京都大学 / 0048 / 新制・課程博士 / 博士(医学) / 甲第21022号 / 医博第4368号 / 新制||医||1028(附属図書館) / 京都大学大学院医学研究科医学専攻 / (主査)教授 朝長 啓造, 教授 萩原 正敏, 教授 髙折 晃史 / 学位規則第4条第1項該当 / Doctor of Medical Science / Kyoto University / DFAM

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The purpose of this study is to explore how girls and boys are portrayed in children’s literature that is specifically aimed towards children in the preschool age. This is a qualitative text analysis, partly combined with some elements of quantitative data. Through an interview questionnaire sent to preschool teachers at different preschools, seven books in the genre humanized animals, were chosen and analyzed from a gender perspective. The analysis is conducted through a theoretical framework including gender theory with correlated concepts. The intent of this study has not been to identify books that follow stereotypical gender norms, and we do not argue that literature should be completely gender neutral. However, we believe that if girls and boys being portrayed in a variety of ways will contribute to more children feeling safe with their own identity and it will also provide them with a broader world view. We had a thought that a certain characterization of girls and boys in the chosen books, i.e. that girls are portrayed as sweet and nice while boys are portrayed as tough and mischievous. The results of this study show that this is partly true but that boys’ characteristics tend to vary more and in different ways than girls’ characteristics do. With that said, we concluded that in general, the chosen books were more gender neutral than our initial expectation.

HIV and Tuberculosis (TB) co-infection place an immense burden on health care systems as they act in synergy to worsen disease prognoses. TB is the most common cause of death in people living with HIV (PLWH) and in turn, HIV is the most significant risk factor for progressing from latent to active TB disease. While HIV and TB are endemic in sub-Saharan Africa, they also disproportionately affect marginalized populations in Canada. Unfortunately, the only licensed TB vaccine, BCG, does not protect from adult pulmonary TB and is not recommended for PLWH. Thus, the development of novel TB vaccines, which are safe and effective in PLWH, remains an urgent global necessity. We have found that humanized mice (hu-mice) are ideal models to research this as they can be successfully infected with HIV, TB and HIV/TB and recapitulate human disease pathology. A next-generation respiratory mucosal (RM) trivalent chimpanzee adenoviral-vectored vaccine (Tri:ChAd68) was developed and tested in our naïve and HIV-infected hu-mice. When immunizing naïve hu-mice, a trend of increased M.tb-specific CD4+ T cells producing IFNγ and TNFα in the lungs and spleen was observed. After subsequent M.tb infection, the vaccinated naïve hu-mice also exhibited significantly reduced lung mycobacterial burden, tissue dissemination and lung pathology. We then investigated the vaccine immunogenicity and ability to protect from TB in the context of HIV. Our immunized HIV-infected hu-mice were also able to produce M.tb-specific T cells and when challenged with M.tb, we observed a decreased trend in mycobacterial load in the lungs, indicating that the vaccine may be able to offer protection against TB when a prior HIV infection is present. These findings demonstrate the protective potential of the RM Tri:ChAd68 vaccine against TB disease for PLWH. In the future, we will test this vaccine in antiretroviral treated HIV-infected hu-mice to increase clinical significance. / Thesis / Master of Science in Medical Sciences (MSMS) / HIV and TB are major diseases that can occur together, severely worsening patients’ health and challenging global healthcare systems. The current TB vaccine, BCG, isn’t ideal for people living with HIV (PLWH), causing this vulnerable population to be at greater risk of getting TB infection. Therefore, developing a new TB vaccine that is safe and effective in PLWH is an urgent global issue. We used humanized mice that develop human immune cells to test a novel TB vaccine delivered to the lungs (Tri:ChAd68) to see if it could protect against TB and overcome immune challenges from HIV. We saw increased immune responses and lower TB infection in our vaccinated humanized mice and the vaccine appeared to also be beneficial in the mice that had prior HIV infection. This suggests the Tri:ChAd68 vaccine may be able to offer protection against TB in PLWH; however, more studies are needed to conclude this.

BACKGROUND: Nearly all birthing people in the Dominican Republic (DR) deliver in a hospital, yet maternal and newborn mortality remain high. Respectful maternity care challenges have been reported but not systematically documented. This observational, mixed-methods study assessed birthing people’s and providers’ experiences at a public hospital in the DR, during the COVID-19 pandemic. METHODS: In May-July 2022, we surveyed postpartum people and providers to adapt the Person-Centered Maternity Care (PCMC) survey. In July-August 2022 we applied the contextually-modified PCMC survey with postpartum people and providers. Possible scores ranged from 0 (poor) to 93 (exceptional). We calculated mean scores and examined associations with socio-demographic factors. A concordance/discordance analysis examined postpartum people’s and providers’ responses. Content analysis of open-ended questions explored PCMC and opportunities for improvement. Results were stratified by nationality (Dominican or Haitian). RESULTS: Respondents felt the PCMC survey was appropriate for the context but recommended adding questions around contraception, maternal-newborn separation, differential treatment, and c-section decision-making. The mean PCMC score was 60.1 for postpartum people and 62.0 for providers. Being of Haitian origin, speaking Creole at home, being older, and living further from the facility were associated with lower scores (p<.001). Nearly 70% of providers reported birthing people were spoken to in understandable language/terms compared to 29.8% of birthing people. Most providers (91.7%) reported that consent was sought before procedures, compared to 58.1% of birthing people. Fewer Haitians, compared to Dominicans, reported favorably regarding friendly treatment (42% v 83%); ability to ask questions (34% v 66%); consent being sought before procedures (52% v 71%); and being spoken to in understandable language/terms (14% v 63%). Sixty-one percent of Haitians and 44% of Dominicans reported maternal-newborn separation for more than 6 hours. Qualitative responses revealed verbal abuse and the emotional toll of maternal-newborn separation, among other issues. Birthing people suggested improvements relating to family connectedness: companions, providers communicating with families, and keeping the mother-baby dyad together. Providers focused on infrastructure, equipment/supplies, training, and policy. CONCLUSION: As the first study to apply the PCMC survey in the DR, this study systematically documented challenges and opportunities to improve birth experiences from the perspectives of postpartum people and obstetric providers. Stakeholder-generated and evidence-based recommendations should be prioritized at Hospital Presidente Estrella Ureña. / 2025-01-04T00:00:00Z

Die Sepsis ist ein gefürchtetes Krankheitsbild, das in hochentwickelten Industrienationen mit einer hohen Mortalität verknüpft ist und damit zu den häufigsten Todesursachen gehört. Die Pathomechanismen dieses komplexen und heterogenen Krankheitsbildes zu entdecken, gehört momentan zu den Hauptinteressengebieten der Sepsisforschung. Da die Interpretation klinischer Studien aufgrund der Heterogenität des Patientenguts schwierig ist, kommt der Entwicklung adäquater Tiermodelle eine entscheidende Bedeutung zu. Die hierbei gängigen Tiermodelle in Mäusen weisen jedoch Unzulänglichkeiten auf, die die Übertragung der in Tierexperimenten gewonnen Daten auf den klinischen Kontext nur teilweise ermöglichen. Eine Brücke kann hierbei das Tiermodell der humanisierten Maus schlagen, in der, durch Transplantation mit humanen hämatopoetischen Stammzellen, ein humanes Immunsystem reift. Die vorliegende Arbeit beschäftigt sich mit der Fragestellung, inwieweit die humanen Immunzellen in der humanisierten Maus in der Lage sind, auf LPS als Stimmulus zu reagieren. Darüberhinaus wird die Nutzung der Endotoxämie in der humanisierten Maus als alternatives Sepsismodell im Bezug zum klinischen Kontext untersucht. Hierbei ergab sich eine mögliche Nutzung des Endotoxämiemodells in der humanisierten Maus zur genaueren Erforschung des Zytokinmilieus, sowie neuer Surrogatmarker wie Pentraxin 3. Bezüglich der Reaktion einzelner immunologischer Subpopulationen und deren Bedeutung für die Klinik scheint eine Untersuchung an Modellen, die eine B- und T-Zell-Reifung nachvollziehen können und in der murine Residualzellen möglichst gering vorhanden sind, als sinnvoll.

Orientador: Genaro Alvarenga Fonseca / Resumo: A reforma psiquiátrica é assunto muito discutido ao longo das últimas décadas com grande foco na preservação dos direitos humanos. O tema tem sido retomado com força na mudança do novo governo do Brasil tornando-se um assunto polêmico e inesgotável. A Lei 10.216/01, nomeada de Lei Paulo Delgado, decreta oficialmente a reforma psiquiátrica, cujas primeiras discussões tiveram início nos anos 1970. Com tantos debates e discussões a respeito e após o Manifesto de Bauru, sobre a Luta Antimanicomial no ano de 1987 com o tema "Por uma Sociedade Sem Manicômios” e a I Conferência Nacional de Saúde Mental realizada em Brasília no mesmo ano, estes movimentos se tornaram um marco para o início da reforma psiquiátrica, que busca a humanização nos tratamentos de saúde mental. Do ano desta lei até a atualidade, várias mudanças foram adotadas nas prestações de serviços da saúde mental e muitos municípios brasileiros buscam se adequar à lei e às portarias referentes a este tipo de serviço. Esta investigação partiu de pesquisa bibliográfica e documental que teve como objetivo analisar se esta lei é de fato aplicada no Hospital Psiquiátrico Allan Kardec, no município de Franca, Estado de São Paulo, e se este serviço oferece um tratamento humanizado das pessoas com transtorno psíquico, tendo em vista que no passado, desde as primeiras instituições psiquiátricas até esta reforma, os chamados “alienados”, eram segregados e totalmente excluídos da sociedade. Os resultados da pesquisa demonstram uma... (Resumo completo, clicar acesso eletrônico abaixo) / Abstract: Psychiatric reform has been a subject much discussed over the last decades with a great focus on the preservation of human rights. The theme has been taken up with force in the change of the new government of Brazil becoming a controversial and inexhaustible subject. Law 10.216 / 01, named Paulo Delgado Law, officially decrees psychiatric reform, whose first discussions began in the 1970s. With so many debates and discussions about and after the Manifesto of Bauru, on the Antimanicomial Struggle in 1987 with the theme "For a Society Without Asylums" and the First National Conference on Mental Health held in Brasília in the same year, these movements became a milestone for the beginning of the psychiatric reform, which seeks to humanize the mental health treatments. Law to date, several changes have been adopted in the provision of mental health services and many Brazilian municipalities seek to comply with the Law and the ordinances referring to this type of service. Law is actually applied at the Allan Kardec Psychiatric Hospital, in the municipality of Franca, State of São Paulo, and if this service it offers the humanized service of people with psychic disorder, since in the past, from the earliest psychiatric institutions up to this reform, theso-called "alienated" were segregated and totally excluded from society. The research results demonstrate na institution concerned with meeting there quirement sof the Law regarding the deinstitutionalization and humanization of car... (Complete abstract click electronic access below) / Mestre

Na assistência ao parto no Brasil, predominam intervenções desnecessárias em detrimento de valores como o cuidado. Algumas políticas públicas têm sido desenvolvidas com o intuito de alterar tal cenário, porém, com lentos resultados. Há também algumas estratégias e ferramentas desenvolvidas e difundidas entre as próprias mulheres. Uma destas é a construção do plano de parto, que objetiva informar e promover uma maior participação durante o parto. Apesar de mais difundida entre camadas médias, tal ferramenta tem sido utilizada em alguns serviços de atenção primária do país como a UBS Thérsio Ventura/São Paulo, campo de estágio para o curso de Obstetrícia EACH/USP. Este estudo objetivou descrever e analisar o uso de plano de parto entre usuárias do SUS e médicos/gestores. De metodologia qualitativa, os dados empíricos foram produzidos a partir de entrevistas com mulheres que vivenciaram a experiência de plano de parto no SUS; entrevistas com médicos/gestores; observação de uma consulta de orientação para o plano e parto; observação de dois grupos de apoio à gestação e ao parto realizados na UBS, e análise documental de material educativo, e de documentos referentes às políticas de saúde materna municipal e nacional. O material foi submetido à análise de conteúdo, da qual emergiram as seguintes categorias: (a) Não é uma incapacidade sua, e sim do sistema; (b) De coitada a poderosa; (c) Intervenção que era ajuda; (d) Resistência e negociação do encontro; (e) Plano de parto como mobilizador do cuidado como valor; (f) A segurança do bebê como chantagem; (g) Sobre comandantes, aviões e a necessidade de novas analogias; (h) Plano de parto como provocação: negligência e retaliação; (i) Limites para a decisão informada no SUS. O plano de parto funciona como uma ferramenta educativa que provoca rupturas simbólicas na relação hierárquica das mulheres com os profissionais. Como não há uma cultura que promova a tomada conjunta de decisões e porque há uma clara contradição entre o tipo de cuidado que as mulheres demandam e a atenção que os profissionais estão preparados e dispostos a oferecer, o plano de parto pode resultar em negligência e retaliação. Pode ser útil na construção de linhas de cuidado entre as instituições. Um modelo a ser discutido deveria garantir espaço para singularidades socioculturais, para a explicação dos momentos em que procedimentos podem ser necessários e também espaço para divulgação de locais de assistência mais amigáveis às mulheres e aos quais a mulher pode recorrer no caso de violação de direitos. / Birth care in Brazil is marked by strong predominance of unnecessary interventions at the expense of values such as care. Some policies have been developed in order to change such a scenario but with slow results. There are also some strategies and tools developed and disseminated among women themselves. One of those is the construction of the birth plan, which aims to inform and expand participation and decision making during childbirth. Widespread among middle class women, this tool has been used in some primary care services in the country such as UBS Thérsio Ventura/São Paulo, a training field for the course of Midwifery EACH/USP. This study aimed to understand and analyse the use of birth plan between women who use the public health system and doctors/managers. Using qualitative methodology, empirical data was produced from interviews with women who experienced birth plan in the public system; interviews with doctors/managers; observation of a guidance for the birth plan construction; observation of two support groups at the studied health center, and document analysis of educational materials and documents relating to municipal and national maternal health policies. The material was subjected to content analysis of which the following categories emerged: (a) It is not your disability, but the systems; (b) From poor thing to powerful; (c) Intervention that once was \'help\'; (d) Resistance and negotiation of the encounter; (e) Birth Plan as a mobilizer of care as a value; (e) The safety of the baby as blackmail; (f) About commanders, airplanes and the need for new analogies; (g) Birth plan as defiance: negligence and retaliation; (h) Limits for \'informed decision\' in the public health system. Birth plan functions as an educational tool that causes fissures in the symbolic hierarchical relationship of women in relation to professionals. As there isnt a culture that promotes joint decision-making and because there is a clear contradiction between the type of care women require and what professionals are ready and willing to offer, birth plan can end in neglect and retaliation. It could be useful in building protocols and care between the institutions. A model to be discussed should ensure space for socio-cultural singularities, to the explanation of times that procedures may be required and also space for disclosure of sites to which woman can turn in case of violation of rights.

Na assistência ao parto no Brasil, predominam intervenções desnecessárias em detrimento de valores como o cuidado. Algumas políticas públicas têm sido desenvolvidas com o intuito de alterar tal cenário, porém, com lentos resultados. Há também algumas estratégias e ferramentas desenvolvidas e difundidas entre as próprias mulheres. Uma destas é a construção do plano de parto, que objetiva informar e promover uma maior participação durante o parto. Apesar de mais difundida entre camadas médias, tal ferramenta tem sido utilizada em alguns serviços de atenção primária do país como a UBS Thérsio Ventura/São Paulo, campo de estágio para o curso de Obstetrícia EACH/USP. Este estudo objetivou descrever e analisar o uso de plano de parto entre usuárias do SUS e médicos/gestores. De metodologia qualitativa, os dados empíricos foram produzidos a partir de entrevistas com mulheres que vivenciaram a experiência de plano de parto no SUS; entrevistas com médicos/gestores; observação de uma consulta de orientação para o plano e parto; observação de dois grupos de apoio à gestação e ao parto realizados na UBS, e análise documental de material educativo, e de documentos referentes às políticas de saúde materna municipal e nacional. O material foi submetido à análise de conteúdo, da qual emergiram as seguintes categorias: (a) Não é uma incapacidade sua, e sim do sistema; (b) De coitada a poderosa; (c) Intervenção que era ajuda; (d) Resistência e negociação do encontro; (e) Plano de parto como mobilizador do cuidado como valor; (f) A segurança do bebê como chantagem; (g) Sobre comandantes, aviões e a necessidade de novas analogias; (h) Plano de parto como provocação: negligência e retaliação; (i) Limites para a decisão informada no SUS. O plano de parto funciona como uma ferramenta educativa que provoca rupturas simbólicas na relação hierárquica das mulheres com os profissionais. Como não há uma cultura que promova a tomada conjunta de decisões e porque há uma clara contradição entre o tipo de cuidado que as mulheres demandam e a atenção que os profissionais estão preparados e dispostos a oferecer, o plano de parto pode resultar em negligência e retaliação. Pode ser útil na construção de linhas de cuidado entre as instituições. Um modelo a ser discutido deveria garantir espaço para singularidades socioculturais, para a explicação dos momentos em que procedimentos podem ser necessários e também espaço para divulgação de locais de assistência mais amigáveis às mulheres e aos quais a mulher pode recorrer no caso de violação de direitos. / Birth care in Brazil is marked by strong predominance of unnecessary interventions at the expense of values such as care. Some policies have been developed in order to change such a scenario but with slow results. There are also some strategies and tools developed and disseminated among women themselves. One of those is the construction of the birth plan, which aims to inform and expand participation and decision making during childbirth. Widespread among middle class women, this tool has been used in some primary care services in the country such as UBS Thérsio Ventura/São Paulo, a training field for the course of Midwifery EACH/USP. This study aimed to understand and analyse the use of birth plan between women who use the public health system and doctors/managers. Using qualitative methodology, empirical data was produced from interviews with women who experienced birth plan in the public system; interviews with doctors/managers; observation of a guidance for the birth plan construction; observation of two support groups at the studied health center, and document analysis of educational materials and documents relating to municipal and national maternal health policies. The material was subjected to content analysis of which the following categories emerged: (a) It is not your disability, but the systems; (b) From poor thing to powerful; (c) Intervention that once was \'help\'; (d) Resistance and negotiation of the encounter; (e) Birth Plan as a mobilizer of care as a value; (e) The safety of the baby as blackmail; (f) About commanders, airplanes and the need for new analogies; (g) Birth plan as defiance: negligence and retaliation; (h) Limits for \'informed decision\' in the public health system. Birth plan functions as an educational tool that causes fissures in the symbolic hierarchical relationship of women in relation to professionals. As there isnt a culture that promotes joint decision-making and because there is a clear contradiction between the type of care women require and what professionals are ready and willing to offer, birth plan can end in neglect and retaliation. It could be useful in building protocols and care between the institutions. A model to be discussed should ensure space for socio-cultural singularities, to the explanation of times that procedures may be required and also space for disclosure of sites to which woman can turn in case of violation of rights.

La voie d’administration d’un vaccin et le modèle préclinique dans le lequel il est évalué sont des facteurs majeurs qui contribuent à son succès chez l’homme. Dans ce contexte, la découverte que la voie transcutanée (TC) induit une réponse immunitaire puissante a fait de la vaccination antitumorale TC une stratégie prometteuse. Une évaluation complémentaire du candidat vaccin dans un modèle de souris humanisée (Hu-SPL-NSG), plus prédictif de la réponse humaine, est aussi nécessaire. L’objectif de cette thèse est i) d'optimiser des constructions liposomiques peptidiques incorporant un agoniste de TLR pour la voie TC et ii) d’évaluer leur immunogénicité dans le modèle Hu-SPL-NSG. Ainsi, nous avons fait varier la nature de l’agoniste de TLR et la déformabilité de la vésicule liposomique, et avons rajouté une molécule de ciblage des cellules dendritiques. L’immunogenicité de ces formulations par voie TC a ensuite été évaluée chez la souris. Enfin, nous avons testé la capacité d’une construction liposomique modèle à induire une réponse cellulaire et humorale dans le modèle Hu-SPL-NSG. L’ensemble de ces travaux a fourni une première preuve de concept sur la faisabilité de la vaccination antitumorale TC par des liposomes et de son applicabilité chez l’homme. / A vaccine administration route and the preclinical model in which it is evaluated are major factors that contribute to its success in humans. In this context, the discovery that the transcutaneous (TC) route induces a powerful immune response has made the TC tumor-specific vaccination a promising strategy. Further evaluation of candidate vaccines in a humanized mouse model (Hu-SPL-NSG), more predictive of the human response, is also needed. The objective of this thesis is to (i) optimize liposomal constructs incorporating peptides and a TLR agonist for the TC pathway and (ii) evaluate their immunogenicity in the Hu-SPL-NSG model. Thus, we have varied the nature of the TLR agonist and the deformability of the liposomal vesicle, and have added a dendritic cell targeting molecule. Immunogenicity of these formulations by the TC route was then evaluated in mice. Finally, we tested the ability of a model liposomal construct to induce a cellular and humoral response in the Hu-SPL-NSG model.All of this work provided a first proof of concept on the feasibility of TC tumor-specific vaccination by liposomes and its applicability in humans.