| 1. |
- Kristensen, Karl, et al.
(författare)
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Continuous glucose monitoring in pregnant women with type 1 diabetes : an observational cohort study of 186 pregnancies
- 2019
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Ingår i: Diabetologia. - : Springer Science and Business Media LLC. - 0012-186X .- 1432-0428. ; 62:7, s. 1143-1153
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Tidskriftsartikel (refereegranskat)abstract
- Aims/hypothesis: The aim of this study was to analyse patterns of continuous glucose monitoring (CGM) data for associations with large for gestational age (LGA) infants and an adverse neonatal composite outcome (NCO) in pregnancies in women with type 1 diabetes. Methods: This was an observational cohort study of 186 pregnant women with type 1 diabetes in Sweden. The interstitial glucose readings from 92 real-time (rt) CGM and 94 intermittently viewed (i) CGM devices were used to calculate mean glucose, SD, CV%, time spent in target range (3.5–7.8 mmol/l), mean amplitude of glucose excursions and also high and low blood glucose indices (HBGI and LBGI, respectively). Electronic records provided information on maternal demographics and neonatal outcomes. Associations between CGM indices and neonatal outcomes were analysed by stepwise logistic regression analysis adjusted for confounders. Results: The number of infants born LGA was similar in rtCGM and iCGM users (52% vs 53%). In the combined group, elevated mean glucose levels in the second and the third trimester were significantly associated with LGA (OR 1.53, 95% CI 1.12, 2.08, and OR 1.57, 95% CI 1.12, 2.19, respectively). Furthermore, a high percentage of time in target in the second and the third trimester was associated with lower risk of LGA (OR 0.96, 95% CI 0.94, 0.99 and OR 0.97, 95% CI 0.95, 1.00, respectively). The same associations were found for mean glucose and for time in target and the risk of NCO in all trimesters. SD was significantly associated with LGA in the second trimester and with NCO in the third trimester. Glucose patterns did not differ between rtCGM and iCGM users except that rtCGM users had lower LBGI and spent less time below target. Conclusions/interpretation: Higher mean glucose levels, higher SD and less time in target range were associated with increased risk of LGA and NCO. Despite the use of CGM throughout pregnancy, the day-to-day glucose control was not optimal and the incidence of LGA remained high.
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| 2. |
- Ahnfeldt-Mollerup, Peder, et al.
(författare)
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Resource allocation and the burden of co-morbidities among patients diagnosed with chronic obstructive pulmonary disease : an observational cohort study from Danish general practice
- 2016
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Ingår i: BMC Health Services Research. - : Springer Science and Business Media LLC. - 1472-6963. ; 16:1
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Chronic obstructive pulmonary disease is a leading cause of mortality, and associated with increased healthcare utilization and healthcare expenditure. In several countries, morbidity-based systems have changed the way resources are allocated in general practice. In primary care, fee-for-services tariffs are often based on political negotiation rather than costing systems. The potential for comprehensive measures of patient morbidity to explain variation in negotiated expenditures for patients with chronic obstructive pulmonary disease has not previously been examined. The aim of this study is to analyze fee-for-service expenditure of patients diagnosed with chronic obstructive pulmonary disease visiting Danish general practice clinics and further to assess what proportion of fee-for-service expenditure variation was explained by patient morbidity and general practice clinic characteristics, respectively.METHODS: We used patient morbidity characteristics such as diagnostic markers and multi-morbidity adjustment based on adjusted clinical groups (ACGs) and fee-for-service expenditure for a sample of primary care patients for the year 2010. Our sample included 3,973 patients in 59 general practices. We used a multi-level approach.RESULTS: The average annual fee-for-service expenditure of caring for patients diagnosed with chronic obstructive pulmonary disease in general practice was about EUR 400 per patient. Variation in the expenditures was driven by multimorbidity characteristics up to 28 % where as characteristics such as age and gender only explained 5 %. Expenditures increased progressively with the degree of multimorbidity. In addition, expenditures were higher for patients who had diagnostic markers based on ICPC-2 (body systems and/or components such as infections and symptoms). Nevertheless, 9.8-15.4 % of the variation in expenditure was related to the clinic in which the patient was cared for.CONCLUSION: Patient morbidity and general practice clinic characteristics are significant patient-related fee-for-service expenditure drivers in chronic obstructive pulmonary disease care.
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| 3. |
- Ayres Pereira, Marina, et al.
(författare)
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Placental Sequestration of Plasmodium falciparum Malaria Parasites Is Mediated by the Interaction Between VAR2CSA and Chondroitin Sulfate A on Syndecan-1
- 2016
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Ingår i: PLoS Pathogens. - : Public Library of Science (PLoS). - 1553-7366 .- 1553-7374. ; 12:8
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Tidskriftsartikel (refereegranskat)abstract
- During placental malaria, Plasmodium falciparum infected erythrocytes sequester in the placenta, causing health problems for both the mother and fetus. The specific adherence is mediated by the VAR2CSA protein, which binds to placental chondroitin sulfate (CS) on chondroitin sulfate proteoglycans (CSPGs) in the placental syncytium. However, the identity of the CSPG core protein and the cellular impact of the interaction have remain elusive. In this study we identified the specific CSPG core protein to which the CS is attached, and characterized its exact placental location. VAR2CSA pull-down experiments using placental extracts from whole placenta or syncytiotrophoblast microvillous cell membranes showed three distinct CSPGs available for VAR2CSA adherence. Further examination of these three CSPGs by immunofluorescence and proximity ligation assays showed that syndecan-1 is the main receptor for VAR2CSA mediated placental adherence. We further show that the commonly used placental choriocarcinoma cell line, BeWo, express a different set of proteoglycans than those present on placental syncytiotrophoblast and may not be the most biologically relevant model to study placental malaria. Syncytial fusion of the BeWo cells, triggered by forskolin treatment, caused an increased expression of placental CS-modified syndecan-1. In line with this, we show that rVAR2 binding to placental CS impairs syndecan-1-related Src signaling in forskolin treated BeWo cells, but not in untreated cells.
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| 4. |
- Erlström, Mikael, et al.
(författare)
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Stratigraphy and geothermal assessment of Mesozoic sandstone reservoirs in the Öresund Basin - exemplified by well data and seismic profiles
- 2018
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Ingår i: Bulletin of the Geological Society of Denmark. - 0011-6297. ; 66, s. 123-149
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Tidskriftsartikel (refereegranskat)abstract
- The Øresund Basin in the transnational area between Sweden and Denmark forms a marginal part of the Danish Basin. The structural outline and stratigraphy of the Mesozoic succession is described, and a novel interpretation and description of the subsurface geology and geothermal potential in the North Sjælland Half-graben is presented. The subsurface bedrock in the basin includes several Mesozoic intervals with potential geothermal sandstone reservoirs. Parts of the succession fulfill specific geological requirements about distribution, composition and quality of the sandstones. A characterisation of these is presently of great interest in the attempt to identify geothermal reservoirs suitable for district heating purposes. The results presented in this paper include for the first time a comprehensive description of the stratigraphic intervals as well as the characteristics of the potential Mesozoic geothermal reservoirs in the Øresund region, including their distribution, composition and physical properties. This is illustrated by seismic cross-sections and well sections. In addition, results from analyses and evaluations of porosity, permeability, formation fluids and temperature are presented. Six potential geothermal reservoirs in the Mesozoic succession are described and assessed. Primary focus is placed on the characteristics of the reservoirs in the Lower Triassic and Rhaetian–Lower Jurassic succession. The study shows that the Mesozoic reservoir sandstones vary considerably with respect to porosity and permeability. Values range between 5–25% for the pre-Rhaetian Triassic sandstones, but are commonly > 25% for the Rhaetian–Lower Jurassic and Lower Cretaceous sandstones. The corresponding permeability rarely reaches above 500 mD for the pre-Rhaetian Triassic reservoirs, but often reach >1 Darcy for the Rhaetian–Lower Jurassic and the Lower Cretaceous sandstones. The interpreted formation temperatures for the reservoirs in the Øresund Basin are: 45–50°C at 1500 m, 60–70°C at 2000 m and 70–90°C at 2500 m depth . The combined results provide a geological framework for making site specific predictions regarding appraisal of viable geothermal projects for district heating purposes in the region as well as reducing the risk of unsuccessful wells
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| 5. |
- Flores-Morales, Amilcar, et al.
(författare)
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Proteogenomic characterization of patient-derived xenografts highlights the role of REST in neuroendocrine differentiation of castration-resistant prostate cancer
- 2019
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Ingår i: Clinical Cancer Research. - 1078-0432. ; 25:2, s. 595-608
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: An increasing number of castration-resistant prostate cancer (CRPC) tumors exhibit neuroendocrine (NE) features. NE prostate cancer (NEPC) has poor prognosis, and its development is poorly understood. Experimental Design: We applied mass spectrometry–based proteomics to a unique set of 17 prostate cancer patient–derived xenografts (PDX) to characterize the effects of castration in vivo, and the proteome differences between NEPC and prostate adenocarcinomas. Genome-wide profiling of REST-occupied regions in prostate cancer cells was correlated to the expression changes in vivo to investigate the role of the transcriptional repressor REST in castration-induced NEPC differentiation. Results: An average of 4,881 proteins were identified and quantified from each PDX. Proteins related to neurogenesis, cell-cycle regulation, and DNA repair were found upregulated and elevated in NEPC, while the reduced levels of proteins involved in mitochondrial functions suggested a prevalent glycolytic metabolism of NEPC tumors. Integration of the REST chromatin bound regions with expression changes indicated a direct role of REST in regulating neuronal gene expression in prostate cancer cells. Mechanistically, depletion of REST led to cell-cycle arrest in G1, which could be rescued by p53 knockdown. Finally, the expression of the REST-regulated gene secretagogin (SCGN) correlated with an increased risk of suffering disease relapse after radical prostatectomy. Conclusions: This study presents the first deep characterization of the proteome of NEPC and suggests that concomitant inhibition of REST and the p53 pathway would promote NEPC. We also identify SCGN as a novel prognostic marker in prostate cancer.
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| 6. |
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| 7. |
- Hollestelle, Antoinette, et al.
(författare)
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No clinical utility of KRAS variant rs61764370 for ovarian or breast cancer
- 2016
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Ingår i: Gynecologic Oncology. - : Elsevier BV. - 0090-8258 .- 1095-6859. ; 141:2, s. 386-401
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Tidskriftsartikel (refereegranskat)abstract
- Objective Clinical genetic testing is commercially available for rs61764370, an inherited variant residing in a KRAS 3′ UTR microRNA binding site, based on suggested associations with increased ovarian and breast cancer risk as well as with survival time. However, prior studies, emphasizing particular subgroups, were relatively small. Therefore, we comprehensively evaluated ovarian and breast cancer risks as well as clinical outcome associated with rs61764370. Methods Centralized genotyping and analysis were performed for 140,012 women enrolled in the Ovarian Cancer Association Consortium (15,357 ovarian cancer patients; 30,816 controls), the Breast Cancer Association Consortium (33,530 breast cancer patients; 37,640 controls), and the Consortium of Modifiers of BRCA1 and BRCA2 (14,765 BRCA1 and 7904 BRCA2 mutation carriers). Results We found no association with risk of ovarian cancer (OR = 0.99, 95% CI 0.94-1.04, p = 0.74) or breast cancer (OR = 0.98, 95% CI 0.94-1.01, p = 0.19) and results were consistent among mutation carriers (BRCA1, ovarian cancer HR = 1.09, 95% CI 0.97-1.23, p = 0.14, breast cancer HR = 1.04, 95% CI 0.97-1.12, p = 0.27; BRCA2, ovarian cancer HR = 0.89, 95% CI 0.71-1.13, p = 0.34, breast cancer HR = 1.06, 95% CI 0.94-1.19, p = 0.35). Null results were also obtained for associations with overall survival following ovarian cancer (HR = 0.94, 95% CI 0.83-1.07, p = 0.38), breast cancer (HR = 0.96, 95% CI 0.87-1.06, p = 0.38), and all other previously-reported associations. Conclusions rs61764370 is not associated with risk of ovarian or breast cancer nor with clinical outcome for patients with these cancers. Therefore, genotyping this variant has no clinical utility related to the prediction or management of these cancers.
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| 8. |
- Holm, Karin, et al.
(författare)
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The role of Fusobacterium necrophorum in pharyngotonsillitis – A review
- 2016
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Ingår i: Anaerobe. - : Elsevier BV. - 1075-9964. ; 42, s. 89-97
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Forskningsöversikt (refereegranskat)abstract
- Fusobacterium necrophorum is a gram-negative anaerobic bacterium that is the causative agent of the invasive disease Lemierre's syndrome. In addition, it is also associated with peritonsillar abscess formation and otitis media in small children. Recent research has shown that F. necrophorum may be involved in pharyngotonsillitis especially in adolescent and young adults and that it may be the second most common bacterial cause of pharyngotonsillitis after Streptococcus pyogenes (Group A streptococci). Peritonsillar abscesses and Lemierre's syndrome due to F. necrophorum are also found in this age group, suggesting that they may be complications of F. necrophorum pharyngotonsillitis. In this review we present the present knowledge about the role of F. necrophorum in pharyngotonsillitis with special emphasis on the age distribution. We argue that F. necrophorum is an important pathogen involved in pharyngotonsillitis in the age group of 13–40 years of age and we urge clinical microbiology labs to set up the appropriate techniques to be able to detect F. necrophorum from throat swabs.
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| 9. |
- Holm, Karin, et al.
(författare)
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Three variants of the leukotoxin gene in human isolates of Fusobacterium necrophorum subspecies funduliforme
- 2017
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Ingår i: Anaerobe. - : Elsevier BV. - 1075-9964. ; 45, s. 129-132
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Tidskriftsartikel (refereegranskat)abstract
- Leukotoxin is a well-known virulence factor of animal isolates of Fusobacterium necrophorum subspecies necrophorum, and is also expressed by animal isolates of subspecies funduliforme, whereas its presence in isolates from humans has not been fully established. In this study we found that the leukotoxin gene was present in all tested F. necrophorum isolates from humans. Three sequence variants were found, two of which have not been described previously. The sequence types correlated to source of infection. Further studies are needed to examine the role of the leukotoxin in human infections.
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| 10. |
- Lawrenson, Kate, et al.
(författare)
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Functional mechanisms underlying pleiotropic risk alleles at the 19p13.1 breast-ovarian cancer susceptibility locus
- 2016
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Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 7
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Tidskriftsartikel (refereegranskat)abstract
- A locus at 19p13 is associated with breast cancer (BC) and ovarian cancer (OC) risk. Here we analyse 438 SNPs in this region in 46,451 BC and 15,438 OC cases, 15,252 BRCA1 mutation carriers and 73,444 controls and identify 13 candidate causal SNPs associated with serous OC (P=9.2 × 10-20), ER-negative BC (P=1.1 × 10-13), BRCA1-associated BC (P=7.7 × 10-16) and triple negative BC (P-diff=2 × 10-5). Genotype-gene expression associations are identified for candidate target genes ANKLE1 (P=2 × 10-3) and ABHD8 (P<2 × 10-3). Chromosome conformation capture identifies interactions between four candidate SNPs and ABHD8, and luciferase assays indicate six risk alleles increased transactivation of the ADHD8 promoter. Targeted deletion of a region containing risk SNP rs56069439 in a putative enhancer induces ANKLE1 downregulation; and mRNA stability assays indicate functional effects for an ANKLE1 3′-UTR SNP. Altogether, these data suggest that multiple SNPs at 19p13 regulate ABHD8 and perhaps ANKLE1 expression, and indicate common mechanisms underlying breast and ovarian cancer risk.
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