The HIV-1 pandemic affects millions of people worldwide with approximately 70% of those affected residing in sub-Saharan Africa (SSA) relying on traditional medicines for treatment. The key aim of the study was to isolate and characterise an active phyto-pharmaceutical ingredient (API) from L. trigonus for use as a vaginal microbicide. The aerial parts of L. trigonus were oven-dried at 80°C, ground and then extracted with boiling water for 30 minutes. Aqueous extracts were screened using an HIV-1 neutralization assay in TZM bl cells. Chromatographic and spectroscopic techniques were used to purify, isolate and identify the API. The API (BP36-117-26464C) was identified as a polymeric macromolecule with IC50 = 0.04 μg/ml against HIV-1 HXB 2 subtype B. This activity is comparable to the ARV drug, enfuvirtide (IC50 = 0.02 μg/ml). The API consists of galacturonic acid polymer and a mixture of seven compounds. Its mode of action may involve inhibiting virus attachment. The activity of this precipitate (BP36-117-26464C) tested against HIV-1 subtype C pseudovirions and shown to compare favorably with that of enfuvirtide (T20). The water-soluble nature of this API and its mode of action identified it as a potential microbicide. In the current form, the precipitate (API) would be difficult to develop as an oral treatment for HIV, as high-molecular weight agents often have poor bioavailability following oral administration. However, large molecules with potent anti-HIV activity are ideal for topical use and potent development as a microbicide. / Life & Consumer Sciences / M.Sc (Life Sciences)

Thesis (PhD)--Stellenbosch University, 2013. / ENGLISH ABSTRACT: This study focuses on the problem of VVF-HIV/AIDS, stigmatization, the threat to the human dignity of women and the role of the church, with specific reference to the role of Evangelical Church Winning All (ECWA). In order to show this, models of practical theology methodology were used as theoretical and methodological basis for the study. Practical theology is as a study area deals with the praxis of God, i.e. salvific and eschatological involvement and engagement with the trajectories of human lives and the suffering of human beings. Within the context of theological reflection, it involves man’s attempt to express and portray the presence and will of God in such a way that meaning in life and comfort is contextually disclosed and discovered (Louw, 2008:71). Having established the latter, the focus falls firstly on the description of the conditions addressed in the study about VVF-HIV/AIDS and its prevalence in Northern Nigeria. A detailed contextual study also shows that a variety of factors impact negatively on the status and well-being of women in the area. Traditional, cultural, economic, political and religious factors are either uniquely applicable to or aggravate the status and well-being of the subjects of the research, namely women suffering from VVF-HIV/AIDS in Northern Nigeria. It specifically involves the social and political context in which they live. It also shows that the existence and extent of these factors increase the vulnerability of women to contracting the HIV as well as VVF. The extent to which these factors, in combination with the latter conditions specifically promote the stigmatization of these women and the forms such stigmatization takes are also explored. Moving on to the issue of human dignity: a historical overview is given of the concept and it is defined for the purposes of the study. The extent to which the human dignity is affected in the study area is then investigated in light of their context, with particular reference to the women suffering from VVF-HIV/AIDS. It is concluded that the stigmatization to which the VVF-HIV/AIDS sufferers in Northern Nigeria are subjected, indeed constitutes a serious threat to their human dignity. In answering the question of whether the church (ECWA) has a responsibility towards these women and to address the issue of their stigmatization, two pastoral theological perspectives were used, that of the nature of the church and that of the concept of human dignity from a theological perspective. According to this perspective human beings have been created in the image of God. Having established that, on theological grounds, such a responsibility exists, a possible pastoral theological model for addressing the issue of the stigmatization of women suffering from VVF-HIV/AIDS was proposed. The church’s response to the challenge of VVF-HIV/AIDS is to come from its deepest theological convictions about the nature of creation, the unshakeable fidelity of God’s love, the nature of creation, the nature of the body of Christ and the reality of Christian hope. The creation narrative, which affirms that humanity is created in the image of God, links human beings to the love of God, which is modelled in the incarnation of Jesus. Moving on to the data analysis, the extent of the challenges of VVF-HIV/AIDS sufferers and the level of knowledge of the pastors of the subject of the stigmatization of young adult females sufferers of VVF-HIV/AIDS and their treatment of the issue were evident. Finally, recommendations were drawn up in order to provide basic understanding and awareness to ECWA on how to objectively address the problem of VVF-HIV/AIDS in Northern Nigeria. / AFRIKAANSE OPSOMMING: Hierdie studie fokus op die probleem van VVF-HIV/AIDS, stigmatisering, die bedreiging van die menslike waardigheid van vroue en die rol van die kerk (ECWA). Om dit aan te toon, word die model van die praktiese teologie metodologie gebruik as 'n teoretiese en metodologiese basis vir die studie. Praktiese teologie handel oor die praxis van God, d.w.s. die verlossingsboodskap en eskatologiese betrokkenheid by en verbintenis met die trajekte van die menslike lewe en die lyding van die mens. Binne die konteks van teologiese refleksie, d.w.s. die menslike poging om aan 'n beeld van die teenwoordigheid en wil van God op so 'n manier uitdrukking te gee, word die betekenis daarvan in die lewe en troos kontekstueel geopenbaar en ontdek (Louw, 2008:71). Na laasgenoemde val die fokus eers op die beskrywing van die voorwaardes in die studie oor VVF-HIV/AIDS en die voorkoms daarvan in die noorde van Nigerië. ’n Gedetailleerde kontekstuele studie toon ook dat 'n verskeidenheid negatiewe faktore ‘n impak op die status en die welsyn van vroue in die area het. Tradisionele, kulturele, ekonomiese, politieke en godsdienstige faktore waarvan 'n paar óf uniek van toepassing is óf ‘n verswarende effek het op die navorsingskonteks van vroue wat in die noorde van Nigerië aan VVF-HIV/AIDS ly en spesifiek op die sosiale, politieke konteks waarin hulle leef. Daar word ook aangetoon dat die bestaan en omvang van hierdie faktore die vatbaarheid van vroue vir die kontraktering van die MIV-virus sowel as VVF, verhoog. Daar word ook gekyk na die wyse waarop hierdie faktore in kombinasie met bogenoemde voorwaardes spesifiek die bevordering van die stigmatisering van hierdie vroue teweegbring en na die vorme wat hierdie stigmatisering aanneem. Die kwessie van menslike waardigheid word ondersoek deur 'n historiese oorsig van die konsep te gee. Dit word vir die doeleindes van die studie gedefinieer. Die mate waarin menslike waardigheid in die studiearea ‘n rol speel, met spesifieke klem op die konteks van vroue wat ly aan VVF-HIV/AIDS, word ook nagegaan. Daar word tot die gevolgtrekking gekom dat die menswaardigheid van die VVF-HIV/AIDS lyers in die noorde van Nigerië tot 'n groot mate in die lig van die stigmatisering hulle aan onderwerp word, aangetas word. Ter beantwoording van die vraag of die kerk (ECWA) 'n verantwoordelikheid teenoor hierdie vroue het om hul stigmatisering aan te spreek, word twee pastorale teologiese perspektiewe gebruik: dié van die aard van die kerk en van die konsep van menswaardigheid vanuit 'n teologiese perspektief waarvolgens die mens na die beeld van God geskep is. Nadat vasgestel is dat, op teologiese gronde, so 'n verantwoordelikheid wel bestaan, word 'n moontlike pastorale teologiese model vir die aanspreek van die kwessie van die stigmatisering van vroue wat ly aan VVF-HIV/AIDS voorgestel. Die kerk se reaksie op die uitdaging van VVF-HIV/AIDS spruit uit sy diepste teologiese oortuigings oor die onwrikbare getrouheid van God se liefde, die aard van die skepping, die aard van die liggaam van Christus en die werklikheid van die Christelike hoop. Die skeppingsverhaal, wat bevestig dat die mensdom in die beeld van God geskep is, verbind die mens aan die liefde van God, wat in die inkarnasie van Jesus gemodelleer word. Daar word dan beweeg na die data-analise, die omvang van die uitdagings van VVF-HIV/AIDS lyers en die vlak van kennis van die pastore oor die onderwerp van die stigmatisering van die jong volwasse vroulike lyers aan VVF-HIV/AIDS en hulle behandeling van die probleem. Ten slotte word aanbevelings gemaak ten einde basiese begrip/bewustheid te verskaf oor hoe die ECWA die probleem van VVF-HIV/AIDS in die noorde van Nigerië objektief kan aanspreek.

Increasing evidence implicates the presence of bacteria in intrauterine tissues as an important risk factor for spontaneous preterm labor. Epigenetic alterations of innate immunity genes may increase the mother’s sensitivity to subclinical levels of bacteria. This study examined the presence of TET2, TLR-2, and TLR-9 in intrauterine tissue, and evaluated whether epigenetic alterations of these genes, as well as IL-8, changed their expression in human decidual tissue and a macrophage cell culture. Immunohistochemicalstaining was used to detect the presence of these proteins in intrauterine tissue. Gene expression changes were evaluated in stimulated monocytes and macrophages. Fluorescence immunohistochemistry was used to track translocation of TET2 in stimulated monocytes and macrophages. Secreted IL-8 concentration was detected with ELISA. Decidual expression of TET2, TLR-2, and TLR-9 increased in the order TNL < TL < sPTL < iPTL. This study found that TET2, TLR-2, TLR-9, and IL-8 are regulated by epigenetic mechanisms. This study was the first to report activation of TET2 involves its translocation from the cytosol to the nucleus in macrophages.

Avec près de 30 millions de morts depuis le début de la pandémie, l’infection par le VIH est un véritable fléau à l’échelle mondiale, surtout en Afrique sub-saharienne. Dans ce contexte, disposer d’une formulation microbicide efficace, facile à administrer par la voie vaginale, représenterait un outil de prévention idéal pour lutter contre cette pandémie. Ainsi, la conception rationnelle de telles formulations représente un enjeu majeur de santé publique.Ce travail décrit la recherche de formulations thermogélifiantes et mucoadhésives à base de pluronics et d’hydroxypropyl méthylcellulose (HPMC). Outre la caractérisation de leurs propriétés rhéologiques et d’adhésion, ainsi que des études en culture cellulaire suggérant une très faible toxicité de contact, ces hydrogels ont montré d’une part, leur capacité à véhiculer efficacement le peptide M48U1 (équipe L. Martin, CEA) destiné à bloquer l’entrée cellulaire du VIH et d’autre part à ralentir considérablement la diffusion de nanoparticules modèles mimant les particules virale matures du VIH-1, en comparaison d’hydrogel d'hydroxy éthylcellulose (HEC) fréquemment utilisés dans divers essais cliniques infructueux et aussi au mucus cervico-vaginal de macaque. L’ensemble des résultats suggère donc la capacité de ces formulations à constituer une double barrière, physique et pharmacologique, protectrice de la muqueuse vaginale vis-à-vis du VIH. / With nearly 30 million deaths since the start of the pandemic, HIV infection is a major problem globally, especially in sub-Saharan Africa. In this context, have an effective microbicide formulation, easily administered by the vaginal route, would be a great prevention tool to fight against this pandemic. Thus, the rational design of such formulations is a major issue of public health.This paper describes research of mucoadhesive and thermogelling formulations based on pluronics and hydroxypropyl methylcellulose (HPMC). Further characterization of their rheological properties and adhesion, and cell culture studies suggesting a very low contact toxicity, these hydrogels showed on one hand, their ability to effectively convey the peptide M48U1 (L. Martin team, CEA) for blocking the entry of HIV cellular and on the other hand to considerably slow down the diffusion of nanoparticles models mimicking viral particles mature HIV-1, compared to hydroxy ethylcellulose hydrogel (HEC) commonly used in various unsuccessful clinical trials and also in cervico-vaginal mucus of macaque. The overall results therefore suggest the ability of these formulations constitute a double barrier, physical and pharmacological, protective of the vaginal mucosa from the HIV.

No Brasil, a maioria absoluta das primíparas, deseja parto normal logo que engravida, porém, em mais da metade dos casos, os nascimentos são cirúrgicos. O fenômeno da falta de correspondência entre o desejado e o efetivamente alcançado não é exclusividade das mulheres brasileiras, mas ocorre em vários países do ocidente. Por meio da Análise Crítica do Discurso (ACD) de relatos de parto normal após cesárea (relatos de VBAC, do inglês, vaginal birth after c-section) à luz da Linguística de Corpus (LC), buscamos elucidar o problema social entre a falta de correspondência entre o tipo de experiência desejada e a experiência obtida. O discurso dos relatos de VBAC nos parece ser o discurso ideal para desvelar os elementos dessa falta de correspondência, pois abordam tanto a experiência da cesárea anterior indesejada e, em regra, mal indicada, como a do parto desejado e alcançado. O recorte teórico-metodológico adotado reúne a ACD (Fairclough, 1989, 1992; Chouliaraki & Fairclough, 1999; Fairclough, 2003); a LC (Stubbs, 1993, McEnery & Wilson, 1997 e 2003, Tognini-Bonelli, 2001) e a Análise Crítica do Discurso Baseada em Corpus (Baker et al 2008; Baker, 2013; Baker & McEnery, 2005; Flowerdew, 2014). Para o estudo, foi compilado um corpus eletrônico em inglês e português. O corpus é composto por textos escritos pelas mulheres que passaram pela experiência de VBAC e não inclui textos mediados (entrevistas e relatos escritos por terceiros não foram incluídos). O Corpus BRABA (Corpus eletrônico de relatos de parto de mulheres brasileiras, estadunidenses, britânicas e australianas) se divide, respectivamente, em quatro subcorpora: Corpus BRA (93 relatos, 250 807 palavras), Corpus EUA (101 relatos, 225 736 palavras), Corpus UK (97 relatos, 92 197 palavras) e Corpus AU (92 relatos, 200 639 palavras. Os primeiros dois subcorpora Corpus BRA e Corpus EUA foram selecionados para esta pesquisa que pretende investigar como as identidades e a experiência do nascimento são representadas nos relatos de mulheres brasileiras e americanas e por meio dessa investigação chegar a elementos que elucidem o problema social. O processamento eletrônico valeu-se do programa AntConc 3.4.0w (Anthony, 2012) e das ferramentas da LC (listas de frequência, lista de palavras-chave, linhas de concordância, padrões lexicais, etc.). A análise foi direcionada pelas palavras-chave que correspondem aos sujeitos envolvidos e pelos colocados mais estatisticamente relevantes dessas palavras. No Corpus BRA, foram analisadas: eu (colocados: desisto, renasci, mamava); bebê (encaixado, morrer/morresse, sexo, batimentos, alto); marido (companheiro, apoiou, cortou); doula (amada, obstetriz, querida, presença); médico (fofa/fofinha, mudar/mudei, cesarista, ginecologista, humanizada); anestesista; enfermeira (obstétrica/obstetra, cadê, soro, chamar); parteira (liguei/ ligar, doula, casa); obstetriz (doula, toque). No Corpus EUA: I (wish, protested, lamented); baby (pound, girl, boy); midwife (certified, asst/assistant, student, assist); doula (hired, friend, called); nurse (practitioner, tells, triage); doctor (office, seen, comes); anesthesiologist; husband (poor, run, children). A análise permitiu que fosse elucidado o problema social em ambas as sociedades e fossem reveladas diferenças discursivas e culturais. A falta de correspondência entre a experiência desejada e a alcançada é representada como tendo sido causada pela sucessão de eventos distintos. Contudo, em ambos os corpora, as experiências são representadas e a autoidentidade e as identidades construídas discursivamente sob a égide dos traços da modernidade, marcadamente, em relação à reflexividade exercida ideologicamente. Porém, a reflexividade é operada, não só como um modo de sustentar, mas principalmente como forma de transformar as relações de dominação. / In Brazil the vast majority of primiparous women, on discovering that they are pregnant, hope to have normal deliveries. However, in over half of such cases surgical deliveries ensue. This mismatch between what pregnant women desire and what they actually experience is not exclusive to Brazil, but takes place in several Western countries. Through Corpus Linguistics (CL)-based Critical Discourse Analysis (CDA) of vaginal birth after c-section (VBAC) stories we seek to shed light on the social problem of a mismatch between the desired experience and the actual experience. VBAC stories seemed to us the ideal discourse for revealing elements of this mismatch, since they address both the experience of an unwanted (and usually wrongly indicated) prior C-section and that of the desired, and achieved, delivery. The theoretical-methodological approach we have adopted brings together CDA (Fairclough, 1989, 1992; Chouliaraki & Fairclough, 1999; Fairclough, 2003); CL (Stubbs, 1993, McEnery & Wilson, 1997 e 2003, Tognini-Bonelli, 2001), and Corpus-based Critical Discourse Analysis (Baker et al 2008; Baker, 2013; Baker & McEnery, 2005; Flowerdew, 2014). An electronic corpus was compiled in English and Portuguese for this study. The corpus is made up of texts written by women who have experienced VBAC and includes no mediated texts (i.e. interviews and third-party reports). The BRABA Corpus (Corpus of the birth stories of Brazilian, American, British and Australian women) encompasses four subcorpora respectively: Corpus BRA (93 stories, 250,807 words), Corpus USA (101 stories, 225,736 words), Corpus UK (97 stories, 92,197 words), and Corpus AU (92 stories, 200,639 words. The first two of these subcorporaCorpus BRA and Corpus USAwere chosen for this study, which investigates how identities and birth experiences are represented in the accounts of Brazilian and American women, and thus through this investigation uncovers elements that will shed light on the selected social problem. The computer processing used AntConc 3.4.0w (Anthony, 2012) and CL tools (frequency lists, keyword lists, concordance lines, etc.). Analysis was guided by keywords corresponding to the people mentioned in the stories and by the most statistically significant collocates of these keywords. From Corpus BRA the words were: eu (collocates: desisto, renasci, mamava); bebê (encaixado, morrer/morresse, sexo, batimentos, alto); marido (companheiro, apoiou, cortou); doula (amada, obstetriz, querida, presença); médico (fofa/fofinha, mudar/mudei, cesarista, ginecologista, humanizada); anestesista; enfermeira (obstétrica/obstetra, cadê, soro, chamar); parteira (liguei/ligar, doula, casa); obstetriz (doula, toque). From Corpus USA: I (wish, protested, lamented); baby (pound, girl, boy); midwife (certified, asst/assistant, student, assist); doula (hired, friend, called); nurse (practitioner, tells, triage); doctor (office, seen, comes); anesthesiologist; husband (poor, run, children). Analysis enabled this social problem to be laid bare in both societies, revealing discourse and cultural similarities and differences. The mismatch between the desired and the experienced outcomes is represented as having been caused by a succession of discrete events. In both corpora, experiences are represented, and self-identity and other identities are notably constructed in discourse under the aegis of features of modernity, above all, under reflexivity, which, in the discourses of VBAC stories takes place through empowerment, understood as self-actualization through newly gathered knowledge and ensuing courses of action/measures (Giddens, 2002).

Um terço dos casos de carcinoma cervical ocorre no período reprodutivo. Sendo que, cerca de 3% dos diagnósticos são realizados durante a gravidez. Evidências atuais indicam que as gestantes apresentam maior chance de terem diagnosticadas lesões iniciais. Pois a gravidez é uma excelente oportunidade para o rastreio desta neoplasia, já que faz parte da rotina pré-natal o exame ginecológico. No entanto, na prática esta oportunidade parece não estar sendo aproveitada na sua totalidade. Com este estudo objetivou-se avaliar o conhecimento das puérperas sobre a prevenção do carcinoma cervical, descrever características associadas a não realização do citopatológico nos últimos três anos e comparar a cobertura da citologia no início e no final do pré-natal. Trata-se de uma avaliação transversal realizada na cidade de Rio Grande-RS, entre maio e junho de 2007. A amostra foi calculada pelo programa Epi-Info 6.04, totalizando 224 puérperas. Durante a internação hospitalar foi aplicado às puérperas um questionário estruturado e pré-codificado. Os dados foram digitados no Epi-Info 6.04, sendo a analise bruta realizada no software SPSS e a multivariada pela Regressão de Poisson no programa Stata. Das 230 puérperas entrevistadas 96,5% referiram conhecer o exame preventivo do câncer do colo uterino. Apesar disso, a prevalência de citopatológico nos últimos 36 meses era de 32,6% no inicio da gestação, chegando a 55,2% no puerpério. Mostrando a associação positiva do pré-natal na cobertura do citopatológico (p>0,001). Mesmo assim, 74 puérperas (32,2%) permaneceram sem nunca terem coletado o citopatológico e 29 (12,6%) continuaram com a citologia desatualizada. Na análise bruta, o grupo de puérperas com idade igual ou inferior a 19 anos, não brancas, de escolaridade igual ou inferior a oito anos, com renda familiar per capita inferior a um salário mínimo, início da vida sexual aos 15 anos ou menos, com inicio do pré-natal no 2º e 3º trimestres, que realizaram cinco consultas ou menos e que fizeram o acompanhamento no SUS, apresentaram diferenças estatísticas significantes para uma menor cobertura do exame citopatológico ao final do pré-natal. Após a análise ajustada, o grupo que consultou no Hospital Universitário da Fundação Universidade Federal do Rio Grande - FURG (IC95%: 0,18 0,82) e as puérperas com idade entre 25 a 29 anos (IC95%: 0,29 0,90), mostraram-se significativamente associadas à melhora da cobertura do citopatológico nos últimos três anos. Portanto, evidenciou-se neste estudo que apesar do pré-natal ter melhorado a cobertura do exame citopatológico. O serviço local de saúde mostra-se pouco efetivo pois cobriu menos mulheres do que o preconizado, e desigual porque o acesso ao exame variou conforme algumas características das usuárias. Além disso, os critérios epidemiológicos de risco para o carcinoma cervical não foram priorizados pela assistência médica. Os resultados revelam a necessidade de aumentar a cobertura do citopatológico e melhorar a qualidade da atenção pré-natal oferecida em Rio Grande. Motivando e capacitando os profissionais de saúde quanto à importância dos procedimentos da rotina pré-natal, pois apenas as gestantes que consultaram no Hospital Universitário da FURG tiveram a cobertura do citopatológico próxima do preconizado pela Organização Mundial da saúde. / One third of the cases of cervical carcinoma occur during the reproductive period and approximately 3% of the diagnoses are made during pregnancy. Current evidence indicates that pregnant women have a better chance of having early lesions diagnosed. Thus, pregnancy represents an excellent opportunity for the screening for this neoplasia, since gynecological examination is part of routine prenatal care. However, in practice this opportunity does not seem to be fully explored. The objective of the present study was to assess the knowledge of puerperae about the prevention of cervical carcinoma, to describe the characteristics associated with the lack of cytopathological examination during the last three years, and to compare the cytology coverage at the beginning and at the end of the prenatal care period. This was a cross-sectional evaluation performed in the city of Rio Grande-RS from May to June 2007. Sample size was calculated using the Epi-Info 6.04 software and corresponded to 224 puerperae. A structured and pre-coded questionnaire was applied to the puerperae during hospitalization. The data were entered in the Epi-Info 6.04 and crude analysis was performed using the SPSS software and multivariate analysis using Poisson regression and the Stata software. Of the 230 puerperae interviewed, 96.5% reported that they knew about the preventive exam for cancer of the uterine cervix. Nevertheless, the prevalence of cytopathological examination in the last 36 months was 32.6% at the beginning of pregnancy, reaching 55.2% during the puerperium, showing a positive association of prenatal care with cytopathological examination (p>0.001). Even so, 74 puerperae (32.2%) had never been submitted to cytopathological examination and 29 (12.6%) had out of date cytology. Crude analysis revealed that the group of puerperae aged 19 years or younger, non-white, with schooling of eight years or less, with a per capita income of less than one minimum wage, with the beginning of sex life at 15 years of age or less, with the beginning of prenatal care in the 2nd and 3rd trimester, who had received five visits or less and who had been followed up at the Unified Health System (SUS) differed in a statistically significant manner regarding a lower cytopathological examination coverage at the end of prenatal care. After adjusted analysis, the group seen at the University Hospital of Fundação Universidade Federal do Rio Grande FURG (95% CI: 0.18 0.82) and the puerperae aged 25 to 29 years (95% CI: 0.29 0.90) showed a significant association with better cytopathology coverage over the last three years. Thus, the present study demonstrated that, even though prenatal care improved the coverage of cytopathological examination, the local health service proved to be poorly effective since it covered fewer women than recommended, and unequal since access to the exam varied according to some characteristics of the users. In addition, the epidemiological criteria of risk for cervical carcinoma were not a priority for the providers of medical care. These results reveal the need to expand the coverage of cytopathological examination and to improve the quality of the prenatal medical care offered in Rio Grande. There is a need to motivate and qualify the health professionals regarding the importance of routine prenatal procedures since only the pregnant women seen at the University hospital of FURG received cytopathological coverage similar to that recommended by the WHO.

Για τις Ευρωπαίες γυναίκες ο καρκίνος του σώματος της μήτρας αποτελεί το τέταρτο συχνότερο νεόπλασμα και την δέκατη σε σειρά αιτία θανάτου από καρκίνο. Ανεξάρτητα από το εάν η διακολπική υπερηχογραφία (TVS) αποτελεί δόκιμο μέσο διαλογής (screening) για την ανίχνευση ενδομητρικού καρκίνου σε ασυμπτωματικές μετεμμηνοπαυσιακές γυναίκες, εντούτοις κυριαρχεί στους διαγνωστικούς αλγόριθμους διερεύνησης κάθε μητρορραγίας προς αποκλεισμό του καρκίνου αυτού. Παράλληλα με τα πιθανά οφέλη από την ενσωμάτωση τεχνικών Υπερηχοϋστερογραφίας (SIS) και Doppler στην ενδομητρική απεικόνιση, η δισδιά- στατη “gray scale” διακολπική υπερηχογραφία οφείλει μεγάλο μέρος της προόδου της στην ώθηση από τις εξελίξεις της τεχνολογίας. Μετά την εισαγωγή των διακολπικών ηχοβολέων πολλαπλών συχνοτήτων (multifrequency) και της “αρμονικής” (harmonic) απεικόνισης, τα σύγχρονα υπερηχογραφικά μηχανήματα διαθέτουν επιλογές λογισμι- κού για ενίσχυση της ανάλυσης της αντίθεσης δομών, λεπτών ρυθμίσεων για εξέταση διαφορετικών τύπων ιστών, πολλαπλού εύρους εστίασης, μετάδοσης της δέσμης σε πλάγια διεύθυνση ως προς το ακουστικό παράθυρο, κ.α. Τα παραπάνω, καθώς και φίλτρα μείωσης του θορύβου βελτιστοποιούν την απεικόνιση του ενδομητρίου διευκολύνοντας την αποτίμησή του, ακόμη και στα χέρια άπειρων εξεταστών. Το πάχος της διπλής ενδομητρικής στιβάδας αποτελεί ιστορικά τον πλέον αδιαμφισβήτητο ποσοτικό δείκτη ενδομητρικού καρκίνου, ειδικά στην παρουσία μετεμμηνοπαυσιακής μητρορραγίας. Η συνδυασμένη μελέτη της ενδομητρικής μορφο- λογίας και πάχους παρέχει περισσότερες πληροφορίες, ειδικά στην αποτίμηση της “γκρίζας ζώνης” των 4-10 χιλιοστών ενδομητρικού πάχους, αν και τα ευρήματα των “μορφολογικών” αυτών μελετών δεν υπήρξαν πάντα σταθερά. Με δεδομένη τη σημασία της μορφολογίας στην αποτίμηση του ενδομητρικού ιστού, και αποσκοπώντας στην υπέρβαση του υποκειμενικού χαρακτήρα της ποιοτικής εκτίμησης της υπερηχογραφικής εικόνας, θα ήταν χρήσιμη η εφαρμογή αυτοματοποιημένων τεχνικών που αξιολογούν αντικειμενικά μορφολογικά χαρακτη- ριστικά, όπως η υποβοηθούμενη από υπολογιστή ανάλυση υφής, (“computerized texture analysis”). Στις ψηφιακές εικόνες, η υφή αντικατοπτρίζει τονικές (ένταση των εικονο- στοιχείων) και δομικές (χωρική κατανομή της έντασης των εικονοστοιχείων) ιδιότητες. Η “ανάλυση υφής” αναφέρεται σε αλγόριθμους που ποσοτικοποιούν περιεχόμενο και στοιχεία υφής που πιθανόν, ή όχι, να γίνονται αντιληπτά με το γυμνό μάτι. Δεδομένου ότι στην ιατρική απεικόνιση οι εικόνες περιλαμβάνουν πολλαπλές ιδιότητες των βιολογικών δομών, η ανάλυση υφής των εικόνων αυτών παρέχει ποσοτικές πληροφο- ρίες σχετικές με τα χαρακτηριστικά, τη μορφολογία και τις ιδιότητες των δομών αυτών. Σχήματα ταξινόμησης στηριζόμενα στην υφή έχουν χρησιμοποιηθεί με επιτυχία σε ποικιλία υπερηχογραφικών εφαρμογών. Η βασισμένη σε υπολογιστή αποτίμηση εικόνων του ενδομητρίου έχει βρει κυρίως εφαρμογή στη Υποβοηθούμενη Αναπαραγωγή, αλλά δεν έχει χρησιμοποιηθεί για τη διάγνωση ενδομητρικών κακοηθειών στην δισδιάστατη υπερηχογραφία. Σκοπός της διδακτορικής αυτής διατριβής είναι η αξιολόγηση του εφικτού της υποβοηθούμενης από υπολογιστή ανάλυσης υφής του ενδομητρικού ιστού όπως απεικονίζεται σε δισδιάστατες “gray scale” υπερηχογραφικές εικόνες. Περαιτέρω, διερευνήθηκε το αποτέλεσμα μιας τεχνικής επεξεργασίας βασισμένης σε μετασχη- ματισμό κυματίου (wavelet) στη διαδικασία τμηματοποίησης και χαρακτηρισμού του ενδομητρικού ιστού. / Cancer of the corpus uteri represents the fourth commonest neoplasm among European women and the tenth most common cause of death attributed to cancer. Irrespective whether the use of transvaginal ultrasonography (TVS) as a screening tool for detecting endometrial cancer in asymptomatic postmenopausal women is warranted, TVS dominates most diagnostic algorithms in assessing metrorrhagias to exclude this cancer. Alongside the potential benefits stemming from the integration of Saline Infusion Sonography) and Doppler modalities in endometrial imaging, gray scale TVS showed remarkable advances in the previous decades, largely attributed to the evolution in computer sciences. Following the introduction of multifrequency transvaginal probes and harmonic imaging, modern scanners are equipped with software options that enhance the resolution or the contrast between different structures, fine tune while assessing different types of tissue, implement different depth of focusing, transmit the ultrasonic beam in oblique directions to the acoustic window; all these features, in addition to de-speckle filters optimize the endometrial depiction, facilitating its assessment, even in the hands of moderately skilled operators. Double stripe endometrial thickness has illustrated a remarkable robustness over time as a quantitative indicator of endometrial cancer, especially in the presence of postmenopausal bleeding. The combined consideration of endometrial morphology and thickness has proven particularly beneficial, especially in the assessment of the 4-10 mm endometrial thickness “grey zone”, although the findings of the “morphologic” studies haven’t always been consistent. Given the importance of morphology in assessing endometrial tissue, and aiming to overcome the inherent subjectivity of the qualitative consideration of ultrasonic images, implementation of automated techniques assessing objective morphologic features such as “computerized texture analysis” would be beneficial. In digital images, texture reflects tonal (intensities of image pixels) and structural (spatial distribution of pixel intensities) properties. Texture analysis refers to algorithms that quantify texture content that may, or may not, be visually perceived. Since medical images capture various properties of biological structures, texture analysis of medical images can provide quantitative metrics relevant to structure, morphology and status of biological tissues. Texture based classification schemes have been successfully implemented in a variety of ultrasound applications. Computerized TVS assessment of endometrial morphology, has been applied mainly in assisted reproduction techniques; however, computerized texture analysis has not been implemented for diagnosing endometrial malignancies in grey scale TVS. The aim of this study is to investigate the feasibility of computerized texture analysis in characterizing endometrial tissue as depicted in 2D grey scale TVS images. Furthermore, we assess the effect of a wavelet-based image processing technique in the segmentation and subsequent characterization tasks of endometrial tissue.

The present study was to diagnose and classify the Human Papilloma Virus (HPV) in pregnant and non-pregnant adolescents, as study the risk factors related to the infection, identify the multiples oncogenics types presents in the study people and associate the differents types of HPV with cytology and colposcopy findings. Methodologic design: the type of study was prospective, descriptive and transversal coorte. Was study 111 sexually active adolescents, between 10 and 19 years old, patients of the Gynecology Service of the Professor Alberto Antunes University Hospital of the Federal University of Alagoas (HUPAA-UFAL). Was utilized the polymerase chain reaction / restriction fragment length polymorphism - sequencing (PCR/RFLPs) to identification of the virus. Results: the viral percentual in the inferior genital tract was 27% of the cases. The molecular genotyping revealed high risk viral genetic material - HPV 16, 33, 51, 58, 66, 1S39, CP8304 and LVX100, in 28,5% of the cases, low oncogenic risk - HPV 6, 11, 53, 61 e CP141, in 40% and, the other 31,4%, considered the indeterminate type, include high and low risk virus. This more incident type is found isolated or associated to other viral types and appears in 40% of the positive cases. The viral infection rate among the pregnant adolescents was 11,7%. The HPV genital infection was associated with a past of sexually transmitted diseases and the consumption of alcohol by the adolescent. The frequency of adolescents infected by HPV, associated to low grade intraepithelial lesion, was 5,0%. No associations were observed between the specific types of HPV and the cytology and colposcopy findings among the studied adolescents. / O objetivo do presente estudo foi para diagnosticar e classificar o papilomavírus humano (HPV) em adolescentes grávidas e não grávidas, bem como estudar os fatores de risco para a infecção, identificar os diversos tipos oncogênicos presentes na população estudada e associar os diferentes tipos de HPV com achados da citologia e colposcopia. Desenho metodológico: o tipo de estudo foi prospectivo, descritivo e de coorte transversal. Foram estudadas 111 adolescentes sexualmente ativas, entre 10 e 19 anos, atendidas no Serviço de Ginecologia do Hospital Universitário Prof. Alberto Antunes da Universidade Federal de Alagoas (HUPAA-UFAL). Utilizou-se a reação de polimerase em cadeia/polimorfismo de comprimento de fragmentos de restrição - sequenciamento (PCR/RFLPs), para a identificação do vírus. Resultados: o percentual do vírus no trato genital inferior foi de 27%. A genotipagem molecular revelou material genético viral de alto risco - HPV 16, 33, 51, 58, 66, 1S39, CP8304 e LVX100, em 28.5% dos casos, enquanto que os de baixo risco oncogênico - HPV 6b, 11, 53, 61 e CP141, em 40%. Os demais 31,4%, foram do tipo considerado indeterminado, que incluem vírus de alto e baixo risco. Esse tipo mais incidente encontra-se isolado ou associado a outros tipos virais e aparece em 40% do total dos casos positivos. A taxa de infecção viral entre as gestantes foi de 11,7%. A infecção genital pelo HPV teve associação com o passado de doenças sexualmente transmissíveis e com o consumo de álcool pela adolescente. A freqüência de adolescentes infectadas pelo HPV, associada à lesão intra-epitelial de baixo grau foi de 5,0%. Não foram observadas associações tipo-específicas do HPV com os achados da citologia e da colposcopia entre as adolescentes estudadas.

The HIV-1 pandemic affects millions of people worldwide with approximately 70% of those affected residing in sub-Saharan Africa (SSA) relying on traditional medicines for treatment. The key aim of the study was to isolate and characterise an active phyto-pharmaceutical ingredient (API) from L. trigonus for use as a vaginal microbicide. The aerial parts of L. trigonus were oven-dried at 80°C, ground and then extracted with boiling water for 30 minutes. Aqueous extracts were screened using an HIV-1 neutralization assay in TZM bl cells. Chromatographic and spectroscopic techniques were used to purify, isolate and identify the API. The API (BP36-117-26464C) was identified as a polymeric macromolecule with IC50 = 0.04 μg/ml against HIV-1 HXB 2 subtype B. This activity is comparable to the ARV drug, enfuvirtide (IC50 = 0.02 μg/ml). The API consists of galacturonic acid polymer and a mixture of seven compounds. Its mode of action may involve inhibiting virus attachment. The activity of this precipitate (BP36-117-26464C) tested against HIV-1 subtype C pseudovirions and shown to compare favorably with that of enfuvirtide (T20). The water-soluble nature of this API and its mode of action identified it as a potential microbicide. In the current form, the precipitate (API) would be difficult to develop as an oral treatment for HIV, as high-molecular weight agents often have poor bioavailability following oral administration. However, large molecules with potent anti-HIV activity are ideal for topical use and potent development as a microbicide. / Life and Consumer Sciences / M.Sc (Life Sciences)

No Brasil, a maioria absoluta das primíparas, deseja parto normal logo que engravida, porém, em mais da metade dos casos, os nascimentos são cirúrgicos. O fenômeno da falta de correspondência entre o desejado e o efetivamente alcançado não é exclusividade das mulheres brasileiras, mas ocorre em vários países do ocidente. Por meio da Análise Crítica do Discurso (ACD) de relatos de parto normal após cesárea (relatos de VBAC, do inglês, vaginal birth after c-section) à luz da Linguística de Corpus (LC), buscamos elucidar o problema social entre a falta de correspondência entre o tipo de experiência desejada e a experiência obtida. O discurso dos relatos de VBAC nos parece ser o discurso ideal para desvelar os elementos dessa falta de correspondência, pois abordam tanto a experiência da cesárea anterior indesejada e, em regra, mal indicada, como a do parto desejado e alcançado. O recorte teórico-metodológico adotado reúne a ACD (Fairclough, 1989, 1992; Chouliaraki & Fairclough, 1999; Fairclough, 2003); a LC (Stubbs, 1993, McEnery & Wilson, 1997 e 2003, Tognini-Bonelli, 2001) e a Análise Crítica do Discurso Baseada em Corpus (Baker et al 2008; Baker, 2013; Baker & McEnery, 2005; Flowerdew, 2014). Para o estudo, foi compilado um corpus eletrônico em inglês e português. O corpus é composto por textos escritos pelas mulheres que passaram pela experiência de VBAC e não inclui textos mediados (entrevistas e relatos escritos por terceiros não foram incluídos). O Corpus BRABA (Corpus eletrônico de relatos de parto de mulheres brasileiras, estadunidenses, britânicas e australianas) se divide, respectivamente, em quatro subcorpora: Corpus BRA (93 relatos, 250 807 palavras), Corpus EUA (101 relatos, 225 736 palavras), Corpus UK (97 relatos, 92 197 palavras) e Corpus AU (92 relatos, 200 639 palavras. Os primeiros dois subcorpora Corpus BRA e Corpus EUA foram selecionados para esta pesquisa que pretende investigar como as identidades e a experiência do nascimento são representadas nos relatos de mulheres brasileiras e americanas e por meio dessa investigação chegar a elementos que elucidem o problema social. O processamento eletrônico valeu-se do programa AntConc 3.4.0w (Anthony, 2012) e das ferramentas da LC (listas de frequência, lista de palavras-chave, linhas de concordância, padrões lexicais, etc.). A análise foi direcionada pelas palavras-chave que correspondem aos sujeitos envolvidos e pelos colocados mais estatisticamente relevantes dessas palavras. No Corpus BRA, foram analisadas: eu (colocados: desisto, renasci, mamava); bebê (encaixado, morrer/morresse, sexo, batimentos, alto); marido (companheiro, apoiou, cortou); doula (amada, obstetriz, querida, presença); médico (fofa/fofinha, mudar/mudei, cesarista, ginecologista, humanizada); anestesista; enfermeira (obstétrica/obstetra, cadê, soro, chamar); parteira (liguei/ ligar, doula, casa); obstetriz (doula, toque). No Corpus EUA: I (wish, protested, lamented); baby (pound, girl, boy); midwife (certified, asst/assistant, student, assist); doula (hired, friend, called); nurse (practitioner, tells, triage); doctor (office, seen, comes); anesthesiologist; husband (poor, run, children). A análise permitiu que fosse elucidado o problema social em ambas as sociedades e fossem reveladas diferenças discursivas e culturais. A falta de correspondência entre a experiência desejada e a alcançada é representada como tendo sido causada pela sucessão de eventos distintos. Contudo, em ambos os corpora, as experiências são representadas e a autoidentidade e as identidades construídas discursivamente sob a égide dos traços da modernidade, marcadamente, em relação à reflexividade exercida ideologicamente. Porém, a reflexividade é operada, não só como um modo de sustentar, mas principalmente como forma de transformar as relações de dominação. / In Brazil the vast majority of primiparous women, on discovering that they are pregnant, hope to have normal deliveries. However, in over half of such cases surgical deliveries ensue. This mismatch between what pregnant women desire and what they actually experience is not exclusive to Brazil, but takes place in several Western countries. Through Corpus Linguistics (CL)-based Critical Discourse Analysis (CDA) of vaginal birth after c-section (VBAC) stories we seek to shed light on the social problem of a mismatch between the desired experience and the actual experience. VBAC stories seemed to us the ideal discourse for revealing elements of this mismatch, since they address both the experience of an unwanted (and usually wrongly indicated) prior C-section and that of the desired, and achieved, delivery. The theoretical-methodological approach we have adopted brings together CDA (Fairclough, 1989, 1992; Chouliaraki & Fairclough, 1999; Fairclough, 2003); CL (Stubbs, 1993, McEnery & Wilson, 1997 e 2003, Tognini-Bonelli, 2001), and Corpus-based Critical Discourse Analysis (Baker et al 2008; Baker, 2013; Baker & McEnery, 2005; Flowerdew, 2014). An electronic corpus was compiled in English and Portuguese for this study. The corpus is made up of texts written by women who have experienced VBAC and includes no mediated texts (i.e. interviews and third-party reports). The BRABA Corpus (Corpus of the birth stories of Brazilian, American, British and Australian women) encompasses four subcorpora respectively: Corpus BRA (93 stories, 250,807 words), Corpus USA (101 stories, 225,736 words), Corpus UK (97 stories, 92,197 words), and Corpus AU (92 stories, 200,639 words. The first two of these subcorporaCorpus BRA and Corpus USAwere chosen for this study, which investigates how identities and birth experiences are represented in the accounts of Brazilian and American women, and thus through this investigation uncovers elements that will shed light on the selected social problem. The computer processing used AntConc 3.4.0w (Anthony, 2012) and CL tools (frequency lists, keyword lists, concordance lines, etc.). Analysis was guided by keywords corresponding to the people mentioned in the stories and by the most statistically significant collocates of these keywords. From Corpus BRA the words were: eu (collocates: desisto, renasci, mamava); bebê (encaixado, morrer/morresse, sexo, batimentos, alto); marido (companheiro, apoiou, cortou); doula (amada, obstetriz, querida, presença); médico (fofa/fofinha, mudar/mudei, cesarista, ginecologista, humanizada); anestesista; enfermeira (obstétrica/obstetra, cadê, soro, chamar); parteira (liguei/ligar, doula, casa); obstetriz (doula, toque). From Corpus USA: I (wish, protested, lamented); baby (pound, girl, boy); midwife (certified, asst/assistant, student, assist); doula (hired, friend, called); nurse (practitioner, tells, triage); doctor (office, seen, comes); anesthesiologist; husband (poor, run, children). Analysis enabled this social problem to be laid bare in both societies, revealing discourse and cultural similarities and differences. The mismatch between the desired and the experienced outcomes is represented as having been caused by a succession of discrete events. In both corpora, experiences are represented, and self-identity and other identities are notably constructed in discourse under the aegis of features of modernity, above all, under reflexivity, which, in the discourses of VBAC stories takes place through empowerment, understood as self-actualization through newly gathered knowledge and ensuing courses of action/measures (Giddens, 2002).