EFFECTS OF A UNILATERAL INTRASTRIATAL 6-HYDROXYDOPAMINE MODEL OF EARLY PARKINSON'S DISEASE ON MIDBRAIN DOPAMINE NEURONS IN RATS: A STEREOLOGICAL STUDY

Parkinson's disease (PD) is a progressive neurodegenerative disorder characterized by loss of dopaminergic function, leading to the classical clinical signs of tremor, bradykinesia and loss of postural balance. These motor symptoms occur late in the disease, and since the treatments for late-stage PD are largely ineffective, a better understanding of the early stages of PD is needed in order to prevent and treat the disease. The early disease process is still poorly understood, however, and current difficulties in diagnosing prodromal or very early-stage PD make clinical studies challenging. Therefore, animal models of early PD are an invaluable resource in discovering the neuropathological, behavioral and biochemical features of the early stages of neurodegeneration found in PD. Early PD is associated with non-motor clinical signs such as changes to sleep patterns, olfactory functions, cognition and mood; while gross motor function is largely compensated for until the later stages of dopaminergic neurodegeneration. The nature of these early clinical signs presents a challenge when assessing PD models, however, as subtle sensory and affective changes can be difficult to quantify in animals. The goal of this work, therefore, was to investigate morphological changes to the dopamine neurons most implicated in the development of PD. Morphological endpoints, which can be robustly quantified using unbiased stereological analysis, provide information about the changes occurring to the neuronal structure during the neurodegenerative process, and offer promise as an objective method to assess the conditions which render dopamine neurons vulnerable in PD, as well as to evaluate new neuroprotectants and therapeutic interventions in early PD animal models. A deficiency in n-3 polyunsaturated fatty acids (n-3 PUFAs), which have been shown to be neuroprotective, has been proposed as a potential factor in the vulnerability of dopamine neurons to PD. In order to determine the effects of n-3 PUFA deficiency on substantia nigra pars compacta (SNpc) dopamine neurons, morphological, behavioral and biochemical endpoints were investigated in the unilateral intrastriatal 6-hydroxydopamine (6-OHDA) model of early to moderate Parkinson's disease in Aim 1. In addition, a method was developed to use a novel staining method combining tyrosine hydroxylase (TH) staining with silver nucleolar (AgNOR) staining and stereological analysis techniques to quantify the morphological changes induced by 6-OHDA lesion in dopaminergic neurons in Aim 2. In Aim 3, this method was then expanded to investigate morphological changes to the dopaminergic nucleoli stained with AgNOR, which may lend valuable insights into the role of the nucleolus in early PD. In Aim 4 the cumulative techniques developed in the previous aims were employed to determine the differential morphological changes to the dopamine neurons and their nucleoli in the A8, A9 and A10 subpopulations of midbrain dopamine neurons, which correspond to the retrorubral field (RRF), SNpc, and ventral tegmental area (VTA), respectively. Although the functions of these different neuronal groups is complex and still not fully understood, these regions are differentially affected in PD; and in particular the A8 and A10 groups have been associated with the early non-motor effects of PD. Therefore the characterization of the differential morphological changes to these neurons and their nucleoli could provide valuable insights into the structural changes to the neurons induced by the neurodegenerative process, and may be useful in assessing early PD interventions in the future. Overall, this dissertation project contributed to a better understanding of the morphological changes to midbrain dopaminergic neurons as determined by stereological analysis in an early model of PD

The Electrochemical Detection of Acetaminophen and the Enantioselective Recognition of Tyrosine Enantiomers using a modified carbon-based electrode

The beginning of this thesis sees the development and characterisation of a β-cyclodextrin (β- CD) based electrochemical sensor for the electrochemical detection of acetaminophen (paracetamol) and the influence of the accompanying activation of the glassy carbon-based substrate. To incorporate the β-cyclodextrin onto the glassy carbon electrode, electropolymerisation from an aqueous solution of the β-CD monomer was carried out, attempting to form a polymeric β-CD film. The modified electrode was characterised using cyclic voltammetry, electrochemical impedance spectroscopy and scanning electron microscopy (SEM) coupled with electron dispersive X-Ray analysis (EDX). Optimum conditions for the formation of the sensor were obtained by selecting an ideal potential window, applied potential and also selecting the suitable number of cycles required for modification. A highly efficient sensor was formed when cycling occurred between -2.0 to 2.2 V (vs. SCE) cycled for 15 cycles. The role of the activation of the GCE was also investigated and found to greatly enhance the electrochemical performance of the sensor. It was found that cycling the GCE in a 1.0 M phosphate buffer solution (PBS) at pH 5.5, from -2.0 to 1.1 V (vs. SCE) for 5 cycles, produced a nearly identical voltammogram when compared to a voltammogram where both activation and the electropolymerizing processes on the GCE surface occurred. The modified sensor achieved good sensitivity towards acetaminophen at a neutral pH with a peak current density of 3.8 mA cm-2, with the oxidation of acetaminophen being influenced by pH in which peak currents became lower in more alkaline solutions. In addition, a wide variety of interfering compounds was examined to establish their effect, if any, on the detection of acetaminophen using the β-CD modified GCE. The study concluded that the oxidation of acetaminophen was not influenced by the addition of any of the interference compounds and the sensor was capable of achieving high selectivity. The final part of this thesis explores the development and characterisation of a chitosan and graphene-modified GCE (CS/GO- GCE) for the electrochemical enantioselective recognition of tyrosine enantiomers. Graphene was incorporated into the sensor by electrodeposition from an aqueous graphene nanoplatelet (GO) dispersed in a 5 mM β-CD solution to prevent agglomeration of the graphene sheets. The biopolymer chitosan was incorporated by electrodeposition from 1% chitosan hydrogel solution (CS) dissolved in 0.2 M acetic acid. The presence of GO and CS were confirmed using cyclic voltammetry, attenuated total reflectance Fourier transform infrared spectroscopy (ATR-FTIR) and potentiostatic measurements. Optimum conditions for development of the CS/GO-modified GCE involved investigating solvent and polymer concentration of the chitosan hydrogel solution, analysis of the supporting electrolyte used and examining the time sensitive diffusion of molecules into the hydrogel. Electrodeposition of graphene was accomplished by cycling from -1.5 to 0.8 V (vs. SCE) for 5 cycles at 50 mV s-1 using cyclic voltammetry, whilst deposition of the adherent hydrogel polymer was achieved by potentiostatic measurements held for 5 min at -1.5 V (vs. SCE). FTIR spectra showed a combination of CS and GO characteristic peaks suggesting the GO become encapsulated in the CS polymer on the surface of the GCE. The CS/GO-modified GCE achieved good enantioselective recognition between the tyrosine (Tyr) enantiomers, with preferential binding towards L-Tyr displayed. The presence of the chiral hydrogel polymer enabled enantioseparation capability of sensor however it reduced the electrochemical sensitivity of the sensor

Exploring how social workers experience and cope with public perception of their profession

The public's perception of the social work profession is a rarely considered perspective and yet a topic that is a concern to front line professionals. This paper explores how social workers experience and attempt to cope with public perception of their profession. It highlights the impact of these concerns on social workers' personal experiences and professional practice. Using semi-structured interviews with sixteen UK social workers, from local authorities and private organisations, we explore the experiences of this group. Thematic analysis of the data identified four concerns: the experience of public perception, drivers of public perception, coping with public perception, and mechanisms to raise the professions profile. Examining public perception through the eyes of social workers provides valuable insights into the lived experiences of these professionals, and offers practical implications at both the micro and macro levels. It reveals two key ways in which the profession can begin to address the prevailing negative perception considered to be emanating from the public: through developing a more co-operative relationship with external sources of public perception (e.g. government and the media) and by engaging in more pro-active self-promotion of the service

The development of a European elearning cultural competence education project and the creation of it’s underpinning literature based theoretical and organising framework

The EU have set standards in relation to cultural competence, and findings from previously funded EU commission projects have illuminated an extensively developed body of knowledge in this area in relation to healthcare. Evidence from contemporary literature shows that education interventions have a positive impact on the cultural competence of health care professionals. Nonetheless, short accessible resources that can be used flexibly to support teaching and learning around cultural competence are not available across many European countries. The aim of the TransCoCon (2017-2020) project has been to develop innovative accessible multi-media learning resources to enable undergraduate nursing students and registered nurses in five countries to develop their cultural self-efficacy and cultural competence for nursing. The purpose of this paper is to describe and discuss this European ERASMUS + funded strategic partnership project (TransCoCon 2017-2020) and the creation of its underpinning theoretical and organising framework. The rationale for this guiding framework will be discussed within the context of supporting literature.info:eu-repo/semantics/publishedVersio

Choices for equity and sustainability: securing solidarity and the common good.

The Review provides both an analysis of the present and a basis for future economic and social policy. It outlines a vision for the future and provides viable pathways to deliver policies that can build a fair and just society. It is a comprehensive resource that should be of interest to policy makers and those who will be directly affected by policy decisions. Using a number of subject headings that will be familiar to past readers, the Socio Economic Review will assist in enabling evidence-based proposals be considered by those who will design our future policy and will ensure social justice is a part of the agenda to be set. 1. Introduction and summary of main proposals p.7 2. A guiding vision and a policy framework p.16 3. Income distribution p.37 4. Taxation p.75 5. Work, unemployment and job-creation p.106 6. Housing and accommodation p.121 7. Healthcare p.150 8. Education and educational disadvantage p.177 9. Other public services p.196 10. People and participation p.209 11. Sustainability p.225 12. Rural development p.250 13. The global south p.263 14. Values p.2

Residential Moving and Preventable Hospitalizations

OBJECTIVES: To investigate the association between moving home in the first year of life and subsequent emergency admissions for potentially preventable hospitalizations. METHODS: We undertook a cohort analysis of linked anonymized data on 237 842 children in the Welsh Electronic Cohort for Children. We included children born in Wales between April 1, 1999 and December 31, 2008. The exposure was the number of residential moves from birth up to 1 year. The main outcome was emergency admissions for potentially preventable hospitalizations (PPH) between the age of 1 and 5 years. RESULTS: After adjustment for confounders, we identified that moving home frequently in the first year of life was associated with an increased risk of emergency PPH between the ages of 1 and 5 when compared with not moving. We found significant differences associated with ≥2 moves for the following: ear, nose, and throat infections (incidence risk ratio [IRR], 1.44; 95% confidence interval [CI], 1.29–1.61); convulsions/epilepsy (IRR, 1.58; 95% CI, 1.23–2.04); injuries (IRR, 1.33; 95% CI, 1.18–1.51); dehydration/gastroenteritis (IRR, 1.51; 95% CI, 1.21–1.88); asthma (IRR, 1.61; 95% CI, 1.19–2.16); influenza/pneumonia (IRR, 1.15; 95% CI, 1.00–1.32); and dental conditions (IRR, 1.30; 95% CI, 1.03–1.64) for ≥1 moves. CONCLUSIONS: Children who move home in the first year of life are at substantially increased risk of emergency admissions for PPH in early childhood. Additional research that focuses on enhancing health and social support services for highly mobile families, educating parents about safety risks, and improving housing quality is warranted