Neurological disorders affect more than 14% of the population worldwide and together with traumatic brain and spinal cord injuries represent major health, public and economic burden of the society. Incidence of inherited and idiopathic neurodegenerative disorders and acute CNS injuries is growing globally while neuroscience society is being challenged by numerous unanswered questions. Therefore, research of the CNS disorders is essential. Since animal models of the CNS diseases and injuries represent the key step in the conversion of the basic research to the clinics, we focused our work on generation of new animal models and on their use in pre-clinical research. We generated and characterized transgenic minipig model of Huntington's disease (HD) which represents the only successful establishment of a transgenic model of HD in minipig which should be valuable for testing of long term safety of HD therapeutics. Next, we crossed the well characterized R6/2 mouse HD model with the gad mouse model which lacks the expression of UCHL1 which led to results that support the theory of "protective" role of mutant huntingtin aggregates and suggest that UCHL1 function(s) may be affected in HD disturbing certain branches of Ubiquitin Proteasome System. Traumatic spinal cord injury and Amyotrophic Lateral...

This study is about the gender dimensions of land reform in South Africa. The case study is that of a housing and resettlement project in Daggakraal, Mpumalanga Province. The aim of the study was to describe and analyse empirical realities for rural women, in relation to land, in Daggakraal. The focus was on the research questions for the study namely the nature of land reform practice; whether gender issues were central in land reform at all stages of the project; whether or not participation of women was truly genuine; and the constraints that were faced in the process of land reform delivery. The study was conducted in Daggakraal, a rural town in Mpumalanga province, South Africa. Research methods employed were both quantitative and qualitative with more emphasis on the latter. A total of 100 respondents participated in the study. This number included 10 key informants 3 of whom were trained as research assistants. The findings indicate that there was very little gender analysis carried out prior to land reform. For this reason land reform has not benefitted the women and men of Daggakraal. Land reform policies and other legislation put in place were not followed to the letter in Daggakraal and in other areas of the country where land reform was implemented; the first land reform (SLAG) has not benefitted the poor, especially women; the rural terrain is an area of contestation and competing interests between women and men. There is also a lack of institutional arrangements to implement a gendered approach to land reform. This study demonstrates the need to tackle and transform the existing power relations at the household level, if government is serious about the gender dimension of land reform in South Africa. In a small way it is hoped that this study will contribute to the limited writing on land reform and gender and also provide a gendered critique of the land reform programme in South Africa. The Gender Analysis Framework (GAF) and the feminist and gender perspectives have helped the researcher to understand and explain the gender dynamics in Daggakraal. / Development Studies / D. Litt. et Phil. (Development Studies)

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Background: Antenatal Psychosocial Assessment (APA) has recently been introduced into routine antenatal care, but the ways in which maternity service providers assess and respond to maternal stress are subject of debate. There is a lack of consensus on the instrument(s) of choice and lack of evidence regarding appropriate interventions. Further, national guidelines have not kept apace with the conceptual shift from ‘postnatal depression’ to ‘perinatal anxiety and depression’. Adopting the Medical Research Council Complex Interventions Framework, the ARMS research aimed to inform the development of interventions that support women who are experiencing, or at risk of, mild-moderate mental health disorder in pregnancy. Methods: A mixed methods approach was adopted. In the quantitative element (Study Part 1) participants (n=191) completed a questionnaire when attending for their first formal antenatal appointment, using a procedure and materials that had been previously tested in a pilot study. Details including mental health assessment and referrals were obtained from their health records, following delivery. In the qualitative element (Study Part 2) a sub-sample of women (n=22) experiencing high levels of maternal stress took part in up to three serial in-depth interviews during pregnancy and the early postnatal period.Findings: Maternal stress was found to be common. Using the Edinburgh Postnatal Depression Scale (EPDS) threshold of ≥10, approximately 1 in 4 women were classed as high depression (halving to 1 in 8 at the more conservative threshold of ≥13). Almost 1 in 3 women were classed as high anxiety, using the state scale of the State-Trait Anxiety Inventory (STAI-S, threshold ≥41), compared with 1 in 5 using the two-item GAD (threshold ≥3). Fewer than half of the women identified as high anxiety were identified by both measures. Factor analyses of the symptom measures were consistent with wider literature suggesting a three-item anxiety component of the EPDS; however, concurrent validation using regression analyses did not indicate that the EPDS could be used as an anxiety case finding instrument. Women reported that maternal stress had significant impact on their lives that may not be captured with existing clinical approaches. Women commonly found it difficult to self-assess severity of maternal stress and the assessment process could itself act as an intervention. The research provided the first validation of the depression case finding questions in UK clinical practice. The Whooley items completed in clinical practice identified only half of the possible cases identified by the EPDS, at both commonly adopted EPDS thresholds. Inclusion of the Arroll 'help' question as a criterion improved specificity of the assessment completed in clinical practice but substantially compromised sensitivity, missing 9 in 10 possible cases. Women’s mental health history and treatment history were similarly under-reported, particularly concerning anxiety. APA was introduced into routine clinical practice without attention to topics of relevance to women, context of disclosure or to provision of adequate resources for consistently responding to identified need. Women experiencing, or at risk of, mild-moderate disorder were thus usually ineligible for further support. Implications: Care pathways are needed that encompass both assessing and responding to maternal stress, where communication with health professionals, subsequent referral and management are addressed. The development, implementation and evaluation of low-cost resources embedded in such pathways are a priority and the research presented in the thesis offers a foundation on which to build.

This study is about the gender dimensions of land reform in South Africa. The case study is that of a housing and resettlement project in Daggakraal, Mpumalanga Province. The aim of the study was to describe and analyse empirical realities for rural women, in relation to land, in Daggakraal. The focus was on the research questions for the study namely the nature of land reform practice; whether gender issues were central in land reform at all stages of the project; whether or not participation of women was truly genuine; and the constraints that were faced in the process of land reform delivery. The study was conducted in Daggakraal, a rural town in Mpumalanga province, South Africa. Research methods employed were both quantitative and qualitative with more emphasis on the latter. A total of 100 respondents participated in the study. This number included 10 key informants 3 of whom were trained as research assistants. The findings indicate that there was very little gender analysis carried out prior to land reform. For this reason land reform has not benefitted the women and men of Daggakraal. Land reform policies and other legislation put in place were not followed to the letter in Daggakraal and in other areas of the country where land reform was implemented; the first land reform (SLAG) has not benefitted the poor, especially women; the rural terrain is an area of contestation and competing interests between women and men. There is also a lack of institutional arrangements to implement a gendered approach to land reform. This study demonstrates the need to tackle and transform the existing power relations at the household level, if government is serious about the gender dimension of land reform in South Africa. In a small way it is hoped that this study will contribute to the limited writing on land reform and gender and also provide a gendered critique of the land reform programme in South Africa. The Gender Analysis Framework (GAF) and the feminist and gender perspectives have helped the researcher to understand and explain the gender dynamics in Daggakraal. / Development Studies / D. Litt. et Phil. (Development Studies)

[pt] Os distúrbios de ansiedade compreendem uma ampla gama de condições psiquiátricas, incluindo transtorno de ansiedade generalizada (TAG) e fobia específica. Nas últimas décadas, o uso de modelos animais de ansiedade ofereceu importantes insights sobre a interação dessas psicopatologias. Aqui nós investigamos se os ratos Cariocas de alto e baixo congelamento (CAC e CBC, respectivamente), um modelo animal de TAG, mostram fenótipos comportamentais de alto e baixo congelamento similar no condicionamento de medo ao som. Ratos adultos das linhagens CAC (n igual 16), CBC (n igual 16) e ratos Wistar normais (controle, CTL) foram testados em um paradigma de condicionamento clássico de medo ao som durante 3 dias. Respostas de congelamento foram medidas e usadas como evidência de condicionamento de medo. No geral, os ratos CAC e CBC, bem como os animais CTL, apresentaram um condicionamento de medo ao estímulo condicionado auditivo. No entanto, os animais CBC também mostraram uma rápida extinção ao estímulo condicionado auditivo. Discutimos esses resultados de acordo com dados comportamentais e neuronais observados em linhagens de roedores de alta e baixa ansiedade. / [en] Anxiety disorders comprise a broad range of psychiatric conditions, including general anxiety (GAD) and specific phobias. For the last decades the use of animal models of anxiety has offered important insights into the understanding of the association between these psychopathologies. Here we investigate whether Carioca high and low conditioned freezing rats (CHF and CLF, respectively), a GAD animal model of anxiety, show similar high and low freezing behavioral phenotypes for cued auditory fear conditioning. Adult CHF (n equal 16), CLF (n equal 16) and normal age-matched Wistar rats (control, CTL) were tested in a classical auditory cued fear conditioning paradigm over 3 days. Freezing responses were measured and used as evidence of fear conditioning. Overall, both CHF and CLF rats as well as CTL animals displayed fear conditioning to the auditory CS. However, CLF animals showed a rapid extinction to the auditory conditioned stimulus compared to CHF and CTL rats. We discuss these findings in the context of the behavioural and neuronal differences observed in rodent lines of high and low anxiety traits.