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  • 651.
    Wang, Chunliang
    et al.
    Linköping University, Department of Medical and Health Sciences, Division of Radiological Sciences. Linköping University, Faculty of Health Sciences. Linköping University, Center for Medical Image Science and Visualization (CMIV).
    Smedby, Örjan
    Linköping University, Department of Medical and Health Sciences, Division of Radiological Sciences. Linköping University, Faculty of Health Sciences. Linköping University, Center for Medical Image Science and Visualization (CMIV). Region Östergötland, Center for Diagnostics, Department of Radiology in Linköping.
    Fully automatic brain segmentation using model-guided level set and skeleton based models2013Conference paper (Other academic)
    Abstract [en]

    A fully automatic brain segmentation method is presented. First the skull is stripped using a model-based level set on T1-weighted inversion recovery images, then the brain ventricles and basal ganglia are segmented using the same method on T1-weighted images. The central white matter is segmented using a regular level set method but with high curvature regulation. To segment the cortical gray matter, a skeleton-based model is created by extracting the mid-surface of the gray matter from a preliminary segmentation using a threshold-based level set. An implicit model is then built by defining the thickness of the gray matter to be 2.7 mm. This model is incorporated into the level set framework and used to guide a second round more precise segmentation. Preliminary experiments show that the proposed method can provide relatively accurate results compared with the segmentation done by human observers. The processing time is considerably shorter than most conventional automatic brain segmentation methods.

  • 652.
    Wang, Peng
    et al.
    Capital Medical University, Peoples R China; Logist University of Peoples Armed Police Force, Peoples R China.
    Li, Hui
    Capital Medical University, Peoples R China.
    Barde, Swapnali
    Karolinska Institute, Sweden.
    Zhang, Ming-Dong
    Karolinska Institute, Sweden; Karolinska Institute, Sweden.
    Sun, Jing
    Capital Medical University, Peoples R China.
    Wang, Tong
    Capital Medical University, Peoples R China.
    Zhang, Pan
    Capital Medical University, Peoples R China.
    Luo, Hanjiang
    Capital Medical University, Peoples R China.
    Wang, Yongjun
    Capital Medical University, Peoples R China.
    Yang, Yutao
    Capital Medical University, Peoples R China.
    Wang, Chuanyue
    Capital Medical University, Peoples R China.
    Svenningsson, Per
    Karolinska Institute, Sweden; Karolinska University Hospital, Sweden.
    Theodorsson, Elvar
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Clinical Chemistry.
    Hokfelt, Tomas G. M.
    Karolinska Institute, Sweden.
    David Xu, Zhi-Qing
    Capital Medical University, Peoples R China.
    Depression-like behavior in rat: Involvement of galanin receptor subtype 1 in the ventral periaqueductal gray2016In: Proceedings of the National Academy of Sciences of the United States of America, ISSN 0027-8424, E-ISSN 1091-6490, Vol. 113, no 32, p. E4726-E4735Article in journal (Refereed)
    Abstract [en]

    The neuropeptide galanin coexists in rat brain with serotonin in the dorsal raphe nucleus and with noradrenaline in the locus coeruleus (LC), and it has been suggested to be involved in depression. We studied rats exposed to chronic mild stress (CMS), a rodent model of depression. As expected, these rats showed several endophenotypes relevant to depression-like behavior compared with controls. All these endophenotypes were normalized after administration of a selective serotonin reuptake inhibitor. The transcripts for galanin and two of its receptors, galanin receptor 1 (GALR1) and GALR2, were analyzed with quantitative real-time PCR using laser capture microdissection in the following brain regions: the hippocampal formation, LC, and ventral periaqueductal gray (vPAG). Only Galr1 mRNA levels were significantly increased, and only in the latter region. After knocking down Galr1 in the vPAG with an siRNA technique, all parameters of the depressive behavioral phenotype were similar to controls. Thus, the depression-like behavior in rats exposed to CMS is likely related to an elevated expression of Galr1 in the vPAG, suggesting that a GALR1 antagonist could have antidepressant effects.

  • 653.
    Ward, Rebecca
    et al.
    Univ Coll Dublin, Ireland.
    Ali, Zaheer
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences.
    Slater, Kayleigh
    Univ Coll Dublin, Ireland.
    Reynolds, Alison L.
    Univ Coll Dublin, Ireland; Univ Coll Dublin, Ireland.
    Jensen, Lasse
    Linköping University, Department of Health, Medicine and Caring Sciences, Division of Diagnostics and Specialist Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Clinical Pharmacology.
    Kennedy, Breandan N.
    Univ Coll Dublin, Ireland.
    Pharmacological restoration of visual function in a zebrafish model of von-Hippel Lindau disease2020In: Developmental Biology, ISSN 0012-1606, E-ISSN 1095-564X, Vol. 457, no 2, p. 226-234Article in journal (Refereed)
    Abstract [en]

    Von Hippel-Lindau (VHL) syndrome is a rare, autosomal dominant disorder, characterised by hypervascularised tumour formation in multiple organ systems. Vision loss associated with retinal capillary hemangioblastomas remains one of the earliest complications of VHL disease. The mortality of Vhl(-/-) mice in utero restricted modelling of VHL disease in this mammalian model. Zebrafish harbouring a recessive germline mutation in the vhl gene represent a viable, alternative vertebrate model to investigate associated ocular loss-of-function phenotypes. Previous studies reported neovascularisation of the brain, eye and trunk together with oedema in the vhl(-/-) zebrafish eye. In this study, we demonstrate vhl(-/-) zebrafish almost entirely lack visual function. Furthermore, hyaloid vasculature networks in the vhl(-/-) eye are improperly formed and this phenotype is concomitant with development of an ectopic intraretinal vasculature. Sunitinib malate, a multi tyrosine kinase inhibitor, market authorised for cancer, reversed the ocular behavioural and morphological phenotypes observed in vhl(-/-) zebrafish. We conclude that the zebrafish yid gene contributes to an endogenous molecular barrier that prevents development of intraretinal vasculature, and that pharmacological intervention with sunitinib can improve visual function and hyaloid vessel patterning while reducing abnormally formed ectopic intraretinal vessels in vhl(-/-) zebrafish.

  • 654.
    Warntjes, Marcel Jan Bertus
    et al.
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Clinical Physiology in Linköping. Linköping University, Center for Medical Image Science and Visualization (CMIV). SyntheticMR AB, Linkoping, Sweden.
    Blystad, Ida
    Linköping University, Department of Medical and Health Sciences, Division of Radiological Sciences. Linköping University, Faculty of Medicine and Health Sciences. Linköping University, Center for Medical Image Science and Visualization (CMIV). Region Östergötland, Center for Diagnostics, Department of Radiology in Linköping.
    Tisell, Anders
    Linköping University, Department of Medical and Health Sciences, Division of Radiological Sciences. Linköping University, Faculty of Medicine and Health Sciences. Linköping University, Center for Medical Image Science and Visualization (CMIV). Region Östergötland, Center for Diagnostics, Medical radiation physics.
    Larsson, E. -M.
    Uppsala Univ, Sweden.
    Synthesizing a Contrast-Enhancement Map in Patients with High-Grade Gliomas Based on a Postcontrast MR Imaging Quantification Only2018In: American Journal of Neuroradiology, ISSN 0195-6108, E-ISSN 1936-959X, Vol. 39, no 12, p. 2194-2199Article in journal (Refereed)
    Abstract [en]

    BACKGROUND AND PURPOSE: Administration of a gadolinium-based contrast agent is an important diagnostic biomarker for blood-brain barrier damage. In clinical use, detection is based on subjective comparison of native and postgadolinium-based contrast agent T1-weighted images. Quantitative MR imaging studies have suggested a relation between the longitudinal relaxation rate and proton-density in the brain parenchyma, which is disturbed by gadolinium-based contrast agents. This discrepancy can be used to synthesize a contrast-enhancement map based solely on the postgadolinium-based contrast agent acquisition. The aim of this study was to compare synthetic enhancement maps with subtraction maps of native and postgadolinium-based contrast agent images. MATERIALS AND METHODS: For 14 patients with high-grade gliomas, quantitative MR imaging was performed before and after gadolinium-based contrast agent administration. The quantification sequence was multidynamic and multiecho, with a scan time of 6 minutes. The 2 image stacks were coregistered using in-plane transformation. The longitudinal relaxation maps were subtracted and correlated with the synthetic longitudinal relaxation enhancement maps on the basis of the postgadolinium-based contrast agent images only. ROIs were drawn for tumor delineation. RESULTS: Linear regression of the subtraction and synthetic longitudinal relaxation enhancement maps showed a slope of 1.02 0.19 and an intercept of 0.05 +/- 0.12. The Pearson correlation coefficient was 0.861 +/- 0.059, and the coefficient of variation was 0.18 +/- 0.04. On average, a volume of 1.71 +/- 1.28 mL of low-intensity enhancement was detected in the synthetic enhancement maps outside the borders of the drawn ROI. CONCLUSIONS: The study shows that there was a good correlation between subtraction longitudinal relaxation enhancement maps and synthetic longitudinal relaxation enhancement maps in patients with high-grade gliomas. The method may improve the sensitivity and objectivity for the detection of gadolinium-based contrast agent enhancement.

  • 655.
    Warntjes, Marcel Jan Bertus
    et al.
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Clinical Physiology in Linköping. Linköping University, Center for Medical Image Science and Visualization (CMIV). SyntheticMR AB, Linkoping, Sweden.
    Persson, Anders
    Linköping University, Department of Medical and Health Sciences, Division of Radiological Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Radiology in Linköping. Linköping University, Center for Medical Image Science and Visualization (CMIV).
    Berge, J.
    Institute Forens Med, Linkoping, Sweden.
    Zech, Wolf-Dieter
    Linköping University, Department of Medical and Health Sciences, Division of Radiological Sciences. Linköping University, Faculty of Medicine and Health Sciences. Linköping University, Center for Medical Image Science and Visualization (CMIV). Institute Forens Med, Linkoping, Sweden; University of Bern, Switzerland.
    Myelin Detection Using Rapid Quantitative MR Imaging Correlated to Macroscopically Registered Luxol Fast Blue-Stained Brain Specimens2017In: American Journal of Neuroradiology, ISSN 0195-6108, E-ISSN 1936-959X, Vol. 38, no 6, p. 1096-1102Article in journal (Refereed)
    Abstract [en]

    BACKGROUND AND PURPOSE: Myelin detection is of great value in monitoring diseases such as multiple sclerosis and dementia. However, most MR imaging methods to measure myelin are challenging for routine clinical use. Recently, a novel method was published, in which the presence of myelin is inferred by using its effect on the intra- and extracellular water relaxation rates and proton density, observable by rapid quantitative MR imaging. The purpose of this work was to validate this method further on the brains of 12 fresh, intact cadavers. MATERIALS AND METHODS: The 12 brains were scanned with a quantification sequence to determine the longitudinal and transverse relaxation rates and proton density as input for the myelin estimations. Subsequently, the brains were excised at postmortem examination, and brain slices were stained with Luxol fast blue to verify the presence of myelin. The optical density values of photographs of the stained brain slices were registered with the MR images and correlated with the myelin estimation performed by quantitative MR imaging. RESULTS: A correlation was found between the 2 methods with a mean Spearman for all subjects of 0.74 0.11. Linear regression showed a mean intercept of 1.50% +/- 2.84% and a mean slope of 4.37% +/- 1.73%/%. A lower correlation was found for the separate longitudinal relaxation rates and proton density ( = 0.63 +/- 0.12 and -0.73 +/- 0.09, respectively). For transverse relaxation rates, the was very low (0.11 +/- 0.28). CONCLUSIONS: The observed correlation supports the validity of myelin measurement by using the MR imaging quantification method.

  • 656.
    Warntjes, Marcel Jan Bertus
    et al.
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Clinical Physiology in Linköping. Linköping University, Center for Medical Image Science and Visualization (CMIV). SyntheticMR AB, Linkoping, Sweden.
    Tisell, Anders
    Linköping University, Department of Medical and Health Sciences, Division of Radiological Sciences. Linköping University, Faculty of Medicine and Health Sciences. Linköping University, Center for Medical Image Science and Visualization (CMIV). Region Östergötland, Center for Diagnostics, Medical radiation physics.
    Håkansson, Irene
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Local Health Care Services in Central Östergötland, Department of Neurology.
    Lundberg, Peter
    Linköping University, Department of Medical and Health Sciences, Division of Radiological Sciences. Linköping University, Faculty of Medicine and Health Sciences. Linköping University, Center for Medical Image Science and Visualization (CMIV). Region Östergötland, Center for Diagnostics, Medical radiation physics.
    Ernerudh, Jan
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Clinical Immunology and Transfusion Medicine.
    Improved Precision of Automatic Brain Volume Measurements in Patients with Clinically Isolated Syndrome and Multiple Sclerosis Using Edema Correction2018In: American Journal of Neuroradiology, ISSN 0195-6108, E-ISSN 1936-959X, Vol. 39, no 2, p. 296-302Article in journal (Refereed)
    Abstract [en]

    BACKGROUND AND PURPOSE: The presence of edema will result in increased brain volume, which may obscure progressing brain atrophy. Similarly, treatment-induced edema reduction may appear as accelerated brain tissue loss (pseudoatrophy). The purpose of this study was to correlate brain tissue properties to brain volume, to investigate the possibilities for edema correction and the resulting improvement of the precision of automated brain volume measurements. MATERIALS AND METHODS: A group of 38 patients with clinically isolated syndrome or newly diagnosed MS were imaged at inclusion and after 1, 2, and 4 years using an MR quantification sequence. Brain volume, relaxation rates (R-1 and R-2), and proton density were measured by automated software. RESULTS: The reduction of normalized brain volume with time after inclusion was 0.273%/year. The mean SDs were 0.508%, 0.526%, 0.454%, and 0.687% at baseline and 1, 2, and 4 years. Linear regression of the relative change of normalized brain volume and the relative change of R-1, R-2, and proton density showed slopes of -0.198 (P amp;lt; .001), 0.156 (P = .04), and 0.488 (P amp;lt; .001), respectively. After we applied the measured proton density as a correction factor, the mean SDs decreased to 24.2%, 4.8%, 33.3%, and 17.4%, respectively. The observed atrophy rate reduced from 0.273%/year to 0.238%/year. CONCLUSIONS: Correlations between volume and R-1, R-2, and proton density were observed in the brain, suggesting that a change of brain tissue properties can affect brain volume. Correction using these parameters decreased the variation of brain volume measurements and may have reduced the effect of pseudoatrophy.

  • 657.
    Watson, Ian D.
    et al.
    European Federat Clin Chemistry and Lab Med, Italy.
    Siodmiak, Joanna
    Nicolaus Copernicus University of Torun, Poland.
    Oosterhuis, Wytze P.
    Atrium Orbis, Netherlands.
    Corberand, Joel
    University Hospital Toulouse, France.
    Jorgensen, Per E.
    Glostrup County Hospital, Denmark.
    Gunnur Dikmen, Zeliha
    Hacettepe University, Turkey.
    Jovicic, Snezana
    University of Belgrade, Serbia; University of Belgrade, Serbia.
    Theodorsson, Elvar
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Clinical Chemistry.
    European views on patients directly obtaining their laboratory test results2015In: Clinical Chemistry and Laboratory Medicine, ISSN 1434-6621, E-ISSN 1437-4331, Vol. 53, no 12, p. 1961-1966Article in journal (Refereed)
    Abstract [en]

    Background: Medicine is a highly professionalized endeavour, by tradition centred on the authority of physicians. Better education and the advent of the information age cater for increased demands on society in general and on health care in particular to enable people to make informed decisions regarding themselves. Participation in medical decisions requires informed knowledge which is hard to obtain without substantial and time consuming professional help. Methods: We performed a survey amongst the member organizations of European Federation of Clinical Chemistry and Laboratory Medicine (EFLM) in order to investigate the recognition and preparedness of providing help to patients in interpreting their laboratory results. Results: Out of 40 EFLM Member Societies, 27 sent their responses to the survey. In most cases the first line delivery of laboratory results to physicians is by computer link (63%). Patients receive their laboratory results on demand from their physician in 60% of cases. However, 34% of laboratory specialists showed a negative attitude for delivering laboratory results to patients. Yet, in 48% of countries 1-5 patients per day ask a laboratory specialist about the significance of laboratory results outside the reference range. When patients are informed about the purpose of laboratory testing, they seek information primarily from their physician, followed by the internet and the Specialist in Laboratory Medicine. Conclusions: Changing practices increasingly enabling patient access to their records are on the increase facilitated by recent innovations in information technologies. Successful transfer of some of the responsibilities of physicians, demands a mutual triangular dialogue between the patient, their physician and laboratory medicine.

  • 658.
    Weinhold, Philipp
    et al.
    Department of Urology, LMU, Munich,Germany; Department of Clinical and Experimental Pharmacology, Lund, Sweden.
    Hennenberg, Martin
    Department of Urology, LMU, Munich,Germany.
    Strittmatter, Frank
    Department of Urology, LMU, Munich,Germany.
    Stief, Christian G
    Department of Urology, LMU, Munich,Germany.
    Gratzke, Christian
    Department of Urology, LMU, Munich,Germany.
    Hedlund, Petter
    Linköping University, Department of Medical and Health Sciences, Division of Drug Research. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Clinical Pharmacology. Department of Clinical and Experimental Pharmacology, Lund, Sweden.
    Transient receptor potential a1 (TRPA1) agonists inhibit contractions of the isolated human ureter.2018In: Neurourology and Urodynamics, ISSN 0733-2467, E-ISSN 1520-6777, Vol. 37, no 2, p. 600-608Article in journal (Refereed)
    Abstract [en]

    AIMS: Mechanoafferent and peristaltic mechanisms of the human ureter involve transient receptor potential V1 (TRPV1)- and purinoceptor-mediated functions. Hydrogen sulphide, an endogenous TRPA1 ligand, is linked to inhibitory neurotransmission of the pig ureter. No information is available on TRPA1 activity in the human ureter. We therefore examined the distribution and function of TRPA1 in the human ureter.

    METHODS: Expression of TRPA1 in human ureter tissue was studied by Western blot and immunofluorescence. The TRPA1 distribution was compared to TRPV1, calcitonin gene related peptide (CGRP), tyrosine hydroxylase (TH), and vimentin. Effects of the TRPA1 agonists allyl isothiocyanate (AI), cinnamaldehyde (CA), sodium hydrogen sulfide (NaHS), and capsaicin (TRPV1 agonist) on human ureter preparations were studied in organ baths.

    RESULTS: By Western blot, bands were detected at the expected molecular weight for TRPA1. TRPA1- and TRPV1-immunoreactivities were located on CGRP-positive nerves, but not on TH-positive nerves. TRPA1 was also located in vimentin-positive interstitial cells. In functional experiments, neither of the TRPA1-agonists (1-100 μM) had any direct effects on ureter tension (baseline/potassium-induced contractions). However, CA, AI, NaHS, and capsaicin (10 μM) decreased (P < 0.01-0.05) tetrodotoxin-sensitive electrically induced (2,4,8,16,32 Hz) contractions. Inhibitory activities were 50-61% (CA), 30-56% (AI), 30-40% (NaHS), and 37-67% (Capsaicin).

    CONCLUSIONS: In the human ureter, TRPA1 is located to sensory nerves and interstitial cells. TRPA1 agonists inhibited electrically induced contractions but had no direct effect on smooth muscle tension of the human ureter. A role for TRPA1 in modulating neurotransmission and possibly peristalsis of the human ureter is proposed.

  • 659.
    Wejryd, Erik
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Children's and Women's health. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center of Paediatrics and Gynaecology and Obstetrics, Department of Paediatrics in Norrköping.
    Generó, Magali Marti
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences.
    Marchini, Giovanna
    Karolinska Univ Hosp, Sweden; Karolinska Inst, Sweden.
    Werme, Anna
    Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Medicine and Health Sciences.
    Jonsson, Baldvin
    Karolinska Univ Hosp, Sweden; Karolinska Inst, Sweden.
    Landberg, Eva
    Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Clinical Chemistry.
    Abrahamsson, Thomas
    Linköping University, Department of Clinical and Experimental Medicine, Division of Children's and Women's health. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center of Paediatrics and Gynaecology and Obstetrics, H.K.H. Kronprinsessan Victorias barn- och ungdomssjukhus.
    Low Diversity of Human Milk Oligosaccharides is Associated with Necrotising Enterocolitis in Extremely Low Birth Weight Infants2018In: Nutrients, ISSN 2072-6643, E-ISSN 2072-6643, Vol. 10, no 10, article id 1556Article in journal (Refereed)
    Abstract [en]

    Difference in human milk oligosaccharides (HMO) composition in breast milk may be one explanation why some preterm infants develop necrotizing enterocolitis (NEC) despite being fed exclusively with breast milk. The aim of this study was to measure the concentration of 15 dominant HMOs in breast milk during the neonatal period and investigate how their levels correlated to NEC, sepsis, and growth in extremely low birth weight (ELBW; amp;lt;1000 g) infants who were exclusively fed with breast milk. Milk was collected from 91 mothers to 106 infants at 14 and 28 days and at postmenstrual week 36. The HMOs were analysed with high-performance anion-exchange chromatography with pulsed amperometric detection. The HMOs diversity and the levels of Lacto-N-difucohexaose I were lower in samples from mothers to NEC cases, as compared to non-NEC cases at all sampling time points. Lacto-N-difucohexaose I is only produced by secretor and Lewis positive mothers. There were also significant but inconsistent associations between 3-sialyllactose and 6-sialyllactose and culture-proven sepsis and significant, but weak correlations between several HMOs and growth rate. Our results suggest that the variation in HMO composition in breast milk may be an important factor explaining why exclusively breast milk fed ELBW infants develop NEC.

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  • 660.
    Welander, Jenny
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Linköping University, Faculty of Health Sciences.
    Lysiak, Malgorzata
    Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Linköping University, Faculty of Medicine and Health Sciences.
    Brauckhoff, Michael
    Haukeland Hosp, Dept Surg, Norway; Univ Bergen, Dept Clin Sci, Norway.
    Brunaud, Laurent
    Department of Digestive, Hepato-Biliary and Endocrine Surgery, CHU Nancy - Hospital Brabois Adultes, University de Lorraine, France.
    Söderkvist, Peter
    Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Clinical genetics.
    Gimm, Oliver
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Surgery in Linköping.
    Activating FGFR1 mutations in sporadic pheochromocytoma2018In: World Journal of Surgery, ISSN 0364-2313, E-ISSN 1432-2323, Vol. 42, no 2, p. 482-489Article in journal (Refereed)
    Abstract [en]

    Pheochromocytomas are neuroendocrine tumors of the adrenal glands that cause hypertension. More than a third of the cases are associated with hereditary mutations in a growing list of susceptibility genes, some of which are also somatically altered in sporadic pheochromocytomas. However, for the majority of sporadic pheochromocytomas, a genetic explanation is still lacking. Here we investigated the genomic landscape of sporadic pheochromocytomas with whole-exome sequencing of 16 paired tumor and normal DNA samples, and discovered on average 33 non-silent somatic mutations per tumor. One of the recurrently mutated genes was FGFR1, encoding the fibroblast growth factor receptor 1, which was recently revealed as an oncogene in pilocytic astrocytoma and childhood glioblastoma. Including a subsequent analysis of a larger cohort, activating FGFR1  mutations were detected in three of 80 sporadic pheochromocytomas (3.8%). Gene expression microarray profiling showed that these tumors clustered with NF1- RET- and HRAS-mutated pheochromocytomas, indicating activation of the MAPK and PI3K-AKT signal transduction pathways. The results advance our biological understanding of pheochromocytoma and suggest that somatic FGFR1 activation is an important event in a subset of these tumors.

  • 661.
    Wesolowska, Paulina
    et al.
    IAEA, Austria.
    Georg, Dietmar
    Med Univ Vienna, Austria; Christian Doppler Lab Med Radiat Res Radiat Oncol, Austria.
    Lechner, Wolfgang
    Med Univ Vienna, Austria; Christian Doppler Lab Med Radiat Res Radiat Oncol, Austria.
    Kazantsev, Pavel
    IAEA, Austria.
    Bokulic, Tomislav
    IAEA, Austria.
    Carlsson Tedgren, Åsa
    Linköping University, Department of Medical and Health Sciences, Division of Radiological Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Medical radiation physics. Karolinska Univ Hosp, Sweden.
    Adolfsson, Emelie
    Linköping University, Department of Medical and Health Sciences, Division of Radiological Sciences. Linköping University, Faculty of Medicine and Health Sciences.
    Campos, Anna Maria
    Inst Nacl Canc, Brazil.
    Leandro Alves, Victor Gabriel
    Inst Nacl Canc, Brazil.
    Suming, Luo
    Chinese Ctr Dis Control and Prevent, Peoples R China.
    Hao, Wu
    Beijing Canc Hosp, Peoples R China.
    Ekendahl, Daniela
    Natl Radiat Protect Inst, Czech Republic.
    Koniarova, Irena
    Natl Radiat Protect Inst, Czech Republic.
    Bulski, Wojciech
    Maria Sklodowska Curie Mem Canc Ctr and Inst Oncol, Poland.
    Chelminski, Krzysztof
    Maria Sklodowska Curie Mem Canc Ctr and Inst Oncol, Poland.
    Alonso Samper, Jose Luis
    Natl Inst Oncol and Radiobiol, Cuba.
    Vinatha, Sumanth Panyam
    Bhabha Atom Res Ctr Trombay, India.
    Rakshit, Sougata
    Bhabha Atom Res Ctr Trombay, India.
    Siri, Srimanoroth
    SSDL, Thailand.
    Tomsejm, Milan
    Hop Andre Vesale, Belgium.
    Tenhunen, Mikko
    Helsinki Univ Helsinki, Finland.
    Povall, Julie
    Univ Leeds, England.
    Kry, Stephen F.
    Anderson Canc Ctr, TX USA.
    Followill, David S.
    Anderson Canc Ctr, TX USA.
    Thwaites, David I.
    Univ Leeds, England; Univ Sydney, Australia.
    Izewska, Joanna
    IAEA, Austria.
    Testing the methodology for a dosimetric end-to-end audit of IMRT/VMAT: results of IAEA multicentre and national studies2019In: Acta Oncologica, ISSN 0284-186X, E-ISSN 1651-226X, Vol. 58, no 12, p. 1731-1739Article in journal (Refereed)
    Abstract [en]

    Introduction: Within an International Atomic Energy Agency (IAEA) co-ordinated research project (CRP), a remote end-to-end dosimetric quality audit for intensity modulated radiation therapy (IMRT)/ volumetric arc therapy (VMAT) was developed to verify the radiotherapy chain including imaging, treatment planning and dose delivery. The methodology as well as the results obtained in a multicentre pilot study and national trial runs conducted in close cooperation with dosimetry audit networks (DANs) of IAEA Member States are presented. Material and methods: A solid polystyrene phantom containing a dosimetry insert with an irregular solid water planning target volume (PTV) and organ at risk (OAR) was designed for this audit. The insert can be preloaded with radiochromic film and four thermoluminescent dosimeters (TLDs). For the audit, radiotherapy centres were asked to scan the phantom, contour the structures, create an IMRT/VMAT treatment plan and irradiate the phantom. The dose prescription was to deliver 4 Gy to the PTV in two fractions and to limit the OAR dose to a maximum of 2.8 Gy. The TLD measured doses and film measured dose distributions were compared with the TPS calculations. Results: Sixteen hospitals from 13 countries and 64 hospitals from 6 countries participated in the multicenter pilot study and in the national runs, respectively. The TLD results for the PTV were all within +/- 5% acceptance limit for the multicentre pilot study, whereas for national runs, 17 participants failed to meet this criterion. All measured doses in the OAR were below the treatment planning constraint. The film analysis identified seven plans in national runs below the 90% passing rate gamma criteria. Conclusion: The results proved that the methodology of the IMRT/VMAT dosimetric end-to-end audit was feasible for its intended purpose, i.e., the phantom design and materials were suitable; the phantom was easy to use and it was robust enough for shipment. Most importantly the audit methodology was capable of identifying suboptimal IMRT/VMAT delivery.

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  • 662.
    Westerlind, Björn
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Department of Geriatrics, County Hospital Ryhov, Jönköping, Sweden.
    Östgren, Carl Johan
    Linköping University, Department of Medical and Health Sciences, Division of Community Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Primary Care Center, Primary Health Care Center Ödeshög.
    Mölstad, Sigvard
    Department of Clinical Sciences in Malmö, Center for Primary Health Care Research, Lund University, Malmö, Sweden.
    Midlöv, Patrik
    Department of Clinical Sciences in Malmö, Center for Primary Health Care Research, Lund University, Malmö, Sweden.
    Hägg, Staffan
    Linköping University, Department of Medical and Health Sciences, Division of Drug Research. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Clinical Pharmacology. Futurum, Jönköping, Sweden.
    Use of non-benzodiazepine hypnotics is associated with falls in nursing home residents: a longitudinal cohort study2019In: Aging Clinical and Experimental Research, ISSN 1594-0667, E-ISSN 1720-8319, Vol. 31, no 8, p. 1078-1095Article in journal (Refereed)
    Abstract [en]

    Background

    Falls and related injuries are common among older people, and several drug classes are considered to increase fall risk.

    Aims

    This study aimed to investigate the association between the use of certain drug classes and falls in older nursing home residents in Sweden, and relate these to different age groups.

    Methods

    Information on falls that occurred in the previous year and regular use of possible fall risk drugs including non-benzodiazepine hypnotics (zopiclone and zolpidem) was collected from 331 nursing home residents during 2008–2011. Over the following 6 months, the occurrence of serious falls, requiring a physician visit or hospital care, was registered. Association between serious falls and drug use was compared between an older (≥ 85 years) and a younger group.

    Results

    An increased fall risk (Downton Fall Risk Index ≥ 3) was found in 93% of the study subjects (aged 65–101 years). Baseline data indicated an association between falls that occurred in the previous year and regular use of non-benzodiazepine hypnotics (p = 0.005), but not with the other studied drug classes. During the following 6 months, an association between use of non-benzodiazepine hypnotics and serious falls in the older group (p = 0.017, odds ratio 4.311) was found. No association was found between the other studied drug classes and serious falls.

    Discussion

    These results indicate an association between falls and the use of non-benzodiazepine hypnotics, compounds that previously have been considered generally well-tolerated in older people.

    Conclusions

    Caution is advocated when using non-benzodiazepine hypnotics regularly in older people living in nursing homes.

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  • 663.
    Westermark, Gunilla T.
    et al.
    Department of Medical Cell Biology, Uppsala University, Uppsala, Sweden.
    Fändrich, Marcus
    Institute of Protein Biochemistry, Ulm University, Ulm, Germany.
    Lundmark, Katarzyna
    Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Clinical pathology.
    Westermark, Per
    Department of Immunology, Genetics and Pathology, Uppsala University, Uppsala, Sweden.
    Noncerebral Amyloidoses: Aspects on Seeding, Cross-Seeding, and Transmission2018In: Cold Spring Harbor Perspectives in Medicine, ISSN 0103-3247, E-ISSN 2157-1422, Vol. 8, no 1, article id a024323Article, review/survey (Refereed)
    Abstract [en]

    More than 30 proteins form amyloid in humans, most of them outside of the brain. Deposition of amyloid in extracerebral tissues is very common and seems inevitable for an aging person. Most deposits are localized, small, and probably without consequence, but in some instances, they are associated with diseases such as type 2 diabetes. Other extracerebral amyloidoses are systemic, with life-threatening effects on the heart, kidneys, and other organs. Here, we review how amyloid may spread through seeding and whether transmission of amyloid diseases may occur between humans. We also discuss whether cross-seeding is important in the development of amyloidosis, focusing specifically on the amyloid proteins AA, transthyretin, and islet amyloid polypeptide (IAPP).

  • 664.
    Wickström, Anne
    et al.
    Umeå University, Sweden.
    Fagerström, Maria
    Linköping University, Department of Medical and Health Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Rehabilitation Center.
    Wickström, Lucas
    Linköping University, Department of Computer and Information Science. Linköping University, Faculty of Science & Engineering.
    Granasen, Gabriel
    Umeå University, Sweden.
    Dahle, Charlotte
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Clinical Immunology and Transfusion Medicine.
    Vrethem, Magnus
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Local Health Care Services in Central Östergötland, Department of Neurology.
    Sundstrom, Peter
    Umeå University, Sweden.
    The impact of adjusted work conditions and disease-modifying drugs on work ability in multiple sclerosis2017In: Multiple Sclerosis, ISSN 1352-4585, E-ISSN 1477-0970, Vol. 23, no 8, p. 1137-1147Article in journal (Refereed)
    Abstract [en]

    Background: Multiple sclerosis (MS) is a neurological disorder that causes significantly reduced ability to work, and the Expanded Disability Status Scale (EDSS) is one of the main predictors for reduced work ability. Objectives: To investigate how work requirements, flexible work conditions and disease-modifying drugs (DMDs) influence the work ability in relation to different EDSS grades in two MS populations. Methods: Work ability was studied in two MS populations: one in the southern and one in the northern part of Sweden, both demographically similar. In the latter population, more active work-promoting interventions have been practised and second-generation DMDs have been widely used from the onset of disease for several years. Results: The proportion of MS patients who participated in the workforce or studied was significantly higher in the northern compared with the southern population (pamp;lt;0.001). The employees in the northern population had significantly lower requirements, greater adapted work conditions and were able to work more hours per week. Higher EDSS was associated with lower reduction in number of worked hours per week in the northern population (p=0.042). Conclusion: Our data indicated that treatment strategy and adjusted work conditions have impact on work ability in MS.

  • 665.
    Wilhelms, Daniel
    et al.
    Linköping University, Department of Medical and Health Sciences, Division of Drug Research. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Local Health Care Services in Central Östergötland, Department of Emergency Medicine in Linköping.
    Dock, Hua
    Linköping University, Department of Clinical and Experimental Medicine, Division of Children's and Women's health. Linköping University, Faculty of Medicine and Health Sciences.
    Brito, Haissa O.
    Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Medicine and Health Sciences.
    Pettersson, Emma
    Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Medicine and Health Sciences.
    Stojakovic, Andrea
    Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Linköping University, Faculty of Medicine and Health Sciences.
    Zajdel, Joanna
    Linköping University, Department of Clinical and Experimental Medicine, Center for Social and Affective Neuroscience. Linköping University, Faculty of Medicine and Health Sciences.
    Engblom, David
    Linköping University, Department of Clinical and Experimental Medicine, Center for Social and Affective Neuroscience. Linköping University, Faculty of Medicine and Health Sciences.
    Theodorsson, Elvar
    Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Clinical Chemistry. Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Chemistry.
    Hammar, Mats
    Linköping University, Department of Clinical and Experimental Medicine, Division of Children's and Women's health. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center of Paediatrics and Gynaecology and Obstetrics, Department of Gynaecology and Obstetrics in Linköping.
    Spetz Holm, Anna-Clara
    Linköping University, Department of Clinical and Experimental Medicine, Division of Children's and Women's health. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center of Paediatrics and Gynaecology and Obstetrics, Department of Gynaecology and Obstetrics in Linköping.
    CGRP Is Critical for Hot Flushes in Ovariectomized Mice2019In: Frontiers in Pharmacology, ISSN 1663-9812, E-ISSN 1663-9812, Vol. 9, article id 1452Article in journal (Refereed)
    Abstract [en]

    Hot flushes are common and troublesome symptoms of menopause. The neuropeptide calcitonin gene-related peptide (CGRP) is increased in plasma during hot flushes but it has not been clear if CGRP is causally involved in the mechanism underpinning the flushes. Here, we examined the effect of interventions with CGRP in a mouse model of hot flushes based on flush-like temperature increases triggered by forced physical activity in ovariectomized mice. Compared to normal mice, ovariectomized mice reacted with an exaggerated, flush-like, temperature increase after physical exercise. This increase was completely blocked by the non-peptide CGRP-antagonist MK-8825 (-0.41 degrees Celsius, 95% CI: -0,83 to 0,012, p amp;lt; 0.0001) at a dose that had no obvious effects on locomotor activity (50 mg/kg). Further, the flush-like temperature increases were strongly attenuated in ovariectomized mice lacking alpha CGRP due to a genetic modification. Collectively, our findings suggest that CGRP is an important mediator of experimentally induced hot flushes and they identify CGRP antagonists as promising treatment candidates for women and possibly also men with hot flushes.

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  • 666.
    Witt, Suzanne T.
    et al.
    Linköping University, Center for Medical Image Science and Visualization (CMIV).
    Drissi, Natasha Morales
    Linköping University, Department of Medical and Health Sciences, Division of Radiological Sciences. Linköping University, Faculty of Medicine and Health Sciences. Linköping University, Center for Medical Image Science and Visualization (CMIV).
    Tapper, Sofie
    Linköping University, Department of Medical and Health Sciences, Division of Radiological Sciences. Linköping University, Faculty of Medicine and Health Sciences. Linköping University, Center for Medical Image Science and Visualization (CMIV). Region Östergötland, Center for Diagnostics, Department of Radiology in Linköping.
    Wretman, Anna
    Linköping University, Department of Behavioural Sciences and Learning, Disability Research. Linköping University, Faculty of Arts and Sciences.
    Szakács, Attila
    Sahlgrenska Academy, University of Gothenburg, Sweden.
    Hallböök, Tove
    Sahlgrenska Academy, University of Gothenburg, Sweden.
    Landtblom, Anne-Marie
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Linköping University, Center for Medical Image Science and Visualization (CMIV). Region Östergötland, Local Health Care Services in Central Östergötland, Department of Neurology. Uppsala University, Uppsala, Sweden.
    Karlsson, Thomas
    Linköping University, Department of Behavioural Sciences and Learning, Disability Research. Linköping University, Faculty of Arts and Sciences. Linköping University, Center for Medical Image Science and Visualization (CMIV).
    Lundberg, Peter
    Linköping University, Department of Medical and Health Sciences, Division of Radiological Sciences. Linköping University, Faculty of Medicine and Health Sciences. Linköping University, Center for Medical Image Science and Visualization (CMIV). Region Östergötland, Center for Diagnostics, Department of Radiology in Linköping. Region Östergötland, Center for Diagnostics, Medical radiation physics.
    Engström, Maria
    Linköping University, Department of Medical and Health Sciences, Division of Radiological Sciences. Linköping University, Faculty of Medicine and Health Sciences. Linköping University, Center for Medical Image Science and Visualization (CMIV).
    Evidence for cognitive resource imbalance in adolescents with narcolepsy2018In: Brain Imaging and Behavior, ISSN 1931-7557, E-ISSN 1931-7565, Vol. 12, no 2, p. 411-424Article in journal (Refereed)
    Abstract [en]

    The study investigated brain activity changes during performance of a verbal working memory task in a population of adolescents with narcolepsy. Seventeen narcolepsy patients and twenty healthy controls performed a verbal working memory task during simultaneous fMRI and EEG acquisition. All subjects also underwent MRS to measure GABA and Glutamate concentrations in the medial prefrontal cortex. Activation levels in the default mode network and left middle frontal gyrus were examined to investigate whether narcolepsy is characterized by an imbalance in cognitive resources. Significantly increased deactivation within the default mode network during task performance was observed for the narcolepsy patients for both the encoding and recognition phases of the task. No evidence for task performance deficits or reduced activation within the left middle frontal gyrus was noted for the narcolepsy patients. Correlation analyses between the spectroscopy and fMRI data indicated that deactivation of the anterior aspect of the default mode in narcolepsy patients correlated more with increased concentrations of Glutamate and decreased concentrations of GABA. In contrast, deactivation in the default mode was correlated with increased concentrations of GABA and decreased concentrations of Glutamate in controls. The results suggested that narcolepsy is not characterized by a deficit in working memory but rather an imbalance of cognitive resources in favor of monitoring and maintaining attention over actual task performance. This points towards dysregulation within the sustained attention system being the origin behind self-reported cognitive difficulties in narcolepsy.

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  • 667.
    Woisetschläger, Mischa
    et al.
    Linköping University, Department of Medical and Health Sciences, Division of Radiological Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Radiology in Linköping. Linköping University, Center for Medical Image Science and Visualization (CMIV).
    Blomma, Johan
    Region Östergötland, Center for Diagnostics, Department of Radiology in Linköping.
    Dahlström, Nils
    Linköping University, Department of Medical and Health Sciences, Division of Radiological Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Radiology in Linköping. Linköping University, Center for Medical Image Science and Visualization (CMIV).
    Bivik Stadler, Caroline
    Linköping University, Department of Medical and Health Sciences, Division of Radiological Sciences. Linköping University, Faculty of Medicine and Health Sciences.
    Forsberg, Daniel
    Linköping University, Department of Science and Technology, Media and Information Technology. Linköping University, Faculty of Science & Engineering. Linköping University, Center for Medical Image Science and Visualization (CMIV).
    Liver data from the Visual Sweden project DROID: Analytic Imaging Diagnostics Arena (AIDA)2019Data set
  • 668.
    Woisetschläger, Mischa
    et al.
    Linköping University, Department of Health, Medicine and Caring Sciences, Division of Diagnostics and Specialist Medicine. Region Östergötland, Center for Diagnostics, Department of Radiology in Linköping. Linköping University, Center for Medical Image Science and Visualization (CMIV).
    Gimm, Oliver
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Surgery in Linköping.
    Johansson, K.
    Orebro Univ Hosp, Sweden; Orebro Univ Hosp, Sweden.
    Wallin, G.
    Orebro Univ Hosp, Sweden.
    Albert-Garcia, I
    Linköping University, Department of Health, Medicine and Caring Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Radiology in Linköping. Linköping University, Center for Medical Image Science and Visualization (CMIV).
    Spångeus, Anna
    Linköping University, Department of Health, Medicine and Caring Sciences, Division of Diagnostics and Specialist Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Endocrinology.
    Dual energy 4D-CT of parathyroid adenomas not clearly localized by sestamibi scintigraphy and ultrasonography - a retrospective study2020In: European Journal of Radiology, ISSN 0720-048X, E-ISSN 1872-7727, Vol. 124, article id 108821Article in journal (Refereed)
    Abstract [en]

    Purpose: At present, the gold standard for diagnosing PAs includes ultrasonography of the neck and sestamibi scans of the parathyroid. The objective of this study was to evaluate scans performed in 4D-DECT (4D-dualenergy mode) at three different time points, in order to analyze spectral information from PAs, lymph nodes (LNs), and thyroid gland (Thy). Method: Fifteen patients (mean age: 57 +/- 18.9 years) with primary hyperparathyroidism, in which previous ultrasound and sestamibi scanning proved to be negative or equivocal, underwent 4D-DECT in three different phases. Hounsfield units (HU), dual-energy information (electron density [Rho], atomic number [Z], dual-energy index [DEW, and spectral information (keV) were determined. Results: For all energies, PAs exhibited significantly lower HU-values than the Thy in non-contrast images, and higher HU-values than LNs in the arterial phase (p amp;lt; 0.05). All three tissues differed significantly in HU in the venous phase at 90 kV, 150 kV, and mixed 0.8 images; the Thy showed significantly higher HU-values than PAs or LNs in non-contrast images at 90 kV, 150 kV, mixed 0.8 images, and [Rho] (p amp;lt; 0.05). LNs exhibited significantly lower HU-values than PAs and Thy in the arterial phase at 90 kV, 150 kV, mixed 0.8, Rho, Z, and DEI (p amp;lt; 0.05). With regards to spectral information, lower energies showed greater HU differences between the three tissues. During the venous phase, there were significant differences between all three tissues up to 100 keV (p amp;lt; 0.05). Conclusions: We identified significant differences in HU-values and spectral information between PAs, LNs, and Thy at different energies and contrast phases.

  • 669.
    Woisetschläger, Mischa
    et al.
    Linköping University, Department of Medical and Health Sciences, Division of Radiological Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Radiology in Linköping.
    Spångeus, Anna
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Endocrinology.
    Model for improved correlation of BMD values between abdominal routine Dual energy CT data and DXA scans2018In: European Journal of Radiology, ISSN 0720-048X, E-ISSN 1872-7727, Vol. 99, p. 76-81Article in journal (Refereed)
    Abstract [en]

    Background

    Osteoporosis is a common but underdiagnosed and undertreated disease causing severe morbidity and economic burden. The gold standard for detection of osteoporosis is DXA (dual energy x-ray absorptiometry), which is a dedicated examination for osteoporosis. Dual energy CT (DECT) examinations are increasingly used in daily routine for a wide variety of diagnoses. In the present study, we wanted to examine whether vBMD (volume bone mass density) could be evaluated as a side product in non-contrast as well as contrast phases as well as to evaluate a correction model taking known shortcomings for DXA into account.

    Methods

    A total of 20 patients, i.e. 79 vertebrae (one excluded due to vertebral fracture), mean age 71 years (range 43–85) with a mean BMI (body mass index) of 26 (range 17–33) were examined with both abdominal/pelvic DECT as well as DXA. Furthermore, aortic calcium was measured as well as the presence of osteoarthritis of the spine (OAS) and osteoarthritis in facet joints (OAF) with a 5-grade scaling system.

    Results

    A significant correlation was found between DXA BMD and vBMD from DECT with no contrast (WNC) (r = 0.424, p = 0.001), and with venous contrast (WVC) (r = 0.402, p < 0.001), but no significant correlation was found with arterial contrast (WAC). Using multivariate linear regression with DXA BMD as dependent, two models were created combining DECT WNC, aortic calciumscore (ACS), OAS and BMI yielding an R2 = 0.616 (model 1) and replacement of WNC to WVC a R2 = 0.612 (model 2). The Pearson correlation between DXA and predictive DXA BMD value of model 1 was r = 0.785 (p < 0.001) and model 2 r = 0.782 (p < 0.001).

    Conclusion

    There is a correlation between DXA BMD and DECT in non-contrast and venous contrast scans but not in arterial scans. The correlation is further improved by quantifying the degree of different confounding factors (osteoarthritis of the spine, body mass index and aortic calcium score) and taking these into account in an explanatory model. Future software solutions with DECT data as input data might be able to automatically measure the BMD in the trabecular bone as well as measuring the confounding factors automatically in order to obtain spinal DXA comparable BMD values.

  • 670.
    Wu, Richard You
    et al.
    Hosp Sick Children, Canada; Univ Toronto, Canada.
    Li, Bo
    Hosp Sick Children, Canada.
    Koike, Yuhki
    Hosp Sick Children, Canada.
    Maattanen, Pekka
    Hosp Sick Children, Canada.
    Miyake, Hiromu
    Hosp Sick Children, Canada.
    Cadete, Marissa
    Hosp Sick Children, Canada.
    Johnson-Henry, Kathene C.
    Hosp Sick Children, Canada.
    Botts, Steven R.
    Hosp Sick Children, Canada.
    Lee, Carol
    Hosp Sick Children, Canada.
    Abrahamsson, Thomas
    Linköping University, Department of Clinical and Experimental Medicine, Division of Children's and Women's health. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center of Paediatrics and Gynaecology and Obstetrics, H.K.H. Kronprinsessan Victorias barn- och ungdomssjukhus Linköping/Motala.
    Landberg, Eva
    Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Clinical Chemistry.
    Pierro, Agostino
    Hosp Sick Children, Canada.
    Sherman, Philip M.
    Hosp Sick Children, Canada; Univ Toronto, Canada; Univ Toronto, Canada.
    Human Milk Oligosaccharides Increase Mucin Expression in Experimental Necrotizing Enterocolitis2019In: Molecular Nutrition & Food Research, ISSN 1613-4125, E-ISSN 1613-4133, Vol. 63, no 3, article id 1800658Article in journal (Refereed)
    Abstract [en]

    Scope Necrotizing enterocolitis (NEC) is a leading cause of morbidity and death in preterm infants, occurring more often in formula-fed than breastfed infants. Studies in both rats and humans show that human milk oligosaccharides (HMOs) lower the incidence of NEC, but the mechanism underlying such protection is currently unclear. Methods and Results By extracting HMOs from pooled human breastmilk, the impact of HMOs on the intestinal mucin levels in a murine model of NEC are investigated. To confirm the results, the findings are validated by exposing human intestinal epithelial cells and intestinal organoids to HMOs and evaluated for mucin expression. HMO-gavage to pups increases Muc2 levels and decreases intestinal permeability to macromolecular dextran. HMO-treated cells have increased Muc2 expression, decreased bacterial attachment and dextran permeability during challenge by enteric pathogens. To identify the mediators involved in HMO induction of mucins, it is demonstrated that HMOs directly induce the expression of chaperone proteins including protein disulfide isomerase (PDI). Suppression of PDI activity removes the protective effects of HMOs on barrier function in vitro as well as NEC protection in vivo. Conclusions Taken together, the results provide insights to the possible mechanisms by which HMOs protect the neonatal intestine through upregulation of mucins.

  • 671.
    Wäster, Petra
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Linköping University, Faculty of Medicine and Health Sciences.
    Eriksson, Ida
    Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Linköping University, Faculty of Medicine and Health Sciences.
    Vainikka, Linda
    Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Linköping University, Faculty of Medicine and Health Sciences.
    Rosdahl, Inger
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Dermatology and Venerology.
    Öllinger, Karin
    Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Clinical Pathology and Clinical Genetics.
    Extracellular vesicles are transferred from melanocytes to keratinocytes after UVA irradiation2016In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 6, no 27890Article in journal (Refereed)
    Abstract [en]

    Ultraviolet (UV) irradiation induces skin pigmentation, which relies on the intercellular crosstalk of melanin between melanocytes to keratinocytes. However, studying the separate effects of UVA and UVB irradiation reveals differences in cellular response. Herein, we show an immediate shedding of extracellular vesicles (EVs) from the plasma membrane when exposing human melanocytes to UVA, but not UVB. The EV-shedding is preceded by UVA-induced plasma membrane damage, which is rapidly repaired by Ca2+-dependent lysosomal exocytosis. Using co-cultures of melanocytes and keratinocytes, we show that EVs are preferably endocytosed by keratinocytes. Importantly, EV-formation is prevented by the inhibition of exocytosis and increased lysosomal pH but is not affected by actin and microtubule inhibitors. Melanosome transfer from melanocytes to keratinocytes is equally stimulated by UVA and UVB and depends on a functional cytoskeleton. In conclusion, we show a novel cell response after UVA irradiation, resulting in transfer of lysosome-derived EVs from melanocytes to keratinocytes.

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  • 672.
    Wäster, Petra
    et al.
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Cell Biology. Linköping University, Faculty of Medicine and Health Sciences.
    Eriksson, Ida
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Cell Biology. Linköping University, Faculty of Medicine and Health Sciences.
    Vainikka, Linda
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Cell Biology. Linköping University, Faculty of Medicine and Health Sciences.
    Öllinger, Karin
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Cell Biology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Clinical Pathology and Clinical Genetics.
    Extracellular vesicles released by melanocytes after UVA irradiation promote intercellular signaling via miR212020In: Pigment Cell & Melanoma Research, ISSN 1755-1471, E-ISSN 1755-148XArticle in journal (Refereed)
    Abstract [en]

    Skin pigmentation is controlled by complex crosstalk between melanocytes and keratinocytes and is primarily induced by exposure to ultraviolet (UV) irradiation. Several aspects of UVA-induced signaling remain to be explored. In skin cells, UVA induces plasma membrane damage, which is repaired by lysosomal exocytosis followed by instant shedding of extracellular vesicles (EVs) from the plasma membrane. The released EVs are taken up by neighboring cells. To elucidate the intercellular crosstalk induced by UVA irradiation, EVs were purified from UVA-exposed melanocytes and added to keratinocytes. Transcriptome analysis of the keratinocytes revealed the activation of TGF-beta and IL-6/STAT3 signaling pathways and subsequent upregulation of microRNA (miR)21. EVs induced phosphorylation of ERK and JNK, reduced protein levels of PDCD4 and PTEN, and augment antiapoptotic signaling. Consequently, keratinocyte proliferation and migration were stimulated and UV-induced apoptosis was significantly reduced. Interestingly, melanoma cells and melanoma spheroids also generate increased amounts of EVs with capacity to stimulate proliferation and migration upon UVA. In conclusion, we present a novel intercellular crosstalk mediated by UVA-induced lysosome-derived EVs leading to the activation of proliferation and antiapoptotic signaling via miR21.

  • 673.
    Wäster, Petra
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Linköping University, Faculty of Medicine and Health Sciences.
    Orfanidis, Kyriakos
    Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Dermatology and Venerology.
    Eriksson, Ida
    Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Linköping University, Faculty of Medicine and Health Sciences.
    Rosdahl, Inger
    Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Dermatology and Venerology.
    Seifert, Oliver
    Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Linköping University, Faculty of Medicine and Health Sciences. Ryhov Hospital, Sweden.
    Öllinger, Karin
    Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Clinical Pathology and Clinical Genetics.
    UV radiation promotes melanoma dissemination mediated by the sequential reaction axis of cathepsins-TGF-beta 1-FAP-alpha2017In: British Journal of Cancer, ISSN 0007-0920, E-ISSN 1532-1827, Vol. 117, no 4, p. 535-544Article in journal (Refereed)
    Abstract [en]

    Background: Ultraviolet radiation (UVR) is the major risk factor for development of malignant melanoma. Fibroblast activation protein (FAP)-alpha is a serine protease expressed on the surface of activated fibroblasts, promoting tumour invasion through extracellular matrix (ECM) degradation. The signalling mechanism behind the upregulation of FAP-alpha is not yet completely revealed. Methods: Expression of FAP-alpha was analysed after UVR exposure in in vitro co-culture systems, gene expression arrays and artificial skin constructs. Cell migration and invasion was studied in relation to cathepsin activity and secretion of transforming growth factor (TGF)-beta 1. Results: Fibroblast activation protein-a expression was induced by UVR in melanocytes of human skin. The FAP-alpha expression was regulated by UVR-induced release of TGF-beta 1 and cathepsin inhibitors prevented such secretion. In melanoma cell culture models and in a xenograft tumour model of zebrafish embryos, FAP-alpha mediated ECM degradation and facilitated tumour cell dissemination. Conclusions: Our results provide evidence for a sequential reaction axis from UVR via cathepsins, TGF-beta 1 and FAP-alpha expression, promoting cancer cell dissemination and melanoma metastatic spread.

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  • 674.
    Wästfelt, Maja
    et al.
    Örebro Univ, Sweden.
    Cao, Yang
    Orebro Univ, Sweden; Karolinska Inst, Sweden.
    Ström, Jakob
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Clinical Chemistry. Orebro Univ, Sweden.
    Predictors of post-stroke fever and infections: a systematic review and meta-analysis2018In: BMC Neurology, ISSN 1471-2377, E-ISSN 1471-2377, Vol. 18, article id 49Article in journal (Refereed)
    Abstract [en]

    Background: fever after stroke is common, and often caused by infections. In the current study, we aimed to test the hypothesis that pneumonia, urinary tract infection and all-cause fever (thought to include at least some proportion of endogenous fever) have different predicting factors, since they differ regarding etiology. Methods: PubMed was searched systematically for articles describing predictors for post-stroke pneumonia, urinary tract infection and all-cause fever. A total of 5294 articles were manually assessed; first by title, then by abstract and finally by full text. Data was extracted from each study, and for variables reported in 3 or more articles, a meta-analysis was performed using a random effects model. Results: Fifty-nine articles met the inclusion criteria. It was found that post stroke pneumonia is predicted by age OR 1.07 (1.04-1.11), male sex OR 1.42 (1.17-1.74), National Institutes of Health Stroke Scale (NIHSS) OR 1.07 (1.05-1.09), dysphagia OR 3.53 (2.69-4.64), nasogastric tube OR 5.29 (3.01-9.32), diabetes OR 1.15 (1.08-1.23), mechanical ventilation OR 4.65 (2.50-8.65), smoking OR 1.16 (1.08-1.26), Chronic Obstructive Pulmonary Disease (COPD) OR 4.48 (1.82-11.00) and atrial fibrillation OR 1.37 (1.22-1.55). An opposite relation to sex may exist for UTI, which seems to be more common in women. Conclusions: The lack of studies simultaneously studying a wide range of predictors for UTI or all-cause fever calls for future research in this area. The importance of new research would be to improve our understanding of fever complications to facilitate greater vigilance, monitoring, prevention, diagnosis and treatment.

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  • 675.
    Wågström, Per
    et al.
    Ryhov County Hospital, Jönköping, Sweden.
    Bengnér, Malin
    Ryhov County Hospital, Jönköping, Sweden.
    Dahle, Charlotte
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Clinical Immunology and Transfusion Medicine.
    Nilsdotter-Augustinsson, Åsa
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Infectious Diseases.
    Neumark, Thomas
    Primary Health in Lindsdal, Kalmar, Sweden.
    Brudin, Lars
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Kalmar County Hospital, Sweden.
    Björkander, Janne
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Ryhov County Hospital, Jönköping, Sweden.
    Does the frequency of respiratory tract infections help to identify humoral immunodeficiencies in a primary health-care cohort?2015In: Scandinavian Journal of Infectious Diseases, ISSN 0036-5548, E-ISSN 1651-1980, Vol. 47, no 1, p. 13-19Article in journal (Refereed)
    Abstract [en]

    Background: Primary immune deficiency (PID) due to humoral defects is associated with recurrent respiratory tract infections (RTIs). Reliable clinical warning signs of PID would facilitate early diagnosis and thereby reduce long-term complications. The aim of the present study was to evaluate the accuracy of the warning sign, 'four or more antibiotic-treated RTIs annually for 3 or more consecutive years,' for detecting PID among adults in a primary health-care setting. Methods: Fifty-three cases with 'four or more antibiotic-treated RTIs annually for 3 or more consecutive years' were selected from a Swedish primary health-care registry of RTIs. In addition, 66 age- and sex-matched controls were selected having a maximum of one antibiotic-treated RTI during the period covered by the study. Levels of immunoglobulin (Ig) IgG, IgA, IgM, IgG subclasses, and IgG antibodies against Haemophilus influenzae and Streptococcus pneumoniae as well as the inflammatory markers, C-reactive protein, interleukin (IL)-6 and IL-8 were determined. Results: IgG subclass deficiencies (IgGsd) were found in 5/53 (9.4%) of the cases and in 7/66 (10.6%) controls. The most frequent deficiency was IgG3sd and this was found in three participants in the case group and seven in the control group. The mean level of IgG3 was lower in the control group (p = 0.02). The mean level of IL-8 was lower in the case group (p = 0.02). Conclusion: The results show that physicians working in primary health care cannot solely rely on the frequency of antibiotic-treated RTIs as a warning sign for the detection of common humoral immune deficiencies.

  • 676.
    Wågström, Per
    et al.
    Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Medicine and Health Sciences. Ryhov Cty Hosp, Sweden.
    Yamada, Naomi
    Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Linköping University, Faculty of Medicine and Health Sciences.
    Dahle, Charlotte
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Clinical Immunology and Transfusion Medicine.
    Nilsdotter-Augustinsson, Åsa
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Infectious Diseases.
    Bengner, Malin
    Ryhov Cty Hosp, Sweden.
    Söderkvist, Peter
    Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Clinical genetics.
    Björkander, Jan Fredrik
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences.
    Fc gamma-receptor polymorphisms associated with clinical symptoms in patients with immunoglobulin G subclass deficiency2018In: Infectious Diseases, ISSN 2374-4235, E-ISSN 2374-4243, Vol. 50, no 11-12, p. 853-858Article in journal (Refereed)
    Abstract [en]

    Background: Immunoglobulin G subclass deficiencies (IgGsd) are associated with recurrent respiratory tract infections. Immunoglobulin substitution therapy may be needed to prevent chronic lung tissue damage but tools for identifying the patients that will benefit from this treatment are still insufficient. Some Fc gamma R polymorphisms seem to predispose for an increased risk for infections. In this study we wanted to evaluate if the Fc gamma R-profile differs between individuals with IgGsd and a control population. Methods: Single nucleotide polymorphisms (SNPs) of Fc gamma RIIa, Fc gamma RIIIa and Fc gamma RIIc in 36 IgGsd patients and 192 controls with similar sex and geographical distribution were analyzed by TaqMan allelic discrimination assay or Sanger sequencing. Results: In the IgGsd-group, homozygous frequency for Fc gamma RIIa-R/R131 (low-binding capacity isoform) was higher (p = .03) as well as for non-classical Fc gamma RIIc-ORF (p = .03) and classical Fc gamma RIIc-ORF tended (p = .07) to be more common compared to the controls. There was no difference between the groups regarding Fc gamma RIIIa. Conclusion: The gene for classical Fc gamma RIIc-ORF tended to be more frequent in individuals with immunoglobulin G subclass deficiency and the genes for non-classical Fc gamma RIIc-ORF as well as low-binding capacity receptor Fc gamma RIIa-R/R131 were more frequent. Further studies on the Fc gamma R polymorphisms may pave way for identifying individuals that will benefit from immunoglobulin substitution.

  • 677.
    Ynnerman, Anders
    et al.
    Linköping University, Department of Science and Technology, Media and Information Technology. Linköping University, Faculty of Science & Engineering. Linköping University, Center for Medical Image Science and Visualization (CMIV). Norrkoping Visualizat Centre C, Sweden.
    Rydell, Thomas
    Interspectral AB, Sweden; Interact Institute Swedish ICT, Sweden.
    Antoine, Daniel
    British Museum, England; UCL, England.
    Hughes, David
    Interspectral AB, Sweden; Interact Institute Swedish ICT, Sweden.
    Persson, Anders
    Linköping University, Department of Medical and Health Sciences, Division of Radiological Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Radiology in Linköping. Linköping University, Center for Medical Image Science and Visualization (CMIV).
    Ljung, Patric
    Linköping University, Department of Science and Technology, Media and Information Technology. Linköping University, Faculty of Science & Engineering. Norrkoping Visualizat Centre C, Sweden.
    Interactive Visualization of 3D Scanned Mummies at Public Venues2016In: Communications of the ACM, ISSN 0001-0782, E-ISSN 1557-7317, Vol. 59, no 12, p. 72-81Article in journal (Refereed)
    Abstract [en]

    BY COMBINING VISUALIZATION techniques with interactive multi-touch tables and intuitive user interfaces, visitors to museums and science centers can conduct self-guided tours of large volumetric image data. In an interactive learning experience, visitors become the explorers of otherwise invisible interiors of unique artifacts and subjects. Here, we take as our starting point the state of the art in scanning technologies, then discuss the latest research on high-quality interactive volume rendering and how it can be tailored to meet the specific demands

  • 678.
    Younis, Shady
    et al.
    Department of Medical Biochemistry and Microbiology, Uppsala University, SE-751 23 Uppsala, Sweden // Department of Animal Production, Ain Shams University, Shoubra El-Kheima, 11241 Cairo, Egypt.
    Kamel, Wael
    Department of Medical Biochemistry and Microbiology, Uppsala University, SE-751 23 Uppsala, Sweden.
    Falkeborn, Tina
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Clinical Microbiology.
    Wang, Hao
    Department of Biochemistry and Biophysics, Stockholm University, SE-10691 Stockholm, Sweden.
    Yu, Di
    Department of Immunology, Genetics and Pathology, Uppsala University, SE-751 23 Uppsala, Sweden.
    Daniels, Robert
    Department of Biochemistry and Biophysics, Stockholm University, SE-10691 Stockholm, Sweden.
    Essand, Magnus
    Department of Immunology, Genetics and Pathology, Uppsala University, SE-751 23 Uppsala, Sweden.
    Hinkula, Jorma
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Department of Microbiology Tumor and Cell Biology, Karolinska Institutet, 17177 Stockholm, Sweden.
    Akusjärvi, Göran
    Department of Medical Biochemistry and Microbiology, Uppsala University, SE-751 23 Uppsala, Sweden.
    Andersson, Leif
    Department of Medical Biochemistry and Microbiology, Uppsala University, SE-751 23 Uppsala, Sweden // Department of Animal Breeding and Genetics, Swedish University of Agricultural Sciences, SE-75007 Uppsala, Sweden // Department of Veterinary Integrative Biosciences, Texas A&M University, College Station, TX 77483, USA.
    Multiple nuclear-replicating viruses require the stress-induced protein ZC3H11A for efficient growth2018In: Proceedings of the National Academy of Sciences of the United States of America, ISSN 0027-8424, E-ISSN 1091-6490, Vol. 115, no 6, p. E3808-E3816Article in journal (Refereed)
    Abstract [en]

    The zinc finger CCCH-type containing 11A (ZC3H11A) gene encodes a well-conserved zinc finger protein that may function in mRNA export as it has been shown to associate with the transcription export (TREX) complex in proteomic screens. Here, we report that ZC3H11A is a stress-induced nuclear protein with RNA-binding capacity that localizes to nuclear splicing speckles. During an adenovirus infection, the ZC3H11A protein and splicing factor SRSF2 relocalize to nuclear regions where viral DNA replication and transcription take place. Knockout (KO) of ZC3H11A in HeLa cells demonstrated that several nuclear-replicating viruses are dependent on ZC3H11A for efficient growth (HIV, influenza virus, herpes simplex virus, and adenovirus), whereas cytoplasmic replicating viruses are not (vaccinia virus and Semliki Forest virus). High-throughput sequencing of ZC3H11A–cross-linked RNA showed that ZC3H11A binds to short purine-rich ribonucleotide stretches in cellular and adenoviral transcripts. We show that the RNA-binding property of ZC3H11A is crucial for its function and localization. In ZC3H11A KO cells, the adenovirus fiber mRNA accumulates in the cell nucleus. Our results suggest that ZC3H11A is important for maintaining nuclear export of mRNAs during stress and that several nuclear-replicating viruses take advantage of this mechanism to facilitate their replication.

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  • 679.
    Zdolsek, Joachim
    et al.
    Linköping University, Department of Medical and Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Department of Anaesthesiology and Intensive Care in Linköping. Linköping University, Faculty of Medicine and Health Sciences. Vrinnevi Hospital, Sweden.
    Bergek, Christian
    Linköping University, Department of Medical and Health Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Department of Anaesthesiology and Intensive Care in Linköping.
    Lindahl, Tomas
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Clinical Chemistry.
    Hahn, Robert
    Linköping University, Department of Medical and Health Sciences, Division of Drug Research. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Department of Anaesthesiology and Intensive Care in Linköping. Sodertalje Hospital, Sweden.
    Colloid osmotic pressure and extravasation of plasma proteins following infusion of Ringers acetate and hydroxyethyl starch 130/0.42015In: Acta Anaesthesiologica Scandinavica, ISSN 0001-5172, E-ISSN 1399-6576, Vol. 59, no 10, p. 1303-1310Article in journal (Refereed)
    Abstract [en]

    BackgroundDuring fluid infusion therapy, plasma proteins are diluted and leak from the intravascular space, which alters the colloid osmotic pressure (COP) and potentially affects coagulation. We hypothesised that acetated Ringers and starch solution, alone or in combination, influence these mechanisms differently. Materials and methodsOn different occasions, 10 male volunteers were infused with 20ml/kg acetated Ringers and 10ml/kg 6% hyroxyethyl starch 130/0.4 (Voluven((R))) alone or in combination (first with starch solution followed by Ringers solution). Blood samples were collected every 30-min for measurements of COP, blood haemoglobin, platelets, and plasma concentrations of albumin, immunoglobulins (IgG and IgM), coagulation factor VII (FVII), fibrinogen, cystatin C, activated partial thromboplastin time (APTT) and prothrombin international normalised ratio (PT-INR). Changes were compared with the haemoglobin-derived plasma dilution. ResultsThe COP increased by 8.4% (SD 3) with starch and decreased by 26.2% (7.9) with Ringers. These infusions diluted the plasma by 23.4% (5.3) and 18.7% (4.9) respectively. The COP changes in the combined experiment followed the same pattern as the individual infusions. Albumin and IgG changes in excess of the plasma dilution were very subtle. The intravascular contents of the IgM and platelets decreased, whereas FVII, fibrinogen and cystatin C increased. PT-INR increased by 1/3 of the plasma dilution, whereas changes in APTT did not correlate with the plasma dilution. ConclusionsThe starch increased COP and only minor capillary leak occurred in healthy volunteers. The fluid-induced plasma dilution correlated with mild impairment of the extrinsic coagulation pathway but not of the intrinsic pathway.

  • 680.
    Zech, Wolf-Dieter
    et al.
    Linköping University, Department of Medical and Health Sciences, Division of Radiological Sciences. Linköping University, Faculty of Medicine and Health Sciences. Institute of Forensic Medicine, University of Bern, Switzerland.
    Hottinger, Anna-Lena
    Institute of Forensic Medicine, University of Bern, Bern, Switzerland.
    Schwendener, Nicole
    Institute of Forensic Medicine, University of Bern, Bern, Switzerland.
    Schuster, Frederick
    Institute of Forensic Medicine, University of Bern, Bern, Switzerland; Department of Diagnostic, Interventional and Pediatric Radiology, University of Bern, Inselspital, Bern, Switzerland.
    Persson, Anders
    Linköping University, Department of Medical and Health Sciences, Division of Radiological Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Radiology in Linköping. Linköping University, Center for Medical Image Science and Visualization (CMIV).
    Warntjes, Marcel Jan Bertus
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Clinical Physiology in Linköping. Linköping University, Center for Medical Image Science and Visualization (CMIV).
    Jackowski, Christian
    Institute of Forensic Medicine, University of Bern, Bern, Switzerland.
    Post-mortem 1.5T MR quantification of regular anatomical brain structures2016In: International journal of legal medicine (Print), ISSN 0937-9827, E-ISSN 1437-1596, Vol. 130, no 4, p. 1071-1080Article in journal (Refereed)
    Abstract [en]

    Recently, post-mortem MR quantification has been introduced to the field of post-mortem magnetic resonance imaging. By usage of a particular MR quantification sequence, T1 and T2 relaxation times and proton density (PD) of tissues and organs can be quantified simultaneously. The aim of the present basic research study was to assess the quantitative T1, T2, and PD values of regular anatomical brain structures for a 1.5T application and to correlate the assessed values with corpse temperatures. In a prospective study, 30 forensic cases were MR-scanned with a quantification sequence prior to autopsy. Body temperature was assessed during MR scans. In synthetically calculated T1, T2, and PD-weighted images, quantitative T1, T2 (both in ms) and PD (in %) values of anatomical structures of cerebrum (Group 1: frontal gray matter, frontal white matter, thalamus, internal capsule, caudate nucleus, putamen, and globus pallidus) and brainstem/cerebellum (Group 2: cerebral crus, substantia nigra, red nucleus, pons, cerebellar hemisphere, and superior cerebellar peduncle) were assessed. The investigated brain structures of cerebrum and brainstem/cerebellum could be characterized and differentiated based on a combination of their quantitative T1, T2, and PD values. MANOVA testing verified significant differences between the investigated anatomical brain structures among each other in Group 1 and Group 2 based on their quantitative values. Temperature dependence was observed mainly for T1 values, which were slightly increasing with rising temperature in the investigated brain structures in both groups. The results provide a base for future computer-aided diagnosis of brain pathologies and lesions in post-mortem magnetic resonance imaging.

  • 681.
    Zech, Wolf-Dieter
    et al.
    Institute of Forensic Medicine University of Bern Switzerland.
    Schwendener, Nicole
    Institute of Forensic Medicine University of Bern Switzerland.
    Persson, Anders
    Linköping University, Center for Medical Image Science and Visualization (CMIV). Linköping University, Department of Medical and Health Sciences, Division of Radiological Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Radiology in Linköping.
    Bertus Warntjes, Marcel, Jan
    Linköping University, Center for Medical Image Science and Visualization (CMIV). Linköping University, Department of Medical and Health Sciences, Division of Radiological Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Clinical Physiology in Linköping.
    Jackowski, Christian
    Institute of Forensic Medicine University of Bern Switzerland.
    Temperature dependence of postmortem MR quantification for soft tissue discrimination2015In: European Radiology, ISSN 0938-7994, E-ISSN 1432-1084, Temperature dependence of postmortem MR quantification for soft tissue discrimination, Vol. 25, no 8, p. 2381-2389Article in journal (Refereed)
    Abstract [en]

    Objectives To investigate and correct the temperature dependence of postmortem MR quantification used for soft tissue characterization and differentiation in thoraco-abdominal organs. Material and methods Thirty-five postmortem short axis cardiac 3-T MR examinations were quantified using a quantification sequence. Liver, spleen, left ventricular myocardium, pectoralis muscle and subcutaneous fat were analysed in cardiac short axis images to obtain mean T1, T2 and PD tissue values. The core body temperature was measured using a rectally inserted thermometer. The tissue-specific quantitative values were related to the body core temperature. Equations to correct for temperature differences were generated. Results In a 3D plot comprising the combined data of T1, T2 and PD, different organs/tissues could be well differentiated from each other. The quantitative values were influenced by the temperature. T1 in particular exhibited strong temperature dependence. The correction of quantitative values to a temperature of 37 °C resulted in better tissue discrimination. Conclusion Postmortem MR quantification is feasible for soft tissue discrimination and characterization of thoracoabdominal organs. This provides a base for computer-aided diagnosis and detection of tissue lesions. The temperature dependence of the T1 values challenges postmortem MR quantification. Equations to correct for the temperature dependence are provided.

  • 682.
    Zech, Wolf-Dieter
    et al.
    University of Bern, Switzerland.
    Schwendener, Nicole
    University of Bern, Switzerland.
    Persson, Anders
    Linköping University, Center for Medical Image Science and Visualization (CMIV). Linköping University, Department of Medical and Health Sciences, Division of Radiological Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Radiology in Linköping.
    Warntjes, Marcel Jan Bertus
    Linköping University, Center for Medical Image Science and Visualization (CMIV). Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Clinical Physiology in Linköping.
    Jackowski, Christian
    University of Bern, Switzerland.
    Postmortem MR quantification of the heart for characterization and differentiation of ischaemic myocardial lesions2015In: European Radiology, ISSN 0938-7994, E-ISSN 1432-1084, Vol. 25, no 7, p. 2067-2073Article in journal (Refereed)
    Abstract [en]

    Recently, an MRI quantification sequence has been developed which can be used to acquire T1- and T2-relaxation times as well as proton density (PD) values. Those three quantitative values can be used to describe soft tissue in an objective manner. The purpose of this study was to investigate the applicability of quantitative cardiac MRI for characterization and differentiation of ischaemic myocardial lesions of different age. Fifty post-mortem short axis cardiac 3 T MR examinations have been quantified using a quantification sequence. Myocardial lesions were identified according to histology and appearance in MRI images. Ischaemic lesions were assessed for mean T1-, T2- and proton density values. Quantitative values were plotted in a 3D-coordinate system to investigate the clustering of ischaemic myocardial lesions. A total of 16 myocardial lesions detected in MRI images were histologically characterized as acute lesions (n = 8) with perifocal oedema (n = 8), subacute lesions (n = 6) and chronic lesions (n = 2). In a 3D plot comprising the combined quantitative values of T1, T2 and PD, the clusters of all investigated lesions could be well differentiated from each other. Post-mortem quantitative cardiac MRI is feasible for characterization and discrimination of different age stages of myocardial infarction. aEuro cent MR quantification is feasible for characterization of different stages of myocardial infarction. aEuro cent The results provide the base for computer-aided MRI cardiac infarction diagnosis. aEuro cent Diagnostic criteria may also be applied for living patients.

  • 683.
    Zech, Wolf-Dieter
    et al.
    University of Bern, Switzerland.
    Schwendener, Nicole
    University of Bern, Switzerland.
    Persson, Anders
    Linköping University, Department of Medical and Health Sciences, Division of Radiological Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Radiology in Linköping. Linköping University, Center for Medical Image Science and Visualization (CMIV).
    Warntjes, Marcel Jan Bertus
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Clinical Physiology in Linköping. Linköping University, Center for Medical Image Science and Visualization (CMIV).
    Riva, Fabiano
    University of Bern, Switzerland.
    Schuster, Frederick
    University of Bern, Switzerland; Hospital and University of Bern, Switzerland.
    Jackowski, Christian
    University of Bern, Switzerland.
    Postmortem quantitative 1.5-T MRI for the differentiation and characterization of serous fluids, blood, CSF, and putrefied CSF2015In: International journal of legal medicine (Print), ISSN 0937-9827, E-ISSN 1437-1596, Vol. 129, no 5, p. 1127-1136Article in journal (Refereed)
    Abstract [en]

    The purpose of the present study was to investigate whether serous fluids, blood, cerebrospinal fluid (CSF), and putrefied CSF can be characterized and differentiated in synthetically calculated magnetic resonance (MR) images based on their quantitative T (1), T (2), and proton density (PD) values. Images from 55 postmortem short axis cardiac and 31 axial brain 1.5-T MR examinations were quantified using a quantification sequence. Serous fluids, fluid blood, sedimented blood, blood clots, CSF, and putrefied CSF were analyzed for their mean T (1), T (2), and PD values. Body core temperature was measured during the MRI scans. The fluid-specific quantitative values were related to the body core temperature. Equations to correct for temperature differences were generated. In a 3D plot as well as in statistical analysis, the quantitative T (1), T (2) and PD values of serous fluids, fluid blood, sedimented blood, blood clots, CSF, and putrefied CSF could be well differentiated from each other. The quantitative T (1) and T (2) values were temperature-dependent. Correction of quantitative values to a temperature of 37 A degrees C resulted in significantly better discrimination between all investigated fluid mediums. We conclude that postmortem 1.5-T MR quantification is feasible to discriminate between blood, serous fluids, CSF, and putrefied CSF. This finding provides a basis for the computer-aided diagnosis and detection of fluids and hemorrhages.

  • 684.
    Zeka, Bleranda
    et al.
    Department of Neuroimmunology, Center for Brain Research, Medical University Vienna, Spitalgasse 4, A-1090, Vienna, Austria.
    Hastermann, Maria
    Department of Neuroimmunology, Center for Brain Research, Medical University Vienna, Spitalgasse 4, A-1090, Vienna, Austria.
    Kaufmann, Nathalie
    Department of Neuroimmunology, Center for Brain Research, Medical University Vienna, Spitalgasse 4, A-1090, Vienna, Austria.
    Schanda, Kathrin
    Clinical Department of Neurology, Innsbruck Medical University, Innsbruck, Austria.
    Pende, Marko
    Medical University Vienna, Section for Bioelectronics, Center for Brain Research, Vienna, Austria.
    Misu, Tatsuro
    Department of Neurology, Tohoku University Graduate School of Medicine, Sendai, Japan.
    Rommer, Paulus
    Department of Neurology, Medical University Vienna, Wien, Austria.
    Fujihara, Kazuo
    Department of Neurology, Tohoku University Graduate School of Medicine, Sendai, Japan.
    Nakashima, Ichiro
    Department of Neurology, Tohoku University Graduate School of Medicine, Sendai, Japan.
    Dahle, Charlotte
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Clinical Immunology and Transfusion Medicine.
    Leutmezer, Fritz
    Department of Neurology, Medical University Vienna, Wien, Austria.
    Reindl, Markus
    Clinical Department of Neurology, Innsbruck Medical University, Innsbruck, Austria.
    Lassmann, Hans
    Department of Neuroimmunology, Center for Brain Research, Medical University Vienna, Spitalgasse 4, A-1090, Vienna, Austria.
    Bradl, Monika
    Department of Neuroimmunology, Center for Brain Research, Medical University Vienna, Spitalgasse 4, A-1090, Vienna, Austria.
    Aquaporin 4-specific T cells and NMO-IgG cause primary retinal damage in experimental NMO/SD.2016In: Acta neuropathologica communications, E-ISSN 2051-5960, Vol. 4, no 1, article id 82Article in journal (Refereed)
    Abstract [en]

    Neuromyelitis optica/spectrum disorder (NMO/SD) is a severe, inflammatory disease of the central nervous system (CNS). In the majority of patients, it is associated with the presence of pathogenic serum autoantibodies (the so-called NMO-IgGs) directed against the water channel aquaporin 4 (AQP4), and with the formation of large, astrocyte-destructive lesions in spinal cord and optic nerves. A large number of recent studies using optical coherence tomography (OCT) demonstrated that damage to optic nerves in NMO/SD is also associated with retinal injury, as evidenced by retinal nerve fiber layer (RNFL) thinning and microcystic inner nuclear layer abnormalities. These studies concluded that retinal injury in NMO/SD patients results from secondary neurodegeneration triggered by optic neuritis.However, the eye also contains cells expressing AQP4, i.e., Müller cells and astrocytes in the retina, epithelial cells of the ciliary body, and epithelial cells of the iris, which raised the question whether the eye can also be a primary target in NMO/SD. Here, we addressed this point in experimental NMO/SD (ENMO) induced in Lewis rat by transfer of AQP4268-285-specific T cells and NMO-IgG.We show that these animals show retinitis and subsequent dysfunction/damage of retinal axons and neurons, and that this pathology occurs independently of the action of NMO-IgG. We further show that in the retinae of ENMO animals Müller cell side branches lose AQP4 reactivity, while retinal astrocytes and Müller cell processes in the RNFL/ganglionic cell layers are spared. These changes only occur in the presence of both AQP4268-285-specific T cells and NMO-IgG.Cumulatively, our data show that damage to retinal cells can be a primary event in NMO/SD.

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  • 685.
    Zetterqvist, Ann
    et al.
    University of Gothenburg, Sweden.
    Aronsson, Patrik
    University of Gothenburg, Sweden.
    Hägg, Staffan
    Linköping University, Department of Medical and Health Sciences, Division of Drug Research. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Clinical Pharmacology.
    Kjellgren, Karin
    Linköping University, Department of Medical and Health Sciences, Division of Nursing Science. Linköping University, Faculty of Medicine and Health Sciences.
    Reis, Margareta
    Linköping University, Department of Medical and Health Sciences, Division of Drug Research. Linköping University, Faculty of Medicine and Health Sciences.
    Tobin, Gunnar
    University of Gothenburg, Sweden.
    Booth, Shirley
    University of Gothenburg, Sweden; University of Witwatersrand, South Africa.
    On the pedagogy of pharmacological communication: a study of final semester health science students2015In: BMC Medical Education, ISSN 1472-6920, E-ISSN 1472-6920, Vol. 15Article in journal (Refereed)
    Abstract [en]

    Background: There is a need to improve design in educational programmes for the health sciences in general and in pharmacology specifically. The objective of this study was to investigate and problematize pharmacological communication in educational programmes for the health sciences. Methods: An interview study was carried out where final semester students from programmes for the medical, nursing and specialist nursing in primary health care professions were asked to discuss the pharmacological aspects of two written case descriptions of the kind they would meet in their everyday work. The study focused on the communication they envisaged taking place on the concerns the patients were voicing, in terms of two features: how communication would take place and what would be the content of the communication. A phenomenographic research approach was used. Results: The results are presented as outcome spaces, sets of categories that describe the variation of ways in which the students voiced their understanding of communication in the two case descriptions and showed the qualitatively distinct ways in which the features of communication were experienced. Conclusions: The results offer a base of understanding the students perspectives on communication that they will take with them into their professional lives. We indicate that there is room for strengthening communication skills in the field of pharmacology, integrating them into programmes of education, by more widely implementing a problem-based, a case-oriented or role-playing pedagogy where final year students work across specialisations and there is a deliberate effort to evoke and assess advanced conceptions and skills.

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  • 686.
    Zhao, Jin J.
    et al.
    Uppsala University, Sweden.
    Halvardson, Jonatan
    Uppsala University, Sweden.
    Zander, Cecilia S.
    Uppsala University, Sweden.
    Zaghlool, Ammar
    Uppsala University, Sweden.
    Georgii-Hemming, Patrik
    Uppsala University, Sweden; Karolinska Institute, Sweden.
    Mansson, Else
    Örebro University Hospital, Sweden.
    Brandberg, Göran
    Pediat Clin, Falun, Sweden.
    Savmarker, Helena E.
    Gävle Central Hospital, Sweden.
    Frykholm, Carina
    Uppsala University, Sweden.
    Kuchinskaya, Ekaterina
    Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Clinical genetics.
    Thuresson, Ann-Charlotte
    Uppsala University, Sweden.
    Feuk, Lars
    Uppsala University, Sweden.
    Exome sequencing reveals NAA15 and PUF60 as candidate genes associated with intellectual disability2018In: American Journal of Medical Genetics Part B: Neuropsychiatric Genetics, ISSN 1552-4841, E-ISSN 1552-485X, Vol. 177, no 1, p. 10-20Article in journal (Refereed)
    Abstract [en]

    Intellectual Disability (ID) is a clinically heterogeneous condition that affects 2-3% of population worldwide. In recent years, exome sequencing has been a successful strategy for studies of genetic causes of ID, providing a growing list of both candidate and validated ID genes. In this study, exome sequencing was performed on 28 ID patients in 27 patient-parent trios with the aim to identify de novo variants (DNVs) in known and novel ID associated genes. We report the identification of 25 DNVs out of which five were classified as pathogenic or likely pathogenic. Among these, a two base pair deletion was identified in the PUF60 gene, which is one of three genes in the critical region of the 8q24.3 microdeletion syndrome (Verheij syndrome). Our result adds to the growing evidence that PUF60 is responsible for the majority of the symptoms reported for carriers of a microdeletion across this region. We also report variants in several genes previously not associated with ID, including a de novo missense variant in NAA15. We highlight NAA15 as a novel candidate ID gene based on the vital role of NAA15 in the generation and differentiation of neurons in neonatal brain, the fact that the gene is highly intolerant to loss of function and coding variation, and previously reported DNVs in neurodevelopmental disorders.

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  • 687.
    Zimdahl Kahlin, Anna
    et al.
    Linköping University, Department of Medical and Health Sciences, Division of Drug Research. Linköping University, Faculty of Medicine and Health Sciences.
    Helander, Sara
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Chemistry. Linköping University, Faculty of Medicine and Health Sciences.
    Skoglund, Karin
    Linköping University, Department of Medical and Health Sciences, Division of Drug Research. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Business support and Development, Department of Health and Care Development.
    Söderkvist, Peter
    Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Clinical genetics.
    Mårtensson, Lars-Göran
    Linköping University, Department of Physics, Chemistry and Biology, Chemistry. Linköping University, Faculty of Science & Engineering.
    Lindqvist Appell, Malin
    Linköping University, Department of Medical and Health Sciences, Division of Drug Research. Linköping University, Faculty of Medicine and Health Sciences.
    Comprehensive study of thiopurine methyltransferase genotype, phenotype, and genotype-phenotype discrepancies in Sweden2019In: Biochemical Pharmacology, ISSN 0006-2952, E-ISSN 1356-1839, Vol. 164, p. 263-272Article in journal (Refereed)
    Abstract [en]

    Thiopurines are widely used in the treatment of leukemia and inflammatory bowel diseases. Thiopurine metabolism varies among individuals because of differences in the polymorphic enzyme thiopurine methyltransferase (TPMT, EC 2.1.1.67), and to avoid severe adverse reactions caused by incorrect dosing it is recommended that the patients TPMT status be determined before the start of thiopurine treatment. This study describes the concordance between genotyping for common TPMT alleles and phenotyping in a Swedish cohort of 12,663 patients sampled before or during thiopurine treatment. The concordance between TPMT genotype and enzyme activity was 94.5%. Compared to the genotype, the first measurement of TPMT enzyme activity was lower than expected for 4.6% of the patients. Sequencing of all coding regions of the TPMT gene in genotype/phenotype discrepant individuals led to the identification of rare and novel TPMT alleles. Fifteen individuals (0.1%) with rare or novel genotypes were identified, and three TPMT alleles (TPMT*42, *43, and *44) are characterized here for the first time. These 15 patients would not have been detected as carrying a deviating TPMT genotype if only genotyping of the most common TPMT variants had been performed. This study highlights the benefit of combining TPMT genotype and phenotype determination in routine testing. More accurate dose recommendations can be made, which might decrease the number of adverse reactions and treatment failures during thiopurine treatment.

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  • 688.
    Zötterman, Johan
    et al.
    Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Department of Hand and Plastic Surgery. Linköping University, Department of Biomedical and Clinical Sciences, Division of Surgery, Orthopedics and Oncology.
    Opsomer, Dries
    Department of Plastic and Reconstructive Surgery, University of Ghent, Ghent, Belgium.
    Farnebo, Simon
    Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Department of Hand and Plastic Surgery. Linköping University, Department of Biomedical and Clinical Sciences, Division of Surgery, Orthopedics and Oncology.
    Blondeel, Phillip
    Department of Plastic and Reconstructive Surgery, University of Ghent, Ghent, Belgium.
    Monstrey, Stan
    Department of Plastic and Reconstructive Surgery, University of Ghent, Ghent, Belgium.
    Tesselaar, Erik
    Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Medical radiation physics. Linköping University, Department of Biomedical and Clinical Sciences, Division of Surgery, Orthopedics and Oncology.
    Intraoperative Laser Speckle Contrast Imaging in DIEP Breast Reconstruction: A Prospective Case Series Study2020In: Plastic and reconstructive surgery. Global open, ISSN 2169-7574, Vol. 8, no 1, p. e2529-e2529Article in journal (Refereed)
    Abstract [en]

    Laser speckle contrast imaging (LSCI) is a laser-based perfusion imaging technique that recently has been shown to predict ischemic necrosis in an experimental flap model and predicting healing time of scald burns. The aims were to investigate perfusion in relation to the selected perforator during deep inferior epigastric artery perforator (DIEP) flap surgery, and to evaluate LSCI in assisting of prediction of postoperative complications. METHODS: Twenty-three patients who underwent DIEP-procedures for breast reconstruction at 2 centers were included. Perfusion was measured in 4 zones at baseline, after raising, after anastomosis, and after shaping the flap. The perfusion in relation to the selected perforator and the accuracy of LSCI in predicting complications were analyzed. RESULTS: After raising the flap, zone I showed the highest perfusion (65 ± 10 perfusion units, PU), followed by zone II (58 ± 12 PU), zone III (53 ± 10 PU), and zone IV (45 ± 10 PU). The perfusion in zone I was higher than zone III (P = 0.002) and zone IV (P < 0.001). After anastomosis, zone IV had lower perfusion than zone I (P < 0.001), zone II (P = 0.01), and zone III (P = 0.02). Flaps with areas <30 PU after surgery had partial necrosis postoperatively (n = 4). CONCLUSIONS: Perfusion is highest in zone I. No perfusion difference was found between zones II and III. Perfusion <30 PU after surgery was correlated with partial necrosis. LSCI is a promising tool for measurement of flap perfusion and assessment of risk of postoperative ischemic complications.

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  • 689.
    Zötterman, Johan
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Department of Hand and Plastic Surgery.
    Tesselaar, Erik
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Medical radiation physics.
    Farnebo, Simon
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Department of Hand and Plastic Surgery.
    The use of laser speckle contrast imaging to predict flap necrosis: An experimental study in a porcine flap model2019In: Journal of Plastic, Reconstructive & Aesthetic Surgery, ISSN 1748-6815, E-ISSN 1532-1959, Vol. 72, no 5, p. 771-777Article in journal (Refereed)
    Abstract [en]

    Background: We evaluated the use of laser speckle contrast imaging (LSCI) in the perioperative planning in reconstructive flap surgery. The aim of the study was to investigate whether LSCI can predict regions with a high risk of developing postoperative necrosis. Our hypothesis was that, perioperatively, such regions have perfusion values below a threshold value and show a negative perfusion trend. Methods: A porcine flap model based on the cranial gluteal artery perforator was used. Images were acquired before surgery, immediately after surgery (t = 0), after 30 min (t =30 min), and after 72h (t = 72 h). Regions of interest (ROIs) were chosen along the central axis of the flap. Clinical evaluation of the flap was made during each time point. Results: At t = 72 h, a demarcation line could be seen at a distance of 15.8 +/- 0.4 cm away from the proximal border of the flaps. At t =0, perfusion decreased gradually from the proximal to the distal ROI. At t =30 min, perfusion was significantly lower in the ROI distal to the final demarcation line than that at t = 0, and in all flaps, these ROIs had a perfusion amp;lt;25 PU. At t= 72 h, perfusion in the ROI proximal to this line returned to baseline levels, whereas perfusion in the distal ROI remained low. Conclusions: In our model, a decrease in perfusion during the first 30 min after surgery and a perfusion amp;lt;25 PU at t = 30 min was a predictor for tissue morbidity 72 h after surgery, which indicates that LSCI is a promising technique for perioperative monitoring in reconstructive flap surgery. (C) 2018 Published by Elsevier Ltd on behalf of British Association of Plastic, Reconstructive and Aesthetic Surgeons.

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  • 690.
    Åkerman, Linda
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Children's and Women's health. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Clinical Chemistry.
    Casas, Rosaura
    Linköping University, Department of Clinical and Experimental Medicine, Division of Children's and Women's health. Linköping University, Faculty of Medicine and Health Sciences.
    Ludvigsson, Johnny
    Linköping University, Department of Clinical and Experimental Medicine, Division of Children's and Women's health. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center of Paediatrics and Gynaecology and Obstetrics, H.K.H. Kronprinsessan Victorias barn- och ungdomssjukhus.
    Tavira Iglesias, Beatriz
    Linköping University, Department of Clinical and Experimental Medicine, Division of Children's and Women's health. Linköping University, Faculty of Medicine and Health Sciences.
    Skoglund, Camilla
    Linköping University, Department of Medical and Health Sciences, Division of Drug Research. Linköping University, Faculty of Medicine and Health Sciences.
    Serum miRNA levels are related to glucose homeostasis and islet autoantibodies in children with high risk for type 1 diabetes2018In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 13, no 1, article id e0191067Article in journal (Refereed)
    Abstract [en]

    Micro RNAs (miRNAs) are promising disease biomarkers due to their high stability. Their expression in serum is altered in type 1 diabetes, but whether deviations exist in individuals with high risk for type 1 diabetes remains unexplored. We therefore assessed serum miRNAs in high-risk individuals (n = 21) positive for multiple islet autoantibodies, age-matched healthy children (n = 17) and recent-onset type 1 diabetes patients (n = 8), using Serum/Plasma Focus microRNA PCR Panels from Exiqon. The miRNA levels in the high-risk group were similar to healthy controls, and no specific miRNA profile was identified for the high-risk group. However, serum miRNAs appeared to reflect glycemic status and ongoing islet auto-immunity in high-risk individuals, since several miRNAs were associated to glucose homeostasis and autoantibody titers. High-risk individuals progressing to clinical disease after the sampling could not be clearly distinguished from non-progressors, while miRNA expression in the type 1 diabetes group deviated significantly from high-risk individuals and healthy controls, perhaps explained by major metabolic disturbances around the time of diagnosis.

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  • 691.
    Östgren, Carl Johan
    et al.
    Linköping University, Department of Health, Medicine and Caring Sciences, Division of Prevention, Rehabilitation and Community Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Primary Care Center, Primary Health Care Center Ödeshög.
    Soderberg, Stefan
    Umea Univ, Sweden.
    Festin, Karin
    Linköping University, Department of Health, Medicine and Caring Sciences, Division of Society and Health. Linköping University, Faculty of Medicine and Health Sciences.
    Angeras, Oskar
    Sahlgrens Univ Hosp, Sweden; Univ Gothenburg, Sweden.
    Bergstrom, Goran
    Univ Gothenburg, Sweden; Sahlgrens Univ Hosp, Sweden.
    Blomberg, Anders
    Umea Univ, Sweden.
    Brandberg, John
    Sahlgrens Univ Hosp, Sweden; Univ Gothenburg, Sweden.
    Cederlund, Kerstin
    Karolinska Inst, Sweden.
    Eliasson, Mats
    Umea Univ, Sweden.
    Engstrom, Gunnar
    Lund Univ, Sweden.
    Erlinge, David
    Lund Univ, Sweden; Skane Univ Hosp, Sweden.
    Fagman, Erika
    Sahlgrens Univ Hosp, Sweden; Univ Gothenburg, Sweden.
    Hagstrom, Emil
    Uppsala Univ, Sweden; Uppsala Univ, Sweden.
    Lind, Lars
    Uppsala Univ, Sweden.
    Mannila, Maria
    Karolinska Univ Hosp, Sweden.
    Nilsson, Ulf
    Umea Univ, Sweden.
    Oldgren, Jonas
    Uppsala Univ, Sweden; Uppsala Univ, Sweden.
    Ostenfeld, Ellen
    Lund Univ, Sweden; Skane Univ Hosp, Sweden.
    Persson, Anders
    Linköping University, Department of Health, Medicine and Caring Sciences, Division of Diagnostics and Specialist Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Radiology in Linköping. Linköping University, Center for Medical Image Science and Visualization (CMIV).
    Persson, Jonas
    Danderyd Hosp, Sweden.
    Persson, Margaretha
    Lund Univ, Sweden; Skane Univ Hosp, Sweden.
    Rosengren, Annika
    Univ Gothenburg, Sweden; Sahlgrens Univ Hosp, Sweden.
    Sundstrom, Johan
    Uppsala Univ, Sweden; Univ New South Wales, Australia.
    Swahn, Eva
    Linköping University, Department of Health, Medicine and Caring Sciences, Division of Diagnostics and Specialist Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Cardiology in Linköping.
    Engvall, Jan
    Linköping University, Department of Health, Medicine and Caring Sciences, Division of Diagnostics and Specialist Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Clinical Physiology in Linköping. Linköping University, Center for Medical Image Science and Visualization (CMIV).
    Jernberg, Tomas
    Danderyd Hosp, Sweden.
    Systematic Coronary Risk Evaluation estimated risk and prevalent subclinical atherosclerosis in coronary and carotid arteries: A population-based cohort analysis from the Swedish Cardiopulmonary Bioimage Study2020In: European Journal of Preventive Cardiology, ISSN 2047-4873, E-ISSN 2047-4881, article id UNSP 2047487320909300Article in journal (Refereed)
    Abstract [en]

    Background It is not clear if the European Systematic Coronary Risk Evaluation algorithm is useful for identifying prevalent subclinical atherosclerosis in a population of apparently healthy individuals. Our aim was to explore the association between the risk estimates from Systematic Coronary Risk Evaluation and prevalent subclinical atherosclerosis. Design The design of this study was as a cross-sectional analysis from a population-based study cohort. Methods From the general population, the Swedish Cardiopulmonary Bioimage Study randomly invited individuals aged 50-64 years and enrolled 13,411 participants mean age 57 (standard deviation 4.3) years; 46% males between November 2013-December 2016. Associations between Systematic Coronary Risk Evaluation risk estimates and coronary artery calcification and plaques in the carotid arteries by using imaging data from a computed tomography of the heart and ultrasonography of the carotid arteries were examined. Results Coronary calcification was present in 39.5% and carotid plaque in 56.0%. In men, coronary artery calcium score amp;gt;0 ranged from 40.7-65.9% and presence of carotid plaques from 54.5% to 72.8% in the age group 50-54 and 60-65 years, respectively. In women, the corresponding difference was from 17.1-38.9% and from 41.0-58.4%. A doubling of Systematic Coronary Risk Evaluation was associated with an increased probability to have coronary artery calcium score amp;gt;0 (odds ratio: 2.18 (95% confidence interval 2.07-2.30)) and to have amp;gt;1 carotid plaques (1.67 (1.61-1.74)). Conclusion Systematic Coronary Risk Evaluation estimated risk is associated with prevalent subclinical atherosclerosis in two major vascular beds in a general population sample without established cardiovascular disease or diabetes mellitus. Thus, the Systematic Coronary Risk Evaluation risk chart may be of use for estimating the risk of subclinical atherosclerosis.

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  • 692.
    Persson, Anders (Contributor)
    Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Radiology in Linköping. Linköping University, Center for Medical Image Science and Visualization (CMIV). Linköping University, Department of Medical and Health Sciences, Division of Radiological Sciences.
    Strategic research agenda for biomedical imaging2019In: Insights into Imaging, no 10, article id 7Article in journal (Refereed)
    Abstract [en]

    This Strategic Research Agenda identifies current challenges and needs in healthcare, illustrates how biomedical imaging and derived data can help to address these, and aims to stimulate dedicated research funding efforts.

    Medicine is currently moving towards a more tailored, patient-centric approach by providing personalised solutions for the individual patient. Innovation in biomedical imaging plays a key role in this process as it addresses the current needs for individualised prevention, treatment, therapy response monitoring, and image-guided surgery.

    The use of non-invasive biomarkers facilitates better therapy prediction and monitoring, leading to improved patient outcomes. Innovative diagnostic imaging technologies provide information about disease characteristics which, coupled with biological, genetic and -omics data, will contribute to an individualised diagnosis and therapy approach.

    In the emerging field of theranostics, imaging tools together with therapeutic agents enable the selection of best treatments and allow tailored therapeutic interventions.

    For prenatal monitoring, the use of innovative imaging technologies can ensure an early detection of malfunctions or disease.

    The application of biomedical imaging for diagnosis and management of lifestyle-induced diseases will help to avoid disease development through lifestyle changes.

    Artificial intelligence and machine learning in imaging will facilitate the improvement of image interpretation and lead to better disease prediction and therapy planning.

    As biomedical imaging technologies and analysis of existing imaging data provide solutions to current challenges and needs in healthcare, appropriate funding for dedicated research is needed to implement the innovative approaches for the wellbeing of citizens and patients.

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