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- Aydogdu, Özgu, 1978, et al.
(författare)
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Urinary tract infection: Europe.
- 2011
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Ingår i: Guide to Pediatric Urology and Surgery in Clinical Practice. - 9781849963664 ; , s. 21-34
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Bokkapitel (övrigt vetenskapligt/konstnärligt)
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| 3. |
- Klaric, Lucija, et al.
(författare)
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Mendelian randomisation identifies alternative splicing of the FAS death receptor as a mediator of severe COVID-19.
- 2021
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Ingår i: medRxiv : the preprint server for health sciences. - : Cold Spring Harbor Laboratory. ; , s. 1-28
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Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- Severe COVID-19 is characterised by immunopathology and epithelial injury. Proteomic studies have identified circulating proteins that are biomarkers of severe COVID-19, but cannot distinguish correlation from causation. To address this, we performed Mendelian randomisation (MR) to identify proteins that mediate severe COVID-19. Using protein quantitative trait loci (pQTL) data from the SCALLOP consortium, involving meta-analysis of up to 26,494 individuals, and COVID-19 genome-wide association data from the Host Genetics Initiative, we performed MR for 157 COVID-19 severity protein biomarkers. We identified significant MR results for five proteins: FAS, TNFRSF10A, CCL2, EPHB4 and LGALS9. Further evaluation of these candidates using sensitivity analyses and colocalization testing provided strong evidence to implicate the apoptosis-associated cytokine receptor FAS as a causal mediator of severe COVID-19. This effect was specific to severe disease. Using RNA-seq data from 4,778 individuals, we demonstrate that the pQTL at the FAS locus results from genetically influenced alternate splicing causing skipping of exon 6. We show that the risk allele for very severe COVID-19 increases the proportion of transcripts lacking exon 6, and thereby increases soluble FAS. Soluble FAS acts as a decoy receptor for FAS-ligand, inhibiting apoptosis induced through membrane-bound FAS. In summary, we demonstrate a novel genetic mechanism that contributes to risk of severe of COVID-19, highlighting a pathway that may be a promising therapeutic target.
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- Kampmann, Christian, 1975-
(författare)
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Go with your gut : The human intestinal microbiota, international travel, Campylobacter and ESBL-producing Enterobacteriaceae
- 2021
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Up to 100 million people travel annually from industrialized countries to resource-limited ones. Each traveller contains an internal ecosystem composed of tens of trillions of microbes, known as the intestinal microbiota, which has a large effect on health. The microbiota seems to be highly individual and mostly stable but can be significantly affected by several factors. Many international travellers are at high risk of getting infected by Campylobacter, the most common cause of bacterial enteritis worldwide. Campylobacter infection can cause a wide range of symptoms, with varying severity, for reasons largely unknown. Travel also radically increases the risk of colonization by antibiotic-resistant intestinal bacteria, notably Extended spectrum beta-lactamase (ESBL)-producing Enterobacteriaceae (EPE). To date, there are no therapies available for EPE-decolonization. In this thesis, it was investigated whether the bacterial intestinal microbiota affected susceptibility to Campylobacter and if international travel as such had an impact on the microbiota. In a prospective, observational study, 67 healthy Swedes, travelling in groups to countries with a high risk of Campylobacter infection, were followed. The travellers answered questionnaires and delivered two faecal samples before and three samples after the trip. These samples were cultured for enteropathogens and analysed for the microbiota composition. Low diversity of microbiota seemed to increase the risk of Campylobacter jejuni infection, whereas a high relative abundance of Lachnospiraceae might decrease the risk (Paper I). Furthermore, the overall bacterial diversity did not seem to change in connection with travelling. However, the bacterial family Enterobacteriaceae (otherwise connected with inflammation, infection and antibiotic-resistance) was shown to be dramatically increased in abundance immediately after travel, and the family Christensenellaceae (otherwise connected with beneficial health conditions) simultaneously decreased (Paper II). Eight travellers, from two different destinations, were infected with closely related C. jejuni isolates (ST353CC). The bacterial analysis of genomic and phenotypic characteristics revealed that the C. jejuni isolates of the travellers returning from one of the destinations and with more severe symptoms actually showed less pathogenic potential, compared to the isolates of travellers from the other destination and with milder symptoms. However, the travellers with more severe symptoms had much higher relative abundances of Bacteroidetes in their intestinal microbiota and, in contrast to the other travellers, excluded meat from their diet. (Paper III) Finally, we investigated in a randomized, placebo-controlled clinical trial of 80 established intestinal carriers of EPE, whether the oral probiotic product Vivomixx® could eradicate EPE. Vivomixx® was not superior to placebo (Paper IV).
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- Byenfeldt, Marie, 1967-
(författare)
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Ultrasound based shear wave elastography of the liver : a non-invasive method for evaluation of liver disease
- 2020
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Background: Detecting liver disease at an early stage is important, given that early intervention decreases the risk of developing cirrhosis and subsequently hepatocellular cancer (HCC). The non-invasive ultrasound-based shear wave elastography (SWE) has been used clinically for a decade to assess liver stiffness. This method is reliable, rapid and can be performed in an outpatient setting without known risks for the patient. However, increased variance in SWE results has been detected, without clear explanation. Factors that affect SWE results needs to be identified. Data are insufficient regarding the reliability of SWE with different body positions and probe pressures. Men have higher SWE results than women, also for unclear reasons. Increasing the reliability of SWE is crucial for understanding how factors such as overweight and obesity, cardiovascular and antiviral medication, age, sex, smoking habits, hepatic steatosis and cirrhosis affect SWE results.Aims: The overall aim of the studies included in this thesis was to increase the reliability of SWE liver. The specific aims were to investigate patient-related factors associated with increased uncertainty in SWE results. Another aim was to investigate the influence of increased intercostal probe pressure on liver stiffness assessment with SWE liver. The final aims were to investigate the influence of postural changes, sagittal abdominal diameter (SAD) and skin-to-liver capsule distance (SCD) on SWE results, along with sex-based differences for SWE results and cardiovascular medication.Methods: All enrolled participants in these studies were consecutive patients with various liver diseases presenting at the radiology department Östersunds Hospital. The patients were examined using SWE liver method at the ultrasound unit between April 2014 and May 2018. Inclusion criteria were that participants be adults (age ≥18 years) who had provided written consent for participating in the study. The exclusion criterion was an inability to communicate. Current guidelines for SWE of the liver were used in the thesis with the following exceptions: In study II, increased intercostal probe pressure was used, and in study III, postural change was used. Study I included 188 patients; study II included 112 patients, and studies III and IV involved 200 patients. The four studies were conducted as cross-sectional and clinical trial, using quantitative methods.Results: Factors associated with low variance for SWE results were age, sex, and presence of cirrhosis, the use of antiviral and/or cardiovascular medication, smoking habits, and body mass index. Factors associated with increased uncertainty in SWE results were increased SCD and the presence of steatosis. With increased probe pressure SCD decreased and the quality of shear wave increased. The results showed that the number of required measurements can be reduced. A postural change to left decubitus decreased SCD. For patients with increased SAD and increased SWE result in the supine position, SWE result decreased with a postural change to left decubitus. The SWE results, SCD and SAD significantly differed between women and men. SWE results was higher in the presence of increased SAD (≥23 cm) among men, but not among women.Conclusions: SWE of the liver is a reliable, non-invasive method for diagnosing liver disease. Results in this thesis suggest that for patients with SCD ≥2.5 cm, shear wave measures could be of poor quality and the SWE exam less reliable. In these cases, increased probe pressure may facilitate a reliable SWE exam. With such adjustments in probe pressure, the ultrasound-based SWE method can be superior for examination in patients with overweight or obesity. An effect of SAD ≥23 cm was seen for men with liver fibrosis only, which may explain the higher SWE result for men compared to women. Depending on the severity of liver disease and SAD, a postural change to left decubitus can produce a different outcome. As SAD increased, liver stiffness did, as well. Increased SAD thus is linked to increased liver stiffness, indicating that SAD should be taken into account when performing SWE of the liver.
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| 10. |
- Wennergren, Göran, 1947
(författare)
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I en sal på lasarettet
- 2022
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Ingår i: Barnläkaren. - 1651-0534. ; :6
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Recension (övrigt vetenskapligt/konstnärligt)
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