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Coming dissertations at MedFak

  • Metabolomic features and viral infections in paediatric inflammatory bowel disease Author: Niklas Nyström Link: Publication date: 2024-04-12 09:37

    Background: Up to 25% of patients with inflammatory bowel disease have a paediatric onset (PIBD). The pathophysiological processes underlying PIBD are complex and largely unknown.  

    Aims: To investigate a hypothesized role for human enterovirus B (HEV-B) in Crohn’s disease (CD) (I). To map and compare the mucosal and plasma metabolomes in new-onset PIBD patients and controls (II). To search for a new blood-based diagnostic biomarker for PIBD (III). To investigate the effect of exclusive enteral nutrition (EEN) treatment on the mucosal and plasma metabolomes in CD patients (IV). 

    Methods: Immunohistochemistry and chromogen in situ hybridisation were used to search for HEV-B in surgical specimens from patients who had undergone surgery for stricturing ileocecal CD, and from volvulus patients as controls. Ultra-high-performance liquid chromatography mass spectrometry were used on biopsies and plasma from patients in the Uppsala PIBD inception cohort for metabolomic (II and IV) and lipidomic analyses (III). Patients were stratified by phenotypic subtypes and treatment responses. Symptomatic patients without PIBD were used as non-IBD controls. In Study III, two other independent PIBD inception cohorts were used for validation and confirmation. 

    Results: I: HEV-B was detected in epithelial cells and neuronal ganglia of the enteric nervous system, and the specific cellular Coxsackie and adenovirus receptor (CAR) was expressed in both the intestinal epithelium and the enteric nervous system. II: Alterations in two metabolic compound classes were seen: decreased levels of lysophospholipids in inflamed ileum of CD patients and altered levels of sphingolipids in inflamed ileum and colon in both CD and ulcerative colitis, as compared with non-IBD controls. III: Discovery, validation and confirmation in three independent PIBD inception cohorts of a blood-based diagnostic two-lipid signature of PIBD. IV: A generalised downregulation of the non-inflamed ileal lipid metabolism after successful remission induction with EEN, as compared with baseline, and also as compared with non-IBD controls. Reduction of several lysophospholipids was a characteristic feature of the post-EEN ileal metabolome.

    Conclusions: The demonstrated presence of HEV-B supports, but does not confirm, its hypothesised role in CD. The CD-associated downregulation of mucosal metabolism both at disease onset and after successful EEN-induced inflammation resolution indicates a central role for the ileal mucosal lipid metabolism in CD, including lysophospholipids. The blood-based two-lipid signature has the potential of becoming a diagnostic tool in the clinical work-up of suspected PIBD.

  • Contextualising a South African social innovation for maternal and child health to mothers with experiences of migration in Sweden Author: Per Kåks Link: Publication date: 2024-04-11 11:17

    Despite a universally accessible and high-quality welfare system, disparities in health and wellbeing persist between families who have migrated to Sweden and the native population. The South African Mentor Mother programme, a social innovation for maternal and child health among socially disadvantaged communities, was transferred and adapted to benefit mothers and pregnant women with experiences of migrating to Sweden.

    This thesis aims to explore the adaptation, implementation and further development of the South African Mentor Mother programme in two locations in Sweden, based on professional and lived experience among various groups of stakeholders.

    In Study I, three workshops and eleven interviews were held with stakeholders to explore central aspects of the adaptation process. These aspects entailed prioritising social determinants of health over health behaviour change, using indirect mechanisms and social ripples to achieve change, prioritising referring clients over intervening directly, recruiting peer supporters with competencies responding to a heterogeneous socio-cultural context, and allowing flexibility in programme content and methods.

    In Study II, nineteen interviews with different stakeholders and digital field logs of peer support meetings (n=1,294) were used to evaluate the implementations of the programme. Contextual factors of importance included institutional mistrust, gender norms, unpredictable funding, and the organisation's third sector affiliation. Peer supporters prioritised linking clients to welfare services over educational intervention components, and sometimes experienced blurring between professional and personal roles. Practical support and trustful relationships emerged as important entry points to support more sensitive issues. 

    In Study III, the photovoice method was used to conduct a focus group discussion and six interviews with Mentor Mothers and their coordinator in Gothenburg, exploring how they developed empowerment strategies perceived to be relevant, feasible and effective. These strategies consisted of various aspects of using both informative, practical, psychosocial and motivational support to meet community health and social needs.

    In Study IV, twenty-one interviews with Mentor Mothers, client mothers and other stakeholders were conducted to explore the emergence and management of mistrust in welfare services in Gothenburg. Mistrust was described to arise through rumours, unclear interactions with services, and lack of familiarity with the welfare system. Mentor Mothers used various strategies to build trusting relations with clients, which enabled them to promote institutional trust through information and humanisation of service providers.

    This thesis illustrates how innovative community-based solutions to complex societal problems can be transferred between contexts, implemented and further developed to ensure their relevance to the target group.

  • Polycystic ovary syndrome and pregnancy complications : Focus on hyperandrogenism and comorbidity Author: Ragnheiður Valdimarsdóttir Link: Publication date: 2024-04-10 12:51

    Polycystic ovary syndrome (PCOS) is the most common endocrine disorder among women, affecting their lives in many ways. PCOS is characterised by ovulatory dysfunction, polycystic ovary morphology and hyperandrogenism, either clinical or biochemical. Women with PCOS face a higher risk of obstetric complications than women without PCOS. There are many factors that contribute to these complications, such as metabolic disturbances, insulin resistance, chronic inflammation, hyperandrogenism and factors related to infertility.

    The overall aim of the research presented in this thesis was to study factors that might affect the association between PCOS and pregnancy complications. The thesis consists of matched cohort studies based on data from the Uppsala Biobank of Pregnant Women (Papers I and II) and national register-based cohort studies (Papers III and IV). In the first two studies, we included women with PCOS (n = 159) and BMI-matched controls (n = 320), and the aim was to study the effect of high anti-Müllerian hormone (AMH) and testosterone on pregnancy complications. The third study (n = 138 219) explored whether the association between PCOS and preeclampsia depends on treated clinical hyperandrogenism and whether PCOS is associated with different subtypes of preeclampsia. In the fourth study (n = 281 806), the aim was to explore association and risk estimates for pregnancy outcomes in women with either or both PCOS and gestational diabetes mellitus (GDM).

    The main results were that women with PCOS have higher levels of AMH and testosterone and a higher free androgen index during second trimester pregnancy than non-PCOS controls. High AMH levels were not associated with adverse pregnancy outcome or birthweight. PCOS women with the highest testosterone levels had the highest risk for preeclampsia. Compared to non-PCOS controls, women with PCOS have increased risk of preeclampsia, especially the more severe subtypes of preeclampsia, early onset or with a birth of an infant born small for gestational age. With available data, we were unable to determine whether hyperandrogenism affects the risk of preeclampsia. The combination of PCOS and GDM exacerbates the risk of adverse pregnancy outcomes for both mother and infant compared with women with either PCOS or GDM alone.

    In conclusion, the research presented in this thesis adds important information about the association of PCOS and the more severe subtypes of preeclampsia and underpins the importance of an increased awareness of PCOS in antenatal care along with early screening for diabetes and hypertensive disorders.