Hepatitis C is the most common chronic blood-borne infection in the United States. Research has focused on contributing factors to the development and progression of liver disease, but few studies have considered nicotine use as a potential prognostic factor with CHC. Research has commonly found that CHC patients report with a diminished quality of life. Several factors have been proposed to account for a decrease in QOL; however, the mechanisms underlying the impairment in QOL have not yet been elicited. 76 CHC patients completed self-report measures on a variety of psychosocial variables and biochemical data for determining the patient's liver disease severity was obtained. The findings revealed strong support for the deleterious effects of smoking cigarettes on liver disease symptomatology and its progression. Smokers endorsed experiencing significantly more severe symptoms of fatigue, poor appetite, and headaches. The CHC smokers tended to present with higher scores on the Aspartate Arninotransferase to platelet ratio index (APRI). The smokers' mean score is above the cut-off value of 1.50 that indicates a .88 predictive value for the presence of hepatic fibrosis. The level of cigarette consumption could also be a factor in the progression of liver disease. Individuals smoking more than one pack per day tended to report more severe symptoms of fatigue and a poorer appetite. Heavy smokers presented with an APRI mean score above the cut-off value of 2.00 that indicates a .93 negative predictive value for the presence of cirrhosis below the cut-off value.General active coping moderated the relationship between liver disease severity and QOL. The results revealed that patients using more avoidant coping reported lower levels of QOL on the physical and mental component of the SF-36. Tobacco use moderated the relationship between liver disease severity and QOL. Interestingly, smokers reported a higher level of QOL compared to nonsmokers when experiencing more severe liver disease. CHC patients with higher levels of psychological distress reported lower QOL on both physical and mental functioning. Individuals smoking marijuana also tended to report lower levels of QOL on mental functioning. Information garnered from this study is aimed to help slow the progression of advanced liver disease in CHC patients in addition to improving their QOL.

Maternal diabetes is associated with increased risk of growth disturbances and congenital malformations. The malformations rate in the offspring of diabetic mothers is 2-3 fold higher compared to infants of nondiabetic mothers. In this thesis we have investigated the role of the protein kinase C (PKC) pathway and the apoptotic machinery in embryopathy. We investigated the involvement of PKC isoforms in the embryopathy of diabetic rat pregnancy. Embryos of diabetic rats showed altered activity and protein distribution of several PKC isoforms compared with embryos of normal rats. Using whole embryo culture we found increased activity of PKC-delta and PKC-zeta after 24h of culture and increased rate of malformations and growth retardation in embryos cultured in high glucose concentration compared to embryos cultured in low glucose concentration. Addition of α-cyano-4-cinnamic acid and N-acetylcysteine to the culture medium normalized malformations and growth retardations whereas specific PKC-inhibitors abolished malformations and partly restored the growth retardations. All treatment normalized glucose-induced increase of PKC activity. Estimated occurrence of apoptosis in embryos of diabetic rats and in embryonic cells exposed to high glucose concentration showed increased rate of pro-apoptotic markers. The increased apoptosis in the high glucose exposed embryonic cells was normalized by supplementation of N-acetylcysteine or apoptosis inhibitor. Treatment with vitamin E and folic acid to diabetic pregnant rats decreased diabetes-induced malformations and resorptions, concomitant with normalization of apoptotic protein levels. These results suggest that oxidative stress is augmented in embryos of diabetic rats and that it also plays a role in the activation of PKC and apoptosis. We used antioxidative treatment with beneficial effect although we could not completely abolish the embryonic demise; this may indicate that other mechanisms are involved in diabetic embryopathy. Further studies are needed to develop multi-nutrient dietary supplement to eliminate embryonic abnormalities induced by maternal diabetes.

In spite of the long-standing tradition of including measures of visual-motor integration in psychological evaluations, visual-motor abilities have not been included in the Cattell-Horn-Carroll (CHC) theory of cognitive abilities or its complementary cross-battery approach to assessment. The purpose of this research was to identify the shared constructs of a popular test of visual-motor integration and a test of intellectual functioning, and to investigate how a test of visual-motor integration would be classified within the CHC model. A large normative sample of 3,015 participants that ranged in age from 5 to 97 years completed the Bender Visual-Motor Gestalt Test, Second Edition (Bender-Gestalt II; Brannigan & Decker, 2003) and the Stanford-Binet Intelligence Scale, Fifth Edition (SB5; Roid, 2003). Correlational analyses indicated positive moderate correlations across all age ranges between the Bender-Gestalt II Copy measure and the SB5 Nonverbal Visual-Spatial Processing subscale and between the Bender-Gestalt II Recall measure and the SB5 Nonverbal Visual-Spatial Processing and Nonverbal Working Memory subscales. Exploratory factor analyses revealed a three-factor model for four age groupings and four-factor model for one age grouping, suggesting factors which represent crystallized ability, fluid reasoning, and visual-motor ability. The results of this study suggest that the Bender-Gestalt II measures abilities that are not included in the SB5. Therefore, the Bender-Gestalt II would complement an intelligence test such as the SB5 in order to form a CHC Visual Processing (Gv) broad ability factor. These findings also address the need for further research to validate the constructs measured by newer versions of widely-used tests of cognitive ability.

This study had three main purposes. First, the relationship between Processing Speed (Gs) and poor word recognition skills was examined. Second, various formats of processing speed tests that measure different types of processing speed (i.e. naming facility, perceptual speed, semantic speed, attention and concentration) were administered to determine what aspects of Gs were more strongly correlated with word reading performance. Pearson correlations and coefficients of determination were used to evaluate the strength of the relationships and the shared variance. Third, the study sample was evaluated to determine what percentage of the poor readers participating in the study had slow processing speed.Forty-four students in grades 1-3, ages six- to ten-years old were administered the Woodcock-Johnson III Achievement reading tests of Letter-Word Identification, Reading Fluency, and Word Attack. The subjects were additionally administered the Woodcock-Johnson III Cognitive Abilities tests of Verbal Comprehension, Visual-Auditory Learning, Sound Blending, Visual Matching, Numbers Reversed, Decision Speed, Rapid Picture Naming, Pair Cancellation, and Cross Out.The results of the study indicated processing speed, as measured by the Gs Cluster score, was strongly correlated with word reading, r = .749, r2=.56. The Gs tests of Visual Matching, (r = .663, r2 = .44) and Decision Speed (r = .811, r2 = .66) were most strongly correlated with poor word reading skill. The Basic Reading Skills Cluster and the Test of Letter-Word Identification were both moderately correlated at various strengths with different formats of Gs tests. Tests of Visual Matching, Rapid Picture Naming, Pair Cancellation and Cross Out all had a moderate, significant correlation.Lastly, 47% of the poor readers (SS<85 on any of the measures of>reading) also had low Gs scores (SS<85).The results from the study demonstrate the need for further exploration of the impact of poor Gs on the development of reading skills, as well as determination of the most effective interventions for poor readers with slow processing speed.

ANTECEDENTES: El diagnóstico precoz del carcinoma hepatocelular es la única opción para poder aplicar tratamientos radicales potencialmente curativos. Por este motivo es necesario desarrollar diferentes técnicas que permitan realizar el diagnóstico precoz.HIPÓTESIS: La vascularización predominantemente arterial del CHC determina un patrón vascular específico caracterizado por intensa captación de contraste en fase arterial seguida de lavado de contraste en fase venosa. De acuerdo a unos criterios propuestos por la AASLD y basados en opinión de expertos, es posible realizar el diagnóstico concluyente de CHC sin necesidad de confirmación histológica si se objetiva este patrón vascular mediante técnicas de imagen dinámicas (RM, TC y eco con contraste (US-C)). En el caso de nódulos entre 1 y 2 cm se recomienda demostrar este patrón de forma coincidente en dos pruebas dinámicas. OBJETIVOS: Determinar la capacidad diagnóstica de la RM de última generación y US con contrastes de segunda generación para el diagnóstico de lesiones con un tamaño < 2 cm en pacientes con cirrosis hepática, con especial énfasis en el diagnóstico diferencial con el colangiocarcinoma intrahepático. Asimismo, como segundo objetivo se evaluará el valor de la captación de contraste para determinar la respuesta tumoral tras la aplicación de tratamientos locorregionales.METODOLOGÍA: Estudio observacional prospectivo en el que se incluirán pacientes cirróticos con función hepática conservada y sin historia previa de CHC en los que se detecta un nódulo único de 5-20 mm por ecografía de screening. Se realizará de forma basal una RM dinámica, US-C, determinación de marcadores tumorales y una biopsia, que se repetirá en caso de diagnóstico negativo. En caso de ausencia de malignidad, se realizará un seguimiento mediante US-C/3m y RM/6m; ante la detección de crecimiento o cambio de vascularización se realizará nueva biopsia. En la segunda parte del estudio se evaluará de forma retrospectiva la respuesta tumoral de una cohorte de pacientes afectos de CHC tratados mediante tratamientos locorregionales (ablación percutánea o quimioembolización) teniendo en cuenta criterios convencionales (medición de diámetros; criterios RECIST) o evaluando la extensión de necrosis reconocida como áreas sin captación de contraste.RESULTADOS: El diagnóstico de CHC puede establecerse en nódulos <20 mm sin necesidad de una biopsia positiva si US-C y RM muestran de forma coincidente hipercaptación en fase arterial seguido de lavado en fase venosa. La presencia de lavado de contraste permite el diagnóstico diferencial con el colangiocarcinoma intrahepático (ICC). Los criterios RECIST evalúan erróneamente la eficacia de los tratamientos locorregionales e infraestiman los beneficios de los tratamientos locorregionales.

Made available in DSpace on 2014-06-12T15:04:07Z (GMT). No. of bitstreams: 2 arquivo4415_1.pdf: 476089 bytes, checksum: bfff2f22f85990f6fb497864f0376cec (MD5) license.txt: 1748 bytes, checksum: 8a4605be74aa9ea9d79846c1fba20a33 (MD5) Previous issue date: 2002 / Atualmente o método de maior interesse adotado para o controle de Boophilus microplus, carrapato de um só hospedeiro que acarreta prejuízos globais de milhões de dólares anuais, baseia-se na utilização de fungos entomopatogênicos, sendo Metarhizium anisopliae e Beauveria bassiana os mais utilizados. Este trabalho avaliou a compatibilidade química dos carrapaticidas Cipermetrina High Cis técnica 100 (CHC) e Amitraz sobre M. anisopliae var. acridum. No ensaio químico as concentrações utilizadas foram: 0,20&#956;g; 0,50&#956;g; 1,00&#956;g; 2,00&#956;g; 5,00&#956;g e 10,00&#956;g. Para cada tratamento foram utilizadas cinco repetições e um controle. Os parâmetros analisados foram, a germinação de conídios, o crescimento linear, a esporulação e a condição nuclear. Foi determinada, também a toxicidade. Os menores percentuais de germinação, 49,50%, 58,07% e 51,06% foram observados nos tratamentos com Amitraz nas concentrações 0,20&#956;g; 5,00&#956;g e 10,00&#956;g, respectivamente. O diâmetro da colônia foi afetado no terceiro dia de cultivo (66,67%) na concentração de 0,50&#956;g de CHC. O carrapaticida Amitraz no sexto dia de cultivo na concentração de 10,00&#956;g promoveu um menor percentual de esporulação (33,35%). M. anisopliae var. acridum não apresentou alterações citológicas quando crescido em meio com carrapaticidas. A toxicidade obtida de 46,98% no sexto dia de cultivo, segundo a metodologia utilizada determinou que o produto Amitraz na concentração de 10,00&#956;g é moderadamente tóxico para este fungo. Os resultados obtidos contribuirão para um emprego futuro do controle integrado do B. microplus utilizando-se carrapaticidas químicos e fungos entomopatogênicos

Thesis (MPH.) -- University of Limpopo, 2022 / BACKGROUND: Exclusive breastfeeding in South Africa to date has not seen progress. The data that is available show that most mothers do initiate breastfeeding immediately after delivery of the baby, but its continuation to the first six months is still a challenge. Although its benefits to the mother and baby are mostly known, it is not translated into positive outcomes as recommended by WHO i.e. to feed the baby with breast milk only, no water, no solids except for medicines that have been prescribed for the first six months. OBJECTIVES: To explore and describe perceptions of breastfeeding mothers regarding factors contributing to exclusive breastfeeding for the first six months at Mugodeni Grace Health centre. METHODS: A qualitative, exploratory and descriptive phenomenological method was used in the study, which was conducted at Mugodeni Grace Health Centre. The convenience sampling strategy was used to recruit participants and the sample size was determined by data saturation. Face-to-face in-depth semi-structured interviews were conducted with nine participants in Xitsonga, using an interview guide and were audio taped with the consent of the participants and transcribed verbatim. Data was analysed using Tesch open coding approach. RESULTS: Three themes and nine subthemes emerged from the data analysis, which includes maternal knowledge of breastfeeding, support systems for exclusive breastfeeding and social and cultural influences leading to non-exclusive breastfeeding CONCLUSION: Exclusive breastfeeding for the first six months is a societal issue, which need the involvement of society as a whole to perceive it differently for it to be successful, a family-centred approach in which the father has a role to be part of it to assist and support the mother. Continuous support from the family and health facilities by knowledgeable health practitioners is desired. The study revealed that some nurses were practising wrong breastfeeding practices in front of community members. This made mothers to lose confidence in them as people who can be consulted in case of breastfeeding challenges. Cultural beliefs and myths should be handled in a culturally sensitive manner. Working mothers should be taught to negotiate and make a plan for breastfeeding with the employer during pregnancy and to know of their rights at work viii regarding breastfeeding. Mothers should be taught to breastfeed for eight to twelve times per day. They should also be taught about the causes of crying in babies and shown practical skills on how to latch and how to calm the crying baby.

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L'objectif principal de la thèse est de montrer les apports de l'évaluation contextualisée à l'évaluation de l'intelligence chez les adolescents.e.s, à travers cinq articles. Le premier fait l'état des lieux de l'évaluation contextualisée de l'intelligence. Le second développe les évaluations auto et hétéro-rapportées de l'intelligence. Les trois suivants rendent compte des apports d'outils d'évaluation contextualisée notamment en termes de preuve de validité. Seul le facteur de raisonnement fluide du questionnaire d'auto-évaluation prédit les résultats scolaires. Les liens avec le comportement adaptatif existent, notamment avec le facteur de vitesse de traitement du questionnaire (r=.69). Les questionnaires d'hétéro-évaluations entretiennent des liens modérés à forts avec les résultats scolaires. Enfin, pour le test de performance composé de sept subtests, seule une épreuve (intelligence cristallisée) corrèle positivement et significativement avec la moyenne scolaire générale (r=.42); et trois avec le comportement adaptatif (corrélations néanmoins faibles). Les résultats et implications de ces résultats sont discutés dans la conclusion et une ouverture sur la réalité virtuelle est proposée. / The main objective of the thesis is to show the contributions of the contextualized evaluation to the evaluation of the intelligence of teenagers, through five articles. The first takes stock of the contextualized evaluation of intelligence. The second develops self and hetero-reported assessments of intelligence. The following three report the contributions of contextualized evaluation tests, particularly in terms of proof of validity. Only the fluid reasoning factor of the self-report questionnaire predicts school results. The links with adaptive behavior exist, notably with the processing speed factor of the questionnaire (r = .69). Hetero-assessment questionnaires have moderate to strong links to school performance. Finally, for the performance test composed of seven subtests, only one subtest (crystallized intelligence) correlates positively and significantly with school results (r = .42); and three with adaptive behavior (yet weak correlations). The results and implications of these results are discussed in the conclusion and an opening on virtual reality is proposed.

Le Glypican-3 (GPC3) est surexprimé dans 72% des carcinomes hépatocellulaire (CHC). C’est un co-récepteur membranaire du récepteur WNT, qui appartient à la famille des protéoglycanes à sulfates d'héparane. L'objectif général de ma thèse vise à étudier les mécanismes de régulation post-transcriptionnelle de l’expression du GPC3 dans le CHC. Pour cela, j’ai développé un test fonctionnel qui m’a permis de cribler une bibliothèque de 876 microARNs humains. Ceci a conduit à l’identification de 5 microARNs régulateurs de l’expression de l’ARNm codant pour le GPC3 via sa région 3’ non traduite (NT). Mon travail de thèse porte plus particulièrement sur le miR-1271 et le miR-1291 car ils sont dérégulés dans le CHC et sont respectivement inhibiteur et inducteur de l’expression du GPC3. Dans un premier projet, j’ai démontré que le miR-1271 cible directement la région 3’NT du GPC3 et diminue la stabilité de son ARNm. Ce microARN est sous-exprimé dans le CHC et son expression corrèle négativement avec celle de l'ARNm du GPC3 dans les CHC associés à une infection par le virus de l’hépatite B. Dans un deuxième projet, j’ai démontré que le miR-1291 régule positivement l’expression du GPC3 en inhibant un facteur intermédiaire. Une analyse in silico a permis d’identifier IRE1α comme candidat. IRE1α est une protéine transmembranaire du réticulum endoplasmique (RE) qui participe à « l’Unfolded Protein Response », une réponse adaptative activée lors de l’accumulation de protéines mal conformées dans le RE. J’ai démontré qu’IRE1α clive l’ARNm codant pour le GPC3 grâce à son activité endoribonucléase. D’autre part, le miR-1291 cible directement l’ARNm codant pour IRE1α dans sa région 5’NT ce qui inhibe son expression et induit une surexpression du GPC3. Le miR-1291 est surexprimé dans le CHC et son expression corrèle positivement avec celle de l’ARNm du GPC3. En conclusion, mon travail de thèse m’a permis de mettre en évidence et de caractériser deux nouveaux microARNs (miR-1271 et miR-1291) contrôlant l’expression du GPC3 par des mécanismes directs ou indirects. La pertinence physiopathologique de ces régulations dans le CHC est en accord avec les niveaux d’expression respectifs de ces microARNs, qui pourraient contribuer à la surexpression du GPC3 dans ces tumeurs. / Glypican-3 (GPC3) is overexpressed in 72% of hepatocellular carcinoma (HCC). It is a co-receptor for WNT receptor and belongs to the heparan sulfate proteoglycans family. The general objective of my PhD thesis was to study the mechanisms by which GPC3 is post-transcriptionnally regulated in HCC. To this end, I developed a functional test that allowed me to screen a library of 876 human microRNAs. This led me to identify 5 microRNAs that regulate the expression of GPC3 mRNA through its 3’Untranslated Region (UTR). The work presented in this thesis particulary focuses on miR-1271 and miR-1291 as both microRNAs present a deregulated expression in HCC and are respectively inhibitor and activator of GPC3 mRNA expression. In a first project, I demonstrated that miR-1271 directly binds to GPC3 mRNA 3’UTR and affects its stability. This microRNA is underexpressed in HCC and its expression negatively correlates with that of GPC3 mRNA in a subgroup of HCC corresponding to those associated with hepatitis B virus infection. In a second project, I demonstrated that miR-1291 postively regulates the expression of GPC3 mRNA by targeting an intermediate factor. An in silico analysis led to the identification of the Inositol Requiring Enzyme 1 alpha (IRE1α) as a potential candidate. IRE1α is an endoplasmic reticulum (ER) resident type I transmembrane protein and contributes to the signaling of the Unfolded Protein Response (UPR). The UPR is an adaptive response activated upon accumulation of improperly folded proteins in the ER. I showed that IRE1α cleaves GPC3 mRNA through its endoribonuclease activity. Moreover I demonstrated that miR-1291 directly targets IRE1α mRNA through its 5’UTR, thereby decreasing its expression and contributing to GPC3 mRNA overexpression. MiR-1291 is overexpressed in HCC and its expression positively correlates with that of GPC3 mRNA. In summary, the work carried out during my PhD allowed the identification and the characterization of two new microRNAs (miR-1271 and miR-1291) that control the expression of GPC3 mRNA through direct or indirect mechanisms. The pathophysiological relevance of these regulatory mechanisms is in agreement with the respective expression levels of these microRNAs in HCC, which could therefore contribute to the overexpression of GPC3 in those tumors.