| 1. |
- Kehoe, Laura, et al.
(författare)
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Make EU trade with Brazil sustainable
- 2019
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Ingår i: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 364:6438, s. 341-
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
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| 2. |
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| 3. |
- Walander, Magnus, 1991, et al.
(författare)
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Use of 3D-printed mixers in laboratory reactor design for modelling of heterogeneous catalytic converters
- 2021
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Ingår i: Chemical Engineering and Processing. - : Elsevier B.V.. - 0255-2701 .- 1873-3204. ; 164
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Tidskriftsartikel (refereegranskat)abstract
- A method for identifying radial concentration maldistribution in synthetic catalyst activity test (SCAT) benches, is presented, where spatially resolved concentration measurements are not available. The developed methodology was successfully tested for an injection-based SCAT. To resolve the radial concentration maldistribution a static mixer was designed, 3D-printed and inserted upstream the test sample. The methodology could also prove the effectiveness of the mixer, which did not only resolve the concentration maldistribution but also avoided causing reaction disturbances. The resulting increased axial dispersion from the turbulence created by the static mixer was evaluated using a 3D CFD model in Ansys Fluent 19. The axial dispersion of the injection-based SCAT bench was compared to a premixed SCAT bench through classical Aris-Taylor calculations. The results from the axial dispersion calculations show that the injection-based design with the use of a static mixer is far superior to the premixed design – both with regards to pulse broadening but also time delay. This is highly desirable for modelling studies towards zero emission exhaust aftertreatment. © 2021 The Authors
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| 4. |
- Ahnström, G., et al.
(författare)
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The effect of dimethyl sulphoxide on the induction and repair of double-strand breaks in human cells after irradiation with γ-rays and accelerated ions : Rapid or slow repair may depend on accessibility of breaks in chromatin of different compactness
- 2000
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Ingår i: International Journal of Radiation Biology. - 0955-3002 .- 1362-3095. ; 76:4, s. 533-538
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: The repair of double-strand breaks (dsb) in mammalian cells is characterized by a rapid phase with a half-life of less than half an hour and a slower phase that lasts for many hours. The proportion of slow repair increase with LET and it has been suggested that the slow repair component consists of more complex damage and is more deleterious to the cells. To see if removal of OH radicals could remove part of the damage in complex dsb and make them easier to repair, human cells were irradiated in the presence of dimethyl sulphoxide (DMSO). Methods: Induction and repair of dsb were studied by neutral elution in human VH10 cells exposed to γ-rays, helium ions (mean LET 40 keV/μm) and 80 and 125 keV/μm monoenergetic nitrogen ions in the presence and absence of 2 M DMSO. Results: Incubation of cells exposed to γ-rays, 40 keV/μm helium and 80 keV/μm N ions demonstrated that scavenging of OH radicals by DMSO removed most of the rapid repair component. The response to DMSO was less marked after 125 keV/μm nitrogen ions, where about half of the repair was resistant to DMSO. Conclusions: It is unlikely that the complexity of dsb is responsible for the slow repair because the removal of OH radicals did not make the breaks easier to repair. Instead, it is suggested that rapid and slow repair can be explained on the basis of how different parts of the chromatin are accessible to repair enzymes.
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| 5. |
- Appelberg, Jonas, 1985-, et al.
(författare)
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Social media in the professional work of Polish, Russian and Swedish journalists
- 2014
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Ingår i: Journal of Print and Media Technology Research. - Darmstadt : International Association of Research Organizations for the Information, Media and Graphic Arts Industrie (IARIGAI). - 2223-8905 .- 2414-6250. ; 3:2, s. 107-118
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Tidskriftsartikel (refereegranskat)abstract
- Professional journalistic culture is a complex of journalistic values, practices, norms and media products. On the one hand it tends to unification across the globe, but on the other hand these cultures varies according to cultural diversities. Technological development leads to a media convergence, increasing interactivity and plenty of opportunities for individualization of media content influence audience’s demands and consequently challenge of traditional routine of journalists’ work, affect professional practices and even undermine traditional role of a journalist in society. Social media creates new conditions for both actors: readers/viewers/listeners and for media professionals who use it as a tool for media work. Journalists in the different countries, however, use social media for professional needs not equally. This paper is discussing differences and similarities in the patterns of social media use by Polish, Russian and Swedish journalists. The research is based on a survey of 500 journalists in each country.
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| 6. |
- Baban, Bayar, 1973-, et al.
(författare)
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Determination of insulin resistance in surgery : the choice of method is crucial
- 2015
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Ingår i: Clinical Nutrition. - : Churchill Livingstone. - 0261-5614 .- 1532-1983. ; 34:1, s. 123-128
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND & AIMS: In elective surgery, postoperative hyperglycaemia and insulin resistance are independent risk factors for complications. Since the simpler HOMA method has been used as an alternative to the hyperinsulinemic normoglycemic clamp in studies of surgery induced insulin resistance, we compared the two methods in patients undergoing elective surgery.METHODS: Data from 113 non-diabetic patients undergoing elective surgery were used. Insulin sensitivity, both before and after surgery, was quantified by the clamp and HOMA. Pre- and postoperatively, the results of the clamp were compared to HOMA using regression- and correlation analysis. Degree of agreement between the methods was studied using weighted linear kappa and the Bland-Altman test.RESULTS: Both the clamp and HOMA recorded a mean relative reduction in insulin sensitivity of 39 ± 24% and 39 ± 61% respectively after surgery; with significant correlations (p < 0.01) for pre- and post-operative measures as well as for relative changes. However r(2) values were low: 0.04, 0.07 and 0.03 respectively. The degree of agreement for the relative change in insulin sensitivity using the Bland-Altman test gave a mean of difference 0% but "limits of agreement" (±2SD) was ±125%. This poor inter-method agreement was consolidated by a weighted linear kappa value of 0.18.CONCLUSION: While the hyperinsulinemic euglycemic clamp measures the postoperative changes in insulin sensitivity, HOMA measures something different. Data using the HOMA method must therefore be interpreted cautiously and is not interchangeable with data obtained from the clamp.
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| 7. |
- Bang, Peter, et al.
(författare)
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Free dissociable IGF-I : Association with changes in IGFBP-3 proteolysis and insulin sensitivity after surgery
- 2016
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Ingår i: Clinical Nutrition. - : Churchill Livingstone. - 0261-5614 .- 1532-1983. ; 35:2, s. 408-413
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Tidskriftsartikel (refereegranskat)abstract
- Background: Patients receiving a carbohydrate drink (CHO) before major abdominal surgery display improved insulin sensitivity postoperatively and increased proteolysis of IGFBP-3 (IGFBP-3-PA) compared to patients undergoing similar surgery after overnight fasting. Aims: We hypothesized that serum IGFBP-3-PA increases bioavailability of circulating IGF-I and preserves insulin sensitivity in patients given CHO. Design: Matched control study. Methods: At Karolinska University Hospital, patients given CHO before major elective abdominal surgery (CHO,n = 8) were compared to patients undergoing similar surgical procedures after overnight fasting (FAST,n = 10). Results from two different techniques for determination of free-dissociable IGF-I (fdIGF-I) were compared with changes in IGFBP-3-PA and insulin sensitivity. Results: Postoperatively, CHO displayed 18% improvement in insulin sensitivity (hyperinsulinemic clamp) and increased IGFBP-3-PA vs. FAST. As determined by IRMA, fdIGF-I increased by 48 +/- 25% in CHO while fdIGF-I decreased by 13 +/- 18% in FAST (p < 0.01 vs. CHO, when corrected for duration of surgery). However, fdIGF-I determined by ultra-filtration decreased similarly in both groups (-22 +/- 8% vs. -25 +/- 8%, p = 0.8) and IGFBP-1 increased similarly in both groups. Patients with less insulin resistance after surgery demonstrated larger increases in fdIGF-I by IRMA (r = 0.58, p < 0.05). Fifty-three % of the variability of the changes in fdIGF-I by IRMA could be explained by changes in IGFBP-3-PA and total IGF-I levels (p < 0.05), while IGFBP-1 did not contribute significantly. Conclusion: During conditions when serum IGF-I bioavailability is regulated by IGFBP-3 proteolysis, measurements of fdIGF-I by IRMA is of physiological relevance as it correlates with the associated changes in insulin sensitivity.
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| 8. |
- Belyaev, I Y, et al.
(författare)
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Effects of ethidium bromide on DNA loop organisation in human lymphocytes measured by anomalous viscosity time dependence and single cell gel electrophoresis
- 1999
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Ingår i: Biochimica et Biophysica Acta - General Subjects. - 0304-4165 .- 1872-8006. ; 1428:2-3, s. 348-356
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Tidskriftsartikel (refereegranskat)abstract
- The effects of ethidium bromide (EtBr) on human lymphocytes were studied by the method of anomalous viscosity time dependence (AVTD) and by the comet assay. EtBr at low concentrations increased the maximum viscosity and time of radial migration as measured with AVTD at neutral conditions of lysis. A pronounced relaxation of DNA loops was observed with the neutral comet assay. The maximal comet length corresponded to 2 Mb DNA loops. At high concentrations of EtBr, 2. mg/ml, significant reduction in AVTD below control level was seen that suggested hypercondensation of chromatin. The hypercondensation was directly observed with the neutral comet assay. EtBr did not induce DNA strand breaks as measured by the alkaline comet assay. The hypercondensed nuclei could be decondensed by irradiation with gamma-rays or exposure to light. The data provide evidence that EtBr at high concentrations resulted in hypercondensation of chromatin below control level. The comet assay confirmed that the increase in AVTD peaks deals with relaxation of loops and AVTD decrease is caused by chromatin condensation. The prediction of the AVTD theory for a correlation between time of radial migration and condensation of chromatin was verified. Further, the data show that the comet assay at neutral conditions of lysis is rather sensitive to DNA loop relaxation in the absence of DNA damage. Finally, donor specificity was found for the hypercondensation.
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| 9. |
- Borch-Johnsen, Peter, et al.
(författare)
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Endoscopic underwater detection and resection of anal squamous intraepithelial lesions in non-anesthetized patients - a feasibility study and comparison with standard surgical treatment
- 2024
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Ingår i: Scandinavian Journal of Gastroenterology. - : Taylor & Francis. - 0036-5521 .- 1502-7708. ; 59:2, s. 232-238
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundAnal squamous intraepithelial lesions (ASILs) correspond to premalignant changes preceding the development of anal squamous cell carcinoma.ObjectiveTo describe a new endoscopic technique to detect and remove ASILs in non-anesthetized patients and compare it with standard surgical treatment.MethodsFor endoscopic treatment, high resolution (HR) flexible endoscopes with a distal attachment were used. Underwater inspection of the anal canal was performed in near-focus mode with white light and narrow-band imaging. Detected lesions were resected with a diathermia snare after local injection of xylocaine/adrenaline. We did a retrospective comparison of all patients who underwent endoscopic or standard surgical treatment for ASILs at Ersta hospital in Stockholm between 2018 and 2020. Patient files were reviewed for number of lesions, treatments until macroscopic radicality, degree of dysplasia, bleeding, pain and other complications.ResultsEndoscopic (n = 37) and surgical (n = 43) treatment displayed comparable number of lesions per patient (p = .37). The number of procedures until macroscopic radicality was higher for endoscopy than surgery (p = .04). However, in endoscopic follow up of 12 of the surgically treated patients, residual ASIL was found in 10 cases. Post-procedural bleeding requiring healthcare occurred in two endoscopy patients and one surgically treated patient.ConclusionsUnderwater resection using a HR flexible endoscope in non-anesthetized is a new, feasible and well tolerated method for ASILs treatment. Its efficacy and risk of complications seem comparable to standard surgical treatment while avoiding general anesthesia. However, minor lesions might be overlooked at surgery.
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| 10. |
- Chaste, Pauline, et al.
(författare)
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Genetic variations of the melatonin pathway in patients with attention-deficit and hyperactivity disorders.
- 2011
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Ingår i: Journal of Pineal Research. - 0742-3098 .- 1600-079X. ; 51:4, s. 394-399
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Tidskriftsartikel (refereegranskat)abstract
- Melatonin is a powerful antioxidant and a synchronizer of many physiological processes. Alteration in melatonin signaling has been reported in a broad range of diseases, but little is known about the genetic variability of this pathway in humans. Here, we sequenced all the genes of the melatonin pathway -AA-NAT, ASMT, MTNR1A, MTNR1B and GPR50 - in 321 individuals from Sweden including 101 patients with attention-deficit/hyperactivity disorder (ADHD) and 220 controls from the general population. We could find several damaging mutations in patients with ADHD, but no significant enrichment compared with the general population. Among these variations, we found a splice site mutation in ASMT (IVS5+2T>C) and one stop mutation in MTNR1A (Y170X) - detected exclusively in patients with ADHD - for which biochemical analyses indicated that they abolish the activity of ASMT and MTNR1A. These genetic and functional results represent the first comprehensive ascertainment of melatonin signaling deficiency in ADHD.
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| 11. |
- Currie, Andrew, et al.
(författare)
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The Impact of Enhanced Recovery Protocol Compliance on Elective Colorectal Cancer Resection Results From an International Registry
- 2015
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Ingår i: Annals of Surgery. - : Lippincott Williams & Wilkins. - 0003-4932 .- 1528-1140. ; 261:6, s. 1153-1159
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Tidskriftsartikel (refereegranskat)abstract
- Background: The ERAS (enhanced recovery after surgery) care has been shown in randomized clinical trials to improve outcome after colorectal surgery compared to traditional care. The impact of different levels of compliance and specific elements, particularly out with a trial setting, is poorly understood.Objective: This study evaluated the individual impact of specific patient factors and perioperative enhanced recovery protocol compliance on postoperative outcome after elective primary colorectal cancer resection.Methods: The international, multicenter ERAS registry data, collected between November 2008 and March 2013, was reviewed. Patient demographics, disease characteristics, and perioperative ERAS protocol compliance were assessed. Linear regression was undertaken for primary admission duration and logistic regression for the development of any postoperative complication.Findings: A total of 1509 colonic and 843 rectal resections were undertaken in 13 centers from 6 countries. Median length of stay for colorectal resections was 6 days, with readmissions in 216 (9.2%), complications in 948 (40%), and reoperation in 167 (7.1%) of 2352 patients. Laparoscopic surgery was associated with reduced complications [odds ratio (OR) = 0.68; P < 0.001] and length of stay (OR = 0.83, P < 0.001). Increasing ERAS compliance was correlated with fewer complications (OR = 0.69, P < 0.001) and shorter primary hospital admission (OR = 0.88, P < 0.001). Shorter hospital stay was associated with preoperative carbohydrate and fluid loading (OR = 0.89, P = 0.001), and totally intravenous anesthesia (OR= 0.86, P < 0.001); longer stay was associated with intraoperative epidural analgesia (OR = 1.07, P = 0.019). Reduced postoperative complications were associated with restrictive perioperative intravenous fluids (OR = 0.35, P < 0.001).Conclusions: This analysis has demonstrated that in a large, international cohort of patients, increasing compliance with an ERAS program and the use of laparoscopic surgery independently improve outcome.
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| 12. |
- Czene, S, et al.
(författare)
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DNA fragmentation and morphological changes in apoptotic human lymphocytes
- 2002
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Ingår i: Biochemical and Biophysical Research Communications - BBRC. - 0006-291X .- 1090-2104. ; 294:4, s. 872-878
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Tidskriftsartikel (refereegranskat)abstract
- Cell suspensions enriched in cells at various stages of apoptosis were obtained by separation of irradiated human peripheral blood lymphocytes on density gradients at different post-irradiation times. The state of DNA fragmentation in the cells was determined by comet assay and pulsed field gel electrophoresis. The morphologically distinguishable features of apoptosis such as chromatin condensation and cell shrinkage correlated with discrete stages of DNA fragmentation. It was found that greater than or equal to50kbp fragmentation of DNA occurs already in cells of normal density whereas the subsequent DNA fragmentation onto fragments <50 kbp occurs in parallel with cell shrinkage and simultaneous increase in cell density. The observed stages of DNA fragmentation seem to be separated in time that could allow in case of abortive apoptosis formation of chromosomal aberrations.
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| 13. |
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| 14. |
- Durand, Christelle M, et al.
(författare)
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Expression and genetic variability of PCDH11Y, a gene specific to Homo sapiens and candidate for susceptibility to psychiatric disorders.
- 2006
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Ingår i: American Journal of Medical Genetics. Part B, Neuropsychiatric Genetics : The Official Publication of the International Society of Psychiatric Genetics. - : Wiley. - 1552-4841. ; 141:1, s. 67-70
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Tidskriftsartikel (refereegranskat)abstract
- Synaptogenesis, the formation of functional synapses, is a crucial step for the development of the central nervous system. Among the genes involved in this process are cell adhesion molecules, such as protocadherins and neuroligins, which are essential factors for the identification of the appropriate partner cell and the formation of synapses. In this work, we studied the expression and the genetic variability of two closely related members of the protocadherin family PCDH11X/Y, located on the X and the Y chromosome, respectively. PCDH11Y is one of the rare genes specific to the hominoid lineage, being absent in other primates. Expression analysis indicated that transcripts of the PCDH11X/Y genes are mainly detected in the cortex of the human brain. Mutation screening of 30 individuals with autism identified two PCDH11Y polymorphic amino acid changes, F885V and K980N. These variations are in complete association, appeared during human evolution approximately 40,000 years ago and represent informative polymorphisms to study Y chromosome variability in populations. We studied the frequency of these variants in males with autism spectrum disorders (n = 110), attention deficit hyperactivity disorder (ADHD; n = 61), bipolar disorder (n = 61), obsessive-compulsive disorder (n = 51), or schizophrenia (n = 61) and observed no significant differences when compared to ethnically-matched control populations. These findings do not support the role of PCDH11Y, or more generally of a frequent specific Y chromosome, in the susceptibility to these neuropsychiatric disorders.
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| 15. |
- Elf, Kristin, et al.
(författare)
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Alterations in muscle proteome of patients diagnosed with amyotrophic lateral sclerosis
- 2014
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Ingår i: Journal of Proteomics. - : Elsevier BV. - 1874-3919 .- 1876-7737. ; 108, s. 55-64
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Tidskriftsartikel (refereegranskat)abstract
- Amyotrophic lateral sclerosis (ALS) is a motor neuron disease characterized by progressive muscle paralysis. Currently clinical tools for ALS diagnostics do not perform well enough and their improvement is needed. The objective of this study was to identify specific protein alterations related to the development of ALS using tiny muscle biopsies. We applied a shotgun proteomics and quantitative dimethyl labeling in order to analyze the global changes in human skeletal muscle proteome of ALS versus healthy subjects for the first time. 235 proteins were quantified and 11 proteins were found significantly regulated in ALS muscles. These proteins are involved in muscle development and contraction, metabolic processes, enzyme activity, regulation of apoptosis and transport activity. In order to eliminate a risk to confuse ALS with other denervations, muscle biopsies of patients with postpolio syndrome and Charcot Marie Tooth disease (negative controls) were compared to those of ALS and controls. Only few proteins significantly regulated in ALS patients compared to controls were affected differently in negative controls. These proteins (BTB and kelch domain-containing protein 10, myosin light chain 3, glycogen debranching enzyme, transitional endoplasmic reticulum ATPase), individually or as a panel, could be selected for estimation of ALS diagnosis and development. Biological significance ALS is a devastating neurodegenerative disease, and luckily, very rare: only one to two people out of 100,000 develop ALS yearly. This fact, however, makes studies of ALS very challenging since it is very difficult to collect the representative set of clinical samples and this may take up to several years. In this study we collected the muscle biopsies from 12 ALS patients and compared the ALS muscle proteome against the one from control subjects. We suggested the efficient method for such comprehensive quantitative analysis by LC-MS and performed it for the first time using human ALS material. This gel- and antibody-free method can be widely applied for muscle proteome studies and has been used by us for revealing of the specific protein alterations associated with ALS.
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| 16. |
- Elmroth, Kerstin, 1970, et al.
(författare)
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Chromatin- and temperature-dependent modulation of radiation-induced double-strand breaks
- 2003
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Ingår i: International Journal of Radiation Biology. - : Informa UK Limited. - 0955-3002 .- 1362-3095. ; 79:10, s. 809-816
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: To investigate the influence of chromatin organization and scavenging capacity in relation to irradiation temperature on the induction of double-strand breaks (DSB) in structures derived from human diploid fibroblasts. Materials and methods: Agarose plugs with different chromatin structures (intact cells±wortmannin, permeabilized cells with condensed chromatin, nucleoids and DNA) were prepared and irradiated with X-rays at 2 or 37°C and lysed using two different lysis protocols (new ice-cold lysis or standard lysis at 37°C). Induction of DSB was determined by constant-field gel electrophoresis. Results: The dose-modifying factor (DMFtemp) for irradiation at 37 compared with 2°C was 0.92 in intact cells (i.e. more DSB induced at 2°C), but gradually increased to 1.5 in permeabilized cells, 2.2 in nucleoids and 2.6 in naked DNA, suggesting a role of chromatin organization for temperature modulation of DNA damage. In addition, DMFtemp was influenced by the presence of 0.1 M DMSO or 30 mM glutathione, but not by post-irradiation temperature. Conclusion: The protective effect of low temperature was correlated to the indirect effects of ionizing radiation and was not dependent on post-irradiation temperature. Reasons for a dose modifying factor <1 in intact cells are discussed.
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| 17. |
- Elmroth, Kerstin, 1970, et al.
(författare)
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Cleavage of cellular DNA by calicheamicin γ1
- 2003
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Ingår i: DNA Repair. - 1568-7864 .- 1568-7856. ; 2:4, s. 363-374
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Tidskriftsartikel (refereegranskat)abstract
- It is assumed that the efficient antitumor activity of calicheamicin γ1 is mediated by its ability to introduce DNA double-strand breaks in cellular DNA. To test this assumption we have compared calicheamicin γ1-mediated cleavage of cellular DNA and purified plasmid DNA. Cleavage of purified plasmid DNA was not inhibited by excess tRNA or protein indicating that calicheamicin γ1 specifically targets DNA. Cleavage of plasmid DNA was not affected by incubation temperature. In contrast, cleavage of cellular DNA was 45-fold less efficient at 0°C as compared to 37° due to poor cell permeability at low temperatures. The ratio of DNA double-strand breaks (DSB) to single-stranded breaks (SSB) in cellular DNA was 1:3, close to the 1:2 ratio observed when calicheamicin γ1 cleaved purified plasmid DNA. DNA strand breaks introduced by calicheamicin γ1 were evenly distributed in the cell population as measured by the comet assay. Calicheamicin γ1-induced DSBs were repaired slowly but completely and resulted in high levels of H2AX phosphorylation and efficient cell cycle arrest. In addition, the DSB-repair deficient cell line Mo59J was hyper sensitive to calicheamicin γ. The data indicate that DSBs is the crucial damage after calicheamicin γ1 and that calicheamicin γ1-induced DSBs are recognized normally. The high DSB:SSB ratio, specificity for DNA and the even damage distribution makes calicheamicin γ1 a superior drug for studies of the DSB-response and emphasizes its usefulness in treatment of malignant disease.
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| 18. |
- Elmroth, Kerstin, 1970, et al.
(författare)
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Radiation and hypothermia: changes in DNA supercoiling in human diploid fibroblasts
- 1999
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Ingår i: Anticancer Res. - 0250-7005 .- 1791-7530. ; 19:6B, s. 5307-11
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Tidskriftsartikel (refereegranskat)abstract
- The influence of hypothermia (2 degrees, 15 degrees and 28 degrees C) upon the effect of X-irradiation on chromatin from human diploid fibroblast cells (AG1518) was studied using the fluorescent halo assay. Rewinding of supercoils was inhibited in a dose-dependent manner when cells were irradiated with 4, 8 or 16 Gy. This inhibition of rewinding was reduced when cells were irradiated at subnormal temperatures compared with cells irradiated at 37 degrees C. One hour's preincubation at low temperature did not influence rewinding. When AG1518 cells were irradiated at 37 degrees C in the presence of the radical scavenger DMSO (0.5 M), the radiation-induced damage was reduced. No additional protection of DMSO in hypothermic cells (2 degrees C) was found, possibly indicating that OH-radical-mediated effects are more temperature dependent. These results are similar to those recently found for the malignant MCF-7 cell line.
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| 19. |
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| 20. |
- Eriksson, S, et al.
(författare)
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Matrix association of early- and late-replicating chromatin studied by single-cell electrophoresis
- 2002
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Ingår i: Biochimica et Biophysica Acta. Molecular Cell Research. - 0167-4889 .- 1879-2596. ; 1590:1-3, s. 103-108
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Tidskriftsartikel (refereegranskat)abstract
- CHO-K1 cells were synchronized at the G(1)/S border by mitotic shake-off and aphidicolin incubation. Pulse-labeling with tritium was done at 30 min, 2 or 5 h into the S-phase, with chase incubations for different times in non-radioactive medium. The cells were subjected to neutral microelectrophoresis to extend the DNA into "comets," after which the label was visualized through autoradiography. At zero chase time, all label was positioned in the head. The displacement of label into the tails increased with time, reaching a maximum at about 5 h after the pulse. A lag phase of 2 - 3 It was observed for the early-labeled cells before the displacement started. Also, more label was released after overnight serum starvation, but this was reversed through a 3-h incubation at normal growth conditions. It was found that late-replicating chromatin is organized in larger domains than early-replicating chromatin, and DNA polymerase seems to be an important organizer. Early-replicating chromatin has other important attachments to the nuclear matrix, dependent on metabolic activity.
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| 21. |
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| 22. |
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| 23. |
- Grundström, Eva, et al.
(författare)
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Increased expression of glial cell line-derived neurotrophic factor mRNA in muscle biopsies from patients with amyotrophic lateral sclerosis
- 1999
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Ingår i: Journal of the Neurological Sciences. - 0022-510X .- 1878-5883. ; 162:2, s. 169-173
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Tidskriftsartikel (refereegranskat)abstract
- The expression of glial cell line-derived neurotrophic factor (GDNF) mRNA and brain-derived neurotrophic factor (BDNF) mRNA were studied in muscle biopsies from five patients with amyotrophic lateral sclerosis (ALS), six patients with other neuromuscular diseases and eight healthy control persons. All five patients with ALS had higher GDNF mRNA expressions in their biopsies than the healthy control group (almost a three fold increase). Among the other patients only one, who had a rapidly progressing toxic polyneuropathy, showed a GDNF mRNA expression above those of the controls. The BDNF mRNA expressions in the biopsies from the ALS patients were in the same range as those from the healthy controls, although the mean value of the ALS patients was higher. The only biopsy that showed a markedly higher BDNF mRNA expression was taken from one patient with progressive muscular atrophy. These results suggest that increased GDNF mRNA expression in muscle is an unspecific response to ongoing denervation and that this response is maintained in ALS, at least temporarily. If increased GDNF mRNA in muscle proves to be a constant finding in ALS the rationale for the use of GDNF as a therapeutic agent in ALS must be questioned.
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| 24. |
- Gustafsson, Ulf O., et al.
(författare)
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Adherence to the enhanced recovery after surgery protocol and outcomes after colorectal cancer surgery
- 2011
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Ingår i: Archives of surgery (Chicago. 1960). - : American Medical Association (AMA). - 0004-0010 .- 1538-3644. ; 146:5, s. 571-577
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Tidskriftsartikel (refereegranskat)abstract
- Objectives: To study the impact of different adherence levels to the enhanced recovery after surgery (ERAS) protocol and the effect of various ERAS elements on outcomes following major surgery. Design: Single-center prospective cohort study before and after reinforcement of an ERAS protocol. Comparisons were made both between and across periods using multivariate logistic regression. All clinical data (114 variables) were prospectively recorded. Setting: Ersta Hospital, Stockholm, Sweden. Patients: Nine hundred fifty-three consecutive patients with colorectal cancer: 464 patients treated in 2002 to 2004 and 489 in 2005 to 2007. Main Outcome Measures: The association between improved adherence to the ERAS protocol and the incidence of postoperative symptoms, complications, and length of stay following major colorectal cancer surgery was analyzed. Results: Following an overall increase in preoperative and perioperative adherence to the ERAS protocol from 43.3% in 2002 to 2004 to 70.6% in 2005 to 2007, both postoperative complications (odds ratio, 0.73; 95% confidence interval, 0.55-0.98) and symptoms (odds ratio, 0.53; 95% confidence interval, 0.40-0.70) declined significantly. Restriction of intravenous fluid and use of a preoperative carbohydrate drink were major independent predictors. Across periods, the proportion of adverse postoperative outcomes (30-day morbidity, symptoms, and readmissions) was significantly reduced with increasing adherence to the ERAS protocol (>70%, >80%, and >90%) compared with low ERAS adherence (<50%). Conclusion: Improved adherence to the standardized multimodal ERAS protocol is significantly associated with improved clinical outcomes following major colorectal cancer surgery, indicating a dose-response relationship.
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| 25. |
- Gustafsson, Ulf O., et al.
(författare)
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Adherence to the ERAS protocol is Associated with 5-Year Survival After Colorectal Cancer Surgery : A Retrospective Cohort Study
- 2016
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Ingår i: World Journal of Surgery. - New York, USA : Springer. - 0364-2313 .- 1432-2323. ; 40:7, s. 1741-1747
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Tidskriftsartikel (refereegranskat)abstract
- Background: Surgical stress can influence oncological outcome and survival. The enhanced recovery after surgery (ERAS) protocol is designed to reduce perioperative stress and has been shown to reduce postoperative morbidity. We studied if adherence to ERAS is associated with increased long-term survival.Methods: Between the years 2002 and 2007, 911 consecutive patients, operated with major colorectal cancer surgery at Ersta Hospital, Stockholm, Sweden were analyzed. The histopathological reports of the resected specimen, date, and cause of death of the patients as well as postoperative CRP levels were obtained. The relation between the rate of adherence to the ERAS protocol at the time of surgery, and the short-term outcomes in relation to 5-year overall and colorectal cancer-specific survival was determined in this retrospective cohort study.Results: In patients with ≥70 % adherence to ERAS interventions (N = 273,), the risk of 5-year cancer-specific death was lowered by 42 %, HR 0.58 (0.39-0.88, cox regression) compared to all other patients (<70 % adherence). Significant independent perioperative predictors of increased 5-year survival were avoiding overload of intravenous fluids, HR 0.53 (0.32-0.86); oral intake on the day of operation, HR 0.55 (0.34-0.78); and low CRP levels on postoperative day 1.Conclusion: High adherence to the ERAS protocol may be associated with improved 5-year cancer-specific survival after colorectal cancer surgery.
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| 26. |
- Gustafsson, Ulf O., et al.
(författare)
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Can nutritional supplements and rectal enema be used as bowel cleansing for colonoscopy? : results of a randomized controlled pilot study
- 2014
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Ingår i: Scandinavian Journal of Gastroenterology. - London : Informa Healthcare. - 0036-5521 .- 1502-7708. ; 49:4, s. 485-491
-
Tidskriftsartikel (refereegranskat)abstract
- Objective. Currently available preparations for colonoscopy have low tolerability and may cause fluid and electrolyte shifts. An alternative method of bowel cleansing is required.Material and methods. Preparation of the gut using oral nutritional supplements (ONS) and rectal enema was tested as an alternative method of bowel cleansing. During 2008-2012, patients were randomized to oral nutritional supplements (n = 27) for 5 days and rectal enema or polyethylene glycol (PEG) (n = 23) prior to colonoscopy. Blinded endoscopists rated the degree of bowel cleansing according to the Ottawa bowel preparation scale (OBS) (primary outcome). Tolerability of either preparation was also assessed (ClinicalTrials.gov. Identifier no: NCT00123456).Results. Due to a high rate of bowel cleansing failure among patients receiving ONS, the study was interrupted prematurely. Colonoscopies were incomplete due to stools in 6 of 27 patients in the ONS group compared to 1 of 23 in the PEG group (ns). The mean total OBS were 8.3 +/- 3.3 and 5.3 +/- 2.8, respectively (p = 0.002). Four patients (15%) in the ONS group and eight patients (35%) receiving PEG had an OBS score <= 4 (good preparation) (ns). ONS was better tolerated than PEG with more patients reporting acceptable taste (27 of 27 [100%] vs. 15 of 23 [65%], p = 0.001), and fewer reporting difficulties with the intake (0 of 27 [0%] vs. 10 of 23 [43%], p < 0.001) and nausea (5 of 27 [19%] vs. 13 of 23 [57%], p < 0.008).Conclusions. For routine use, ONS with enema instead of traditional preparation for colonoscopy with PEG cannot be generally recommended.
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| 27. |
- Henningsson, Anja, et al.
(författare)
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Population pharmacokinetic modelling of unbound and total plasma concentrations of paclitaxel in cancer patients
- 2003
-
Ingår i: European Journal of Cancer. - 0959-8049 .- 1879-0852. ; 39:8, s. 1105-1114
-
Tidskriftsartikel (refereegranskat)abstract
- The aim of this study was to validate and further develop a mechanism-based population pharmacokinetic model for paclitaxel (Taxol; Bristol-Myers Squibb Co, Princeton, NJ, USA) based on the knowledge of Cremophor EL (CrEL) micelle entrapment and to evaluate the exposure/toxicity relationships. Paclitaxel (total and unbound) and CrEL concentrations were obtained according to a sparse sampling scheme with on average only 3.5 samples per course from 45 patients with solid tumours who received 3-hour infusions of paclitaxel (final dose range 112-233 mg/m(2)). The present data were predicted well by the mechanism-based model. In addition, bilirubin and body size were found to be significant as covariates. A change in body surface area (BSA) of 0.1 m(2) typically caused a change in clearance (CL) of 22.3 l/h and an increase in bilirubin of 10 microM typically caused a decrease in CL of 41 l/h. Toxicity was best described by a threshold model. In conclusion, even with a sparse sampling scheme, the same mechanism-based binding components as in the previously developed model could be identified. Once the CrEL and total paclitaxel plasma concentrations are known, the unbound concentrations, which are more closely related to the haematological toxicity, can be predicted.
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| 28. |
- Henningsson, Susanne, 1977, et al.
(författare)
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Possible association between the androgen receptor gene and autism spectrum disorder.
- 2009
-
Ingår i: Psychoneuroendocrinology. - : Elsevier BV. - 0306-4530 .- 1873-3360. ; 34:5, s. 752-761
-
Tidskriftsartikel (refereegranskat)abstract
- Autism is a highly heritable disorder but the specific genes involved remain largely unknown. The higher prevalence of autism in men than in women, in conjunction with a number of other observations, has led to the suggestion that prenatal brain exposure to androgens may be of importance for the development of this condition. Prompted by this hypothesis, we investigated the potential influence of variation in the androgen receptor (AR) gene on the susceptibility for autism. To this end, 267 subjects with autism spectrum disorder and 617 controls were genotyped for three polymorphisms in exon 1 of the AR gene: the CAG repeat, the GGN repeat and the rs6152 SNP. In addition, parents and affected siblings were genotyped for 118 and 32 of the cases, respectively. Case-control comparisons revealed higher prevalence of short CAG alleles as well as of the A allele of the rs6152 SNP in female cases than in controls, but revealed no significant differences with respect to the GGN repeat. Analysis of the 118 families using transmission disequilibrium test, on the other hand, suggested an association with the GGN polymorphism, the rare 20-repeat allele being undertransmitted to male cases and the 23-repeat allele being overtransmitted to female cases. Sequencing of the AR gene in 46 patients revealed no mutations or rare variants. The results lend some support for an influence of the studied polymorphisms on the susceptibility for autism, but argue against the possibility that mutations in the AR gene are common in subjects with this condition.
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| 29. |
- Hultman, Bo, et al.
(författare)
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Costs and clinical outcome of neoadjuvant systemic chemotherapy followed by cytoreductive surgery and hyperthermic intraperitoneal chemotherapy in peritoneal carcinomatosis from gastric cancer
- 2012
-
Ingår i: Acta Oncologica. - 0284-186X .- 1651-226X. ; 51:1, s. 112-121
-
Tidskriftsartikel (refereegranskat)abstract
- BackgroundThe costs for loco-regional treatment of peritoneal carcinomatosis from gastric cancer are not well investigated. The aims of this study were to evaluate the costs and clinical outcome of systemic chemotherapy followed by cytoreductive surgery and intraperitoneal chemotherapy compared to systemic chemotherapy only in patients with peritoneal carcinomatosis from gastric cancer.Material and methodsTen patients were scheduled for systemic chemotherapy followed by loco-regional treatment. A reference group of 10 matched control patients treated with systemic chemotherapy only were used and both groups were evaluated with respect to clinical outcome and cost.ResultsThe mean overall cost in the loco-regional group was $145 700 (range $49 900-$487 800) and $59 300 (range $23 000-$94 800) for the control group. The mean overall survival for the loco-regional group was 17.4 months (range 6.0-34.3), and 11.1 months (range 0.1-24.2) for the systemic chemotherapy only group. The gain in life-years was 0.52 and in quality-adjusted life-years 0.49, leading to incremental cost per life-year and quality-adjusted life-years gained of $166 716 and $175 164, for loco-regional group compared to systemic chemotherapy.DiscussionTreatment of peritoneal carcinomatosis from gastric cancer is costly irrespective of treatment modality. If the survival benefit from adding loco-regional treatment to systemic chemotherapy indicated from this comparison is true, the incremental cost is considered high.
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| 30. |
- Ismail, Ismail Hassan, 1975, et al.
(författare)
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Activation of ataxia telangiectasia mutated by DNA strand break-inducing agents correlates closely with the number of DNA double strand breaks.
- 2005
-
Ingår i: The Journal of biological chemistry. - 0021-9258. ; 280:6, s. 4649-55
-
Tidskriftsartikel (refereegranskat)abstract
- The protein kinase ataxia telangiectasia mutated (ATM) is activated when cells are exposed to ionizing radiation (IR). It has been assumed that ATM is specifically activated by the few induced DNA double strand breaks (DSBs), although little direct evidence for this assumption has been presented. DSBs constitute only a few percent of the IR-induced DNA damage, whereas the more frequent single strand DNA breaks (SSBs) and base damage account for over 98% of the overall DNA damage. It is therefore unclear whether DSBs are the only IR-induced DNA lesions that activate ATM. To test directly whether or not DSBs are responsible for ATM activation, we exposed cells to drugs and radiation that produce different numbers of DSBs and SSBs. We determined the resulting ATM activation by measuring the amount of phosphorylated Chk2 and the numbers of SSBs and DSBs in the same cells after short incubation periods. We found a strong correlation between the number of DSBs and ATM activation but no correlation with the number of SSBs. In fact, hydrogen peroxide, which, similar to IR, induces DNA damage through hydroxyl radicals but fails to induce DSBs, did not activate ATM. In contrast, we found that calicheamicin-induced strand breaks activated ATM more efficiently than IR and that ATM activation correlated with the relative DSB induction by these agents. Our data indicate that ATM is specifically activated by IR-induced DSBs, with little or no contribution from SSBs and other types of DNA damage. These findings have implications for how ATM might recognize DSBs in cells.
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| 31. |
- Johansson, Clara, et al.
(författare)
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Down-regulation of oxidative DNA lesions in human mononuclear cells after antioxidant supplementation correlates to increase of gamma-tocopherol
- 2008
-
Ingår i: International Journal for Vitamin and Nutrition Research. - : Hogrefe Publishing Group. - 0300-9831 .- 1664-2821. ; 78:4-5, s. 183-194
-
Tidskriftsartikel (refereegranskat)abstract
- The protective effect of vitamin E supplements has been questioned, possibly because they often contain only alpha-tocopherol, and recent studies indicate that gamma-tocopherol also has important properties. The aim of this study was to investigate whether the levels of DNA lesions in middle-aged, overweight males could be reduced by consumption of low doses of an antioxidant supplement for six weeks, designed to imitate a balanced diet. The participants (n=60) were randomly divided into: placebo, single-, and double-dose groups. Genotoxic and oxidative DNA lesions in mononuclear cells were measured with the Comet assay, before and after supplement administration. Furthermore, a cell study was performed to investigate if pre-incubation of a human lung cell line (A549) with alpha- and gamma-tocopherol (5 and 50 microM for 23 hours) could protect against induced oxidative DNA lesions as measured by the Comet assay. The level of oxidative DNA lesions in the double-dose group was significantly lower than in the control group. Oxidative DNA lesions correlated only to changes in serum gamma-tocopherol, and not alpha-tocopherol. In the cell study, only gamma-tocopherol protected cells against induced oxidative DNA lesions. We therefore hypothesize that gamma-tocopheol rather than alpha-tocopherol is involved in reducing oxidative DNA lesions.
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| 32. |
- Lassen, Kristoffer, et al.
(författare)
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Consensus review of optimal perioperative care in colorectal surgery : Enhanced Recovery After Surgery (ERAS) Group recommendations
- 2009
-
Ingår i: Archives of surgery (Chicago. 1960). - : American Medical Association (AMA). - 0004-0010 .- 1538-3644. ; 144:10, s. 961-969
-
Forskningsöversikt (refereegranskat)abstract
- OBJECTIVES: To describe a consensus review of optimal perioperative care in colorectal surgery and to provide consensus recommendations for each item of an evidence-based protocol for optimal perioperative care. DATA SOURCES: For every item of the perioperative treatment pathway, available English-language literature has been examined. STUDY SELECTION: Particular attention was paid to meta-analyses, randomized controlled trials, and systematic reviews. DATA EXTRACTION: A consensus recommendation for each protocol item was reached after critical appraisal of the literature by the group. DATA SYNTHESIS: For most protocol items, recommendations are based on good-quality trials or meta-analyses of such trials. CONCLUSIONS: The Enhanced Recovery After Surgery (ERAS) Group presents a comprehensive evidence-based consensus review of perioperative care for colorectal surgery. It is based on the evidence available for each element of the multimodal perioperative care pathway.
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| 33. |
- Lassen, Kristoffer, et al.
(författare)
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Nutritional support and oral intake after gastric resection in five northern European countries
- 2005
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Ingår i: Digestive Surgery. - Basel, Switzerland : S. Karger. - 0253-4886 .- 1421-9883. ; 22:5, s. 346-52; discussion 352
-
Tidskriftsartikel (refereegranskat)abstract
- Background: A comprehensive evidence base for perioperative care in upper gastrointestinal (GI) surgery is lacking. Little is known about the routines currently practiced in the absence of such evidence. We describe postoperative practice after gastric resections in five northern European countries. METHOD AND SETTING: Questionnaire survey in all major digestive surgical centres in Scotland, the Netherlands, Denmark, Sweden and Norway.Results: 76% of all centres (n = 200/263) responded. Routines varied extensively both nationally and between countries. No uniformity was traced although a conservative trend was noticeable in the use of nasogastric decompression tubes and 'nil-by-mouth' regimens. Nutritional support during the first 5 days is generally offered in Denmark, but not in Scotland. Drinking at will is generally allowed in Denmark and Norway by the first postoperative day. Eating at will is uniformly restricted.Conclusion: The paucity of evidence is reflected by the marked heterogeneity in practice. Large groups of patients may be treated suboptimally. Best perioperative care for these patients must be defined and documented. Especially, the role of early oral intake at will in upper GI surgery needs to be clarified by sufficiently powered trials.
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| 34. |
- Leblond, Claire S, et al.
(författare)
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Genetic and functional analyses of SHANK2 mutations suggest a multiple hit model of autism spectrum disorders.
- 2012
-
Ingår i: PLoS Genetics. - : Public Library of Science (PLoS). - 1553-7390 .- 1553-7404. ; 8:2
-
Tidskriftsartikel (refereegranskat)abstract
- Autism spectrum disorders (ASD) are a heterogeneous group of neurodevelopmental disorders with a complex inheritance pattern. While many rare variants in synaptic proteins have been identified in patients with ASD, little is known about their effects at the synapse and their interactions with other genetic variations. Here, following the discovery of two de novo SHANK2 deletions by the Autism Genome Project, we identified a novel 421 kb de novo SHANK2 deletion in a patient with autism. We then sequenced SHANK2 in 455 patients with ASD and 431 controls and integrated these results with those reported by Berkel et al. 2010 (n=396 patients and n=659 controls). We observed a significant enrichment of variants affecting conserved amino acids in 29 of 851 (3.4%) patients and in 16 of 1,090 (1.5%) controls (P=0.004, OR=2.37, 95% CI=1.23-4.70). In neuronal cell cultures, the variants identified in patients were associated with a reduced synaptic density at dendrites compared to the variants only detected in controls (P=0.0013). Interestingly, the three patients with de novo SHANK2 deletions also carried inherited CNVs at 15q11-q13 previously associated with neuropsychiatric disorders. In two cases, the nicotinic receptor CHRNA7 was duplicated and in one case the synaptic translation repressor CYFIP1 was deleted. These results strengthen the role of synaptic gene dysfunction in ASD but also highlight the presence of putative modifier genes, which is in keeping with the "multiple hit model" for ASD. A better knowledge of these genetic interactions will be necessary to understand the complex inheritance pattern of ASD.
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| 35. |
- Lindman, Henrik, et al.
(författare)
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Individually tailored toxicity-based 5-fluorouracil, epirubicin and cyclophosphamide (FEC) therapy of metastatic breast cancer
- 2007
-
Ingår i: Acta Oncologica. - : Informa UK Limited. - 0284-186X .- 1651-226X. ; 46:2, s. 165-171
-
Tidskriftsartikel (refereegranskat)abstract
- Chemotherapy dosing only based on body surface area (BSA) results in marked pharmacokinetic and toxicity variations, which may result in an inferior outcome for some patients. A toxicity-based dosing schedule for individually tailored treatment with granulocyte colony-stimulating factor (G-CSF) supported 5-fluorouracil (F), epirubicin (E) and cyclophosphamide (C) (dFEC) was developed and studied in patients with metastatic breast cancer with the purpose to determine its efficiency and toxicity. Twenty-six women, median age 48 years, were included and the individual E and C doses were tailored stepwise based on the recorded hematological toxicity. Twenty-one patients (81%; 95% confidence interval (CI), 66% to 96%) had an objective response, including six complete responses (23%; CI, 7%-39%). At median follow-up of 113 months, the median time to progression and median overall survival were 14 and 36 months, respectively. The delivered dose intensity was high but varied substantially between patients (ranges F 126-202, E 14.4-36.0, C 160-510 mg/m2/w). The dominating grade III/IV toxicity was nausea (12% of patients) and febrile neutropenia (31% of patients). The tailored and dose-escalated FEC was highly active and feasible in metastatic breast cancer and may provide a pragmatic way of overcoming the shortcomings of standard BSA-based dosing.
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| 36. |
- Lindman, Henrik, 1963-
(författare)
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Individually Tailored Toxicity-based Chemotherapy : Studies on Patients with Primary and Metastatic Breast Cancer
- 2003
-
Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Standard dosing of chemotherapy based on body surface area (BSA) results in large individual differences in toxicity due to a large inter-patient variability in pharmacokinetics (PK) and pharmacodynamics (PD). This results in under-dosing in certain patients with a potentially weaker antitumoral effect.Three clinical studies of individually tailored dosing of chemotherapy, based on haematological toxicity were conducted. In the first study, 26 women with metastatic breast cancer were treated with tailored and dose-escalated 5-fluorouracil, epirubicin and cyclophosphamide, supported by G-CSF (dFEC). In the second study 525 patients with high-risk primary breast cancer were randomised between dFEC and high-dose chemotherapy with autologous bone-marrow transplantation. The feasibility of a FEC regimen with doubled cyclophosphamide dose to mobilise peripheral stem cells was investigated. In the third study, 44 metastatic patients were treated with tailored epirubicin and docetaxel (ET). PK and PD were also investigated in these patients. The potential effects of G-CSF on MRI tumour evaluation were studied in 18 patients with skeletal metastases.Toxicity-based dosing entailed an evenly distributed two- to three-fold range of tolerated doses in all three studies. Efficacy and toxicity were not correlated to tolerated dose-levels. Tailored dFEC resulted in a response rate of 81% and the same regimen resulted in fewer breast cancer relapses compared with standard FEC followed by high-dose therapy. Toxicity was manageable except for an increased rate of secondary leukaemia. The modified FEC could safely mobilise sufficient numbers of stem-cells. Tailored ET resulted in a response rate of 63%. The inter-individual variability in drug clearance was larger than the inter-occasion variability and a semi-physiological model of PK and PD could predict leukocyte nadir and duration. An increased diffuse MR signal in the long TE IR-TSE sequence was observed in normal bone-marrow during G-CSF treatment; this could be mistaken as disseminated metastatic disease and could obscure focal metastases.In conclusion, the concept of individually tailored toxicity-based dosage of chemotherapy was equally feasible in primary and metastatic breast cancer, in two different chemotherapy regimens and in treatment with or without G-CSF support and may provide a pragmatic way of overcoming the shortcomings of standard BSA-based dosing.
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| 37. |
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| 38. |
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| 39. |
- Linnsand, Petra, et al.
(författare)
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Intervention in autism based on Early Start Denver Model in a multiethnic immigrant setting—experiences of preschool staff involved in its implementation
- 2024
-
Ingår i: Frontiers in Child and Adolescent Psychiatry. - 2813-4540. ; 3
-
Tidskriftsartikel (refereegranskat)abstract
- Background: Early interventions for young children with autism have been shown to enhance developmental outcomes. However, opportunities for targeted interventions in autism, both in care and preschool, are often lacking, particularly in immigrant communities. The early start denver model (ESDM) stands as one of the most well-established intervention models, including improvement in core developmental domains and reduction of maladaptive behaviours, also delivered in preschool settings. An intervention program based on the ESDM was implemented in collaboration with parents, preschool staff, and health care professionals locally in a multiethnic immigrant and socioeconomically disadvantaged area in Gothenburg, Sweden. Purpose: The present study aimed to describe a low intensity intervention program based on the ESDM for young children with autism in a multiethnic immigrant setting and capture the experiences of the preschool staff involved in implementing the program. Method: Fifteen preschool professionals were interviewed through focus group interviews. Data were analyzed using content analysis. The interviews focused on capturing the crucial factors in the intervention program and to get more in-depth information about the intervention program's influence on the children with autism, their parents, the preschool staff, and preschool activities. Results: Central components of the intervention program were emphasized by the preschool staff. These encompassed contextual prerequisites, such as the preschool staff's participation in intervention program fostered by the local environment and features linked to the ESDM methodology. The preschool staff emphasized that shared objectives and regular network meetings as fundamental components of the model. They also underscored the seamless alignment between the ESDM and the preschool curriculum emphasizing how ESDM strategies could be easily integrated into the preschool's daily routines. The staff's experience indicated that the implementation of ESDM enriched the learning experiences of children with autism and yielded benefits to their parents, fellow peers in the preschool, and the preschool staff. Conclusions: The intervention program based on the ESDM presents a promising model for young children with autism in a multiethnic immigrant setting. Several critical factors based on the preschool staff's experiences were essential for implementation: contextual prerequisites such as organizational support, close collaboration with healthcare professionals, good competence among preschool staff, and the ESDM itself.
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| 40. |
- Ljungqvist, Olle, 1954-, et al.
(författare)
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Metabolic perioperative management : novel concepts
- 2005
-
Ingår i: Current Opinion in Critical Care. - Philadelphia, USA : Lippincott Williams & Wilkins. - 1070-5295 .- 1531-7072. ; 11:4, s. 295-9
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Forskningsöversikt (refereegranskat)abstract
- Purpose of review: This review summarizes novel information regarding the role of metabolic control in the perioperative period.Recent findings: Managing perioperative metabolism has recently been shown to be an important way to improve outcomes in surgical care. In particular, postoperative insulin resistance and hyperglycemia have been linked to many common complications. Recent studies have explored the toxicity of hyperglycemia and suggest a causal relation between insulin resistance and complications in the postoperative state. Controlling glucose concentrations with insulin has been shown to also improve protein balance and fat metabolism. In addition, insulin may affect other hormones including insulinlike growth factor-I during surgical stress. Lastly, recent data suggest that hyperglycemia plays an important role in aggravating the inflammatory response, in that overflow of substrates in the mitochondria causes the formation of excess free oxygen radicals and may also alter gene expression to enhance cytokine production. Although overcoming insulin resistance by insulin infusion is one way of combating hyperglycemia, prevention of its development can also be achieved by using epidural blockade to reduce the release of adrenal stress hormones and to control pain, by preoperative carbohydrates instead of overnight fasting, and by minimal invasive surgical techniques.Summary: Minimizing the effects of insulin resistance has been shown to substantially improve outcome after surgical stress.
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| 41. |
- Ljungqvist, Olle, 1954-, et al.
(författare)
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Modulation of post-operative insulin resistance by pre-operative carbohydrate loading
- 2002
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Ingår i: Proceedings of the nutrion society. - Oxon, United Kingdom : C A B I Publishing. - 0029-6651. ; 61:3, s. 329-36
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Tidskriftsartikel (refereegranskat)abstract
- Insulin resistance develops as a response to virtually all types of surgical stress. There is an increasing body of evidence that suggests that insulin resistance in surgical stress is not beneficial for outcome. A recent large study in intensive-care patients showed that aggressive treatment of insulin resistance using intravenous insulin reduced mortality and morbidity substantially. Similarly, in burn patients, intensive insulin and glucose treatment has been shown to improve N economy and enhance skin-graft healing. In surgical patients insulin resistance has been characterized in some detail, and has been shown to have many similarities with metabolic changes seen in patients with type 2 diabetes. This finding may be important since insulin resistance has been shown to be one independent factor that influences length of stay. When patients about to undergo elective surgery have been treated with glucose intravenously or a carbohydrate-rich drink instead of overnight fasting, insulin resistance was reduced by about half. A small meta-analysis showed that when post-operative insulin resistance was reduced by pre-operative carbohydrates, length of hospital stay was shortened. Overnight intravenous glucose at high doses improved post-operative N economy. This type of treatment has also been shown repeatedly to reduce cardiac complications after open-heart surgery. Furthermore, if the carbohydrates are given as a drink pre-operatively, pre-operative thirst, hunger and anxiety are markedly reduced. In summary, preventing or treating insulin resistance in surgical stress influences outcome. Fasting overnight is not an optimal way to prepare patients for elective surgery. Instead, pre-operative carbohydrates have clinical benefits.
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| 42. |
- Ljungqvist, Olle, et al.
(författare)
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Pre- och postoperativ vård
- 2010. - 3
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Ingår i: Kirurgi. - Lund : Studentlitteratur AB. - 9789144057149 ; , s. 23-38
-
Bokkapitel (övrigt vetenskapligt/konstnärligt)
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| 43. |
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| 44. |
- Machado, Mikael, et al.
(författare)
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Functional and physiologic assessment of the colonic reservoir or side-to-end anastomosis after low anterior resection for rectal cancer : a two-year follow-up
- 2005
-
Ingår i: Diseases of the Colon & Rectum. - Philadelphia, USA : Lippincott Williams & Wilkins. - 0012-3706 .- 1530-0358. ; 48:1, s. 29-36
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: Functional disturbances are common after anterior resection for rectal cancer. This study was designed to compare functional and physiologic outcome after low anterior resection and total mesorectal excision with a colonic J-pouch or a side-to-end anastomosis.Methods: Functional and physiologic variables were analyzed in patients randomized to a J-pouch (n = 36) or side-to-end anastomosis (n = 35). Postoperative functional outcome was investigated with questionnaires. Anorectal manometry was performed preoperatively and at six months, one year, and two years postoperatively.Results: There was no statistical difference in functional outcome between groups at two years. Maximum neorectal volume increased in both groups but was approximately 40 percent greater at two years in pouches compared with the side-to-end anastomosis. Anal sphincter pressures volumes were halved postoperatively and did not recover during follow-up of two years. Male gender, low anastomotic level, pelvic sepsis, and the postoperative decrease of sphincter pressures were independent factors for more incontinence symptoms.Conclusions: Colonic J-pouch and side-to-end anastomosis gives comparable functional results two years after low anterior resection. Neorectal volume had no detectable influence on function. There was a pronounced and sustained postoperative decrease in sphincter pressures.
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| 45. |
- Machado, Mikael, et al.
(författare)
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Similar outcome after colonic pouch and side-to-end anastomosis in low anterior resection for rectal cancer : a prospective randomized trial.
- 2003
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Ingår i: Annals of Surgery. - Philadelphia, USA : Lippincott Williams & Wilkins. - 0003-4932 .- 1528-1140. ; 238:2, s. 214-20
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Tidskriftsartikel (refereegranskat)abstract
- Objectives: To compare a colonic J-pouch or a side-to-end anastomosis after low-anterior resection for rectal cancer with regard to functional and surgical outcome.Summary beckground data: A complication after restorative rectal surgery with a straight anastomosis is low-anterior resection syndrome with a postoperatively deteriorated anorectal function. The colonic J-reservoir is sometimes used with the purpose of reducing these symptoms. An alternative method is to use a simple side-to-end anastomosis.Methods: One-hundred patients with rectal cancer undergoing total mesorectal excision and colo-anal anastomosis were randomized to receive either a colonic pouch or a side-to-end anastomosis using the descending colon. Surgical results and complications were recorded. Patients were followed with a functional evaluation at 6 and 12 months postoperatively.Results: Fifty patients were randomized to each group. Patient characteristics in both groups were very similar regarding age, gender, tumor level, and Dukes' stages. A large proportion of the patients received short-term preoperative radiotherapy (78%). There was no significant difference in surgical outcome between the 2 techniques with respect to anastomotic height (4 cm), perioperative blood loss (500 ml), hospital stay (11 days), postoperative complications, reoperations or pelvic sepsis rates. Comparing functional results in the 2 study groups, only the ability to evacuate the bowel in <15 minutes at 6 months reached a significant difference in favor of the pouch procedure.Conclusions: The data from this study show that either a colonic J-pouch or a side-to-end anastomosis performed on the descending colon in low-anterior resection with total mesorectal excision are methods that can be used with similar expected functional and surgical results.
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| 46. |
- Melke, Jonas, 1971, et al.
(författare)
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Abnormal melatonin synthesis in autism spectrum disorders.
- 2008
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Ingår i: Molecular Psychiatry. - : Springer Science and Business Media LLC. - 1359-4184 .- 1476-5578. ; 13:1, s. 90-98
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Tidskriftsartikel (refereegranskat)abstract
- Melatonin is produced in the dark by the pineal gland and is a key regulator of circadian and seasonal rhythms. A low melatonin level has been reported in individuals with autism spectrum disorders (ASD), but the underlying cause of this deficit was unknown. The ASMT gene, encoding the last enzyme of melatonin synthesis, is located on the pseudo-autosomal region 1 of the sex chromosomes, deleted in several individuals with ASD. In this study, we sequenced all ASMT exons and promoters in individuals with ASD (n=250) and compared the allelic frequencies with controls (n=255). Non-conservative variations of ASMT were identified, including a splicing mutation present in two families with ASD, but not in controls. Two polymorphisms located in the promoter (rs4446909 and rs5989681) were more frequent in ASD compared to controls (P=0.0006) and were associated with a dramatic decrease in ASMT transcripts in blood cell lines (P=2 x 10(-10)). Biochemical analyses performed on blood platelets and/or cultured cells revealed a highly significant decrease in ASMT activity (P=2 x 10(-12)) and melatonin level (P=3 x 10(-11)) in individuals with ASD. These results indicate that a low melatonin level, caused by a primary deficit in ASMT activity, is a risk factor for ASD. They also support ASMT as a susceptibility gene for ASD and highlight the crucial role of melatonin in human cognition and behavior.
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| 47. |
- Nair, Monika, 1985-, et al.
(författare)
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Barriers and Enablers for Implementation of an Artificial Intelligence–Based Decision Support Tool to Reduce the Risk of Readmission of Patients With Heart Failure : Stakeholder Interviews
- 2023
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Ingår i: JMIR Formative Research. - Toronto, ON : JMIR Publications. - 2561-326X. ; 7
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Tidskriftsartikel (refereegranskat)abstract
- Background: Artificial intelligence (AI) applications in health care are expected to provide value for health care organizations, professionals, and patients. However, the implementation of such systems should be carefully planned and organized in order to ensure quality, safety, and acceptance. The gathered view of different stakeholders is a great source of information to understand the barriers and enablers for implementation in a specific context.Objective: This study aimed to understand the context and stakeholder perspectives related to the future implementation of a clinical decision support system for predicting readmissions of patients with heart failure. The study was part of a larger project involving model development, interface design, and implementation planning of the system.Methods: Interviews were held with 12 stakeholders from the regional and municipal health care organizations to gather their views on the potential effects implementation of such a decision support system could have as well as barriers and enablers for implementation. Data were analyzed based on the categories defined in the nonadoption, abandonment, scale-up, spread, sustainability (NASSS) framework.Results: Stakeholders had in general a positive attitude and curiosity toward AI-based decision support systems, and mentioned several barriers and enablers based on the experiences of previous implementations of information technology systems. Central aspects to consider for the proposed clinical decision support system were design aspects, access to information throughout the care process, and integration into the clinical workflow. The implementation of such a system could lead to a number of effects related to both clinical outcomes as well as resource allocation, which are all important to address in the planning of implementation. Stakeholders saw, however, value in several aspects of implementing such system, emphasizing the increased quality of life for those patients who can avoid being hospitalized.Conclusions: Several ideas were put forward on how the proposed AI system would potentially affect and provide value for patients, professionals, and the organization, and implementation aspects were important parts of that. A successful system can help clinicians to prioritize the need for different types of treatments but also be used for planning purposes within the hospital. However, the system needs not only technological and clinical precision but also a carefully planned implementation process. Such a process should take into consideration the aspects related to all the categories in the NASSS framework. This study further highlighted the importance to study stakeholder needs early in the process of development, design, and implementation of decision support systems, as the data revealed new information on the potential use of the system and the placement of the application in the care process. © The Author(s) 2023.
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| 48. |
- Nelson, Gregg, et al.
(författare)
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Guidelines for perioperative care in gynecologic/oncology : Enhanced Recovery After Surgery (ERAS) Society recommendations-2019 update
- 2019
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Ingår i: International Journal of Gynecological Cancer. - : Lippincott Williams & Wilkins. - 1048-891X .- 1525-1438. ; 29:4, s. 651-668
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Forskningsöversikt (refereegranskat)abstract
- BACKGROUND: This is the first updated Enhanced Recovery After Surgery (ERAS) Society guideline presenting a consensus for optimal perioperative care in gynecologic/oncology surgery.METHODS: A database search of publications using Embase and PubMed was performed. Studies on each item within the ERAS gynecologic/oncology protocol were selected with emphasis on meta-analyses, randomized controlled trials, and large prospective cohort studies. These studies were then reviewed and graded according to the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) system.RESULTS: All recommendations on ERAS protocol items are based on best available evidence. The level of evidence for each item is presented accordingly.CONCLUSIONS: The updated evidence base and recommendation for items within the ERAS gynecologic/oncology perioperative care pathway are presented by the ERAS® Society in this consensus review.
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| 49. |
- Nordling, M M, et al.
(författare)
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Toxicological characterization of a novel in vivo benzo[a]lpyrene metabolite, 7-oxo-benz[d]anthracene-3,4-dicarboxylic acid anhydride
- 2002
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Ingår i: Chemical Research in Toxicology. - : American Chemical Society (ACS). - 0893-228X .- 1520-5010. ; 15:10, s. 1274-1280
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Tidskriftsartikel (refereegranskat)abstract
- Recently, we described a new in vivo pathway in the metabolism of benzo[a]pyrene (BP) that involves an opening of the aromatic ring system. One of the products of this pathway, isolated from rat urine, was the anhydride of 7-oxo-benz[d]anthracene-3,4-dicarboxylic acid (ABADA). We have now investigated the effect of ABADA on several cellular targets, known to be important in tumor formation. ABADA was as efficient as BP-7,8-diol-9,10-epoxide in inducing direct strand breaks but not alkali labile sites in DNA in HT-29 cells and exhibited weak mutagenic activity in Salmonella typhimurium strain TA 102. The cytotoxicity of ABADA to HCT 116 cells appeared to be due to apoptosis, as caspase-3 activity and poly-ADP-ribose polymerase (PARP) cleavage was observed. COX-2 promoter activity was induced by ABADA in HCT 116 cells. In conclusion, this novel metabolic pathway may also be contributing to the carcinogenicity of BP.
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| 50. |
- Nygren, David, et al.
(författare)
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Association between SARS-CoV-2 and exposure risks in health care workers and university employees – a cross-sectional study
- 2021
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Ingår i: Infectious Diseases. - : Informa UK Limited. - 1651-1980 .- 2374-4235 .- 2374-4243. ; 53:6, s. 460-468
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundIn health care workers SARS-CoV-2 has been shown to be an occupational health risk, often associated with transmission between health care workers. Yet, insufficient information on transmission dynamics has been presented to elucidate the precise risk factors for contracting SARS-CoV-2 in this group.MethodsIn this cross-sectional study, we investigated association between questionnaire answers on potential exposure situations and SARS-CoV-2-positivity. Health care workers with and without COVID-19-patient contact at nine units at Skåne University Hospitals in Malmö and Lund, Sweden and university employees from Lund University, Sweden were enrolled. To limit impact of health care worker to health care worker transmission, units with known outbreaks were excluded. A SARS-CoV-2-positive case was defined by a previous positive PCR or anti-SARS-CoV-2 IgG in the ZetaGene COVID-19 Antibody Test.ResultsSARS-CoV-2-positivity was detected in 11/51 (22%) health care workers in COVID-19-units, 10/220 (5%) in non-COVID-19-units and 11/192 (6%) University employees (p = .001, Fischer’s exact). In health care workers, SARS-CoV-2-positivity was associated with work in a designated COVID-19-unit (OR 5.7 (95CI 2.1–16)) and caring for COVID-19-patients during the majority of shifts (OR 5.4 (95CI 2.0–15)). In all participants, SARS-CoV-2-positivity was associated with a confirmed COVID-19 case (OR 10 (95CI 2.0–45)) in the household.ConclusionOur study confirmed previous findings of elevated risk of acquiring SARS-CoV-2 in health care workers in COVID-19-units, despite exclusion of units with known outbreaks. Interestingly, health care workers in non-COVID-19-units had similar risk as University employees. Further measures to improve the safety of health care workers might be needed.
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