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Coming dissertations at MedFak

  • Studies on maternal body fat distribution in relation to infant outcomes Author: Emelie Lindberger Link: Publication date: 2021-11-19 08:35

    Background: Overweight and obesity are common amongst pregnant women and associated with adverse pregnancy outcomes for both the mother and the infant. Today, body mass index (BMI), not accounting for body fat distribution, is used for risk stratification during pregnancy. We hypothesize that maternal central adiposity is associated with pregnancy complications, independent of BMI, and that blood-based protein biomarkers differ between women with dissimilar body fat distributions, reflecting biological discrepancies.

    Objectives: This thesis aims at 1) systematically reviewing the current knowledge on the relation of maternal central adiposity with infant outcomes, 2) evaluating the association of ultrasound measured early mid pregnancy visceral and subcutaneous fat depths with infant birth size and adverse neonatal outcomes, and 3) investigating the relations of fat depth measures with maternal blood-based protein biomarkers. 

    Methods: A systematic review was performed including six databases searched from inception until November 2019. Studies evaluating maternal central adiposity in relation to infant outcomes were included. Two cohort studies were conducted during 2015–2018 at Uppsala University Hospital. Visceral and subcutaneous fat depths were measured by ultrasound at the second-trimester anomaly scan. Fat depths of 2,498 women were evaluated in relation to infant birth size. Body mass index and fat depths of 2,771 women were evaluated in relation to neonatal hypoglycaemia, a composite of adverse neonatal outcomes (5-minute Apgar score <7, umbilical artery pH ≤7.0, or admission to neonatal intensive care unit), and the individual components of the composite outcome. Olink Cardiovascular II panel was used to analyse 92 blood-based protein biomarkers in 201 pregnant women. The protein concentrations were evaluated in relation to the ultrasound measured fat depths.

    Results: The systematic review demonstrated associations of maternal central adiposity with infant birth size and caesarean section. The results of the cohort studies showed an association of early mid pregnancy visceral fat depth with infant birth size. Additionally, BMI (but not fat depths) was associated with neonatal hypoglycaemia and adverse neonatal outcomes. Four blood-based protein biomarkers differed between pregnant women with dissimilar body fat distributions.

    Conclusions: Early mid pregnancy visceral fat depth is associated with infant birth size and may be useful in models predicting infant macrosomia. However, more research is needed to determine the usefulness of fat depth measures in addition to BMI as markers of adverse neonatal outcomes. Further research on blood-based biomarkers might enlighten biological mechanisms linking maternal body fat distribution types to neonatal outcomes.

  • Deciphering neural networks in the somatosensory system using single-cell transcriptomics and rabies tracing Author: Jon E. T. Jakobsson Link: Publication date: 2021-11-17 13:10

    Itch has evolved to protect us from malicious parasites keen to suck our blood or lay their eggs in our skin. We can detect both the movement of these parasites and the toxins they introduce with specialized neurons called pruriceptors. When we feel an itch, we get a desire to scratch it. Scratching an itch eases the itch sensation, and this is thought to be regulated by neuronal circuits in the spinal cord. This reactive aspect of itch makes is an interesting system to study as it involves both sensory and motor circuitry. The spinal cord hosts a vast number of different neuronal cell types, and better understanding of these are needed to efficiently delineate the circuitry between them. 

    To find these cell types, we sequence the transcriptome of thousands of individual neurons in the dorsal horn of the spinal cord and identified 15 excitatory and 15 inhibitory neuronal populations (Paper I). Furthermore, we found that cell types expressing neuropeptide Y (NPY) contributed to the inhibition of chemically induced itch via the NPY receptor 2 (Paper II) and inhibition of somatostatin-induced itch via NPY receptor 1 (Paper III). We are currently mapping the neurons presynaptic to the NPY neurons using a Npy-Cre mouse line combined with monosynaptic rabies tracing and find inputs from the dorsal root ganglions, the spinal cord, and the brain (Paper IV). To help decipher circuit connectivity, we developed a method that links cell types expressing matching ligand and receptor pairs in single cell RNA-sequencing (scRNA-seq) datasets (Paper V). We furthermore used scRNA-seq to identify differences and similarities of locomotor circuitry related cells expressing doublesex and mab-3 related transcription factor 3 in zebrafish and mouse (Paper VI).

    In this thesis, we used a combination of powerful and novel tools to investigate questions that were previously difficult to address. It is my belief that spatial transcriptomics, now poised with the knowledge gained from scRNA-seq, will transform how we think about cell types in the central nervous system, since the location of a neuron is critical for its role in a circuit.

  • Treatment of abdominal and thoracic aortic aneurysms :  Aspects on epidemiology and surgical outcome Author: Kim Gunnarsson Link: Publication date: 2021-11-12 10:25

    Aortic Aneurysm (AA) is a life-threatening condition when ruptured (RAA), requiring immediate repair for survival. Since the 50´s, open repair, replacing the diseased vessel with a prosthetic (synthetic) graft, has been the gold standard. In the 90's, a new minimal invasive surgical technique, endovascular aneurysm repair (EVAR) was developed and has since become the dominant surgical method of choice in RAA treatment. The aim of this thesis is to assess trends in epidemiology, treatment and outcome of aortic aneurysms, with special focus on RAA.

    Paper I is a population-based registry study of all surgical procedures performed for ruptured abdominal aortic aneurysm (RAAA) in Sweden 2008-2012. In this time period, some centres adhered to a distinct EVAR first strategy for treatment of RAAA, whilst others primarily performed open repair for RAAA. The analysis demonstrated no difference in mortality comparing centres with EVAR or open repair as primary treatment strategy. 

    Paper II is a nationwide population-based register study presenting the epidemiology of all RAAA in Sweden from 1994 to 2013. The study demonstrated a decreasing mortality in RAAA over time, due to the combination of a falling incidence, increasing hospital admissions and increasing proportion of patients undergoing surgical repair. The survival after surgical intervention improved over time, mainly due to the introduction of EVAR.

    Paper III is a nationwide population-based register study to investigate long-term survival after ruptured abdominal aortic aneurysms (RAAA) repair in Sweden during twenty-four years (1994-2017). The study found that the long-term survival has improved over time, mainly explained by improved perioperative survival, despite that the operated patients generally became older and more fragile.

    Paper IV is a nationwide population-based register study covering the time period 1997 to 2017, assessing the epidemiology of operated intact and ruptured descending thoracic aortic aneurysms (dTAA and RdTAA) in Sweden. This analysis shows increased incidence of intact dTAA repair due to broad introduction of thoracic EVAR (TEVAR). Early postoperative mortality decreased, despite an increasing proportion of those undergoing repair being ≥80 years and with more comorbidities. No changes on incidence or mortality was detected among RdTAA repairs.

    In conclusion, modern treatment of aortic disease with endovascular techniques has resulted in a significant change in practice for treatment of RAA, and dTAA. The above-mentioned nationwide population-based register studies indicate that EVAR/TEVAR have resulted in improved survival of patients suffering from RAAA and the results after dTAA repair have improved.