Coming dissertations at MedFak
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Optimizing diagnostics and follow-up of patients with ureterolithiasis
Link: http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-525618
Urolithiasis is increasing in incidence worldwide and subsequently so is the demand for customized imaging. Optimizing imaging strategies is needed to reduce radiation dose, time, and cost. This thesis investigated aspects of CT-diagnostics for patients with ureterolithiasis.
In paper I the rate of urinary obstruction, the predictive value of secondary signs of obstruction, stone size and location, and renal cortical enhancement was assessed in 49 patients with a remaining stone at follow-up CT after a renal colic attack. A dynamic protocol was used to grade urinary obstruction and associated radiation doses evaluated. In paper II, renal parenchymal volumes were measured in CT-scans before, during and after an acute ureteral obstruction using 3D-segmentation in 20 patients. In paper III the interreader variability in stone size measurements in four different window settings was investigated in 124 patients with a proximal ureteral stone. In paper IV, patient reported symptoms was correlated to the degree of obstruction (defined with the dynamic protocol) in 81 patients with a remaining ureteral stone at follow-up.
Obstruction was present in 28% (n=14). The absence of hydronephrosis and hydroureter had a negative predictive value (NPV) of 1.0. Stone characteristics were not associated with obstruction. Cortical enhancement was lower in obstructed kidneys. 1.8 mSv was saved using a dynamic scan compared to an excretory phase. Renal parenchymal volume decreased with 24% in the obstructed and 5% in the healthy kidney after obstruction. Interreader variability was ±1.6 mm (bone window), ±0.4 mm (soft tissue window), ±0.3 mm (half-value MEAN window) and ±0.2 mm (half-value MAX window). In total 47% (n=38) with a remaining stone were asymptomatic. Of these 11% (n=4) had a mild degree of obstruction. All patients with moderate or severe obstruction reported symptoms at follow-up.
In conclusion, urinary obstruction was scarce in patients with a remaining ureteral stone at follow-up. Absence of hydronephrosis and hydroureter was a strong negative predictor of obstruction. A dynamic protocol saved radiation dose. Obstructed kidneys increased in parenchymal volume during obstruction and so did the contralateral kidney to a lesser extent. Interreader variability in stone size measurements is unsatisfying in the bone window and smallest in the half-value MAX window. Symptoms is an uncertain tool to rule out the presence of a remaining ureteral stone and obstruction at follow-up.
The findings in this thesis contribute to the knowledge of CT-diagnostics in ureterolithiasis that may help sharpen the radiological work-up for patients with ureterolithiasis.
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A Mosquito's Guide to Viral Emergence : Unveiling Mosquito-Borne Virus Transmission Dynamics, Vector Competence, and Genetic Evolution
Link: http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-525544
In the complex world of disease transmission, mosquitoes often take centre stage as unwitting actors in the spread of viruses that threaten human and animal health. Imagine this: a tiny mosquito, often overlooked in the grand scheme of nature, carrying within it the potential to cause widespread disease, earning it the title of the world's deadliest animal. This doctoral thesis explores the captivating realm of mosquito-borne viruses, shedding light on their emergence, transmission dynamics, and evolutionary development.Arboviruses such as Japanese encephalitis virus (JEV), Usutu virus (USUV) and chikungunya virus (CHIKV) pose a significant global health problem given their increasing spread, particularly in growing urban areas, and amid today’s climate variations and change. It is important to understand the transmission dynamics of these viruses. In particular, USUV, which is transmitted by Culex mosquitoes, is increasingly being reported in Europe. This warrants an understanding of the vector competence of different European mosquito species to predict and manage potential outbreaks. Similarly, JEV is widespread in Asia and, given the climatic similarities, warrants an investigation into the vector competence of European mosquito species. CHIKV with its different lineages emphasises the need to understand its evolutionary history in order to predict and contain future outbreaks.This work has three objectives. To determine the abundance of JEV vector mosquitoes in Hanoi, Vietnam, to assess the vector competence of Swedish mosquitoes for USUV and JEV, and to analyse the factors that contributed to the 2018 CHIKV outbreak in Thailand. Field collections in Vietnam analysed Culex populations and correlated seasonal abundance with disease incidence. Vector competence experiments revealed USUV transmission potential and emphasised the inability of JEV transmission by Swedish Cx. pipiens. A genomic analysis of CHIKV traced its evolutionary development and provided insight into the dynamics of the 2018 outbreak.The historical context of mosquito-borne viruses emphasises their evolutionary origins and highlights the need for a comprehensive understanding. The results of the thesis contribute to insights into vector abundance dynamics, vector competence, and viral evolution, all critical aspects for disease surveillance and control. Future research approaches include assessing the competence of additional mosquito species, investigating environmental influences on transmission and exploring the immune responses of mosquitoes.Continuous surveillance, molecular epidemiology and innovative methods of vector control are crucial for containing the spread of viruses. Interdisciplinary collaboration and a "One Health" approach are essential for comprehensive disease prevention and control strategies. By improving our understanding of the dynamics of mosquito-borne viruses, we can better protect public health in the face of emerging infectious diseases.
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Astrocytes in Alzheimer’s disease : Exploring the impact of amyloid-β pathology on neurotoxicity, metabolism and inflammation.
Link: http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-525110
Astrocytes play a central role in brain homeostasis, but are also tightly connected to the pathogenesis of Alzheimer’s disease (AD). Yet, their exact role in amyloid-beta (Aβ) pathology and chronic neuroinflammation is unclear. The aim of this thesis was to elucidate the impact of astrocytes in AD progression. For this purpose, astrocytes in different culture set-ups were exposed to soluble Aβ aggregates. The astrocytes engulf and process, but fail to fully degrade the Aβ aggregates, which are instead stored as large intracellular deposits. In Paper I, we show that extracellular vesicles (EVs), secreted from the Aβ-containing cells induce synaptic loss, axonal swelling and vacuolization of primary neurons, which consequently leads to apoptosis.
Astrocytes play a central role in the brain’s energy metabolism and we were therefore interested in how Aβ pathology affects their metabolism. In Paper II, we report that Aβ accumulation in astrocytes disrupts mitochondrial fission/fusion homeostasis, resulting in decreased mitochondrial respiration and altered glycolysis. Interestingly, the astrocytes switch to fatty acid β oxidation with the aid of peroxisomes to maintain stable energy production.
Another important task is to understand how astrocytes modify the ingested Aβ. In Paper III, we characterized the astrocytic Aβ inclusions by isolating them with magnetic beads. Our analysis showed that the astrocytes truncate and pack together the Aβ aggregates. Moreover, we found that astrocytes release specifically truncated forms of Aβ via different routes.
Astrocytes’ involvement in lipid metabolism and inflammation has recently gained much interest, but many questions remain about the connection between these processes. In Paper IV, we show that Aβ pathology causes lipid droplet (LD) accumulation in astrocytes. Moreover, we could show that astrocytes frequently transfer LDs to neighboring cells, both through direct cell-to-cell contacts and via secretion. Astrocytes have previously been reported to express major histocompatibility complex II (MHCII) and have the capacity to perform as professional antigen presenting cells. Interestingly, our results demonstrate that LDs contain MHCII, identifying a link between LDs and inflammation in astrocytes.
Taken together, this thesis contributes with important knowledge of the role of astrocytes in AD pathology.