Coming theses from other universities
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Various aspects of hemithyroidectomy : Towards individualized treatment
Link: http://urn.kb.se/resolve?urn=urn:nbn:se:liu:diva-208071
There are mainly two indications in patients with enlarged thyroid for which a hemithyroidectomy is recommended: (1) surgery as a therapeutic procedure to improve compression symptoms and (2) surgery as a diagnostic procedure to confirm or rule out thyroid malignancy. This thesis evaluates which patients benefit more from hemithyroidectomy and examines the patients' perspectives, which can provide knowledge that can be implemented in meetings with patients.
Paper I was a preclinical study of fine-needle aspiration cytology (FNAC) from the thyroid gland. The study evaluated if the addition of a molecular BRAF-V600E mutation analysis could detect more papillary thyroid cancers in the palpation-guided FNAC group. The results showed that adding BRAF-V600E mutation analysis might significantly increase the proportion of papillary thyroid cancers diagnosed preoperatively in the palpation-guided FNAC group.
Paper II was a retrospective cohort study from a well-established Scandinavian quality register (SQRTPA). Retrospective data for two different hemithyroidectomy indications were collected, to exclude malignancy or as a therapeutic procedure. The study showed that the excised thyroid weight was an independent risk factor for bleeding, and permanent recurrent laryngeal nerve paresis was less common in the excluding malignancy group.
Paper III was a prospective cohort study of patients with compressive symptoms who underwent hemithyroidectomy due to an enlarged thyroid. Seventy-two patients filled in four different questionnaires before and after hemithyroidectomy and objective measurements of the enlarged thyroid were registered before the operation. Most of the patients benefited from hemithyroidectomy, however, many patients had voice impairments 6 weeks after the operation. No correlation was found between the symptom changes and the preoperative measurements of the thyroid lobe.
Paper IV was a qualitative interview study on 16 patients with compression symptoms from an enlarged thyroid who underwent a hemithyroidectomy. The data were analysed using conventional content analysis. The analysis revealed two main categories. Patients experienced postoperative symptoms that affected their daily life and postoperative symptoms that made the patients develop coping strategies. A subcategory showed that the patients had concerns about the future.
This thesis reinforces that a successful choice of hemithyroidectomy begins with a well-informed patient and professional counselling based on the patient's condition and preferences. A holistic perspective of the patients is central for individualized treatment.
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In vitro and in silico approach methods for developmental neurotoxicity assessment : Examining acrylamide
Link: http://urn.kb.se/resolve?urn=urn:nbn:se:su:diva-232557
Developmental neurotoxicity (DNT) is a branch of toxicology that examines the effects of chemicals on the developing nervous system. Traditional methods for assessing DNT mainly rely on animal testing, which raises ethical concerns, is time-consuming, and expensive. Consequently, there is a shift towards alternative methods, such as in vitro and in silico approaches, which offer faster and more efficient testing. The overall aim of this thesis was to contribute to the development and integration of alternative methods for DNT assessment, employing both in vitro and in silico techniques. In this work, the human neuroblastoma SH-SY5Y cell line was utilized as a robust, cost-effective, and easy-to-use model for DNT evaluation. Through RNA sequencing and morphological observation, it was determined that the SH-SY5Y cell line can differentiate into a more neuron-like phenotype (Paper I). Additionally, neurite outgrowth and the mRNA expression of genes important for neuronal development were studied by exposing the cells to chemicals known to induce DNT (Paper II). The thesis has also focused on acrylamide, a neurotoxic compound that may also cause DNT. In Paper I, it was found that acrylamide inhibited neuronal differentiation by suppressing neurite outgrowth at non-cytotoxic concentrations. Moreover, acrylamide altered the expression of several genes involved in the retinoic acid and CREB signaling pathways. The hypothesis that acrylamide impairs neuronal differentiation by depleting glutathione, leading to oxidative stress, was tested but not supported in the SH-SY5Y cells (Paper III). In Paper IV, we performed an in vitro to in vivo extrapolation by using a novel physiologically based toxicokinetic (PBTK) model for pregnant women, to assess the biological relevance of the acrylamide concentrations that affected neuronal differentiation of SH-SY5Y cells. The results revealed that doses that humans may be exposed to through food intake, resulted in fetal plasma acrylamide concentrations in the low nanomolar range. At these concentrations, attenuated neuronal differentiation has been observed in the SHSY5Y cells. Additionally, effects seen at micromolar concentrations were considered concerning for fetal health in cases of accidental exposure. In conclusion, human neuroblastoma SH-SY5Y cells can serve as a useful cell model for initial screening in DNT assessment, particularly for studying neuronal differentiation as a key neurodevelopmental process. Furthermore, this thesis suggests that acrylamide may pose a risk to the developing brain, as indicated by its effects on differentiation in SH-SY5Y cells and the extrapolation of in vitro concentrations to in vivo doses, by PBTK modeling. However, to validate these findings, further testing in more complex cell culture models is necessary.
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Nutrition, growth, and feeding problems in preterm infants
Link: http://urn.kb.se/resolve?urn=urn:nbn:se:umu:diva-229538
Background: Nutrition and growth in the preterm infant are fundamentally intertwined. Nutrition plays an important role in the care of the preterm infant, and especially so in the extremely preterm (EPT) infant. EPT infants have a high risk of malnutrition and poor growth, known to be associated with adverse outcomes. It is therefore important to study the nutrient intakes, factors affecting growth and other outcomes in this population of infants. Infants born preterm are at risk for developing iron overload due to erythrocyte transfusions. It is established that infants born preterm are at an increased risk of developing feeding difficulties in later childhood, but the underlying mechanisms remain unclear.
Methods: Three cohorts of infants born preterm were studied in this thesis. In Paper I (macronutrient intakes), data from a cohort of EPT infants born at two Swedish hospitals between 2011 and 2021 were collected. Paper II (transfusion and iron overload) used data from a cohort of very low birth weight infants (WLBW; <1500 g) treated at Umeå University Hospital born between 2010 and 2013. Papers III (catch-up growth) and IV (feeding problems after discharge) used data from the national EXtremely PREterm infants in Sweden Study (EXPRESS) between 2004 and 2007. Data collection for the three study populations included parenteral and enteral nutritional intakes, all anthropometric measurements during the hospitalisation, results of laboratory analyses, perinatal data, and neonatal morbidity.
Results: Paper I: Energy intakes between gestational weeks (GA) 29+0 and 33+6 were significantly different between the two studied hospitals. There were no differences regarding the intake of protein or carbohydrates, but intake of fat from lipid supplements was significantly higher at the hospital with higher energy intake, where a lower proportion of mother’s own milk was noted as well. There were no differences in growth between the two hospitals during the study period. Paper II: Almost all (91%) of the infants received erythrocyte transfusions, and a majority received multiple transfusions. Serum ferritin was significantly correlated with the total transfusion volume. Almost two thirds of the infants met criteria for iron overload. No effects on longitudinal growth could be found in relation to the erythrocyte transfusion dose. Paper III: Catch-up growth ≥1 SD was found in 67% of the EPT infants, with a mean increase of 1.9 standard deviation scores in z-weight during the catch-up growth. Infants that started a catch-up period had a higher enteral energy percentage from protein. Paper IV: Feeding problems diagnosed before 2 years of age and/or underweight at 2.5 years of age was found in 19% of the EPT infants in the cohort. The strongest risk factor for feeding problems was found to be longer duration of mechanical ventilation (≥10 d) during the neonatal period.
Conclusions: There was no difference in growth between the two hospitals although the energy and fat intakes were significantly different, suggesting that the lipid supplements may have limited absorption in general and when given with donor milk in particular. Almost two-thirds of VLBW infants had serum ferritin levels indicating iron overload, however, no association to longitudinal growth could be shown. A majority of EPT infants showed a period of catch-up growth in weight during the initial hospital stay. Infants with catch-up received a higher energy proportion from enteral protein during the week of catch-up growth initiation. Moreover, post discharge feeding problems are common in EPT infants, and the strongest perinatal risk factor was treatment with mechanical ventilation.