Objective: Currently, there does not exist a cohesive and predictive set of criteria that can be used to identify patients that are at risk of being non-adherent to antibiotic regimens. In this study, we sought to answer the question of whether patients’ knowledge of the scientific background of antibiotic resistance is related to their likelihood to adhere to antibiotic regimens. Additionally, we explored other facets of the profiles of adherent and non-adherent subjects. Methods: All responses were collected via questionnaire. Subjects were split into two groups (adherent and non-adherent) based upon four patient-behavior questions. These two groups of subjects were compared in a variety of ways to test for significant differences in categories such as science knowledge, age, and self-reported understanding of the problem of antibiotic resistance. Results: It was determined that the adherent group of subjects had significantly higher science scores (mean=5.46, n=384) than the non-adherent subjects (mean=4.99, n=460); t(842)= -2.73, p=0.0064. Subjects majoring in STEM were more likely to be adherent than biology or non-STEM majors. There were no differences in adherence or science scores across age groups. About 26% of subjects had not previously heard of the problem of antibiotic resistance. Discussion: Increasing patient education on the topic of antibiotic resistance could increase patient adherence, which could in turn lead to a reduction in the rate at which bacteria develop resistance. Initiatives to educate patients and health care professionals have the potential to increase understanding and improve rates of adherence.

O tema desta Tese é a interpretação dos sonhos no tratado hipocrático Da dieta, como uma forma de conhecimento do corpo. Trata-se de uma forma de mapeamento das perturbações do corpo que não são evidentes a uma mera observação diagnóstica e que serve como um tipo específico de prognose para a manutenção da saúde: a prodiagnose. O conhecimento e reconhecimento dos sonhos enquanto material da prodiagnose depende da compreensão do processo de conformação do corpo e da alma, que ocorre por meio da apomímesis toû hólou. Essa apomímesis supõe uma relação analógica de correspondência e reciprocidade entre uma esfera macrocósmica relativa aos elementos de uma parte da phýsis que é imutável, e uma microcósmica, relativa ao corpo, que, por sua vez possui elementos da phýsis passíveis de modificação por meio da dieta. A Tese procura mapear nos escritos hipocráticos coevos ao Da dieta elementos que deem conta de delinear uma conceituação do sono, do sonho, da alma e do corpo. / The theme of this Thesis is the interpretation of dreams in the Hippocratic treatise On Regimen, considered as a form of body knowledge. This body knowledge is a form of mapping bodily disorders that are not visible to a mere medical diagnosis, and also configures itself as a specific type of prognosis in regard of health maintenance: the prodiagnosis. The knowledge and recognition of dreams as prodiagnosis material depends on the understanding of body and soul formation processes, which occur by the concept of apomímesis toû hólou. This apomímesis could be considered as an analog relationship of correspondence and reciprocity between a macrocosmic sphere, regarding a part of phýsis which is immutable, and a microcosmic sphere of the body, which, on the other hand, has some elements of phýsis that can be modified through the diet. The thesis seeks to link some coeval Hippocratic writings to that of On regimen that give account to draw up the concepts of sleep, dream, soul and body.

The dose regimen of a drug gives important information about the dose sizes, dose frequency and the duration of treatment. Optimisation of dose regimens is critical to ensure therapeutic success of the drug and to minimise its possible adverse effects. The central theme of this thesis is the Efficient Dosing (ED) algorithm - a computation algorithm developed by us for optimisation of dose regimens. In this thesis, we have attempted to develop a quantitative framework for measuring the efficiency of a dose regimen for specified criteria and computing the most efficient dose regimen using the ED algorithm. The criteria considered by us seek to prevent over- and under-exposure to the drug. For example, one of the criteria is to maintain the drug's concentration around a desired target level. Another criterion is to maintain the concentration within a therapeutic range or window. The ED algorithm and its various extensions are programmed in MATLAB R . Some distinguishing features of our methods are: mathematical explicitness in the optimisation process for a general objective function, creation of a theoretical base to draw comparisons among competing dose regimens, adaptability to any drug for which the PK model is known, and other computational features. We develop the algorithm further to compute the optimal ratio of two partner drugs in a fixed dose combination unit and the efficient dose regimens. In clinical trials, the parameters of the PK model followed by the drug are often unknown. We develop a methodology to apply our algorithm in an adaptive setting which enables estimation of the parameters while optimising the dose regimens for the typical subject in each cohort. A potential application of the ED algorithm for individualisation of dose regimens is discussed. We also discuss an application for computation of efficient dose regimens for obliteration of a pre-specified viral load.

Submitted by lariza Maza (lariza.maza@hotmail.com) on 2018-04-16T14:40:41Z No. of bitstreams: 1 Dissertação Final Mestrado Lariza Maza pdf.pdf: 2708028 bytes, checksum: d776645b08f3ecce08017c07afc27ae3 (MD5) / Approved for entry into archive by ROSANGELA APARECIDA LOBO null (rosangelalobo@btu.unesp.br) on 2018-04-17T13:47:03Z (GMT) No. of bitstreams: 1 maza_l_me_bot.pdf: 2708028 bytes, checksum: d776645b08f3ecce08017c07afc27ae3 (MD5) / Made available in DSpace on 2018-04-17T13:47:03Z (GMT). No. of bitstreams: 1 maza_l_me_bot.pdf: 2708028 bytes, checksum: d776645b08f3ecce08017c07afc27ae3 (MD5) Previous issue date: 2018-02-26 / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) / Introdução. A Paracoccidioidomicose (PCM) é micose sistêmica causada por fungos termo dimórficos do gênero Paracocidioides. A associação sulfametoxazol trimetoprim, também denominada Cotrimoxazol (CMX), é uma das principais opções terapêuticas. No atual tratamento da PCM, o CMX é utilizado na dose de 2400 mg de sulfametoxazol, o que corresponde a seis comprimidos, divididos em duas tomadas diárias, fato que tem levado a menor adesão do paciente à terapia antifúngica. Estudos experimentais têm observado que a dose única diária pode ser suficiente para tratar a PCM. Objetivo. Este estudo teve como objetivo avaliar a eficácia do tratamento da PCM Murina com CMX administrado em uma e duas doses diárias. Material e métodos. Utilizou-se camundongos machos, isogênicos da linhagem Balb/c e o isolado Pb 326, de uma paciente atendida no Hospital das Clínicas da Faculdade de Medicina de Botucatu em 2012 com a forma aguda e subaguda. Este estudo apresentou três experimentos. No experimento I, 100 animais foram sorteados em 4 grupos: controle saudável (G1), controle infectado (G2) e os grupos infectados que receberam CMX uma vez (G3) e duas vezes ao dia (G4). Após 28 dias da infecção, iniciou-se o tratamento, com avaliação da recuperação fúngica em pulmão e baço, exame histopatológico dos pulmões e pesquisa de anticorpos séricos específicos anti P. brasiliensis, pela imunodifusão dupla em gel de ágar (IDD) nas semanas 8, 12, 16 e 20 após a infecção. No experimento II, os mesmos animais foram avaliados quanto a sobrevida cumulativa em 140 dias. No experimento III, 40 camundongos infectados e tratados por 10 dias com dose única diária e com duas tomadas ao dia foram avaliados quanto ao perfil sérico de sulfametoxazol em quatro medidas durante o dia e foi determinado a concentração inibitória mínima deste isolado utilizado no estudo. Os testes de Kruskal-Wallis e Mann-Whitney foram utilizados para comparação de medianas, regressão linear para analisar os parâmetros nos sucessivos momentos de sacrifício e Kaplan-Meier para a avaliação de sobrevida. Foi considerado significativo os valores de p menores que 0,05. Resultados. Os dois grupos tratados com CMX (G3 e G4) apresentaram resposta ao tratamento, caracterizada pela melhora do aspecto e do comportamento do animal, queda dos níveis de anticorpos séricos pela IDD (G3: p=0,005; G4: p=0,01), redução da carga fúngica pulmonar, analisada pelo exame histopatológico, na 16ª e 20ª se- manas comparadas com a 8ª e 12ª (p<0,01) e menor porcentagem de fibras colágenas por área peribronquiolar na 20ª semana comparados com a 12ª semana (p<0,05). Não houve diferença na recuperação fúngica em pulmões e baço, na carga fúngica contada pelo exame histopatológico de pulmão e nem na porcentagem de fibra colágena por área peribronquiolar entre G3 e G4 nas semanas 8, 12, 16 e 20. No entanto, os níveis de IDD tenderam a ser mais baixos no G4 do que no G3 na 8ª semana de tratamento (1:4 vs 1:16, p = 0,08). O grupo G4 apresentou menor recuperação fúngica dos pulmões na 8ª e 12ª semanas e no baço nas semanas 16 e 20 quando comparado ao controle infectado. Não houve diferença na mortalidade cumulativa entre G3 e G4 (0,0% vs 4,0%). Conclusões. Esses achados demonstram eficácia em ambos os esquemas de tratamento da PCM Murina com CMX. Embora não se observou diferenças diretas entre os dois esquemas de tratamento com CMX, o grupo que recebeu duas doses ao dia apresentou maior resposta quando comparado com o controle infectado, fato que não ocorreu com o grupo tratado com dose única diária. Isto sugere que diferenças podem existir entre os dois esquemas e que estudo futuros são necessários para se conhecer melhor a eficácia destes esquemas terapêuticos. / Introduction. Paracoccidioidomycosis (PCM) is systemic mycosis caused by termodimorphic fungi of the genus Paracoccidioides. The association of sulfamethoxazole-trimethoprim, also called cotrimoxazole (CMX), is one of the main therapeutic options. In the current treatment of PCM, CMX is used in the dose of 2,400 mg of sulfamethoxazole, which corresponds to six tablets divided into two daily doses, a fact that has led to the patient's lesser adherence to anti-fungal therapy. Experimental studies have observed that the single daily dose may be suffi-cient to treat PCM. Goal. This study aimed to evaluate the efficacy of murine PCM treatment with CMX administered in one and two daily doses. Material and methods. Male, isogenic mice of the Balb / c gem line and Pb 326 isolate were collected from a patient attended at the Hospital das Clínicas of the Faculty of Medicine of Botucatu in 2012 with the acute and sub-acute form. This study presented three experiments. In the experiment I, 100 animals were randomly assigned to 4 groups: healthy control (G1), infected control (G2) and infected groups receiving CMX once (G3) and twice daily (G4). After 28 days of infection, treatment with the evaluation of fungal recovery in the lung and spleen, histopathological examination of the lungs and the detection of specific serum antibodies to P. brasiliensis by double agar gel immunodiffusion (IDD) in the weeks 8, 12, 16 and 20 after infection. In Experiment II, the same animals were evaluated for cumulative survival at 140 days. In Experiment III, 40 mice infected and treated for 10 days with single daily dose and with two intakes per day were evaluated for the serum sulfamethoxazole profile in four measures during the day and the minimum inbred concentration of this isolate used in the study. The Kruskal-Wallis and Mann-Whitney tests were used for comparison of medians, linear regression to analyze the parame-ters in the successive moments of sacrifice and Kaplan-Meier for the evaluation of survival. P value of less than 0.05 was considered significant. Results. The two groups treated with CMX (G3 and G4) presented a response to treatment, characterized by an improvement in the ap-pearance and behavior of the animal, a decrease in serum antibody levels by IDD (G3: p = 0.005, G4: p = 0.01), reduction of lung fungal load, analyzed by histopathological examination, at the 16th and 20th week periods compared with the 8th and 12th days (p <0.01), and a low-er percentage of collagen fibers by peribronchiolar area at week 20 compared to at week 12 (p <0.05). There was no difference in fungal recovery in the lungs and spleen, in the fungal load counted by histopathological examination of the lung, nor in the percentage of collagen fiber per peri-brachial area between G3 and G4 at weeks 8, 12, 16 and 20. However, levels of IDD tended to be lower in G4 than in G3 at week 8 of treatment (1: 4 vs. 1:16, p = 0.08). The G4 group presented lower fungal recovery of the lungs at the 8th and 12th weeks and in the spleen at weeks 16 and 20 when compared to the infected control. There was no difference in cumulative mortality between G3 and G4 (0.0% vs 4.0%). Con-clusions. These findings demonstrate efficacy in both murine PCM treatment regimens with CMX. Although there were no direct differences between the two treatment regimens with CMX, the group receiving two doses per day presented a higher response when compared to the infected control, a fact that did not occur with the single daily dose group. This suggests that differences may exist between the two schemes and that future studies are needed to better understand the efficacy of these therapeutic regimens

Orientador: Ricardo de Souza Cavalcante / Resumo: Introdução. A Paracoccidioidomicose (PCM) é micose sistêmica causada por fungos termo dimórficos do gênero Paracocidioides. A associação sulfametoxazol trimetoprim, também denominada Cotrimoxazol (CMX), é uma das principais opções terapêuticas. No atual tratamento da PCM, o CMX é utilizado na dose de 2400 mg de sulfametoxazol, o que corresponde a seis comprimidos, divididos em duas tomadas diárias, fato que tem levado a menor adesão do paciente à terapia antifúngica. Estudos experimentais têm observado que a dose única diária pode ser suficiente para tratar a PCM. Objetivo. Este estudo teve como objetivo avaliar a eficácia do tratamento da PCM Murina com CMX administrado em uma e duas doses diárias. Material e métodos. Utilizou-se camundongos machos, isogênicos da linhagem Balb/c e o isolado Pb 326, de uma paciente atendida no Hospital das Clínicas da Faculdade de Medicina de Botucatu em 2012 com a forma aguda e subaguda. Este estudo apresentou três experimentos. No experimento I, 100 animais foram sorteados em 4 grupos: controle saudável (G1), controle infectado (G2) e os grupos infectados que receberam CMX uma vez (G3) e duas vezes ao dia (G4). Após 28 dias da infecção, iniciou-se o tratamento, com avaliação da recuperação fúngica em pulmão e baço, exame histopatológico dos pulmões e pesquisa de anticorpos séricos específicos anti P. brasiliensis, pela imunodifusão dupla em gel de ágar (IDD) nas semanas 8, 12, 16 e 20 após a infecção. No experimento II, os mesmos animais fo... (Resumo completo, clicar acesso eletrônico abaixo) / Abstract: Introduction. Paracoccidioidomycosis (PCM) is systemic mycosis caused by termodimorphic fungi of the genus Paracoccidioides. The association of sulfamethoxazole-trimethoprim, also called cotrimoxazole (CMX), is one of the main therapeutic options. In the current treatment of PCM, CMX is used in the dose of 2,400 mg of sulfamethoxazole, which corresponds to six tablets divided into two daily doses, a fact that has led to the patient's lesser adherence to anti-fungal therapy. Experimental studies have observed that the single daily dose may be suffi-cient to treat PCM. Goal. This study aimed to evaluate the efficacy of murine PCM treatment with CMX administered in one and two daily doses. Material and methods. Male, isogenic mice of the Balb / c gem line and Pb 326 isolate were collected from a patient attended at the Hospital das Clínicas of the Faculty of Medicine of Botucatu in 2012 with the acute and sub-acute form. This study presented three experiments. In the experiment I, 100 animals were randomly assigned to 4 groups: healthy control (G1), infected control (G2) and infected groups receiving CMX once (G3) and twice daily (G4). After 28 days of infection, treatment with the evaluation of fungal recovery in the lung and spleen, histopathological examination of the lungs and the detection of specific serum antibodies to P. brasiliensis by double agar gel immunodiffusion (IDD) in the weeks 8, 12, 16 and 20 after infection. In Experiment II, the same animals were evaluated f... (Complete abstract click electronic access below) / Mestre

O tema desta Tese é a interpretação dos sonhos no tratado hipocrático Da dieta, como uma forma de conhecimento do corpo. Trata-se de uma forma de mapeamento das perturbações do corpo que não são evidentes a uma mera observação diagnóstica e que serve como um tipo específico de prognose para a manutenção da saúde: a prodiagnose. O conhecimento e reconhecimento dos sonhos enquanto material da prodiagnose depende da compreensão do processo de conformação do corpo e da alma, que ocorre por meio da apomímesis toû hólou. Essa apomímesis supõe uma relação analógica de correspondência e reciprocidade entre uma esfera macrocósmica relativa aos elementos de uma parte da phýsis que é imutável, e uma microcósmica, relativa ao corpo, que, por sua vez possui elementos da phýsis passíveis de modificação por meio da dieta. A Tese procura mapear nos escritos hipocráticos coevos ao Da dieta elementos que deem conta de delinear uma conceituação do sono, do sonho, da alma e do corpo. / The theme of this Thesis is the interpretation of dreams in the Hippocratic treatise On Regimen, considered as a form of body knowledge. This body knowledge is a form of mapping bodily disorders that are not visible to a mere medical diagnosis, and also configures itself as a specific type of prognosis in regard of health maintenance: the prodiagnosis. The knowledge and recognition of dreams as prodiagnosis material depends on the understanding of body and soul formation processes, which occur by the concept of apomímesis toû hólou. This apomímesis could be considered as an analog relationship of correspondence and reciprocity between a macrocosmic sphere, regarding a part of phýsis which is immutable, and a microcosmic sphere of the body, which, on the other hand, has some elements of phýsis that can be modified through the diet. The thesis seeks to link some coeval Hippocratic writings to that of On regimen that give account to draw up the concepts of sleep, dream, soul and body.

Magister Public Health - MPH / Background: First line regimens give patients the best chance of long-term treatment success. It is imperative that patients stay on their original first line regimens to ensure program viability. As the ART programme matures in Namibia the proportion of patients who have had their first line regimens modified continues to increase. It is estimated that 3.1% of adults in Namibia are on second line regimens. Second line or other modified regimens are generally reserved for clinical, immunological or virological failure and toxicity related complications. These modified regimens often involve a higher pill burden, more toxicities and are often more expensive. A more detailed understanding of the factors associated with first line regimen modification could allow healthcare providers in Namibia to target these factors for intervention to reduce regimen modification and improve treatment outcomes. Methodology: This quantitative descriptive retrospective cohort study sought to describe factors associated with first line HAART regimen modification in treatment naïve adult patients who started HAART at Gobabis State Hospital between 1st January 2007 and 31st December 2010. Utilizing data from an existing electronic patient management system, quantitative methods were used to assess the prevalence, reasons and factors associated with first line HAART regimen modification. Results: The prevalence of HAART regimen modification was 14.1%. Treatment toxicity was the major reason (35%) for HAART regimen modification and this was largely due to D4T containing regimens. This was followed by treatment modification due to concurrent TB disease (27.3%), new drug availability (19%), pregnancy (6.6%) and virological failure (2%). A death rate of 9% was recorded by the end of the study period in each of the two groups, of those who had their first line HAART regimen modified and those who remained on original regimens respectively. There were statistically significant associations between regimen modification and type of regimen, care entry point, duration from HIV diagnosis to entry into HIV care, sex and functional status. Regimen modifications resulted in more AZT and TDF based regimes while 88.7% of patients had D4T taken off their HAART regimens. Conclusions: HAART regimen modification at Gobabis State hospital is lower than in other settings was largely due to treatment toxicity. The death rate is high and warrants further exploration. Regimen modifications resulted in more AZT and TDF based regimes and more patients had D4T taken off their HAART regimens. Recommendations: Patients still on D4T need close monitoring for side effects associated with this drug and should be promptly changed if this is the case. This study raises the important programmatic issue of the need for good data collection practices. HIV positive patients who are pregnant and those with concurrent TB disease need close monitoring to ensure that HAART regimens are modified appropriately.

[EN] The general aim of this thesis was to reproductively characterize females from a rabbit line selected for growth rate and to evaluate the effect of different nutritional strategies (ad libitum and restricted), in order to improve the reproductive performance. In chapter 1, the influence of maternal and embryonic genotype on prenatal survival and fetal growth was evaluated and contrasted with a maternal line. Prenatal survival, fetal weight and fetal placenta weight were affected by both embryonic and maternal genotype. Nevertheless, no differences were detected either at transcriptomic level in fetal placenta or in progesterone and IGF-I plasma levels in these females. It may be concluded that in rabbit females from paternal lines both embryonic and maternal genotypes are key factors in the reproductive performance of these females. The aim of chapter 2 was to explore the causes of ovulation failures in these rabbit females. Results showed that non-ovulated females presented lower LH plasma concentration as well as higher body weight and leptin and BOHB plasma levels than ovulated females. Thus, ovulation failures in females from line R could be attributed to decreased LH plasma concentrations in these females which may be related with their higher body weight and leptin levels. The following three chapters were focused on improvement of the reproductive performance of these females through a different nutritional strategy: a feed-to-appetite diet of these females after the rearing period and prior to insemination. The initial hypothesis was that the females are submitted to a restricted nutritional regimen which is not enough to cope with their needs during reproduction, causing long-term disturbances of energy balance which leads to the subsequent reproductive problems. Chapter 3 aimed to determine if a feed-to-appetite nutritional strategy would affect the hypothalamus-hypophysis axis and the quality of the produced oocytes, by transcriptomic analysis. While no differences were found in the microarray analysis of the hypothalamus-hypophysis, small differences were detected in the transcript expression analysis in oocytes of a group of genes selected. MSY2 was found to be downregulated in oocytes from restricted females. As a key regulator of maternal RNA transcription and translation, changes in this essential gene could explain some of the reproductive problems of these females. Whether the differences found at oocyte level were inherent at embryonic level and so involved in the drop of fertility was studied in Chapter 4. Although no significant differences were revealed in ovulation, embryo recovery, and implantation rate, higher fetal and gestational losses were found in restricted females, as well as lower fetal growth. Thus, we concluded that the nutritional strategy employed may have an impact on the oocyte (Chapter 3), but we also demonstrated that these changes were inherited by the embryo, and result in disturbances in gestational losses and fetal growth. The final chapter of this thesis was conducted to determine whether these effects on reproductive and metabolic elements were also evident in females following the common semi-intensive farm production system. Although the results obtained showed small variances in NEFAs and BOHB plasma levels, and also in body weight, no differences were detected in global reproductive performance in terms of fertility, prolificacy and productivity. The results obtained established that although differences are found at oocyte level and inherited by embryo and fetus, no improvements are reached with the proposed nutritional strategy in terms of reproductive performance when females selected for growth rate lead a normal semi-intensive production system. / [ES] El objetivo general fue la caracterización reproductiva de las hembras de una línea de conejo seleccionada por velocidad de crecimiento y el efecto de distintas estrategias nutricionales (ad libitum y restringidas), con la finalidad de mejorar el rendimiento reproductivo. En el capítulo 1 se evaluó la influencia de los genotipos materno y embrionario en la supervivencia prenatal y crecimiento fetal, entre las hembras de esta línea y una línea maternal. La supervivencia prenatal, peso fetal y el peso de la placenta resultaron afectados por los genotipos tanto embrionario como materno, pero no se detectaron diferencias sobre la placenta fetal a nivel del transcriptoma ni en los niveles de progesterona e IGF-I. Por lo tanto, se puede concluir que en éstas tanto el genotipo embrionario como el materno son factores clave en su rendimiento reproductivo. El objetivo del capítulo 2 fue explorar las causas de los fallos reproductivos en estas hembras. Los resultados mostraron que las hembras que no ovularon presentaban menores niveles de LH, un mayor peso corporal y mayor concentración en sangre de leptinas y BOHB, que aquellas que había ovulado. Por ello, los fallos en ovulación detectados en estas hembras podrían estar relacionados con una reducción en los niveles de LH, consecuencia del mayor peso de estas hembras y de los incrementados niveles de leptinas. Los siguientes capítulos se enfocaron a la mejora del rendimiento reproductivo de estas hembras empleando una estrategia nutricional distinta: la ingesta ad libitum de alimento tras el periodo de crianza hasta el momento del comienzo de su vida reproductiva. La hipótesis de partida fue que estas hembras son sometidas a un régimen nutricional restringido que no es suficiente para satisfacer sus necesidades energéticas durante la reproducción, lo que causa alteraciones en su balance energético que se manifestarían en los problemas reproductivos observados. El capítulo 3 trató de determinar a través de un análisis trasncriptómico si la estrategia nutricional planteada afectaría el eje hipotalámico-hipofisario y la calidad de los ovocitos. Aunque no se encontraron diferencias en el análisis de un micrarray realizado sobre el hipotálamo-hipófisis, sí que se detectaron en la expresión génica de los ovocitos. El transcrito MSY2 mostró una menor expresión en los ovocitos de las hembras restringidas. Este gen es un regulador clave en la maduración ovocitaria, por lo tanto, cambios en la expresión de este gen podrían explicar algunos de los problemas reproductivos de estas hembras. En el capítulo 4 se estudió si las diferencias a nivel ovocitario eran heredadas por el embrión pudiendo causar la baja fertilidad de estas hembras. Aunque no se encontraron diferencias en las tasas de ovulación, recuperación embrionaria e implantación, sí que aparecieron diferencias en las pérdidas fetales y gestacionales, así como un menor crecimiento fetal en los embriones procedentes de hembras con restricción alimentaria. Por ello, concluimos que la estrategia nutricional empleada tiene unas consecuencias en el ovocito (Capítulo 3), y demostramos que estos cambios parecen continuar en el embrión, resultando en alteraciones en pérdidas gestacionales y crecimiento fetal. El capítulo final fue desarrollado para evidenciar si los efectos reproductivos y metabólicos observados en los capítulos previos se manifestaban en las hembras que se encuentran en un sistema de producción tradicional en granja. A pesar de que los resultados mostraron variaciones en los niveles circulantes de NEFAs y BOHB y de peso corporal, no se encontraron diferencias en el rendimiento reproductivo global a nivel de fertilidad, prolificidad y productividad. Los resultados obtenidos parecen indicar que a pesar de las diferencias encontradas a nivel ovocitario, embrionario y fetal, con el régimen nutricional propuesto no se logra alcanzar mejoras en la eficiencia reproductivo de las h / [CAT] L'objectiu general va ser la caracterització reproductiva de les femelles d'una línia de conill seleccionada per velocitat de creixement i l'efecte de diferents estratègies nutricionals (ad libitum i restringides), amb la finalitat de millorar el rendiment reproductiu. En el capítol 1 s'avaluà la influència dels genotipus matern i embrionari en la supervivència prenatal i el creixement fetal, entre les femelles d'aquesta línia i les de una altra línia maternal. La supervivència prenatal, el pes fetal i el pes de la placenta resultaren afectats pels genotipus embrionari i matern, però no es detectaren diferències en la placenta fetal a nivell de trascriptoma ni en els nivells de progesterona i IGF-I. Per tant, en les femelles de conill seleccionades per velocitat de creixement, tant el genotipus embrionari com el matern són factors clau en el seu rendiment reproductiu. L'objectiu del capítol 2 va ser explorar les causes de les fallades reproductives en aquestes femelles. Les femelles que no ovularen presentaren menor nivells de LH, major pes corporal i major concentració de leptines i BOHB que aquelles que sí que hi havia ovulat. Per això, les fallades d'ovulació detectades en aquestes femelles podrien estar relacionades amb la reducció en els nivells de LH, com a conseqüència del major pes d'aquestes femelles i dels incrementats nivells de leptines. Els capítols següents s'enfocaren a la millora del rendiment reproductiu d'aquestes femelles mitjançant una estratègia nutricional distinta: la ingesta ad libitum d'aliment després del període de criança i fins al moment de l'inici de la vida reproductiva. La hipòtesi de partida fiu que aquestes femelles són sotmeses a un règim nutricional restringit que no és suficient per a satisfer les seves necessitats energètiques durant la reproducció, la qual cosa provoca alteracions en el balanç energètic que podrien manifestar-se en els problemes reproductius observats. El capítol 3 tractà de determinar mitjançant un anàlisi trasncritòmic si la estratègia nutricional plantejada podria afectar l'eix hipotalàmic-hipofisiari i la qualitat dels ovòcits. Metre que no es detectaren diferències en el anàlisi del microarray realitzat en el hipotàlem-hipòfisi, sí que es detectaren en l'expressió gènica del ovòcits. El transcrit MSY2 mostrà una menor expressió en els ovòcits de les femelles restringides. Aquest gen es un regulador clau en la maduració ovocitària, per aquest motiu, canvis en la seva expressió gen podrien explicar alguns dels problemes reproductius de les femelles. En el capítol 4 s'estudià si aquestes diferències a nivell ovocitari eren heretades per l'embrió i podrien causar la baixa fertilitat d'aquestes femelles. Encara que no se trobaren diferències en les taxes d'ovulació, recuperació embrionària i implantació, sí que es trobaren diferències en les pèrdues fetals i gestacionals, així com un menor creixement fetal en els embrions de les femelles provinents d'un règim alimentari restringit. Per això concloíem que l'estratègia nutricional emprada té conseqüències en el ovòcit (Capítol 3), i demostrarem que aquest canvis pareixen continuar en l'embrió, resultant en alteracions en pèrdues gestacionals i creixement fetal. El capítol final fou desenvolupat per evidenciar si els efectes reproductius i metabòlics observats en els capítols previs eren manifestats en les femelles que es troben en un sistema productiu tradicional de granja. Tot i que el resultats mostraren variacions en els nivells circulants de NEFAs i BOHB i pes corporal, no es trobaren diferències en el rendiment reproductiu global, en termes de fertilitat, prolificitat i productivitat. Els resultats obtinguts pareixen indicar que tot i que les diferències trobades a nivell ovocitari i embrionari amb un efecte significatiu en el desenvolupament i creixement fetal, amb el règim nutricional proposat no s'aconsegueix assolir millores en / Naturil Alfonso, C. (2016). EFFECT OF FEED RESTRICTION IN A RABBIT LINE SELECTED FOR GROWTH RATE ON REPRODUCTIVE PERFORMANCE: OVULATION INDUCTION, OOCYTE QUALITY, EMBRYONARY AND FETAL LOSSES [Tesis doctoral no publicada]. Universitat Politècnica de València. https://doi.org/10.4995/Thesis/10251/73065 / TESIS

Type I Diabetes Mellitus (T1DM) is a major health problem and a burden for affected young individuals, as well as for society. It is among the most prevalent paediatric disorders, affecting an estimated 1.7 per 100 children and adolescents. Given the complexity of diabetes treatment regimens, it is not surprising that children, adolescents, and their families often have difficulty adhering to these regimens. Studies have found that the overall adherence rate among children and adolescents with diabetes is about 50%. It has also been found that adherence to T1DM often tends to decrease when the adolescent begins to assume most of the responsibility for managing the disease and the parents‟ role starts to decline. However, literature indicates that adolescent patients‟ adherence is poor and an important strategy to improving their metabolic control is to increase self-care. The most common age of onset for T1DM is between 10-14 years. The adolescent population is highly neglected in current research on diabetes, because the focus tends to favour children and not adolescents. It is widely recognised that glycaemic control in adolescents is complex, challenging and dependent on interconnected relationships between numerous inputs at individual, family, community and health service levels. Optimal care of adolescents with diabetes has not been subjected to rigorous scientific studies, and research results related to optimal glycaemic control are conflicting. Development and continuous evaluation of best practices pertaining to diabetes mellitus remains one of the major objectives of diabetes care, possibly allowing a delay in and/or prevention of later complications. Research indicates that adolescence is the one age group where there has been no discernible improvement in health over the last 20 years. A great number of research studies on the subject of diabetes are done globally, but less literature, especially in the South African context, can be found that focuses on and explain the experiences of adolescents with T1DM with regard to their treatment adherence. This qualitative study explored the experiences of adolescents with T1DM. A purposive sample (n=7) of young adolescents between the ages of 13 and 15 willingly participated in the research study to explore and describe their experiences with managing their treatment regimen. In-depth interviews were conducted to collect rich descriptive data, followed by participants‟ verbal reflections once a week for the duration of a month. After the in-depth interviews and weekly reflections, the researcher held a focus group interview with all the participants. Transcribed data were analysed by means of thematic analysis from which themes and subthemes were derived. The participants expressed both positive and negative emotions associated with their diabetes; they experienced a lack of understanding by significant others because of a lack of knowledge, interest or support regarding their diabetes; they mentioned that they continually need age-appropriate support and parental involvement, even though they manage diabetes through their own processes; and lastly, participants struggled with a fear of friends‟ and peers‟ perceptions. From the findings it is clear that in order to cope, the adolescents need not only medical treatment and education about diabetes (T1DM), but emotional support, supervision and repeated reinforcement to achieve effective self-management. The basic suggestion is that diabetes care for children and young people should include routine assessment of the psychological and social pressures on the adolescent and the family so that strategies can be put in place to give support and education as needed and as appropriate. The researcher also recommends that school personnel must be educated about diabetes so that they can understand the changing medical and psychosocial needs of the adolescent and can help him/her to participate fully in all the available work, sport, and leisure activities. Models of legislation and training programmes for school staff specifically addressing the needs of children with diabetes in school have been developed in a number of countries such as Greece, Germany, Italy, Poland, Spain, Sweden, the UK and the USA. These programmes should be considered as an example to other countries. These best practices can serve as a foundation for national improvement. / MA (Psychology), North-West University, Potchefstroom Campus, 2015

Type I Diabetes Mellitus (T1DM) is a major health problem and a burden for affected young individuals, as well as for society. It is among the most prevalent paediatric disorders, affecting an estimated 1.7 per 100 children and adolescents. Given the complexity of diabetes treatment regimens, it is not surprising that children, adolescents, and their families often have difficulty adhering to these regimens. Studies have found that the overall adherence rate among children and adolescents with diabetes is about 50%. It has also been found that adherence to T1DM often tends to decrease when the adolescent begins to assume most of the responsibility for managing the disease and the parents‟ role starts to decline. However, literature indicates that adolescent patients‟ adherence is poor and an important strategy to improving their metabolic control is to increase self-care. The most common age of onset for T1DM is between 10-14 years. The adolescent population is highly neglected in current research on diabetes, because the focus tends to favour children and not adolescents. It is widely recognised that glycaemic control in adolescents is complex, challenging and dependent on interconnected relationships between numerous inputs at individual, family, community and health service levels. Optimal care of adolescents with diabetes has not been subjected to rigorous scientific studies, and research results related to optimal glycaemic control are conflicting. Development and continuous evaluation of best practices pertaining to diabetes mellitus remains one of the major objectives of diabetes care, possibly allowing a delay in and/or prevention of later complications. Research indicates that adolescence is the one age group where there has been no discernible improvement in health over the last 20 years. A great number of research studies on the subject of diabetes are done globally, but less literature, especially in the South African context, can be found that focuses on and explain the experiences of adolescents with T1DM with regard to their treatment adherence. This qualitative study explored the experiences of adolescents with T1DM. A purposive sample (n=7) of young adolescents between the ages of 13 and 15 willingly participated in the research study to explore and describe their experiences with managing their treatment regimen. In-depth interviews were conducted to collect rich descriptive data, followed by participants‟ verbal reflections once a week for the duration of a month. After the in-depth interviews and weekly reflections, the researcher held a focus group interview with all the participants. Transcribed data were analysed by means of thematic analysis from which themes and subthemes were derived. The participants expressed both positive and negative emotions associated with their diabetes; they experienced a lack of understanding by significant others because of a lack of knowledge, interest or support regarding their diabetes; they mentioned that they continually need age-appropriate support and parental involvement, even though they manage diabetes through their own processes; and lastly, participants struggled with a fear of friends‟ and peers‟ perceptions. From the findings it is clear that in order to cope, the adolescents need not only medical treatment and education about diabetes (T1DM), but emotional support, supervision and repeated reinforcement to achieve effective self-management. The basic suggestion is that diabetes care for children and young people should include routine assessment of the psychological and social pressures on the adolescent and the family so that strategies can be put in place to give support and education as needed and as appropriate. The researcher also recommends that school personnel must be educated about diabetes so that they can understand the changing medical and psychosocial needs of the adolescent and can help him/her to participate fully in all the available work, sport, and leisure activities. Models of legislation and training programmes for school staff specifically addressing the needs of children with diabetes in school have been developed in a number of countries such as Greece, Germany, Italy, Poland, Spain, Sweden, the UK and the USA. These programmes should be considered as an example to other countries. These best practices can serve as a foundation for national improvement. / MA (Psychology), North-West University, Potchefstroom Campus, 2015