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Coming dissertations at MedFak

  • Early identification of motor problems in very preterm infants : An evaluation of the Structured Observation of Motor Performance in Infants Author: Cecilia Montgomery Link: http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-437358 Publication date: 2021-04-12 14:35

    Infants born very preterm are at risk of adverse neurodevelopment. It is important to identify motor problems early to initiate interventions aiming at ameliorating outcomes. Evaluating motor development in high-risk infants is a complex task. There is a need for assessment methods for early identification of abnormal motor performance. 

    The aim of this thesis was to evalute the Structured Observation of Motor Performance in Infants (SOMP-I) method for early identification of motor problems in very preterm children and to investigate early motor performance in relation to neonatal characteristics, cerebral imaging and later outcome. Level of motor development and quality of motor performance was assessed at 2, 4, 6, and 10 months’ of corrected age. 

    Study I validated the revised SOMP-I, and compared early motor performance in 111 very preterm infants with 72 full-term infants. The preterm infants were more delayed and had more quality deficits than the term infants, and the groups had different motor trajectories. We concluded that convergent validity and discriminant validity of the SOMP-I was supported and facilitated early identification of infants with atypical motor development.

    Study II investigated SOMP-I results in relation to motor outcome (Bayley-III motor index at 2.5 years) in 98 very preterm children. The 28 children with delayed development had significantly poorer SOMP-I scores in infancy. We concluded that level and quality of motor performance were significant markers of later motor problems and quality became more significant with increasing age. 

    Study III investigated early motor performance (SOMP-I), in relation to neurodevelopment and motor competence at 12 years (Movement ABC-2) in 78 very preterm children. At all assessment ages, there were significant associations between SOMP-I and MABC-2 scores. At 6 and 10 months, SOMP-I level and quality scores separately explained unique variance of the MABC-2 scores at 12 years. 

    Study IV explored the relation between neonatal cerebral MRI (morphology, apparent diffusion coefficient, regional brain volumes) and 4-month motor performance (SOMP-I), in relation to 2-year motor outcome in 66 very preterm infants (11 with motor problems). SOMP-I results correlated with several MRI measures and with motor outcome. The level of motor performance had the highest predictive value for motor outcome. 

    Overall conclusion: The two SOMP-I domains, level and quality, explain unique variances towards later motor outcomes, meaning that the two separate domains give added value to the motor assessment and are useful markers of motor outcome in very preterm infants.

  • Exploring medical applications of a bioactive polymer Author: Felix Sellberg Link: http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-437508 Publication date: 2021-04-07 13:29

    In this thesis, we have studied a polymeric compound called PVAC, designed as a scavenger of reactive electrophilic substances. We explored several diseases where these substances are overproduced.

    In Paper I, adhesion formation was induced via bowel anastomosis surgery in rats. Formation of adhesions is a process driven by hypoxia and reactive electrophilic substances; we hypothesised that PVAC could stop the processes if administered peri-surgery. PVAC was administered in two different ways, as a peritoneal lavage post-surgery and as an addition to the sutures used during the surgery. When sutures were impregnated with PVAC before surgery, weaker adhesion formation was observed at the surgery site. No difference was noted between PVAC treated and control animals when it was delivered via lavage. Another situation where electrophiles are a problem was studied in Paper II, haemolysis. Haemolysis in vitro is a process driven by oxidative processes during the storage of red blood cells. When storage media was supplemented with PVAC, a dose-dependent decrease in haemolysis and increased red blood cell stability was observed.

    In Paper III, we investigated the effects of PVAC as an anti-tumoural agent based on observations in cell cultures. When cell lines were cultured in the presence of PVAC, a reduction in viability of cells was observed. When PVAC was studied in animal models, we found an effect of the polymer in melanoma in immunocompetent mice but not in breast cancer in athymic mice. When tumour biopsies were studied, increased T cell infiltration was noted in PVAC treated animals. An immune-mediated mechanism might explain why no effect was seen in the athymic mice since they lack an adaptive immune system.

    In Paper IV, we labelled PVAC using a radioactive tracer, [18F]FBA, to detect PVAC in a PET camera. Rats underwent surgery to induce ischaemia reperfusion injury in kidneys or limbs. [18F]FBA PVAC accumulated in the ischaemic tissue after I.V administration, it was possible to distinguish the injured area after 20 minutes. Since reactive electrophiles are also mediators of disease in ischaemia reperfusion injury we aim to investigate if PVAC has therapeutic potential in addition to the ability to detect ischaemia.

    To conclude, we have explored PVAC as an example of a bioactive polymer. We feel that the compound group is underused in medicine that we hope this thesis will prime more researchers to explore.

  • Polycystic Ovary Syndrome and Pregnancy : Prenatal Exposures and Pregnancy Complications Author: Heiddis Valgeirsdóttir Link: http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-435482 Publication date: 2021-04-01 13:09

    Polycystic ovary syndrome (PCOS) is the most common endocrine disorder in women of fertile age. The aetiology of PCOS is not fully understood and might be affected by foetal exposures. Women with PCOS have an increased risk of pregnancy complications, but information on rare severe complications is scarce.

    The overall aim of this thesis was to gain further knowledge of the association between the intrauterine environment and development of PCOS in offspring, and the association between maternal PCOS and adverse pregnancy outcomes, with a focus on preterm birth and stillbirth.

    This thesis includes three nationwide register-based cohort studies and one matched cohort study including early second-trimester blood samples. Associations were estimated with multivariate Cox, logistic and linear regression models, with adjustment for confounders including body mass index. Correlations were estimated with Spearman’s rank correlation coefficient.

    It was found that maternal overweight and obesity, and smoking during pregnancy, were associated with increased risk for female offspring to develop PCOS later in life compared with offspring of normal weight and non-smoking mothers, respectively. Size at birth was not associated with the risk of PCOS development. During pregnancy, women with PCOS had higher second-trimester levels of anti-Müllerian hormone (AMH) and testosterone than non-PCOS women, and AMH levels were positively correlated with total testosterone levels. High AMH levels were not associated with an increased risk of pregnancy complications. Women with PCOS seemed at increased risk of extremely, very, and moderately preterm birth compared with non-PCOS women. The association was strongest for extremely preterm birth of spontaneous onset. Women with PCOS also seemed at increased risk of stillbirth compared with non-PCOS women, and the rate of stillbirth in PCOS women was particularly high in term pregnancy.

    In conclusion, increased maternal BMI and maternal smoking may increase the risk of PCOS in offspring. Even though second-trimester AMH levels are higher in pregnant women with PCOS than controls, AMH seems not to be a mediator of increased risk for pregnancy complications in PCOS women. PCOS should be considered a risk factor for severe pregnancy complications such as extremely preterm birth and stillbirth.

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