to 24%). CONCLUSIONS: Overall, there are some positives for the campaign but intentions need to be a focus of future campaign phases. Continued investment over the medium- to long-term is needed. IMPLICATIONS: Mass media campaigns can play a role in obesity prevention but robust evaluations are needed to identify the characteristics of effective campaigns.

The impact of a community-led program promoting weight loss and healthy living in Aboriginal communities: the New South Wales Knockout Health Challenge.

BACKGROUND: Aboriginal people in Australia experience significant health burden from chronic disease. There has been limited research to identify effective healthy lifestyle programs to address risk factors for chronic disease among Aboriginal people. METHODS: The Knockout Health Challenge is a community-led healthy lifestyle program for Aboriginal communities across New South Wales, Australia. An evaluation of the 2013 Knockout Health Challenge was undertaken. Participants' self-reported physical activity and diet were measured at four time points - at the start and end of the Challenge (via paper form), and 5 and 9 months after the Challenge (via telephone survey). Participants' weight was measured objectively at the start and end of the Challenge, and self-reported (via telephone survey) 5 and 9 months after the Challenge. Changes in body composition, physical activity and diet between time points were analysed using linear mixed models. As part of the telephone survey participants were also asked to identify other impacts of the Challenge; these were analysed descriptively (quantitative items) and thematically (qualitative items). RESULTS: A total of 586 people registered in 22 teams to participate in the Challenge. The mean weight at the start was 98.54kg (SD 22.4), and 94% of participants were overweight or obese. Among participants who provided data at all four time points (n=122), the mean weight loss from the start to the end of the Challenge was 2.3kg (95%CI -3.0 to -1.9, p<0.001), and from the start to 9 months after the Challenge was 2.3kg (95%CI -3.3 to -1.3, p<0.001). Body mass index decreased by an average of 0.9kg/m2 (95%CI -1.0 to -0.7, p<0.001) from the start to the end of the Challenge, and 0.8kg/m2 (95%CI -1.2 to -0.4, p<0.001) 9 months after. At the end of the Challenge, participants reported they were more physically active and had increased fruit and vegetable consumption compared with the start of the Challenge, and identified a range of other positive impacts. CONCLUSIONS: The Challenge was effective in reducing weight and promoting healthy lifestyles among Aboriginal people across New South Wales, and has potential to contribute to closing the health gap between Aboriginal and non-Aboriginal people.

Weight-Related Goal Setting in a Telephone-Based Preventive Health-Coaching Program: Demonstration of Effectiveness.

PURPOSE: This study investigated whether participants in a 6-month telephone-based coaching program, who set physical activity, nutrition, and weight loss goals had better outcomes in these domains. DESIGN: Quasi-experimental design. SETTING: The Australian Get Healthy Information and Coaching Service (GHS), a free population-wide telephone health-coaching service that includes goal setting as a key component of its coaching program. PARTICIPANTS: Consenting GHS coaching participants who had completed coaching between February 2009 and December 2012 (n = 4108). MEASURES: At baseline, participants select a goal for the coaching program, and sociodemographic variables are collected. Self-reported weight, height, waist circumference, physical activity, and nutrition-related behaviors are assessed at baseline and 6 months. ANALYSIS: Descriptive analysis was performed on key sociodemographic variables, and the relationship between goal type and change in health outcomes was assessed using a series of linear mixed models that modeled change from baseline to 6 months. RESULTS: Participants who set goals in relation to weight management and physical activity achieved better results in these areas than those who set alternate goals, losing more than those who set alternate goals (1.5 kg and 0.9 cm in waist circumference) and increasing walking per week (40 minutes), respectively. There was no difference in food-related outcomes for those that set nutrition-related goals. CONCLUSION: Goal setting for weight management and increasing physical activity in the overweight and obese population, undertaken in a telephone-based coaching program, can be effective.

The reach and flow of health information in two Aboriginal communities: a social network analysis.

The aim of the present paper was to explore how social networks enable dissemination of health information within two Aboriginal communities in New South Wales. The study design was modelled on a social network analysis socio-centric model. Data collection was conducted primarily by Aboriginal community members who were trained as community researchers. Participants reported on their patterns of interaction and who they provided or received health information from, and awareness of the Aboriginal Enhancement of the Get Healthy Information and Coaching Service. In total, 122 participants across two sites participated in the study. Aboriginal Community Controlled Health Services (ACCHSs) and Aboriginal Community Controlled Health Organisations (ACCHOs) were cited as the main provider of health information in both sites. Between-ness, degree and closeness centrality showed that certain community members, ACCHS and ACCHO within the two communities in the present study were considerable enablers [actors] in enhancing the reach and flow of health information to their respective Aboriginal community. There is potential for future health-promotion activities to be increasingly targeted and effective in terms of reach and influence, if guided by local Aboriginal organisations and by key Aboriginal community members within and across family networks and communities.

Pragmatic cluster randomised trial of a free telephone-based health coaching program to support women in managing weight gain during pregnancy: the Get Healthy in Pregnancy Trial.

BACKGROUND: Excessive gestational weight gain can result in poor maternal and child health outcomes. Estimates from single studies indicate the prevalence of excessive gestational weight gain in Australia could lie between 38 and 67 %. The risk of excessive weight gain can be reduced through healthy eating and exercise. We describe the rationale and methods of the Get Healthy in Pregnancy Service, a trial service which aims to support women in achieving appropriate gestational weight gain through an existing telephone-based health coaching service. METHODS/DESIGN: This study aims to compare the effectiveness of a telephone-based health coaching program versus provision of information only in supporting pregnant women to achieve appropriate gestational weight gain. A pragmatic stratified clustered randomised controlled trial will be conducted with 710 women who present to 5 hospitals for their first antenatal appointment during the recruitment period (6-8 months), have a pre-pregnancy body mass index (BMI) ≥ 18.50 (healthy weight or above), are 18 years and over, singleton gestation, English speaking, have no pre-existing medical conditions that may limit their ability to exercise or require a restricted diet and are 18 weeks or less gestation. Hospitals will be randomised into one of two intervention models: a) information only; or b) information plus 10 telephone-based health coaching sessions with a university qualified coach. Both interventions will set a weight-range target with pregnant women. The women attending antenatal clinics at participating hospitals will be screened at their initial hospital appointment to assess their eligibility. Women recruited to the trial will have a number of measures recorded including anthropometrics (self-reported height and weight) and dietary and physical activity scores during and following pregnancy. These measurements will be collected at baseline (prior to 18 weeks gestation), 36 weeks gestation and 12 months post-birth. DISCUSSION: This study responds to a need for an effective intervention that targets excessive gestational weight gain at a population level. This study investigates the potential for an innovative intervention combining two existing services; a free state-wide telephone-based health coaching service and hospital-based antenatal care to support pregnant women to achieve healthy weight gain during pregnancy. The use of existing services provides the potential for immediate post-study implementation. While the impacts of telephone-based lifestyle programmes have been tested in a number of settings, there are few studies which evaluate the effectiveness and acceptability of telephone support in achieving healthy gestational weight gain in association with routine antenatal care. TRIAL REGISTRATION: ACTRN12615000397516 (Registration date: 26 June 2014, retrospectively registered).

PET imaging studies show enhanced expression of mGluR5 and inflammatory response during progressive degeneration in ALS mouse model expressing SOD1-G93A gene.

BACKGROUND: Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative motor neuron disorder. Genetic studies have linked mutation of the gene SOD1 to ALS pathology as well as several other pathological processes including modulation of glutamatergic function and inflammatory processes. Since therapeutic approaches for ALS are focused on glutamatergic function, we investigated modulation of glutamate transport based on its receptor function as well as excitotoxicity-induced inflammatory response. METHODS: In vivo positron emission tomography (PET) imaging studies of metabotropic glutamate receptor subtype 5 (mGluR5) using [(18)F]FPEB ([(18)F]3-fluoro-5-(2-pyridylethynyl)benzonitrile) and inflammatory response using [(11)C]PBR28 (peripheral benzodiazepine receptor ligand 28) were done in an early and a late phase of neurodegeneration in four ALS mice expressing SOD1-G93A gene and four control base mice (C57/BL6). Accumulation of [(18)F]FPEB and [(11)C]PBR28 were quantitated in several brain areas and spinal cord to determine degeneration-induced modulation. The studies were completed with immunohistochemical analyses of mGluR5 and inflammatory response. RESULTS: These studies showed enhanced binding potential of [(18)F]FPEB in several brain areas including striatum, hippocampus, and frontal cortex. In the whole brain, the binding potential increased 49 ± 9 % from base mice to ALS-type mice and further enhanced 23 ± 4 % during disease progression. Also, in the spinal cord 6-22 %, enhanced accumulation of [(18)F]FPEB was observed during progression of the disease. The accumulation of [(11)C]PBR28 increased by 110 ± 33 % in the whole brain during progression of the disease indicating significant inflammatory process. [(11)C]PBR28 accumulation enhanced 89-264 % in the spinal cord and 204 % in the lungs. The end point immunohistochemical analyses verified the enhanced mGluR5 expression and inflammation. CONCLUSIONS: These results confirm the role of glutamate and inflammation in ALS-type pathology. These data also support the hypothesis that excessive glutamate may contribute to inflammation in the chronic neurodegenerative processes in ALS.

The sirtuin-2 inhibitor AK7 is neuroprotective in models of Parkinson's disease but not amyotrophic lateral sclerosis and cerebral ischemia.

Sirtuin deacetylases regulate diverse cellular pathways and influence disease processes. Our previous studies identified the brain-enriched sirtuin-2 (SIRT2) deacetylase as a potential drug target to counteract neurodegeneration. In the present study, we characterize SIRT2 inhibition activity of the brain-permeable compound AK7 and examine the efficacy of this small molecule in models of Parkinson's disease, amyotrophic lateral sclerosis and cerebral ischemia. Our results demonstrate that AK7 is neuroprotective in models of Parkinson's disease; it ameliorates alpha-synuclein toxicity in vitro and prevents 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced dopamine depletion and dopaminergic neuron loss in vivo. The compound does not show beneficial effects in mouse models of amyotrophic lateral sclerosis and cerebral ischemia. These findings underscore the specificity of protective effects observed here in models of Parkinson's disease, and previously in Huntington's disease, and support the development of SIRT2 inhibitors as potential therapeutics for the two neurodegenerative diseases.

A pre-and-post study of an urban renewal program in a socially disadvantaged neighbourhood in Sydney, Australia.

BACKGROUND: Urban renewal programs aim to target both the physical and social environments to improve the social capital, social connectedness, sense of community and economic conditions of residents of the neighbourhoods. We evaluated the impact of an urban renewal program on the health and well-being of residents of a socially disadvantaged community in south-western Sydney, Australia. METHODS: Pre- and post-urban renewal program surveys were conducted with householders by trained interviewers. The urban renewal program was conducted over 16 months and consisted of internal upgrades (including internal painting; replacement of kitchens, bathrooms and carpets; general maintenance), external upgrades (including property painting; new fencing, carports, letterboxes, concrete driveways, drainage and landscaping), general external maintenance, and social interventions such as community engagement activities, employment initiatives, and building a community meeting place. The questionnaire asked about demographic characteristics, self-reported physical activity, psychological distress, self-rated health, and perceptions of aesthetics, safety and walkability in the neighbourhood. We used the paired chi-square test (McNemars test) to compare paired proportions. A Bonferroni corrected p-value of <0.0013 denoted statistical significance. RESULTS: Following the urban renewal program we did not find statistically significant changes in perceptions of aesthetics, safety and walkability in the neighbourhood. However, post-urban renewal, more householders reported there were attractive buildings and homes in their neighbourhood (18% vs 64%), felt that they belonged to the neighbourhood (48% vs 70%), that their area had a reputation for being a safe place (8% vs 27%), that they felt safe walking down their street after dark (52% vs 85%), and that people who came to live in the neighbourhood would be more likely to stay rather than move elsewhere (13% vs 54%). Changes in psychological distress and self-rated health were not statistically significant. CONCLUSIONS: We found an increase, in the short-term, in the proportion of householders reporting improvements in some aspects of their immediate neighbourhood following the urban renewal program. It will be important to repeat the survey in the future to determine whether these positive changes are sustained.

Building capacity for evidence-based practice in the health promotion workforce: evaluation of a train-the-trainer initiative in NSW.

ISSUE ADDRESSED: Evidence-based practice (EBP) is essential for effective health promotion practice, but not all health promotion staff have the required skills. In New South Wales this issue was addressed by implementing an EBP train-the-trainer (TTT) program to build workforce capacity. METHODS: The success of the program was assessed through surveys completed by EBP-TTT participants and AHS participants of the disseminated EBP training activities. RESULTS: Ten formal EBP training activities were delivered in five of the eight NSW Areas, reaching a total of 133 practitioners. Participants reported significant improvements in their EBP knowledge and skills, and that these had been incorporated into their practice. A range of informal activities were also conducted. Barriers to delivery of training activities in the three remaining areas included resource restrictions, staff movement and organisational change, and insufficient confidence. CONCLUSIONS: The EBP-TTT program was an effective means of disseminating EBP knowledge and skills when the local 'training-team' felt sufficiently prepared and the Area Health Service was able to support local training activities.

A health impact assessment on the construction phase of a major hospital redevelopment.

A prospective health impact assessment (HIA) was conducted to identify potential health impacts arising from the planned redevelopment of Liverpool Hospital, a major teaching hospital in New South Wales, Australia. A multidisciplinary team of health professionals oversaw the HIA and a core project team led by population health practitioners conducted the HIA using a structured, stepwise process. Methods used to gather data for the identification of impacts were a literature review, development of a population profile and consultation with stakeholders. A range of positive and negative health impacts were identified and an assessment matrix was used to prioritise the health impacts and develop recommendations for the proponents of the redevelopment plan. The HIA added value to the planning process for the hospital redevelopment, increasing capacity to conduct future HIAs.

A health impact assessment of the Liverpool Hospital redevelopment.

This case study describes the process and results of a prospective health impact assessment that was conducted on a major hospital redevelopment in NSW. Undertaking the health impact assessment has raised awareness of the potential intended and unintended consequences of redevelopment in relation to health. It has also enhanced the capacity and commitment for health impact assessment within the Area Health Service.

Promoting evidence-based practice in population health at the local level: a case study in workforce capacity development.

This paper describes a service-based initiative to enhance capacity for evidence-based practice (EBP) in the South Western Sydney Area Health Service Division of Population Health. A working group planned an organisational response to a customised EBP needs assessment using the New South Wales Department of Health's framework for capacity building focussing on five key action areas; organisational development, workforce development, resource allocation, leadership and partnerships. Innovative strategies to promote EBP were developed and implemented and on-site training programs that targeted specific groups of staff were conducted. Because there was commitment and leadership from senior staff for the initiative, a comprehensive approach to building capacity for EBP in population health was possible. Evidence of impact needs to be collected in the future.

Ontology-based interactive information extraction from scientific abstracts.

Over recent years, there has been a growing interest in extracting information automatically or semi-automatically from the scientific literature. This paper describes a novel ontology-based interactive information extraction (OBIIE) framework and a specific OBIIE system. We describe how this system enables life scientists to make ad hoc queries similar to using a standard search engine, but where the results are obtained in a database format similar to a pre-programmed information extraction engine. We present a case study in which the system was evaluated for extracting co-factors from EMBASE and MEDLINE.