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1.
J Neuroinflammation ; 13(1): 107, 2016 05 13.
Article in English | MEDLINE | ID: mdl-27178303

ABSTRACT

BACKGROUND: In the developing brain, self-renewing neural stem/progenitor cells (NSPC) give rise to neuronal and glial lineages. NSPC survival and differentiation can be altered by neurotropic viruses and by the anti-viral immune response. Several neurotropic viruses specifically target and infect NSPCs, in addition to inducing neuronal loss, which makes it difficult to distinguish between effects on NSPCs that are due to direct viral infection or due to the anti-viral immune response. METHODS: We have investigated the impact of anti-viral immunity on NSPCs in measles virus (MV)-infected neonates. A neuron-restricted viral infection model was used, where NSPCs remain uninfected. Thus, an anti-viral immune response was induced without the confounding issue of NSPC infection. Two-transgenic mouse lines were used: CD46+ mice express the human isoform of CD46, the MV entry receptor, under the control of the neuron-specific enolase promoter; CD46+/IFNγ-KO mice lack the key anti-viral cytokine IFNγ. Multi-color flow cytometry and Western Blot analysis were used to quantify effects on NSPC, neuronal, and glial cell number, and quantify effects on IFNγ-mediated signaling and cell markers, respectively. RESULTS: Flow cytometric analysis revealed that NSPCs were reduced in CD46+/IFNγ-KO mice at 3, 7, and 10 days post-infection (dpi), but were unaffected in CD46+ mice. Early neurons showed the greatest cell loss at 7 dpi in both genotypes, with no effect on mature neurons and glial cells. Thus, IFNγ protected against NSPC loss, but did not protect young neurons. Western Blot analyses on hippocampal explants showed reduced nestin expression in the absence of IFNγ, and reduced doublecortin and ßIII-tubulin in both genotypes. Phosphorylation of STAT1 and STAT2 occurred independently of IFNγ in the hippocampus, albeit with distinct regulation of activation. CONCLUSIONS: This is the first study to demonstrate bystander effects of anti-viral immunity on NSPC function. Our results show IFNγ protects the NSPC population during a neonatal viral CNS infection. Significant loss of NSPCs in CD46+/IFNγ-KO neonates suggests that the adaptive immune response is detrimental to NSPCs in the absence of IFNγ. These results reveal the importance and contribution of the anti-viral immune response to neuropathology and may be relevant to other neuroinflammatory conditions.


Subject(s)
Brain/pathology , Brain/virology , Gene Expression Regulation, Viral/physiology , Interferon-gamma/metabolism , Measles/pathology , Neural Stem Cells/physiology , Animals , Animals, Newborn , Apoptosis/physiology , Cell Differentiation/genetics , Disease Models, Animal , Doublecortin Domain Proteins , Gene Expression Regulation, Viral/genetics , Interferon-gamma/genetics , Killer Cells, Natural/metabolism , Measles/complications , Measles/virology , Measles virus/physiology , Membrane Cofactor Protein/genetics , Membrane Cofactor Protein/metabolism , Mice , Mice, Transgenic , Microtubule-Associated Proteins/metabolism , Nestin/genetics , Nestin/metabolism , Neuroglia/metabolism , Neuroglia/pathology , Neuroglia/virology , Neuropeptides/metabolism , STAT2 Transcription Factor/metabolism , Tubulin/metabolism
2.
Bariatr Surg Pract Patient Care ; 10(3): 105-109, 2015 Sep 01.
Article in English | MEDLINE | ID: mdl-26421247

ABSTRACT

Purpose: The aims of this study were to describe the most common medications reported by candidates for weight loss surgery and to consider the potential implications for patient care. Methods: A secondary data analysis of data from bariatric surgery patients enrolled in a randomized, controlled trial. At study entry, participants recorded their use of prescription medications they had taken in the previous 90 days. The Anatomical Therapeutic Chemical (ATC)/Defined Daily Dose (DDD) Index 2014 was used to classify medications. Results: Participants (n=265) were 85.7% female and 83.0% white. Mean body mass index was 47.9±6.5 kg/m2, and age was 45.1±11 years. The average number of medications was 4.4±4.1, and the median was 3. The top three anatomical main groups were the cardiovascular system, alimentary tract and metabolism, and nervous system (28.2%, 21.6%, and 21.3% of all medications, respectively). The top therapeutic subgroups were drugs used in diabetes, psychoanaleptics, and agents acting on the renin-angiotensin system (12%, 11.3%, and 8.2% of all medications, respectively). Conclusions: Candidates for weight loss surgery report taking medications associated with obesity-related comorbidities such as diabetes, depression, and hypertension. Although many may be able to eliminate these medications, others will require close monitoring and dosage adjustment after surgery.

3.
N S W Public Health Bull ; 18(9-10): 174-6, 2007.
Article in English | MEDLINE | ID: mdl-17949588

ABSTRACT

OBJECTIVE: To describe the main differences between conducting a rapid health impact assessment (HIA) and an intermediate HIA on foreshore development plans and their feasibility from a health service perspective. METHODS: A rapid HIA and an intermediate HIA were undertaken on two foreshore development plans. RESULTS: The main differences between the two HIAs were in the identification, assessment and decision-making stages of the HIA. CONCLUSION: While the rapid HIA was less resource intensive than the intermediate HIA, there are several factors that affect the feasibility of conducting this type of HIA within a short time period.


Subject(s)
Decision Making , Health Planning Guidelines , Health Planning , Health Policy , Program Evaluation , Technology Assessment, Biomedical , Community Health Services , Feasibility Studies , Humans , Organizational Case Studies , Time Factors
4.
Health Promot J Austr ; 18(1): 77-9, 2007 Apr.
Article in English | MEDLINE | ID: mdl-17501716

ABSTRACT

ISSUE ADDRESSED: To identify a model for a process that will support schools to implement environmental modifications in playgrounds aimed at increasing physical activity. METHODS: Kidsafe NSW (Playground Advisory Unit) was commissioned by the former Illawarra Health Promotion Unit (IHPU) to develop playground concept designs, safety audits and detailed reports for three primary schools. Each report contained several environmental recommendations to increase participation in physical activity. During this study one school was destroyed by fire. The former IHPU supported the remaining two schools to implement environmental modifications for increasing physical activity through a process of meetings and interviews. RESULTS: Principals of both schools said they found the process to be valuable and it encouraged them to implement changes to their school environment for the purpose of increasing physical activity. School staff and the Parents and Friends Association felt that having a report from Kidsafe NSW increased the credibility and importance of the recommendations. Both schools made several changes to their playgrounds that were recommended in the report. CONCLUSIONS: The process of providing a Kidsafe NSW playground report, as well as support through meetings and interviews, appears to promote environmental change in schools.


Subject(s)
Environment Design , Motor Activity , Play and Playthings , Schools/organization & administration , Adolescent , Child , Health Promotion/organization & administration , Humans
5.
Health Promot J Austr ; 16(3): 194-200, 2005 Dec.
Article in English | MEDLINE | ID: mdl-16375034

ABSTRACT

ISSUE ADDRESSED: This article describes a prospective health impact assessment (HIA) on a local government environmental management plan, the Shellharbour Foreshore Management Plan (SFM Plan). The health outcomes of interest were physical activity and social cohesion. METHODS: The procedures undertaken include: screening; scoping; assessment of potential health impacts; negotiation; and decision-making. The potential positive and negative health impacts of the SFM Plan were assessed and opportunities to enhance the positive and mitigate the negative were identified. RESULTS: Implementation of the SFM Plan was supported as the HIA showed a potential to benefit the health of local residents and visitors to the Shellharbour Foreshore area by increasing physical activity and social cohesion. CONCLUSION: The HIA provided a useful framework for establishing a collaborative relationship between the local government and health sector. It improved the local government's understanding of the inter-relationship between the environment and physical activity and social cohesion and enabled health authorities to have an impact on a capital works program to maximise health gain.


Subject(s)
Community Health Planning/organization & administration , Environment Design , Evaluation Studies as Topic , Motor Activity , Humans , Interinstitutional Relations , Social Facilitation
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