Metabolomic Profiling of In Vivo Plasma Responses to DioxinAssociated Dietary Contaminant Exposure in Rats: Implications for Identification of Sources of Animal and Human Exposure

Dioxin contamination of the food chain typically occurs when cocktails of combustion residues or polychlorinated biphenyl (PCB) containing oils become incorporated into animal feed. These highly toxic compounds are bioaccumulative with small amounts posing a major health risk. The ability to identify animal exposure to these compounds prior to their entry into the food chain may be an invaluable tool to safeguard public health. Dioxin-like compounds act by a common mode of action and this suggests that markers or patterns of response may facilitate identification of exposed animals. However, secondary co-contaminating compounds present in typical dioxin sources may affect responses to compounds. This study has investigated for the first time the potential of a metabolomics platform to distinguish between animals exposed to different sources of dioxin contamination through their diet. Sprague-Dawley rats were given feed containing dioxin-like toxins from hospital incinerator soot, a common PCB oil standard and pure 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) (normalized at 0.1 µg/kg TEQ) and acquired plasma was subsequently biochemically profiled using ultra high performance liquid chromatography (UPLC) quadropole time-of-flight-mass spectrometry (QTof-MS). An OPLS-DA model was generated from acquired metabolite fingerprints and validated which allowed classification of plasma from individual animals into the four dietary exposure study groups with a level of accuracy of 97-100%. A set of 24 ions of importance to the prediction model, and which had levels significantly altered between feeding groups, were positively identified as deriving from eight identifiable metabolites including lysophosphatidylcholine (16:0) and tyrosine. This study demonstrates the enormous potential of metabolomic-based profiling to provide a powerful and reliable tool for the detection of dioxin exposure in food-producing animals.

Child Welfare: Connecting Research, Policy and Practice,

Chapter explores the literature as it relates to kinship and foster care outcomes. The chapter analyses the similarities and differences between the two placements and provides a framework for practice, policy and future research.

Promoting Evidence-informed Practice in Child Welfare in Ontario: Progress, Challenges and Future Directions.

Paper explores the findings from a province-wide program evaluation of Practice and Research Together (PART: www. partcanada.org); The paper is a unique evaluation of a knowledge exchange program and provides interesting analysis of how front-line practitioners, supervisors and senior leaders engage, utilize and contribute to evidence-informed practice.

Designing for Success: The Development of a Child Welfare Research Utilization Initiative

Paper explores the evolution of a knowledge exchange program based on the world-renowned Research in Practice initiative at Dartington Hall, UK

Moving Beyond the Administrative: Supervisors' Perspectives on Clinical Supervision in Child Welfare

This study contributes to the emerging knowledge base of child welfare supervision. An exploratory study examined the beliefs, practices, and experiences of 51 child welfare supervisors in Ontario, Canada. Eight focus groups were held with supervisors from a range of settings cross the province. The study identified a number of interwoven factors at the organizational, supervisory, and practice level that affect the nature of supervision offered. Implications are drawn for child welfare practice, models of supervision which integrate administrative, clinical and educational features, organizational culture, and training new supervisors.

Walking the Tightrope: Using Power and Authority in Child Welfare Supervision

Recognizing the importance of understanding the way in which supervisors in child welfare perceive their administrative responsibilities and use of power and authority, an exploratory study was conducted. Supervisors in child welfare agencies in urban and rural settings participated in focus groups and discussed the impact of macro and micro factors on their performance. Policy changes, including using new approaches to child welfare, and organizational culture had a major affect on the way they offered supervision. At the micro level, their use of power was related to elements in their relationships with frontline workers and their own professional development. Implications for child welfare practice and for new and experienced supervisors are presented.

Impact of Stressors on Child Welfare Supervisors

The death of children, intense media scrutiny, and million
dollar lawsuits are all potential stressors faced by child welfare professionals.
Despite this, very little research or literature has explored the specific
realities of stressors for the individual front-line child welfare supervisor.
Therefore, as a contribution to the field of child welfare practice, this paper
expands our understanding of this unique supervisory population
through a detailed examination of the literature. This review links theory
to practice through a series of case examples involving situations of child
welfare supervisors who have been affected by workplace stressors. The
paper provides both individual and organizational solutions to either prevent
or intervene in situations involving child welfare supervisors who may
be at risk of burnout and/or compassion fatigue.

Gender implications of UK welfare reform and government equality duties: evidence from qualitative studies

The UK coalition government is bound by equality duties to have regard to the impact of its policies on various groups, including women. This article investigates how far this legislative commitment is influencing debates about current welfare reforms, especially plans for ‘universal credit’ (a new means-tested benefit).
The authors draw on findings from recent studies of within-household distribution from a gender perspective, including in particular their own qualitative research involving separate semi-structured interviews with men and women in 30 low/moderate-income couples in Britain. A major aim of this research was to facilitate more nuanced analysis of the effects of welfare reforms in terms of gender roles and relationships within the household.
This article therefore explores how far these findings, together with key principles for assessing the gender impact of welfare reforms, can be used to assess ‘universal credit’, and to what extent they influenced the UK government’s proposals and analysis.

Activation of the Wnt pathway plays a pathogenic role in diabetic retinopathy in humans and animal models

Although Wnt signaling is known to mediate multiple biological and pathological processes, its association with diabetic retinopathy (DR) has not been established. Here we show that retinal levels and nuclear translocation of beta-catenin, a key effector in the canonical Wnt pathway, were increased in humans with DR and in three DR models. Retinal levels of low-density lipoprotein receptor-related proteins 5 and 6, coreceptors of Wnts, were also elevated in the DR models. The high glucose-induced activation of beta-catenin was attenuated by aminoguanidine, suggesting that oxidative stress is a direct cause for the Wnt pathway activation in diabetes. Indeed, Dickkopf homolog 1, a specific inhibitor of the Wnt pathway, ameliorated retinal inflammation, vascular leakage, and retinal neovascularization in the DR models. Dickkopf homolog 1 also blocked the generation of reactive oxygen species induced by high glucose, suggesting that Wnt signaling contributes to the oxidative stress in diabetes. These observations indicate that the Wnt pathway plays a pathogenic role in DR and represents a novel therapeutic target.

Polyamine system in developing rat eye and an animal model of retinopathy of prematurity

BACKGROUND: In experimental models of retinopathy of prematurity (ROP), a vasoproliferative disorder of the retina, retinal lesions are usually assessed by morphological examination. However, studies suggest that the polyamine system may be useful in monitoring proliferation processes. For this reason, polyamine concentrations in rat erythrocytes (RBC) and the regulation of polyamine system in rat eyes under the conditions relevant to ROP were investigated. METHODS: Newborn Wistar rats were reared in room air (control) or exposed first to hyperoxia (60% or 80% oxygen, 2 weeks) and then to normoxia (relative hypoxia, 1 or 2 weeks). Blood was collected from orbital vessels at 2 weeks of age and before death. Polyamine system-related enzyme activities were measured in retina and lens with radioassays. Polyamines were quantified by fluorometry after extraction, dansylation and HPLC separation. RESULTS: Oxygen (80% only) significantly decreased RBC polyamine concentrations, which then markedly increased after rats were transferred for a week to normal air, suggesting retardation of growth processes and compensatory stimulation, respectively. However, polyamine system changes in the rat eye were not so pronounced. Enzyme activities and polyamine concentrations tended to be lower in retina after hyperoxia and were only slightly higher, with the exception of ornithine decarboxylase, after a subsequent 1 week of normoxia. In litters subjected to normoxia for longer periods no changes were found. CONCLUSION: The transient and short-lived alteration in polyamine metabolism, especially in the eye, suggests that exposure of newborn rats to high oxygen supplementation followed by normoxia does not necessarily result in marked retinopathy.

Acoustic rhinometry in the dog:a novel large animal model for studies of nasal congestion

The aim of this project was to develop and pharmacologically characterize an experimental dog model of nasal congestion in which nasal patency is measured using acoustic rhinometry. Solubilized compound 48/80 (0.3-3.0%) was administered intranasally to thiopental anesthetized beagle dogs to elicit nasal congestion via localized mast cell degranulation. Compound 48/80-induced effects on parameters of nasal patency were studied in vehicle-treated animals, as well as in the same animals pretreated 2 hours earlier with oral d-pseudoephedrine or chlorpheniramine. Local mast cell degranulation caused a close-related decrease in nasal cavity volume and minimal cross-sectional area (Amin) together with a highly variable increase in nasal secretions. Maximal responses were seen at 90-120 minutes after 48/80 administration. Oral administration of the adrenergic agonist, d-pseudoephedrine (3.0 mg/kg), significantly antagonized all of the nasal effects of compound 48/80 (3.0%). In contrast, oral administration of the histamine H1 receptor antagonist chlorpheniramine (10 mg/kg) appeared to reduce the increased nasal secretions but was without effect on the compound 48/ 80-induced nasal congestion (i.e., volume and Amin). These results show the effectiveness of using acoustic rhinometry in this anesthetized dog model. The observations that compound 48/80-induced nasal congestion was prevented by d-pseudoephedrine pretreatment, but not by chlorpheniramine, suggest that this noninvasive model system may provide an effective tool with which to study the actions of decongestant drugs in preclinical investigations.