Coming dissertations at MedFak
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Diagnostic boundaries and developmental pathways of borderline personality disorder
Link: http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-541012
Background: Borderline personality disorder (BPD) is a heterogenous disorder with indistinct developmental trajectories. Diagnosing BPD is challenging, partly due to overlapping features with disorders such as attention deficit hyperactivity disorder (ADHD) and bipolar disorder (BD). The main aims of this thesis were to explore models of BPD development and examine the diagnostic boundaries between BPD, ADHD, and BD.
Methods: In Study I we investigated the psychometric properties of the Swedish version of the Wender Utah Rating Scale (WURS) self-report questionnaire in 121 patients with BPD and/or AHD and/or BD.
In Study II we evaluated the temperament profiles and childhood trauma of 19 patients with BPD and compared them to 95 patients with ADHD, BD, and subclinical cases. We also explored a theoretical model of BPD development based on the interaction between temperament traits and childhood trauma.
In Study III we conducted a cluster analysis in 150 patients with BPD, and/or ADHD, and/or BD based on the Attachment Style Questionnaire (ASQ).
In Study IV we investigated the prevalence of autistic traits in patients with BPD. Autistic traits were measured by the Autism Spectrum Quotient (AQ). We compared autistic traits between three groups: 1) patients with BPD (n=20), 2) patients with BPD with comorbidity (n=37), and 3) patients without BPD but with BD, and/or ADHD, and subclinical cases (n=98). Additionally, we investigated the association between autistic traits, childhood trauma, gender and BPD.
Results: The Swedish version of the WURS displayed good psychometric properties and the proposed three-factor structure. Analyses suggested a cut-off score of 39.
The TCI subscales for Harm Avoidance (HA) and Novelty Seeking (NS) differed significantly between the groups. The interaction model between temperament (HA and NS) and trauma (TT) explained a small part of the variance of BPD.
Three clusters with adult attachment were identified. The three clusters differed in attachment characteristics, temperament, and percentage of patients with BPD with comorbidity and ADHD, but did not differ regarding frequency of childhood trauma.
Autistic traits were significantly higher in females with BPD with comorbidity compared to females without BPD. There was a correlation between autistic traits and the number of fulfilled BPD criteria in females. Autistic traits, childhood trauma, and gender individually predicted a BPD diagnosis.
Conclusions: Patients with BPD differed in temperament, attachment, and autistic traits compared to patients with ADHD and BD. A multifactorial model offers the best explanation for BPD development.
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Regulation of Lymphatic Development and (Dys)Function : A Matter of Cellular Competition and Dynamics
Link: http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-540956
Lymphatic vessels are essential for maintaining fluid homeostasis, immune cell trafficking and lipid absorption in the gut. Postnatal expansion of the lymphatic vasculature occurs through sprouting lymphangiogenesis from pre-existing lymphatic networks, which is regulated primarily by vascular endothelial growth factor C (VEGF-C) and its receptors, VEGFR2 and VEGFR3. While the role of VEGFR3 in lymphangiogenesis is well established, the function of VEGFR2 remains less understood. In Paper I, we use high-fidelity conditional genetics for VEGFR2 deletion and adeno-associated viruses (AAVs) overexpressing selective VEGFR2 and VEGFR3 ligands to reveal a critical role of VEGFR2 in lymphatic biology. In Paper II, we extend our studies to the mature lymphatic vasculature, composed of specialized lymphatic capillaries and collecting vessels. Fluid absorption occurs in lymphatic capillaries, which are composed of oak leaf shaped lymphatic endothelial cells (LECs) connected by discontinuous junctions. However, it is unclear how these capillaries maintain endothelial integrity while taking up fluid from the interstitial space. We show that capillary LECs dynamically remodel their shape during homeostasis and in response to increased interstitial fluid in a process driven by cytoskeletal actin remodelling. We further identify isotropic stretch as an upstream regulator of LEC cell shape and use mathematical modelling to show that the oak leaf cell shape provides increased resilience, preventing luminal collapse upon increased pressure on the vessel wall. While the development of blood and lymphatic vasculature is tightly controlled, certain pathologies are associated with aberrant expansion of these vessels. In Paper III and IV, we investigate the mechanisms underlying vascular malformations, which are a spectrum of diseases characterised by focal lesions of malformed blood or lymphatic vessels. The majority of vascular malformations are caused by somatic activating mutations in genes involved in (lymph-)angiogenesis, leading to ectopic growth of endothelial cells. Using genetic mouse models of vascular malformations, Paper III characterized organ-specific responses of LECs driving lymphatic malformations, while Paper IV identified a venous-specific feedback loop that amplifies upstream growth factor signalling, promoting venous malformations. These results illustrate that the same activating mutations can elicit distinct responses in endothelial cells depending on the organs or vessel type involved. In summary, by using various in vivo genetic models coupled with advanced imaging techniques, this thesis work uncovers critical new molecular mechanisms and the underlying cellular dynamics involved in the development, maintenance and pathological expansion of the blood and lymphatic vasculature.
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Co-creating Respectful Maternity Care Intervention to Improve Perinatal Mental Health in Nepal
Link: http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-540880
Background: Mistreatment during institutional childbirth is a global health concern, with 80% of births taking place in hospitals. Postpartum depression remains inadequately addressed in many maternal health settings. There is an urgent need for research to investigate mistreatment during childbirth as exposure and its linkage with postpartum depression.
Aims: The overarching aim was to investigate mistreatment during institutional childbirth in Nepal and to co-design intervention prototypes for respectful maternity care. The specific objectives were: to assess mistreatment during childbirth in tertiary care facilities (Paper I), to measure its association with postpartum depressive symptoms (Paper II), to explore mistreatment from women’s perspectives (Paper III), and to co-design early-stage respectful maternity care interventions (Paper IV).
Methods: Prospective cohort design was employed in paper I to measure the prevalence of mistreatment during childbirth in 11 hospitals and in Paper II to assess its association with postpartum depressive symptoms in one hospital. Paper III involved 16 in-depth interviews to explore women’s lived experiences of mistreatment during childbirth. Paper IV adopted a human-centered co-design process involving 28 midwives to develop prototypes of respectful care.
Results: Altogether, 84.3% (n = 53,047) of women had no opportunity to discuss their concerns; 80.4% (n = 50,593) were not adequately informed; 42.1% (n = 26,492) did not receive breastfeeding counselling; 1.5% (n = 944) were refused postpartum care for inability to pay. Women aged 30–34 years old (β,− 0.38013; p-value, 0.000) were less likely to expereince mistreatment compared to women aged 18 years or younger. Furthermore, women from relatively disadvantaged (Dalit) ethnic groups were more likely to experience mistreatment (β, 0.29596; p-value, 0.000) than women from more advantaged (Chettri) ethnic groups. Paper II found that a third of women (n = 360, 29.5%) experienced mistreatment during childbirth and these women were almost 50% more likely (cRR 1.47; 95% CI 1.14, 1.89; p = 0.003) to experience postpartum depressive symptoms compared to those who did not report mistreatment. Paper III identified adverse hospital culture, systemic constraints and territorial behavior as perceived drivers of mistreatment during childbirth. Paper IV codesigned respectful care prototypes: bottom-up communication system, communication skills for midwives, and community-based health education for clients.
Conclusion: Thesis demonstrates high burden of mistreatment during childbirth and its potential linkage to postpartum depression, and highlight the capacity of co-designed interventions to address the root causes of mistreatment. Personalized care with effective communication in a supportive hospital environment, is essential for positive health outcomes.