Coming dissertations at MedFak
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Vaginal microbiota composition and function : Its relation to HPV, cervical dysplasia, and reproductive and general health
Link: http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-536918
The overall aim of this thesis was to study the vaginal microbiota and its role in both health and pathogenic processes, with a particular focus on HPV infection and the dysplastic progression to cervical cancer.
In paper I, a systematic review and meta-analysis were conducted to assess current findings on the association between the vaginal microbiota and HPV-related disease. It was found that a vaginal microbiota dominated by non-Lactobacilli species or L. iners was associated with HPV infection and dysplasia/cervical cancer, while L. crispatus was associated with healthy women.
Paper II investigated the association between different compositions of the vaginal microbiota and HPV infection in a population of young Swedish women. A strong association was identified between non-lactobacilli dominated vaginal microbiota and HPV infection. This association was observed for both low-risk and high-risk HPV, as well as for infections involving single and multiple HPV types. Bacteria more prevalent among women with HPV infection included BVAB 1, BVAB 2, Sneathia, Prevotella and Megasphaera.
In paper III, the association between different compositions of the vaginal microbiota and cervical dysplasia was explored. The study demonstrated that women with cervical dysplasia had higher microbiota diversity and were more likely to have a non-lactobacilli dominated microbiota. Women with dysplasia exhibited a higher abundance of Gardnerella vaginalis, Aerococcus christensenii, Peptoniphilus lacrimalis and Fannyhessae vaginae, while healthy controls had higher abundance of L. crispatus. Furthermore, differences in functional pathways were found, suggesting a more active role of the vaginal microbiota in the development of cervical dysplasia.
In paper IV, the vaginal microbiota among healthy women was characterised, and health and lifestyle factors that contribute to microbial variations were identified. The study revealed that the most prevalent species in the vaginal microbiota were L. crispatus, followed by L. iners and G. vaginalis. Furthermore, it showed that the main factors influencing microbial composition were age, BMI and having biological children.
In conclusion, the vaginal microbiota of most women consists mainly of lactobacilli species. Both intrinsic factors (e.g. age and BMI) as well as external factors (e.g. infections) contribute to compositional and functional variations of the vaginal microbiota. Further studies are needed to better understand the potential role of the microbiota in both gynaecological health and disease. In addition, more research on the vaginal microbiota and its association with HPV-related disease could prove beneficial for prevention, early detection and treatment.
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Spinal Stenosis : Clinical and Radiological Studies
Link: http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-534193
Background: Lumbar spinal stenosis (LSS) causes back pain, leg pain and restricted walking ability. There is sometimes a coexisting degenerative spondylolisthesis (DS), where one vertebra has slipped anteriorly to the one below. LSS is the most common cause for spinal surgery, and the annual rate of surgery is increasing in Europe and the US. The original surgical method is decompression-alone, in which the surgeon resects just enough tissue to create space for the neural structures, while maintaining motion and stability between the vertebrae. Decompression with fusion is a more complex method in which a stabilising bone bridge is created at the decompressed level, usually supported by screws and rods.
Aims: The primary aim of the thesis was to determine whether decompression-alone is sufficient, or if decompression with fusion generates better outcomes. A secondary aim, explored in paper IV, was to explore if patients with new radiological stenosis also had worse clinical outcome at two-year follow-up.
Methods: All papers are based on the Swedish Spinal Stenosis Study, an RCT randomising 233 LSS patients with or without DS to decompression-alone or decompression with fusion. Clinical, radiological and health economical parameters were collected from baseline up to five years after surgery. In papers I-III, data were analysed according to randomisation. In paper IV, SSSS patients are analysed as a cohort, disregarding the original randomisation.
Results: In papers I-III the fusion group had longer operating time, more perioperative bleeding and higher direct cost per procedure than decompression-alone. Two-year clinical outcomes did not differ between the groups, whereas at five years three secondary clinical outcomes were better for decompression-alone. The rate of new radiological stenosis at two-year MRI was higher in the fusion group. Reoperation rates did not differ between the groups. In paper IV no correlation was found between clinical outcomes and new radiological stenosis at two year follow-up. The presence of preoperative DS did not affect any of the results.
Conclusion: In LSS surgery, decompression-alone should generally be the method of choice, with or without preoperative DS present. Findings of new radiological stenosis two years after spinal stenosis surgery may well be present also among asymptomatic individuals.
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Finding stroke with a blood test
Link: http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-536281
In contrast to many other diseases and conditions, there is no established blood-based biomarker to aid in the diagnosis, prognosis, or outcome prediction of stroke. The neurospecific proteins glial fibrillary acidic protein (GFAP), myelin basic protein, neurofilament light (NFL), tau, and ubiquitin carboxy-terminal hydrolase L1 are released into blood in response to injurious processes affecting the central nervous system. This thesis aims to enhance the understanding of if, how, and when these biomarkers can provide important information in stroke and stroke-related disorders and which should be the focus for further translation into a useful blood test for stroke.
Firstly, we determined how and at which concentrations these biomarkers are distributed in the human CNS. We found substantial variation between brain regions, indicating that these biomarkers' circulating levels are likely affected by both the size and location of a cerebral insult.
After that, we investigated how plasma levels of these biomarkers change during the first week after an ischemic stroke and determined the optimal time point for assessing infarct volume. Undoubtedly, GFAP was the most optimal biomarker to assess infarct volume in the acute phase, while NFL was better suited to evaluate infarct volume one week to three months after symptom onset.
The findings indicated that NFL holds information long after a cerebrovascular event, so we analyzed plasma NFL in patients undergoing the cardiac procedure transcatheter aortic valve implantation, which is associated with a high frequency of relatively small and covert brain infarcts. We found that NFL increased by 60% after the procedure, which in approximative numbers corresponds to 1 cm3 infarcted brain tissue, similar to the previously reported mean lesion size after the procedure, indicating that NFL may contribute to the detection of procedure-related insults.
Finally, we analyzed serum NFL in patients with atrial fibrillation (AF), a cardiac disease associated with both overt and covert brain infarcts, and in matched controls. We discovered that patients with AF had slightly elevated levels of NFL and that patients with ongoing AF rhythm had the highest levels, indicating that the cerebrovascular pathologies associated with AF may, at least in part, be reflected by NFL.
In summary, this thesis has contributed to the understanding of how and when these biomarkers provide information about stroke and stroke-related disorders. Future studies should aim to further NFL and GFAP into the clinical management of cerebrovascular disease.