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Coming dissertations at MedFak

  • Seasonal aspects of peripartum depressive symptoms Author: Hanna E. Henriksson Link: Publication date: 2019-05-21 13:08

    Every year, a large proportion of pregnant and newly delivered women develop peripartum depression, a condition that may cause long-term suffering for the entire family. Although there is a lack of consensus, some studies propose an association between season and the risk of developing depression during pregnancy and the postpartum period. Furthermore, the immune system, which undergoes numerous structural changes during pregnancy, has been suggested to exhibit seasonal variations. In addition, discrepancies in metabolic profiles have been reported between women with and without depression after childbirth. This thesis aimed to investigate seasonal aspects of peripartum depressive symptoms (PPDS) and biological markers during the peripartum period. The data mainly derived from the prospective population-based Biology, Affect, Stress, Imaging, and Cognition (BASIC) study, but data were also included from the longitudinal population-based Uppsala-Athens (UPPSAT) study. The presence of depressive symptoms was primarily assessed using the Edinburgh Postnatal Depression Scale (EPDS). There were no consistent associations between season, meteorological parameters, air pollen count, and PPDS. Moreover, a number of inflammatory markers were identified as having seasonal variations among samples from pregnant women. On the contrary, only one marker had a seasonal pattern during the early postpartum period. Furthermore, metabolic profiles were not discriminatory between pregnant women with and without depressive symptoms. However, when divided into summer and winter childbirths, discrepancies were identified in metabolic profiles between summer cases and controls, as well as between summer and winter controls. In summary, the studies included in this thesis suggest that season, specifically, is not associated with PPDS. However, season may have a moderating effect on the association between depressive symptoms and the metabolic profile of pregnant women. In addition, the seasonal variations appears more prominent among inflammatory markers during late pregnancy, compared with the early postpartum period. These findings suggest that women need equal attention in clinical care regardless of the season during which they give birth. Future studies on biological aspects of PPDS and immune-associated conditions are encouraged to also assess seasonality.

  • If only I could sleep, maybe I could remember Author: Frida H Rångtell Link: Publication date: 2019-05-20 14:55

    Memory lies the ground for human cognitive skills, enabling complex social interaction, abstract thinking, and execution of precise motor skills. Development of these memory functions can be modified by several factors, including previous knowledge, reward, and sleep. In Paper I, skill level already when learning a motor skill determined whether the newly encoded memory would be enhanced during a subsequent post-learning period without training. Those already performing at a high level during learning gained less until recall, whereas those who performed at a lower level during learning demonstrated an enhanced improvement at recall.

    Thus, in Paper I we determined modulators of skill enhancement. In Paper II, we actively intended to modulate subsequent motor skill gain by delivering a praise immediately following learning. We found that praise had a positive effect on performance gain, which demonstrates that there are interventions that can easily be applied to enhance motor skill learning across time.

    Sleep is vital for healthy cognitive functions, and sleep disruption has not only been correlated with impaired cognitive function in the short-term, it has also been implicated as a risk factor for development of neurodegenerative disorders such as Alzheimer’s disease. In paper I, nighttime sleep between learning and recall of a motor memory was beneficial for learning compared to a daytime wake period. In Paper III, depriving participants from sleep negatively influenced performance on a working memory task; as did auditory distractions, but independent from sleep deprivation. However, working memory functions were not equally effected in women and men; working memory functions in women were more affected by sleep deprivation.

    Although it is well-known that sleep is good for health and well-being, in today’s modern society, most people have access to electricity and internet 24/7, and it is not uncommon to exchange sleep time with spending time in front of screen-based devices, such as smartphones. Access to screen-based devices in the evening and during the night are negatively correlated with a good night’s rest. In Paper IV, we did not find support for that the light emitted from those screens play a role for this negative correlation.

  • Gastroenteropancreatic Neuroendocrine Neoplasms Grade 3 : Biological and Clinical Aspects Author: Abir Salwa Ali Link: Publication date: 2019-05-20 10:14

    The aim of this thesis was to investigate biological and clinical aspects of G3 gastroenteropancreatic neuroendocrine neoplasms (G3 GEP-NENs).

    In our first study, the expression of the tumor suppressor p53 was investigated. In a cohort of G3 GEP-NENs we found the expression of p53 protein to be present in 39% of 124 cases. Expression of p53 correlated to poorer progression-free survival (PFS) and overall survival (OS) for patients with G3 GEP-NENs originating from colon or rectum. In the next study, we aimed to demonstrate the prevalence of PD-L1 expression in G3 GEP-NENs and its possible clinical importance. Ten per cent of 136 tumor specimens were immunoreactive for PD-L1 in either tumor cells or immune cells. In contrast to p53 expression that could be correlated to PFS and OS in a subgroup of patients the expression of PD-L1 did not correlate to any clinicopathological variables and conclusively, PD-L1 may not have a vital role for the pathogenesis of G3 GEP-NENs. In a further study, we sought to identify new potential biomarkers and a panel of immuno-oncological proteins were measured in serum collected from pancreatic G3 NENs and healthy controls. Out of 87 proteins, 62% were significantly lower in serum concentration in healthy controls compared to patients. One protein, FasL, was present in significantly higher levels in healthy controls compared to patients. FasL may have a protective role in its ability to activate T cells in the immune system. Other proteins of interest were chemokine (c-c motif) ligand and interleukin 8 that both correlated to poorer prognosis in G3 pancreatic NEN patients. More studies are needed for further understanding of the roles and clinical relevance of immuno-oncological proteins in G3 pancreatic NENs.

    Finally, we evaluated whether intravenous or oral administration of etoposide differed with regards to PFS and OS in patients with G3 GEP-NENs. There was no significant difference in PFS nor OS between patients receiving oral compared to intravenous etoposide; demonstrating that an oral option of etoposide is not inferior in its efficacy as compared to the more used intravenous formulation. These results suggest that considering oral options of etoposide is important since they are more often preferred by patients, increase the quality of life for the patients and reduce hospital costs.

    This thesis has contributed to an understanding of the distribution and clinical relevance of p53 and PD-L1 in GEP-NENs. A potential role of FasL, chemokine and interleukin 8 as prognostic and/or diagnostic factors in pancreatic G3 NENs has been identified and should be further investigated. The thesis also gave some insight into the role of oral etoposide as an alternative option to intravenous formulation with regards to efficacy. Oral formulations are preferred by many patients and improve quality of life while decreasing hospital-related costs. Further studies are needed to compare the tolerability of oral formulation compared to the intravenous formulation.