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Coming dissertations at MedFak

  • Social Stratification of Children's Diet and Nutrition: Understanding Women's Situation in Addis Ababa Author: Hanna Yemane Berhane Link: http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-407952 Publication date: 2020-05-19 10:50

    Background: Childhood undernutrition is the cause of nearly half of all deaths in under-five children. In sub-Saharan African countries, this problem is further complicated by the rising prevalence of overweight. Mothers play a key role in child care and nutrition, however, in cities that are undergoing rapid social and economic changes, little is known about their lived experiences and challenges. Moreover, little is known about the influence of the neighbourhood food environment and family socio-economic conditions of food acquisition and intake in sub-Saharan Africa. Therefore, the study aims to understand the nexus between mothers’ child care and feeding experiences, neighbourhood food environment, diet diversity, and family socioeconomic status. Methods: A mixed qualitative and quantitative study design was used. The qualitative component involved thirty-six in-depth interviews with mothers who had children under the age of five years. A thematic analysis approach was used to analyse verbatim transcripts. For the quantitative component, two rounds of cross-sectional household surveys were conducted. The sample was drawn from all districts of Addis Ababa; a total of 5467 households with mother-child pairs. Data were analysed using a generalised estimating equation (GEE) and mixed-effect logistic regression model. Results: Urban mothers are under pressure to ensure their child gets adequate care and food; the changes in their environment owing to the reconstruction of city and migration further limit their ability to do so. Mothers expressed that their decision of what to feed their children is influenced by children’s preferences, perceived safety of the food, familiarity with the food, and affordability.

    Children receiving the recommended minimum diet diversity totaled 59.9% (58.5–61.3). Having an adequately diverse diet was associated with having an educated mother, and being from the wealthier and more food-secure households. Animal source and vitamin-A-rich food groups are the least affordable and consumed food groups in the study settings. Families with uneducated mothers, in the lowest wealth group and those who perceived food groups to be unaffordable, consumed a less diverse diet.

    The prevalence of stunting was 19.6% (18.5–20.6) and that of over-weight/obesity was 11.4% (10.6–12.2). Maternal education level was associated with both forms of malnutrition; children with uneducated mothers were more likely to be stunted (AOR: 1.8; 1.4–2.2) and less likely to be overweight/obese (AOR: 0.61; 0.44–0.84), while being from the highest wealth household and from a severely food insecure household were associated with a higher likelihood of obesity and stunting, respectively. Conclusion: Child nutritional outcomes and diet quality vary by the socioeconomic status of the family; particularly that of mothers. Therefore, efforts to improve diet and nutritional outcomes of children need to consider mechanisms to strongly support mothers.

  • The activation and regulation of plasmacytoid dendritic cells in SLE : and possible therapeutic interventions Author: Karin Hjorton Link: http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-409504 Publication date: 2020-05-18 14:03

    Systemic Lupus Erythematosus (SLE) is an autoimmune disease, characterized by the presence of anti-nuclear antibodies and the formation of nucleic acid containing immune complexes (ICs), which can cause organ damage by deposition in tissues. ICs strongly trigger the plasmacytoid dendritic cells (pDCs) to produce interferon (IFN)-α, which potently activates the immune system. An activated type I IFN system is seen in a majority of SLE patients. Natural killer (NK) cells enhance the IC triggered response of pDCs. Other NK cell alterations are described in SLE. Standard SLE treatment, hydroxychloroquine (HCQ), reduces flare risks, and HCQ concentration measurement can optimize its dosing. However, new treatments are needed.

    In paper I, we screened for autoantibodies to lectin-like NK cell receptors. In 3.4% of SLE patient sera, autoantibodies to CD94/NKG2A and CD94/NKG2C were found, which interfered with HLA-E mediated regulation of NK cell cytotoxicity, and facilitated elimination of target cells expressing expressing these receptors. Autoantibody levels correlated with SLE disease activity and with a more severe disease phenotype.

    In paper II, we found that RNA-IC triggered proinflammatory cytokine production in immune cells from healthy blood donors and SLE patients. After RNA-IC stimulation of pDCs, RNA sequencing detected 975 differentially expressed genes, connected to cytokine pathways, cell regulation and apoptosis. An IRAK4i had a broader inhibitory effect on RNA-IC triggered cytokine production and pro-inflammatory pathways than HCQ.

    In paper III we showed that RNA-IC induced type III IFN production in a subset of pDCs (3%) which also produced type I IFN. Type III IFN production by pDCs was enhanced by NK and B cells, as well as by IFN-λ2, IFN-α2b, interleukin (IL)-3, IL-6 and GM-CSF. Type III IFN production by RNA-IC stimulated immune cells of SLE patients was detected in a minority. IFN-α2b and GM-CSF increased the proportion of responders to RNA-IC from 11 to 33%.

    In paper IV a LC-HRMS method, was evaluated for HCQ concentration measurement in whole blood (WB), serum and plasma from 26 SLE patients. The levels in WB were approximately 2-fold compared to serum and plasma, and correlated with weekly HCQ-dose. Large inter-individual variations were observed, despite equal doses. The WB matrix showed superior reproducibility in patient samples (CV<5%).

    These findings add to the knowledge of how cytokine production by pDCs in SLE is regulated, and support a role for NK cells in the pathogenesis of SLE. Moreover WB was the superior matrix for HCQ measurement in SLE patients.

  • A nutrition intervention in men with prostate cancer : Exploring effects on bowel symptoms from radiotherapy, patient experience, and nutrient intake Author: Marina Forslund Link: http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-408823 Publication date: 2020-05-13 13:33

    Objective The main objective of this thesis was to explore the effects of a nutrition intervention on acute and late bowel symptoms in men with localised prostate cancer treated with pelvic radiotherapy (study I), participants’ experiences from receiving the nutrition intervention (study II), and associations with nutrient intakes (study III).

    Methods A total of 180 men with localised prostate cancer referred to curative radiotherapy targeting the prostate gland and pelvic lymph nodes were recruited to the trial. The participants were randomised to standard care plus a nutrition intervention aiming to modify fibre and lactose intakes (NIG; n=92) or standard care alone (SCG; n=88). Data on bowel symptoms and dietary intake were collected pre-treatment and at seven time points during a 26-month study period. Analyses of the effects of the nutrition intervention on bowel symptoms were conducted for the acute phase (up to 2 months post radiotherapy), and the late phase (7 to 24 months post radiotherapy). Semi-structured interviews were conducted with 15 participants from the NIG to explore experiences of the nutrition intervention.

    Results The nutrition intervention was associated with statistically significantly, but not clinically significantly, less bother from blood in stools and flatulence during the acute phase. The nutrition intervention was also associated with more bloated abdomen during the late phase (Study I). Social support, contributing to the greater good, prior knowledge, dietary information, and a small need for change facilitated adherence. While feeling limited, wanting to decide for themselves, the timing of the intervention, unmet expectations, and loss of motivation were described as barriers for adherence (Study II). A greater reduction of lactose was associated with decreased intake of calcium at the end of the radiotherapy period. A more modified fibre intake during the radiotherapy period was associated with increased vitamin C, but decreased selenium intake (Study III).

    Conclusions The effects from the nutrition intervention were small and inconclusive and do not support routine dietary advice aiming to modify fibre and lactose intakes as a mean to substantially reduce adverse effects from pelvic radiotherapy. Tailored nutritional interventions based on individual preferences, prior knowledge, and context, could enhance adherence. There were few associations between modified fibre and lactose intakes and nutrient intakes, thus, no recommendations can be made on whether such dietary advice should continue to be provided to men with prostate cancer undergoing pelvic radiotherapy.

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