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2361.
  • Kraft, Jamie D., et al. (författare)
  • Specialized Pro-Resolving Mediators and the Lymphatic System
  • 2021
  • Ingår i: International Journal of Molecular Sciences. - : MDPI AG. - 1422-0067 .- 1661-6596. ; 22:5
  • Tidskriftsartikel (refereegranskat)abstract
    • Diminished lymphatic function and abnormal morphology are common in chronic inflammatory diseases. Recent studies are investigating whether it is possible to target chronic inflammation by promoting resolution of inflammation, in order to enhance lymphatic function and attenuate disease. Resolution of inflammation is an active process regulated by bioactive lipids known as specialized pro-resolving mediators (SPMs). SPMs can modulate leukocyte migration and function, alter cytokine/chemokine release, modify autophagy, among other immune-related activities. Here, we summarize the role of the lymphatics in resolution of inflammation and lymphatic impairment in chronic inflammatory diseases. Furthermore, we discuss the current literature describing the connection between SPMs and the lymphatics, and the possibility of targeting the lymphatics with innovative SPM therapy to promote resolution of inflammation and mitigate disease.
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2362.
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2363.
  • Kreu, S., et al. (författare)
  • Alkalosis in Critically III Patients with Severe Sepsis and Septic Shock
  • 2017
  • Ingår i: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 12:1
  • Tidskriftsartikel (refereegranskat)abstract
    • Introduction Although metabolic alkalosis is a common occurrence in intensive care units (ICUs), no study has evaluated its prevalence or outcomes in patients with severe sepsis or septic shock. This is a retrospective cohort study of critically ill patients suffering from severe sepsis and septic shock admitted to the ICUs of Halmstad and Varberg County hospitals. From 910 patient records, 627 patients met the inclusion criteria. We investigated the relationship between metabolic alkalosis and mortality. Further, we studied the relationship between metabolic alkalosis and ICU length of stay (LOS). Metabolic alkalosis was associated with decreased 30-day and 12-month mortalities. This effect was however lost when a multivariate analysis was conducted, correcting for age, gender, pH on admission, base excess (BE) on admission, Simplified Acute Physiology Score III (SAPS III) and acute kidney injury (AKI). We then analyzed for any dose-response effect between the severity of metabolic alkalosis and mortality and found no relationship. Bivariate analysis showed that metabolic alkalosis had a significant effect on the length of ICU stay. When adjusting for age, sex, pH at admission, BE at admission, SAPS III and AKI in a multivariate analysis, metabolic alkalosis significantly contributed to prolonged ICU length of stay. In two separate sensitivity analyses pure metabolic alkalosis and late metabolic alkalosis (time of onset > 48 hours) were the only significant predictor of increased ICU length of stay. Metabolic alkalosis did not have any effect on 30-day and 12-month mortalities after adjusting for age, sex, SAPS III-score, pH and BE on admission and AKI in a multivariate analysis. The presence of metabolic alkalosis was independently associated with an increased ICU length of stay.
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2364.
  • Kruczyk, Marcin, et al. (författare)
  • Monte Carlo feature selection and rule-based models to predict Alzheimer's disease in mild cognitive impairment.
  • 2012
  • Ingår i: Journal of neural transmission (Vienna, Austria : 1996). - : Springer Science and Business Media LLC. - 1435-1463 .- 0300-9564. ; 119:7, s. 821-31
  • Tidskriftsartikel (refereegranskat)abstract
    • The objective of the present study was to evaluate a Monte Carlo feature selection (MCFS) and rough set Rosetta pipeline for generating rule-based models as a tool for comprehensive risk estimates for future Alzheimer's disease (AD) in individual patients with mild cognitive impairment (MCI). Risk estimates were generated on the basis of age, gender, Mini-Mental State Examination scores, apolipoprotein E (APOE) genotype and the cerebrospinal fluid (CSF) biomarkers total tau (T-tau), phospho-tau(181) (P-tau) and the 42 amino acid form of amyloid β (Aβ42) in two sets of longitudinally followed MCI patients (n=217 in total). The predictive model was created in Rosetta, evaluated with the standard tenfold cross-validation approach and tested on an external set. Features were ranked and selected by the MCFS algorithm. Using the combined pipeline of MCFS and Rosetta, it was possible to predict AD among patients with MCI with an area under the receiver operating characteristics curve of 0.92. Risk estimates were produced for the individual patients and showed good correlation with actual diagnosis in cross validation, and on an external dataset from a new study. Analysis of the importance of attributes showed that the biochemical CSF markers contributed the most to the predictions, and that added value was gained by combining several biochemical markers. Despite a correlation with the biochemical markers, the genetic marker APOE ε4 did not contribute to the predictive power of the model.
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2365.
  • Kruger, D., et al. (författare)
  • High-resolution ex vivo analysis of the degradation and osseointegration of Mg-xGd implant screws in 3D
  • 2022
  • Ingår i: Bioactive Materials. - : Elsevier BV. - 2452-199X. ; 13, s. 37-52
  • Tidskriftsartikel (refereegranskat)abstract
    • Biodegradable magnesium (Mg) alloys can revolutionize osteosynthesis, because they have mechanical properties similar to those of the bone, and degrade over time, avoiding the need of removal surgery. However, they are not yet routinely applied because their degradation behavior is not fully understood. In this study we have investigated and quantified the degradation and osseointegration behavior of two biodegradable Mg alloys based on gadolinium (Gd) at high resolution. Mg-5Gd and Mg-10Gd screws were inserted in rat tibia for 4, 8 and 12 weeks. Afterward, the degradation rate and degradation homogeneity, as well as bone-to-implant interface, were studied with synchrotron radiation micro computed tomography and histology. Titanium (Ti) and polyether ether ketone (PEEK) were used as controls material to evaluate osseointegration. Our results showed that Mg-5Gd degraded faster and less homogeneously than Mg-10Gd. Both alloys gradually form a stable degradation layer at the interface and were surrounded by new bone tissue. The results were correlated to in vitro data obtained from the same material and shape. The average bone-to-implant contact of the Mg-xGd implants was comparable to that of Ti and higher than for PEEK. The results suggest that both Mg-xGd alloys are suitable as materials for bone implants.
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2366.
  • Kukk, E., et al. (författare)
  • Energy-dependent timescales in the dissociation of diiodothiophene dication
  • 2023
  • Ingår i: Physical Chemistry Chemical Physics. - : Royal Society of Chemistry (RSC). - 1463-9076 .- 1463-9084. ; 25:7, s. 5795-5807
  • Tidskriftsartikel (refereegranskat)abstract
    • Photodissociation molecular dynamics of gas-phase 2,5-diiodothiophene molecules was studied in an electron-energy-resolved electron-multi-ion coincidence experiment performed at the FinEstBeAMS beamline of MAX IV synchrotron. Following the photoionization of the iodine 4d subshell and the Auger decay, the dissociation landscape of the molecular dication was investigated as a function of the Auger electron energy. Concentrating on an major dissociation pathway, C4H2I2S2+ -> C4H2S+ + I+ + I, and accessing the timescales of the process via ion momentum correlation analysis, it was revealed how this three-body process changes depending on the available internal energy. Using a generalized secondary dissociation model, the process was shown to evolve from secondary dissociation regime towards concerted dissociation as the available energy increased, with the secondary dissociation time constant changing from 1.5 ps to 129 fs. The experimental results were compared with simulations using a stochastic charge-hopping molecular mechanics model. It represented the observed trend and also gave a fair quantitative agreement with the experiment.
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2367.
  • Kumlien, Christine, et al. (författare)
  • Validity and test retest reliability of the vascular quality of life Questionnaire-6: a short form of a disease-specific health-related quality of life instrument for patients with peripheral arterial disease
  • 2017
  • Ingår i: Health and Quality of Life Outcomes. - : Springer Science and Business Media LLC. - 1477-7525. ; 15
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Many existing patient-reported outcome measures are extensive regarding both patient burden and administration, and in terms of analysing and reporting results. The VascuQoL-6 (VQ6) - a short version of the original Vascular Quality of Life Questionnaire (VascuQoL), a disease-specific instrument for peripheral arterial disease - was recently developed. However, the VQ6 has not yet been empirical tested with regard to content validity, construct validity and test retest reliability. Our aim was, therefore, to explore both the validity and the reliability of the VQ-6 in a target population with established peripheral arterial disease. Methods: Two hundred patients treated at two vascular centres were consecutively recruited for the survey. Administered questionnaires included VQ6 and the Short Form Health Survey-36 (SF-36). Out of the 200 patients, 150 also received a second VQ6 questionnaire for a test-retest assessment. Further, a purposive sample of 22 patients consented to participate in cognitive interviews. All included patients suffer from peripheral arterial disease. The questionnaire data was tested by both Rasch analysis and traditional psychometric methods, while the cognitive interviews were analysed descriptively. Results: The validity and reliability of the VQ6, as tested in a target population without the surrounding 19 items from the original VascuQoL, was high, in general, and a good fit to the Rasch model was observed. Further, an excellent internal consistency and significant correlations between comparable dimensions in SF-36 were demonstrated. In the test-retest analysis, the percentage agreement was somewhat poor (<70%) in the six items. However, no systematic disagreements between the two assessments were seen in any of the six items, and the test-retest assessment for the VQ6 sum score showed an acceptable intraclass correlation coefficient (0.86). Finally, all items in the VQ6 were considered as both understandable and relevant by the interviewed patients. Conclusions: The VQ6 has acceptable to good psychometric properties with regard to data quality, scale assumptions, targeting, validity and reliability. Further, VQ6 seems to be easy to use and comprehend within the target population of patients with PAD.
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2368.
  • Kverneng Hultberg, Daniel, et al. (författare)
  • Nonsteroidal anti-inflammatory drugs and the risk of anastomotic leakage after anterior resection for rectal cancer
  • 2017
  • Ingår i: European Journal of Surgical Oncology. - : Elsevier BV. - 0748-7983 .- 1532-2157. ; 43:10, s. 1908-1914
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Nonsteroidal anti-inflammatory drugs (NSAIDs) have been widely used in colorectal surgery due to their opioid-sparing effect. However, several studies have indicated an increased risk of anastomotic leakage following NSAID treatment, although conflicting results exist. The primary goal of this study was to further examine whether postoperative NSAIDs are independently associated with anastomotic leakage after anterior resection for rectal cancer. Methods: Patients who underwent anterior resection for rectal cancer during 2007-2013 in 15 different hospitals in three healthcare regions in Sweden were included in the study. Registry data and information from patient records were retrieved. The association between NSAID treatment (for at least two days in the first postoperative week) and symptomatic anastomotic leakage (within 90 days) was evaluated with multiple logistic regression, with adjustment for pertinent confounding factors. Results: Some 1495 patients were included in the study. Of these, 27% received postoperative NSAIDs for at least two days in the first postoperative week. Symptomatic anastomotic leakage occurred in 11% and 14% in the NSAID and non-NSAID group, respectively. With adjustment for confounders, the odds ratio for leakage among patients who received NSAIDs compared with those who did not was 0.88 (95% CI 0.65-1.20). No differences were seen between non-selective and COX-2-selective NSAIDs. Conclusion: Postoperative NSAID treatment does not seem to increase the risk of symptomatic anastomotic leakage after anterior resection for rectal cancer. NSAID use appears to be safe, but a well-powered randomized clinical trial is warranted. (C) 2017 Elsevier Ltd, BASO similar to The Association for Cancer Surgery, and the European Society of Surgical Oncology. All rights reserved.
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2369.
  • Kwan, Tony, et al. (författare)
  • Tissue effect on genetic control of transcript isoform variation.
  • 2009
  • Ingår i: PLoS genetics. - : Public Library of Science (PLoS). - 1553-7404 .- 1553-7390. ; 5:8
  • Tidskriftsartikel (refereegranskat)abstract
    • Current genome-wide association studies (GWAS) are moving towards the use of large cohorts of primary cell lines to study a disease of interest and to assign biological relevance to the genetic signals identified. Here, we use a panel of human osteoblasts (HObs) to carry out a transcriptomic survey, similar to recent studies in lymphoblastoid cell lines (LCLs). The distinct nature of HObs and LCLs is reflected by the preferential grouping of cell type-specific genes within biologically and functionally relevant pathways unique to each tissue type. We performed cis-association analysis with SNP genotypes to identify genetic variations of transcript isoforms, and our analysis indicates that differential expression of transcript isoforms in HObs is also partly controlled by cis-regulatory genetic variants. These isoforms are regulated by genetic variants in both a tissue-specific and tissue-independent fashion, and these associations have been confirmed by RT-PCR validation. Our study suggests that multiple transcript isoforms are often present in both tissues and that genetic control may affect the relative expression of one isoform to another, rather than having an all-or-none effect. Examination of the top SNPs from a GWAS of bone mineral density show overlap with probeset associations observed in this study. The top hit corresponding to the FAM118A gene was tested for association studies in two additional clinical studies, revealing a novel transcript isoform variant. Our approach to examining transcriptome variation in multiple tissue types is useful for detecting the proportion of genetic variation common to different cell types and for the identification of cell-specific isoform variants that may be functionally relevant, an important follow-up step for GWAS.
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2370.
  • Källén, Bengt, et al. (författare)
  • In vitro fertilisation in Sweden: obstetric characteristics, maternal morbidity and mortality
  • 2005
  • Ingår i: Bjog. - : Wiley. ; 112:11, s. 1529-1535
  • Tidskriftsartikel (refereegranskat)abstract
    • OBJECTIVE: To investigate obstetric characteristics, maternal morbidity and mortality among Swedish women giving birth after in vitro fertilisation (IVF) treatment. DESIGN: Register study. SETTING: Nationwide study in Sweden. SAMPLE: All women known to have had IVF in Sweden 1982-2001. METHODS: Using Swedish health registers, women who had given birth after IVF were identified from all Swedish IVF clinics and compared with all women who gave birth. Analysis was performed with the Mantel-Haenszel technique. MAIN OUTCOME MEASURES: Diagnoses during pregnancy, at delivery and at re-admission within 60 days after delivery and risk of cancer. RESULTS: IVF women had an increased risk of bleeding in early pregnancy [odds ratio (OR) = 4.59, 95% confidence interval (95% CI) 4.08-5.15] and of ovarian torsion during pregnancy (OR = 10.6, 5.69-10.7). They were also more likely to encounter pre-eclampsia (OR = 1.63, 1.53-1.74), placental abruption (2.17, 1.74-2.72), placenta praevia (3.65, 3.15-4.23), bleeding in association with vaginal delivery (1.40, 1.38-1.50) and premature rupture of membranes (PROM) (2.54, 2.34-2.76). Interventions including caesarean sections (1.38, 1.32-1.43) and induction of labour (1.37, 1.29-1.46) in singleton pregnancies was more frequent. The type of IVF method had little effect on these results, but there was a tendency for women who had received intra-cytoplasmatic sperm injection (ICSI) to have slightly fewer complications than women having standard IVF. There was a significant decrease in cancer risk after IVF (0.79, 0.69-0.91) but a suggested increase in the risk of ovarian cancer both before (2.70, 1.49-4.91) and after (2.08, 1.15-3.76) IVF. No change in mortality was observed. CONCLUSIONS: Women treated with IVF had an increased obstetric morbidity. This seems to contribute little to the well-known increased risk of preterm delivery.
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