239 research outputs found
People at Centre Stage: evaluation summary report
This report presents the results of an evaluation of consumer-directed community aged care.
Consumer-Directed Care (CDC) is central to the aim of rendering community aged care more flexible and responsive. In Australia, it builds on experiences of consumer-directed community-based disability care and is intended to offer greater decisional authority to care recipients over the services they receive.
Since the 1990s, there has been growing interest among Australian community care providers, service users, and policy makers to āmoderniseā and reform community aged care. A suite of reports were commissioned that highlighted the facts that:
fragmented programme arrangements in community care create planning and operational difficulties and inefficiencies;
the service provision model is too complex, making it difficult for lay people to access the services they need or are entitled to;
funding gaps exist throughout the care pathways;
the system is inflexible and unresponsive to transitions in peopleās lives and/or illness trajectories;
the needs of a significant minority of care recipients are not sufficiently addressed, resulting in poor quality of care as well as resource wastage.
The People at Centre Stage (PACS) project aimed to address some of these issues. The aim of the project was toāwithin the limitations of current legislation and guidelinesādevelop, implement and evaluate a community aged care model that gives care recipients with more complex needs the option to have as much control of their own care as they aspire to and feel comfortable with. The project intended to offer a continuum of care ranging from customary case management to CDC.
This summary report provides a brief outline of the results of this evaluation. It is structured in two parts: following a brief overview of the PACS model, Part 1 outlines the key findings from the quantitative analysis, while Part 2 offers an overview of the qualitative findings. Part 2 deals exclusively with the experience of people participating in the intervention group
Making it work: a workforce guide for disability service providers
This guide provides strategies for disability service providers to draw upon when creating and sustaining a workforce of support workers to meet the aims of DisabilityCare Australia and implement the National Disability Insurance Scheme Act 2013. In particular, the Guide is designed to assist providers develop a workforce strategy that will enable support workers to:
i) support the independence and social and economic participation of people with disability
ii) provide reasonable and necessary supports, and
iii) enable people with disability to exercise choice and control in the pursuit of their goals and the planning and delivery of their supports.
The essence of DisabilityCare Australia is to be supportive, responsive, flexible and creative. This Guide offers a wealth of ideas and practical suggestions without being prescriptive. It includes ideas relating directly to support workers as well as to their interactions with service users and their employing service provider, and there are varying cost implications. The Guide does not attempt to provide one integrated workforce management strategy. Instead, it is intended
that providers will take away ideas to develop their own unique workforce strategy relevant to their environment and provider type. The aim of this guide is to contribute to the development of enthusiastic, competent and satisfied workers who will embrace the aims of DisabilityCare Australia and provide excellent support to people with disability.
The Guide is organised around the following themes:
Communication
Organisational culture, values and expectations
Recruitment
Flexible, responsive and creative work
Training, mentoring and support
Recognition and incentives
Career Pathways
Authors: Dr Carmel Laragy, RMIT University Associate Professor Paul Ramcharan, RMIT University Associate Professor Karen Fisher, Social Policy Research Centre, University of NSW Karen McCraw, CEO, Karden Disability Support Foundation Robbi Williams, CEO, Purple Orange (Julia Farr Foundation
Nrf2 and Nrf2-related proteins in development and developmental toxicity : insights from studies in zebrafish (Danio rerio)
Ā© The Author(s), 2015. This is the author's version of the work and is distributed under the terms of the Creative Commons Attribution License. The definitive version was published in Free Radical Biology and Medicine 88B (2015): 275-289, doi:10.1016/j.freeradbiomed.2015.06.022.Oxidative stress is an important mechanism of chemical toxicity, contributing to developmental
toxicity and teratogenesis as well as to cardiovascular and neurodegenerative diseases and
diabetic embryopathy. Developing animals are especially sensitive to effects of chemicals that
disrupt the balance of processes generating reactive species and oxidative stress, and those
anti-oxidant defenses that protect against oxidative stress. The expression and inducibility of
anti-oxidant defenses through activation of NFE2-related factor 2 (Nrf2) and related proteins is
an essential process affecting the susceptibility to oxidants, but the complex interactions of Nrf2
in determining embryonic response to oxidants and oxidative stress are only beginning to be
understood. The zebrafish (Danio rerio) is an established model in developmental biology and
now also in developmental toxicology and redox signaling. Here we review the regulation of
genes involved in protection against oxidative stress in developing vertebrates, with a focus on
Nrf2 and related capānācollar (CNC)-basic-leucine zipper (bZIP) transcription factors. Vertebrate
animals including zebrafish share Nfe2, Nrf1, Nrf2, and Nrf3 as well as a core set of genes that
respond to oxidative stress, contributing to the value of zebrafish as a model system with which
to investigate the mechanisms involved in regulation of redox signaling and the response to
oxidative stress during embryolarval development. Moreover, studies in zebrafish have revealed
nrf and keap1 gene duplications that provide an opportunity to dissect multiple functions of
vertebrate NRF genes, including multiple sensing mechanisms involved in chemical-specific
effects.This work was
supported in part by National Institutes of Health grants R01ES016366 (MEH), R01ES015912
(JJS), and F32ES017585 (ART-L).2016-06-2
Embryonic Exposures to Perfluorooctanesulfonic Acid (PFOS) Disrupt Pancreatic Organogenesis in the Zebrafish, Danio rerio
Perfluorooctanesulfonic acid (PFOS) is a ubiquitous environmental contaminant, previously 16 utilized as a non-stick application for consumer products and firefighting foam. It can cross the 17 placenta, and has been repeatedly associated with increased risk for diabetes in epidemiological 18 studies. Here, we sought to establish the hazard posed by embryonic PFOS exposures on the 19 developing pancreas in a model vertebrate embryo, and develop criteria for an adverse outcome 20 pathway (AOP) framework to study the developmental origins of metabolic dysfunction. 21 Zebrafish (Danio rerio) embryos were exposed to 16, 32, or 64 Ī¼M PFOS beginning at the mid-22 blastula transition. We assessed embryo health, size, and islet morphology in Tg(insulin-GFP) 23 embryos at 48, 96 and 168 hpf, and pancreas length in Tg(ptf1a-GFP) embryos at 96 and 168 24 hpf. QPCR was used to measure gene expression of endocrine and exocrine hormones, digestive 25 peptides, and transcription factors to determine whether these could be used as a predictive 26 measure in an AOP. Embryos exposed to PFOS showed anomalous islet morphology and 27 decreased islet size and pancreas length in a U-shaped dose-response curve, which resemble 28 congenital defects associated with increased risk for diabetes in humans. Expression of genes 29 encoding islet hormones and exocrine digestive peptides followed a similar pattern, as did total 30 larval growth. Our results demonstrate that embryonic PFOS exposures can disrupt pancreatic 31 organogenesis in ways that mimic human congenital defects known to predispose individuals to 32 diabetes; however, future study of the association between these defects and metabolic 33 dysfunction are needed to establish an improved AOP framework
Regulation of Ahr signaling by Nrf2 during development : effects of Nrf2a deficiency on PCB126 embryotoxicity in zebrafish (Danio rerio)
Author Posting. Ā© The Author(s), 2015. This is the author's version of the work. It is posted here by permission of Elsevier for personal use, not for redistribution. The definitive version was published in Aquatic Toxicology 167 (2015): 157-171, doi:10.1016/j.aquatox.2015.08.002.The embryotoxicity of co-planar PCBs is regulated by the aryl hydrocarbon receptor (Ahr), and
has been reported to involve oxidative stress. Ahr participates in crosstalk with another
transcription factor, Nfe2l2, or Nrf2. Nrf2 binds to antioxidant response elements to regulate the
adaptive response to oxidative stress. To explore aspects of the crosstalk between Nrf2 and Ahr
and its impact on development, we used zebrafish (Danio rerio) with a mutated DNA binding
domain in Nrf2a (nrf2afh318/fh318), rendering these embryos more sensitive to oxidative stress.
Embryos were exposed to 2 nM or 5 nM PCB126 at 24 hours post fertilization (prim-5 stage of
pharyngula) and examined for gene expression and morphology at 4 days post fertilization (dpf;
protruding āmouth stage). Nrf2a mutant eleutheroembryos were more sensitive to PCB126
toxicity at 4 dpf, and in the absence of treatment also displayed some subtle developmental
differences from wildtype embryos, including delayed inflation of the swim bladder and smaller
yolk sacs. We used qPCR to measure changes in expression of the nrf gene family, keap1a,
keap1b, the ahr gene family, and known target genes. cyp1a induction by PCB126 was
enhanced in the Nrf2a mutants (156-fold in wildtypes vs. 228-fold in mutants exposed to 5 nM).
Decreased expression of heme oxygenase (decycling) 1 (hmox1) in the Nrf2a mutants was
accompanied by increased nrf2b expression. Target genes of Nrf2a and AhR2,
NAD(P)H:quinone oxidoreductase 1 (nqo1) and glutathione S-transferase, alpha-like (gsta1),
showed a 2-5-fold increase in expression in the Nrf2a mutants as compared to wildtype. This
study elucidates the interaction between two important transcription factor pathways in the
developmental toxicity of co-planar PCBs.University of Massachusetts Amherst Commonwealth Honors College Research grant (to M.R.),
National Institutes of Health grants R01ES016366 (MEH), R01ES006272 (MEH), and
F32ES017585 (ART-L)
Antioxidant responses and NRF2 in synergistic developmental toxicity of PAHs in zebrafish
Author Posting. Ā© The Authors, 2009. This is the author's version of the work. It is posted here by permission of Oxford University Press for personal use, not for redistribution. The definitive version was published in Toxicological Sciences 109 (2009): 217-227, doi:10.1093/toxsci/kfp038.Early piscine life-stages are sensitive to polycyclic aromatic hydrocarbon (PAH) exposure,
which can cause pericardial effusion and craniofacial malformations. We previously reported that
certain combinations of PAHs cause synergistic developmental toxicity, as observed with co-exposure
to the aryl hydrocarbon receptor (AHR) agonist Ī²-naphthoflavone (BNF) and cytochrome P4501A
inhibitor Ī±-naphthoflavone (ANF). Herein, we hypothesized that oxidative stress is a component of
this toxicity. We examined induction of antioxidant genes in zebrafish embryos (Danio rerio)
exposed to BNF or ANF individually, a BNF+ANF combination, and a pro-oxidant positive control,
tert-butylhydroperoxide (tBOOH). We measured total glutathione, and attempted to modulate
deformities using the glutathione synthesis inhibitor buthionine sulfoxamine (BSO) and increase
glutathione pools with N-acetyl cysteine (NAC). In addition, we used a morpholino to knockdown
expression of the antioxidant response element transcription factor NRF2 to determine if this would
alter gene expression or increase deformity severity. BNF+ANF co-exposure significantly increased
expressions of superoxide dismutase1 and2, glutathione peroxidase 1, pi class glutathione-s-transferase,
and glutamate cysteine-ligase to a greater extent than tBOOH, BNF, or ANF alone. BSO
pretreatment decreased some glutathione levels, but did not worsen deformities, nor did NAC
diminish toxicity. Knockdown of NRF2 increased mortality following tBOOH challenge, prevented
significant upregulation of antioxidant genes following both tBOOH and BNF+ANF exposures, and
exacerbated BNF+ANFārelated deformities. Collectively, these findings demonstrate that antioxidant
responses are a component of PAH synergistic developmental toxicity, and that NRF2 is protective
against prooxidant and PAH challenges during development.This work was supported by the National Institute for Environmental Health Sciencessupported
Duke University Superfund Basic Research Program (P42 ES10356), National Institute for
Environmental Health Sciencesāsupported Duke University Integrated Toxicology & Environmental
Health Program (TS ES07031), United States Environmental Protection Agency STAR fellowship (to
A.T.āL.), Duke University RJRāLeon Golberg Memorial Postdoctoral Training Program in Toxicology
(to A.T.āL.), and the Postdoctoral Scholar Program at the Woods Hole Oceanographic Institution,
with funding provided by the J. Seward Johnson Fund and The Walter A. and Hope Noyes Smith
Chair (to A.TāL)
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Modulating Glutathione Thiol Status Alters Pancreatic Ī²-cell Morphogenesis in the Developing Zebrafish (Danio rerio) Embryo
Emerging evidence suggests that redox-active chemicals perturb pancreatic islet development. To better understand potential mechanisms for this, we used zebrafish (Danio rerio) embryos to investigate roles of glutathione (GSH; predominant cellular redox buffer) and the transcription factor Nrf2a (Nfe2l2a; zebrafish Nrf2 coortholog) in islet morphogenesis. We delineated critical windows of susceptibility to redox disruption of beta-cell morphogenesis, interrogating embryos at 24, 48 and 72 h post fertilization (hpf) and visualized Nrf2a expression in the pancreas using whole-mount immunohistochemistry at 96 hpf. Chemical GSH modulation at 48 hpf induced significant islet morphology changes at 96 hpf. Pro-oxidant exposures to tert-butylhydroperoxide (77.6 mu M; 10-min at 48 hpf) or tert-butylhydroquinone (1 mu M; 48-56 hpf) decreased beta-cell cluster area at 96 hpf. Conversely, exposures to antioxidant N-acetylcysteine (bolsters GSH pools; 100 mu M; 48-72 hpf) or sulforaphane (activates Nrf2a; 20 mu M; 48-72 hpf) significantly increased islet areas. Nrf2a was also stabilized in beta-cells: 10-min exposures to 77.6 mu M tert-butylhydroperoxide significantly increased Nrf2a protein compared to control islet cells that largely lack stabilized Nrf2a; 10-min exposures to higher (776 mu M) tert-butylhydroperoxide concentration stabilized Nrf2a throughout the pancreas. Using biotinylated-GSH to visualize in situ protein glutathionylation, islet cells displayed high protein glutathionylation, indicating oxidized GSH pools. The 10-min high (776 mu M) tert-butylhydroperoxide exposure (induced Nrf2a globally) decreased global protein glutathionylation at 96 hpf. Mutant fish expressing inactive Nrf2a were protected against tert-butylhydroperoxide-induced abnormal islet morphology. Our data indicate that disrupted redox homeostasis and Nrf2a stabilization during pancreatic beta-cell development impact morphogenesis, with implications for disease states at later life stages. Our work identifies a potential molecular target (Nrf2) that mediates abnormal beta-cell morphology in response to redox disruptions. Moreover, our findings imply that developmental exposure to exogenous stressors at distinct windows of susceptibility could diminish the reserve redox capacity of beta-cells, rendering them vulnerable to later-life stresses and disease
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Developmental exposures to perfluorooctanesulfonic acid (PFOS) impact embryonic nutrition, pancreatic morphology, and adiposity in the zebrafish, \u3cem\u3eDanio rerio\u3c/em\u3e
Perfluorooctanesulfonic acid (PFOS) is a persistent environmental contaminant previously found in consumer surfactants and industrial fire-fighting foams. PFOS has been widely implicated in metabolic dysfunction across the lifespan, including diabetes and obesity. However, the contributions of the embryonic environment to metabolic disease remain uncharacterized. This study seeks to identify perturbations in embryonic metabolism, pancreas development, and adiposity due to developmental and subchronic PFOS exposures and their persistence into later larval and juvenile periods. Zebrafish embryos were exposed to 16 or 32 Ī¼M PFOS developmentally (1ā5 days post fertilization; dpf) or subchronically (1ā15 dpf). Embryonic fatty acid and macronutrient concentrations and expression of peroxisome proliferator-activated receptor (PPAR) isoforms were quantified in embryos. Pancreatic islet morphometry was assessed at 15 and 30 dpf, and adiposity and fish behavior were assessed at 15 dpf. Concentrations of lauric (C12:0) and myristic (C14:0) saturated fatty acids were increased by PFOS at 4 dpf, and PPAR gene expression was reduced. Incidence of aberrant islet morphologies, principal islet areas, and adiposity were increased in 15 dpf larvae and 30 dpf juvenile fish. Together, these data suggest that the embryonic period is a susceptible window of metabolic programming in response to PFOS exposures, and that these early exposures alone can have persisting effects later in the lifecourse
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