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MEDISIN- OG ODONTOLOGISTUDENTENES FORSKNINGSKONFERANSE 21.-23. okt 2016, Bergen 2 Contents Contents........................................................................................................ 3 Dear participant, .......................................................................................... 4 Committee .................................................................................................... 5 Program ......................................................................................................... 6 Information ................................................................................................... 8 Maps ............................................................................................................ 10 Academic content ..................................................................................... 12 Friday ....................................................................................................... 13 Saturday .................................................................................................. 14 Program for oral presentations .......................................................... 16 Abstracts in clinical medicine ............................................................. 17 Abstracts in basal research and genetics ......................................... 32 Abstracts in cancer research .............................................................. 47 Abstracts in epidemiology ................................................................... 55 Poster presentations ............................................................................ 62 Saksliste til generalforsamling ................................................................ 68 Participants ................................................................................................. 69 Sponsors 2016 .......................................................................................... 73 3 Dear participant, Finally, the day has come, and we are proud and excited to welcome you to Frampeik 2016 in Bergen! As you may or may not have noticed, this year we have changed the sub-title of Frampeik to include the beloved and devoted odontology students, as they have been a substantial part of The Medical Student Research Program for years, and we hope that research during the professional education will continue to inspire interdisciplinary collaboration and friendships, and we hope that you as a participant will make some new friends and contacts this weekend! We are happy to announce that our program this year includes both local and external speakers, and we´ll start Friday off with Gunnar Tjomlid, who has a book release the week after Frampeik, but gives you the chance to buy his book here today! We also have the leader of the hypochondriac clinic, Ingvard Wilhelmsen, talking about being in control in your own life. Hopefully, the program reflects on the topics of self-judgment and worst-case-thinking, and how we should cope with this. This Saturday we can tempt you with a special treat of West Side culinary experience, as we have a Gala event at the sea-food restaurant Cornelius, a mere boat ride away from bryggen. After a delicious three-course dinner, the party continues in Kalfaret, a 3 minutes’ walk from Hotel Terminus. We wish you all an enjoyable conference, we hope to see you seize the opportunity to make this a learning experience for yourself and others, discussing ideas, results and experience from your line of research. And good luck to all the presenters! Lastly, but not least: we really appreciate everyone who has contributed to this conference, and a big thank you to our sponsors, this would not be accomplished without your engagement in this project! On behalf of the Committee, Tony Elvegaard, Chairman of the committee 4 Committee Chairman Tony Elvegaard Academic program Christiane H. Gjerde Economics Lisa Willassen Social program Amalie Svanøe Social program Benedicte Sjo Tislevoll Sponsorship Hanne Borge Sponsorship Vera Ericher PR Martha Rolland Jacobsen 5 Program Friday 21th of October 2016 Store Auditorium, 3.etg, Haukeland universitetssykehus (HUS) 14:30-15:30 Registration 15:30:16:15 Welcome to Frampeik 2016 Opening speech by rector Dag Rune Olsen Introduction by dean Nina Langeland Presentation of LVS by Tiina Rekand 16:15-17:15: Key lecture by Gunnar Tjomlid 17:30-18:15: Key lecture by Ingvard Wilhelmsen 18:15-19:00: Information about the programme Guided walk from HUS to Overlegen 19:00-01:00: Tapas dinner and socializing at Overlegen Saturday 22nd of October 2016 Ground floor, small auditoriums, Odontologen (OD) 10:00-12:00: 12:00-12:30: 12:30-13:30: 13:30-14:20: 14:30-16:00: Parallel symposia 1 (with introductory lectures) Poster session Lunch Lecture by Trond Nordseth Parallel symposia 2 18:30: 19:00: Bus from Grand Hotel Terminus to Bryggen Boat ride to sea-food restaurant Cornelius 6 19.30: 23:30: 00:30-late Gala dinner event Entertainment by the Magician Snorre Sævraas Boat ride back to Bryggen, bus to Terminus Party at Nord-Norge huset (a 3 min walk) Sunday 23rd of October 2016 Ground floor, small auditoriums, Odontologen (OD) 11:00-13:00: Parallel symposia 3 13:00-14:00: General Assembly of Frampeik Closing of Frampeik 14:00-14:30: Lunch 7 Information Internet access There is wireless internet in both Store Auditorium at Haukeland Universitessykehus, and at doontologen. At Haukeland you should log onto ”gjest ihelse” and get a username and password sent by SMS. At odontologen, Eduroam is provided, so feel free to go wild. Access to the conference building The front door and all the rooms at Odontologen is closed outside of working hours. All UiB students should have access to all buildings and rooms. The main entrance will be manned before lectures start and at break time. Should the door be closed, this would be a perfect time to befriend a Bergenser, or call or text 41445857 to get someone to open for you. Organised transport At Saturday, the transport from Terminus to Bryggen will be by bus, and transport over the sea will be by boat. The same procedure on the way back. Food We will provide some coffee and fruits and stuff at registration time Friday, and an amazing tapas dinner in the evening. Saturday you will be provided lunch, snacks, lots of coffee and dinner in the night time, and a lunch on Sunday as well. Enjoy the hotel breakfast (or your regular oatmeal/knekkebrød/leverpostei-kitchen-breakfast for those living here). Anything else you might wish can be purchased at Rema 1000 at Haukeland (indicated on the map), or in any other shop of your choosing. Drink Water is in the sink or machines, coffee and some mineral water will be provided. There is a water machine in the main floor of odontologen, but it tends to go on strike sometimes; in that case there are plenty more of them in the floor above. Friday night, a small amount of alcoholic and non-alcoholic beverages will be provided, should you wish anything else, we will pass Rema 1000 on our way to Overlegen, so you can buy there. 8 Or bring from home. Saturday you will get three glasses of wine at the restaurant. We´re allowed to bring our own drink at Nord Norge-huset. On our way back from the restaurant, we´ll have a pit stop at the hotel so you can collect anything you want to bring. Remember that polet closes at 3pm Saturday, when we´re still at Odontologen, so either make sure you can buy provisions on Friday, or bring from home. Cornelius sjømatrestaurant Extracted directly from their webpage; ”Just outside the City of Bergen, you will find one of the most exotic attractions in the whole of Western Norway’s archipelago. Cornelius is one of Norway’s best seafood restaurants. It is situated right by the sea on a small island with spectacular views of the fjord, mountains, skerries and passing boats and ships.” Inspired by the weather of the day, Cornelius serves its famous Meteorological Menu of exquisite seafood and trimmings, prepared using innovative culinary techniques and with a genuine passion for seafood. All those who´ve registered with special diets or allergies will be provided food according to this. Please let us know asap if you forgot to register your allergy, or developed one during the last few weeks. Any questions? Please contact us by message on Facebook, this is where we are most active, or call or send a text to 41445857. 9 Maps Busstopp for flybussen Grand Hotel Terminus Busstopp for buss 2/3/80 til Haukeland Nord-Norgehuset selskapslokale (festlokale lørdag) Rema 1000 Overlegen (festlokale fredag) Odontologen (konferanse lørdag og søndag, Busstopp: Statsarkivet) Busstopp Haukeland universitetssykehus nord 10 11 Academic content 12 Friday 16:15-17:15: Gunnar Tjomlid ”La meg se litt nærmere på akkurat det...” Gunnar Tjomlid has a half degree in most subjects, and describes himself as a bit of a nerd. He´s got a day-job as a web developer in Thin AS, but as soon as he quits work he becomes a blogger, a writer, and a lecturer. Many of you might know him as the writer of Placebodefekten, where he explains why alternative medicine does not work, which is not the easiest task, but he does it, and he does it well. He also runs the blog at Saksynt, where he comments on every aspect of the society. His writing is amazing, always critical, and (almost) always on the point. Right now he´s actual with his new book Håndbok i krisemaksimering, where he debates the fact that based on the headlines in the paper, the world and humans has never been worse off, when actually it´s quite the opposite. We are more healthy and safer than ever, but somehow we always seem to think that the world is going to end tomorrow. With this book, Tjomlid tries to provide us with a tool for critical thinking, especially when it comes to the media. Hopefully he will tell us more about this in the lecture! 17:30-18:50: Ingvard Wilhelmsen We are proud to present our very own, and greatly appreciated professor Wilhelmsen. Wilhelmsen finished his medical studies in 1976, and has since taken specialities in internal medicine, digestive disorders and psychiatry. He now works in the field of hypochondria, and runs the only clinic of hypochondria in the Norway. Due to his competence in several fields of medicine, he is especially interested in connecting the body to the spirit. 13 He compared hypochondria to having a loaded gun pointing towards you at all times, and suggests that it can and should be treated. Wilhelmsen has published several books during his career, where his latest one published in 2011 with the title “Det er ikke mer synd på deg enn andre” got excellent reviews. If you´de like to learn more about Wilhelmsen,, we recommend to watch his interview with Torp at nrk.no. Saturday 13:30-14:20 Trond Nordseth Trond Nordseth is currently working as an associate professor and consultant at the department of circulation and medical imaging at NTNU. He has studied heart rhythms in people who are about to die of cardiac arrest, and that's got a little chance to come back to life because health professionals have started resuscitation with cardiopulmonary resuscitation. When the defibrillator is connected to the patient's chest, it will monitor the different heart signals and stores them. Such data has Nordseth researched. Trond Nordseth defended his PhD at NTNU in 2014, with the title: Clinical state transitions during the Provision of advanced life support (ALS) Patients in cardiac arrest. He also went forskerlinjen during his medical studies at NTNU, which is of course one of the reasons why we like him so much. 14 Introductory lectures The remaining topics will be presented Saturday. Daniela Costea; Cancer research Daniela Costea has a degree in odontology, and is positioned as professor at the pathology department at Haukeland. Her research group are studying the interactions between epithelial cells and the surrounding tissue, and between epithelium/connective tissue cells and microbiota in normal conditions and during cancer development. Daniela is an expert in establishing friendships and collaborative agreements with other universities, both I Norway and abroad. She is a motivating and enthusiastic researcher, lecturer and supervisor, and is loved by all her students. Cecilie Gjerde; basal research and genetics Cecilie has a master in dentistry, has specialised in oral surgery, and is currently doing her PhD here at UiB. She is appreciated and admired by all our students, and the role model for what a researcher ought to be like. She is a fabulous presenter, just so good that she won forsknings grand prix last year. Her project involves stem cells from the spinal cord of the patient being used to regrow bone in the mandibula. So yeah, she basically grows bone, which is pretty exciting. 15 Program for oral presentations Saturday 10.00-12.00 – Parallel symposia 1 Clinical medicine 10.30 Giriteka 10.45 Bremnes 11.00 Amundsen 11.15 Willassen 11:30: Lund Epidemiology 10.30 Madsen 10.45 Ellingsen 11:00 MClean Cancer research 10.30 Skjefstad 10.45 Barua 11.00 Jacobsen 11.15 Grindstad Basal research and genetics 10.30 Solvin 10.45 Willems 11.00 Schanche 11.15 Johansen Saturday 14.30-16.00 – Parallel symposia 2 Clinical Medicine Cancer research 14.30 Taraldsen 14.45 Staniszewski 15.00 Olsen 15.15 Sulen 14.30 Knutsen 14.45 Svanøe 15.00 Yi 14.30 Pannu 14.45 Tran 15.00 Warlo 14.30 Schanche 14.45 Myklebust 15.00 Radunovic 15.15 Aarebrot Epidemiology Basal research and genetics Sunday 11.00-13.00 – Parallel symposia 3 Clinical medicine Basal research and genetics 11.00 Koppen 11.15 Halvåg 11.30 Larsen 11.45 Stangeland 12.00 Runde 12.15 Leiten 11.00 Bakken 11.15 Hoel 11.30 Hjøllo 11.45 Kristiansen 12.00 Korkosh 12.15 Klæstad 16 Abstracts in clinical medicine Giriteka, Lionel UiB [email protected] Bremnes, Thomas UiT [email protected] Amundsen, Vivian S. UiO [email protected] Willassen, Lisa UiB [email protected] Lund, Anders UiB [email protected] Taraldsen, Maria Dalen NTNU [email protected] Staniszewski, Kordian UiB [email protected] Olsen, Eirik Birkelund UiT [email protected] Sulen, Åsta UiB [email protected] Koppen, Elias NTNU [email protected] Halvåg, Ranghild UiB [email protected] Larsen, Christopher Storm UiO [email protected] Stangeland, Marcus UiB [email protected] Runde, Henrik Alexander NTNU [email protected] Leiten, Elise Orvedal UiB [email protected] 17 Multimodal Neuroimaging: A study of brain activity in patients with IBS Lionel Giriteka Objective: We want to see if we can replicate previous findings of altered brain structure in IBS using soup as a trigger for discomfort. Primarily we will research on PI-IBS patients. Experience show that patients get symptoms with this soup, and this will make a more realistic approach then triggering pain using, for instance, a balloon. It is interesting to see whether we can observe differences between HC and IBS patients during resting state. Using DTI we can look upon the connectivity between different brain structures. Pre stimulus: 3DT1 SPGR DTI (6 b=0, 30 b=1000) Post stimulus: 3DT1 SPGR Stimulus: RS-fMRI (240 volumes, TR=2 s) RS-fMRI (240 volumes, TR=2 s) 500 ml Toro meat soup per os (outside magnet) Repositioning in scanner: 3T GE Signa Excite HD fMRI_111005_suppe_kk Materials and methods: We will start with fMRI uptakes of 10 HCs before we start with the IBS patients. Our exact protocol for the fMRI uptakes is: 1. Localizer - ca 30 sec 2. 3D T1-w anatomy – ca 8 min 3. Resting state 240 volumes (TR=2 sec) - 8 min 10 sec 4. DTI – ca 9 min 5. Soup, 500 ml, outside of scanner ca 4 min 6. Localizer - ca 30 sec 7. 3D T1-w anatomy – ca 8 min 8. Resting state 240 volumes (TR=2 sec) - 8 min 10 sec Figure'1.'Multimodal'MR'imaging'protocol'pre'–stimulus'and'post7stimulus.'Blue'='DTI'overlay'on'3D'anatomy,'Red'=' fMRI'overlay'on'3D'anatomy. Future: A larger study is in the making. A bigger team consisting of both reginal, national and international collaborators is ready. The goal is to take scientific understanding from several domains into account and integrates them through a multidisciplinary and multivariate approach (including MRI), providing a more comprehensive and broader understanding of IBS and its pathophysiological mechanisms. ! Brain-Gut-Microbiota Interaction in Irritable Bowel Syndrome: A Multidimensional Approach Project manager: Trygve Hausken National collaborators: Lovisenberg Diakonale Sykehus Jørgen Valeur Regional collaborators: Arvid Lundervold, Jan G. !Hatlebakk, Odd Helge Gilja, Gülen Arslan Lied, Magdy El Salhy, Astri J. Lundervold, Synne Ystad, Harald Wiker, Dag Arne Hoff, Tarek Mazzawi, Eivind Valestrand, Kiniena F Tekie, Lionel Giriteka. 18 PCI - a Theoretically Based Index of Consciousness Assessing Human Consciousness with TMS-EEG Thomas René Bremnes, UiT, Professor Johan Frederik Storm, M.D.-Ph.D., UiO, Pål Gunnar Larsson, M.D.-Ph.D., OUS, Professor II Rune Otto Hennig, M.D., UNN, UiT Research group: Brain Signalling – Institute of Basic Medical Sciences, Faculty of Medicine, UiO One clinical challenge in the care of patients with disorders of consciousness (DOC) is the lack of methods for assessing the level of consciousness in an objective way. Nowadays, the clinical evaluation is based on the patients ability to somehow demonstrate her own subjective experience, but this can be misleading since experience shows that unresponsiveness not always equal unconsciousness. Recently, a theory-driven index of the level of consciousness called the perturbational complexity index (PCI) has been developed. It has shown good power for classifying the level of consciousness of test subjects in the lab. Our aim is to further develop this objective measure of consciousness independent of sensory processing and behavior using electroencephalography (EEG). EEG is recorded while perturbing the cortex with transcranial magnetic stimulation (TMS) during different conscious states (awake, sleep, anesthesia and brain injured patients). From a data-driven algorithm, the PCI is calculated by compressing the TMS-EEG data of the electrocortical responses to find the complexity (value between 0 – 1) of the cortical pattern. The results so far show that conscious subjects (awake) have high PCI values (~ 0,4 – 0,6), while unconscious subjects (sleep and anesthesia) have low PCI values (~ 0,1 – 0,3). PCI is in the future expected to be used in the clinical assessment of brain injured, unresponsive patients to determine the level of consciousness. 19 Skin microvascular assessemnts of periheral oxygen delivery in severe heart faiure a Vivian Shubira Amundsena,b, Lars Gullestadb,d and Knut Kverneboa,b,c Circulation laboratory, Department of Cardio-thoracic Surgery, Oslo University Hospital, Ullevaal, Norway b Medical Faculty, University of Oslo, Norway c Department of Cardiothoracic Surgery, Oslo University Hospital, Ullevål, Oslo, Norway d Department of Cardiology, Oslo University Hospital, Rikshospitalet, Oslo, Norway Introduction: All cells are dependent on delivery of nutrients and oxygen from the microcirculation, and circulatory failure can be defined as insufficient capacity for peripheral oxygen delivery. Chronic sever heart failure leads to systemic circulatory failure. Our group has developed a concept: an oxygen delivery index (ODIN) where a microscope and a spectroscope are used for 3 microvascular assessments in a tissue volume of 0.1mm . From the files information of capillary density, blood flow velocities and microvascular oxygen saturation are extracted. Aim: In this study we will examine skin nutritive microcirculation of patients with severe heart failure who are candidates for heart transplant (HTx), as compared with healthy controls. Follow up examinations will be performed post HTx. Methods: Study 1) 24 patients with terminal heart failure above 18 years are examined with skin computer assisted video microscope (CAVM) and diffuse reflectance spectroscopy (DRS), before and following HTx or established treatment with “Left ventricle assist device” (LVAD) treatment. Subjects are their own controls. 10 healthy sex and age-adjusted controls are also examined. Results: Regional ethics committee approval is obtained, and data collection start in September 2016. Implications: Published and ongoing studies of ODIN findings in acute heart failure treated with extra corporeal membrane oxygenations (ECMO) have shown that the ODIN concept is a sensitive and reliable measure of circulatory failure. The present study will clarify the sensitivity for skin application of the ODIN concept for assessing systemic circulatory failure caused by heart failure. If this study confirms the sensitivity and reproducibility of the concept, we have added a diagnostic tool that can be used for assessing of effect of treatment of drug and operative therapy for chronic heart failure. 20 Temporomandibular disorders assessed with provoked and experienced pain measurements: a case-control study § § Willassen L,* Kvinnsland S,* Helgeland E,* Staniszewski K,* Johansson A, * Berge T, * § Rosén A, * § Department of Oral and Maxillofacial Surgery , Haukeland University Hospital, Bergen; Department of Clinical Dentistry, University of Bergen*. Aims of Investigation: Temporomandibular disorders (TMD) involves moderate to severe pain in the masticatory muscles as well as an impaired mandibular function. A healthy control group was recruited for comparison with a TMD patient group that was evaluated in a TMD/TMJD project. The aim of the study was to investigate if the TMD patients differed from the controls in terms of pain detection threshold. The hypothesis was that TMD patients have a lower pain detection threshold than healthy subjects. Methods: The present study was a part of a multidisciplinary project on TMD/TMJD initiated by the Norwegian Ministry of Health. Sixty healthy controls were recruited, without TMD symptoms or other musculoskeletal symptoms in the head and neck area, matched to the cohort of patients with TMD. The mean age of the control group was forty-six years and it consisted of fifty women and ten men. The TMD group with sixty patients had a mean age of forty-five years and consisted of fifty-one women and nine men. All subjects underwent a clinical examination which included muscle palpation (pain intensity), PainMatcher and pressure algometry (in a sub group of twelve matched pairs) in order to obtain an objective measurement of the pain threshold. Furthermore, the controls answered a questionnaire that was a shortened version of the same questionnaire answered by the TMD patients. General Pain Intensity (NRS-scale) and Roland Morrison Scale (disability scale) were some of the assessment methods included in the questionnaire used to measure the subjects experienced pain. Preliminary results: Preliminary results indicate that the TMD patients have higher disability because of pain and had lower pain thresholds than the controls, with significant differences between the two groups with regards to Roland Morrison Scale (p<0.0001), General Pain Intensity (p <0.0001), pressure algometry (p<0.05-p<0.0001) and the muscle palpation (p<0.0001). The PainMatcher did not indicate a significant difference between the two groups. Conclusions:The primary results indicate that the TMD patients have higher disability because of pain and experience more intense general pain andintense pain in muscle palpation while pain magnitude matching and pain thresholds (PainMatcher) did not differed compared to healthy controls. The hypothesis that TMD patients have lower pain detection threshold was in part fulfilled. 21 Antibodies to signaling molecules and receptors relate to apoptosis and inflammation in heart failure 1 1,2 1,3 Anders Lund, Medical Student* , Lasse M. Giil, MD , Einar Kristoffersen, MD, PhD , 4 5,6 Christian Vedeler, MD, PhD , Ralf Dechend, MD, PhD , Gabriela Riemekasten, MD, 7 8 1 PhD Harald Heidecke, MScPharm, PhD , Jan Erik Nordrehaug, MD, PhD 1 2 Department of Clinical Science, University of Bergen, Bergen, Norway; Department of Internal 3 Medicine, Haraldsplass Deaconess Hospital, Bergen, Norway; Department of Immunology and 4 Transfusion Medicine, Haukeland University Hospital, Bergen, Norway; Institute of Clinical Medicine, 5 6 University of Bergen, Bergen, Norway; HELIOS-Klinikum Berlin-Buch, Berlin, Germay; Experimental and Clinical Research Center, Charité Medical Faculty and the Max-Delbruck Center for Molecular Medicine, 7 Berlin, Germany; Department of Rheumatology, University Hospital Schleswig-Holstein, Lübeck, 8 Germany; CellTrend GmbH, Luckenwalde, Berlin, Germany Background. Antibodies to signaling molecules and receptors form networks of correlated antibodies to multiple receptors, even in healthy individuals. Physiological antibodies have been linked to inflammation and apoptosis, both important pathophysiological processes in heart failure (HF). We investigated if there is a link between antibodies to a broad range of signaling molecules and receptors and biomarkers of inflammation and apoptosis. Methods. Antibodies (ab) in pre-analytically randomized sera from patients (n=202) with ischemic cardiomyopathy (ICM) (n = 166) and non-ICM (n = 36) were measured with full-receptor sandwich enzyme-linked immunosorbent assays. Non-parametric statistics were used for analysis of association, reported as effect size (r) and corrected for multiple testing. Troponin-T (TNT) elevation not due to ischemia was used as a marker for myocardial apoptosis. C reactive protein (CRP), leukocyte count, kynurenine-tryptophan ratio, (KTR, a marker of interferon-g activity), fibrinogen (coagulation and inflammation) and neopterin (a marker of activated monocytes) were measured as immunemarkers. Results. TNT correlated with Stabilin1-ab (r 0.29, p < 0.001). CRP correlated with soluble endoglin-ab (sENG-ab, r 0.20, p = 0.01), fibrinogen with sENG-ab (r 0.28, p < 0.001), neopterin with platelet-derived growth factor β-ab (r 0.27, p < 0.001). There were both positive (dopamin D2s receptor, r 0.26, p < 0.001) and negative (soluble pro-renin receptor, r -0.32, p < 0,001) correlations with KTR. Conclusion. Antibodies to vascular and immune-related receptors were correlated with apoptosis and innate immune activation in patients with predominantly ICM. These processes, linked to physiological antibodies, are also important mediators of disease progression in HF. Both endoglin and the pro-renin receptors are linked to myocardial fibrosis. Depending on which effects these antibodies have on their receptor-antigens, they could provide new links to key pathophysiological processes in HF. *corresponding author 22 Coronary artery wall shear stress and the impact on coronary atherosclerosis and response to aerobic exercise Stud.med Maria Dalen Taraldsen, Faculty of Medicine, NTNU Supervisor: Erik Madssen, MD, PhD, Department of Cardiology, St.Olavs Hospital Assistant supervisor: Rune Wiseth, MD, PhD, Department of Circulation and Medical Imaging, NTNU and Department of Cardiology, St.Olavs Hospital Background: Coronary atherosclerosis is a leading cause of morbidity and mortality. Treatment of coronary artery disease (CAD) includes either percutaneous coronary intervention with stent implantation or coronary artery bypass surgery, as well as drug therapy. Several studies have demonstrated beneficial effects of physical exercise on the vasculature and heart function in patients with CAD, but the mechanisms behind these positive effects are not known in detail. Although the entire circulatory system is exposed to cardiovascular risk factors that leads to inflammation, oxidative stress, and endothelial dysfunction, it is recognized that changes in coronary flow and wall shear stress (WSS) play an important role for the development of the focal distribution of coronary plaques. Aims: The primary aim of this study is to correlate WSS with the degree and extent of coronary atherosclerosis measured with intravascular ultrasound (IVUS) in patients with CAD. Our hypothesis is that WSS is an important factor for the distribution and composition of coronary plaques. The secondary aim is to correlate WSS and IVUS findings after patients have undergone an aerobic exercise intervention. Our hypothesis is that coronary segments with the lowest WSS at baseline have the biggest potential for beneficial changes after exercise, compared with coronary segments with high WSS at baseline. This study may increase our knowledge of the dynamics of plaque development in coronary arteries. Methods: This project is based on a single-center, open, parallel, randomized controlled trial that was performed between 2011 and 2013. Thirty-six patients with significant CAD on optimal medical treatment underwent 12 weeks of aerobic exercise after stent implantation. Coronary angiography and grayscale and radiofrequency IVUS was performed at baseline and follow- up. Calculation of WSS will be performed by computational fluid dynamics modelling based on a 3D model of the index coronary vessel, before correlating WSS to IVUS data. 23 Temporomandibular disorders with a psychosocial approach: Preliminary data from a clinical case-control study § § § Staniszewski K,* Kvinnsland S,* Helgeland E,* Willassen L,* Berge T, * Johansson A, * ¤ ¤ ¤ # !& § Schjødt B, Bell RF, Paulsberg AG, Geitung JT, Aandal G, * Lygre H,* Rosén A, * ¤ Department of Oral and Maxillofacial Surgery, Centre for Pain Management and Palliative Care , Haukeland University Hospital, Bergen; *Department of Clinical Dentistry, University of Bergen*; & Department of Radiology, Haraldsplass Deaconess University Hospital , Bergen; Department of # ! Radiology, Akershus University Hospital and University of Oslo , Oslo, Norway; Department of Clinical Science Introduction: Temporomandibular disorders (TMD) may cause severe pain, jaw dysfunction, social withdrawal, and a reduced quality of life. Psychosocial factors as somatic awareness, psychosocial stress and catastrophizing, additionally to pain amplification, has been associated with TMD. Aims of study: To detect risk factors that can be associated with the onset and maintenance of severe TMD. Specific aims were to investigate TMD patients stress- and catastrophizing scores, social factors, and cortisol levels as well as cortisol/cortisone ratio in saliva, with the purpose of examining HPA-axis function. Material and Methods: This is a study which is part of a multidisciplinary investigation of TMD patients at Haukeland University Hospital. Our study population consists of 60 TMD patients (51 women and 9 men), and 60 healthy individuals gender- and age-matched in a control group. Fill-in questionnaires included the Hospital Anxiety and Depression scale (HADS) schemes, two-item version of the Coping Strategies Questionnaire schemes regarding catastrophizing, and several other questionnaires regarding social, economic and health related factors. Saliva-samples were taken by Salivette Cortisol Code Blue (Sarstedt) for tandem mass spectrometry (LC-MSMS) analysis of cortisol as a stress marker. A clinical examination of jaw function, muscle pain and tenderness, and dental status was performed. Blood sampling and MR imaging of the TMJ was taken. Results: Preliminary results show that TMD patients compared to healthy individuals have a significantly higher anxiety- and depression- scores (HADS) (p<0.0001), and catastrophizing scores (p<0.0001). The frequency of selfconsidered poor economy as well as pain related sleeping disorders are also remarkably higher in the TMD group. Conclusion: Preliminary results indicate that patients with severe TMD can be associated with significant higher levels of stress, including anxiety, depression and catastrophizing. The TMD patients also seems to have a higher frequency of pain related sleeping disorders, as well as an undesirable self-consideration of their own social and economic status compared with healthy individuals. 24 From insulin injections to sulfonylurea tablets in a child with neonatal diabetes 1 1,2 Authors: Åsta Nordsveen Sulen , Pål R. Njølstad Supervisor: Pål R. Njølstad, Professor MD, PhD 1 Department of Clinical Science, University of Bergen, Bergen, Norway 2 Department of Paediatrics, Haukeland University Hospital, Bergen, Norway Introduction: Children with diabetes are dependent on life-long insulin injections to control their disease. About 1-3% of all diabetes cases are monogenic, i.e. resulting from mutations in one single gene. Neonatal diabetes mellitus is a monogenic form of diabetes that occurs in the first 6 months of life. This form of diabetes can be treated with sulfonylurea (SU) instead of insulin because SU works directly on the ATP-sensitive potassium (K-ATP) channels where the mutated protein is found. Aims: To perform a treatment trial switching from insulin to oral SU treatment in a 6 year old girl with a mutation in the SUR1 subunit of the K-ATP channel. Methods: Before the trial started we did an oral glucose tolerance test, a meal challenge and an intravenous glucose tolerance test. For the treatment protocol, we gradually lowered the insulin dose and raised the SU dose, and after 10 days the girl was treated with SU alone. The patient was followed up for one year with oral glucose tolerance tests and intravenous glucose tolerance tests every third month to monitor changes in beta cell function. Results: The patient was successfully converted from insulin injections to SU tablets. During the trial, the HbA1c dropped from 6.4% to 5.3%. The beta cell function increased every third month up to 9 months, and after 9 months it was stabilized. Conclusion: Genetic testing is advised on children that debut with diabetes before 6 months of age. If their diabetes is caused by mutations in the K-ATP channel, treatment can be successfully changed from insulin injections to sulfonylurea tablets, with a concomitant increase in metabolic control and quality of life. This study is a great example of personalized medicine, not everyone with diabetes needs insulin injections to survive. 25 Troponin T course before and after coronary artery bypass grafting 1 2,3 2,4 2,4 2,5 2,3 E. Koppen , E. Madssen , R. Stenseth , G. Greiff , H. Pleym , R. Wiseth , A. 2,6 1,7 Wahba and V. Videm Corresponding author e-mail: [email protected] 1 Department of Laboratory Medicine, Children’s and Women’s Health, NTNU, 2 Department of Circulation and Medical Imaging, NTNU, 3 Department of Cardiology, St. Olavs Hospital, 4 Department of Cardiothoracic Anaesthesia and Intensive Care, St. Olavs Hospital, 5 Clinic of Anaesthesia and Intensive Care, St. Olavs Hospital, 6 Clinic of Cardiothoracic Surgery, St. Olavs Hospital, 7 Department of Immunology and Transfusion Medicine, St. Olavs Hospital, Introduction: Troponin T (cTnT) is a biomarker used to diagnose of myocardial infarction. After open heart surgery, the values are difficult to interpret because of tissue damage. We hypothesized that increased knowledge about factors affecting postoperative concentrations will contribute to more accurate diagnostics of myocardial infarction after open heart surgery. The aim of the study was to investigate associations between perioperative cTnT concentrations and important clinical and operative variables. Methods: 645 patients who underwent isolated coronary artery bypass grafting (CABG) between April 2008 and April 2010 were included in the study. Perioperative variables were prospectively registered in a database. The degree of diffuse coronary atherosclerosis and number of significant stenoses were assessed by preoperative coronary angiography and scored as an “atherosteno score”. Mixed model analysis was used to construct a statistical model to explain the course of troponin T concentrations. The model was adjusted for intra- and postoperative myocardial infarction. Results: The cTnT course was associated with complex interactions between C-reactive protein, “atherosteno score” and intraoperative transfusion of red blood cells. Factors associated with increased cTnT concentrations after surgery were longer times on cardiopulmonary bypass (p<0.01) and high preoperative creatinine concentrations (p<0.001). A large body surface area (p<0.001) and intraoperative treatment with inotropic drugs (p<0.05) were variables associated with lower cTnT concentrations. Conclusion: A possible interpretation of the results is that increased inflammation (longer operation times with larger tissue damage) gives increased release of cTnT, independent of myocardial infarction. It is known that the elimination of cTnT depends on the kidney function. Intraoperative transfusion of red blood cells may have a dilution effect and may also protect against tissue damage. The tissue damage may be larger than the cTnT concentration suggests in larger patients who have received an intraoperative transfusion of red blood cells. 26 Exploring the feasibility and acceptability of introducing symphysiotomy in emergency obstetric care in Ethiopia: A formative qualitative WHO associated study. Ragnhild Sørbøen Halvåg, Karen Marie Moland, Astrid Blystad, Torvid Kiserud, Mulu Muleta. Associated with the research group: Global Health Anthropology. Background: Eight percent of all maternal deaths in Ethiopia is caused by obstructed labor, which can also cause obstetric fistula that is associated with a stillbirth rate of 92%. Obstructed labor is when the fetus cannot progress into the birth canal because of disproportion between the fetal head and the size of the pelvic ring. Cesarean section (CS) is the standard procedure for obstructed labor. However, this procedure is not widely accessible in low-income settings, where potential harms also are more likely to occur. Symphysiotomy may imply an alternative to improve the outcome for mother and child in low-income settings. Objective: This formative study explores the feasibility and acceptability of introducing symphysiotomy in order to evaluate whether a RCT (randomized test control trial) can be initiated in Ethiopia. Method: This is a formative qualitative study. Data collection took place from February to May 2015 in Gondar University Hospital and in rural communities in North Gondar zone. 50 in-depth-interviews were conducted from informants with different backgrounds: health care providers in maternity wards in the hospital, health care providers in rural communities and rural and urban women who had given birth. Systematic text condensation was applied in the analysis. Results: Symphysiotomy appears to be an unknown practice in and around Gondar University Hospital. No health worker has practical experience of the procedure, while knowledge of the procedure varies significantly. When describing knowledge and perceptions of symphysiotomy there is a discrepancy trend between the informant groups in the study. Principally the hospital health workers perceive CS as the golden standard in emergency obstetric care, whereas symphysiotomy is described as an outdated and complicated procedure. Amongst the rural health workers and mothers symphysiotomy is considered easy, lifesaving and preferable to CS when planning more children. Conclusion: This formative study found that lack of knowledge and a general skepticism towards symphysiotomy makes initiation of a RCT in Gondar University Hospital little feasible. 27 Probiotic intervention in HIV decreases gut microbial genes related to biosynthesis of lipopolysaccharide 3,8,11 , Birgitte Stiksrud , Kristian Holm , Piotr Nowak , Dag Kvale , 4 4 7 6 Felix C Nwosu , Anders Thalme , Anders Sonnerborg , Stein-Erik Birkeland , Knut Rudi , Anne-Ma 1,2,5 2,3,5,8,9 1,5,8,10 Dyrhol-Riise , Johannes R Hov* , Marius Trøseid* Christopher Storm-Larsen 1, 2 3 4 1,2,5 6 Introduction: Microbial translocation and chronic inflammation may contribute to non-AIDS morbidity in patients with HIV. Several strategies have been applied to reduce microbial translocation, however none of them have been showed to be successful. In a recent paper our group reported reduced levels of inflammatory markers d-dimer and CRP after probiotic intervention in HIV-Infected individuals on stable anti-retroviral treatment, but no change in levels of serum markers of microbial translocation. In this study we aimed to expand the analyses of microbial translocation by investigating gut microbial functions. Methods: Data from the subgroup of patients with 16S rRNA based gut microbiota profiles available were included (n=10 in the probiotics and n=12 in the combined control/placebo group). The PiCRUST software was used to predict the functional genetic composition of the microbiota and an in-house method to distinguish between bacteria producing hexa- and penta-acylated LPS, which have different pro-inflammatory potential. Results: In patients receiving probiotics, there was a significant reduction in both KEGG-categories related to LPS biosynthesis (-23%, P = 0,05 and –18%, P = 0,03). The decrease correlated positively with s-LPS (r = 0.68, P = 0,03 and r = 0.73, P = 0,02) and sCD14 (r = 0.63, P = 0.05 and r = 0.65 and P = 0.04). The relative abundance of gram-negative bacteria decreased from 0.39 to 0.19 (p = 0.05) and bacteria producing penta-acylated LPS reduced from 0.38 to 0.18 (p = 0.05). No significant change where seen in hexa-acylated bacteria. At baseline, increased ratio of Hexa-/penta-acylated LPS was associated with increased levels of Kyn/Trp-ratio and Neopterin. Conclusions: Functional profiling of the metagenome showed a decrease in genes related to LPS biosynthesis, which correlated with a reduction in circulating markers. However, the reduction was primarily related to the non-inflammatory penta-acylated LPS, suggesting that other mechanisms than LPS are responsible for the inflammatory activity. 1 Department of Infectious Diseases, Oslo University Hospital, Oslo, Norway; 2 Department of Infectious Diseases, Institute of Clinical Medicine,University of Oslo, Oslo, Norway; 3 Norwegian PSC Research Center, Department of Transplantation Medicine, Oslo University Hospital 4 Department of Infectious Diseases, Karolinska University Hospital, Stockholm, Sweden; 5 K.G. Jebsen Center for Inflammation Research, Institute of Clinical Medicine, University of Oslo 6 Department of Chemistry, Biotechnology and Food Science, Norwegian University of Life Sciences; 7 TINE SA, TINE R&D, Oslo, Norway 8 Research Institute of Internal Medicine, Division of Cancer Medicine, Surgery and Transplantation, Oslo University Hospital 9 Section of Gastroenterology, Department of Transplantation Medicine, Oslo University Hospital 10 Section of Clinical Immunology and Infectious Diseases, Oslo University Hospital, Oslo, Norway. 11 Institute of Clinical Medicine, University of Oslo, Oslo, Norway 28 Interobserver variation of the bolus-and-burst method for pancreatic perfusion with dynamic contrast-enhanced ultrasound 1 1, 2 3 4 Marcus Stangeland , Trond Engjom , Martin Mezl , Radovan Jirik , Odd Helge Gilja 2, 1 1, 2 2 , Georg Dimcevski , Kim Nylund 1) Department of Clinical Medicine, University of Bergen, Norway 2) National Centre of Ultrasound in Gastroenterology, Department of Medicine, Haukeland University Hospital, Bergen 3) Dept. of Biomedical Engineering, Brno Univ. of Technology, Brno, Czech Rep. 4) Institute of Scientific Instruments, AS CR, Brno, Czech Rep. Introduction/background: Dynamic contrast-enhanced ultrasound (DCE-US) can be used for calculating organ perfusion. By combining bolus injection with burst replenishment the arterial input function can be estimated and thus the actual mean transit time (MTT). Blood volume (BV) can be obtained by scaling the data to a vessel in the imaging plane. Objectives/aims: The study aim was to test interobserver agreement for repeated recordings using the same ultrasound scanner and agreement between results on two different scanner systems. Methods: Ten patients under evaluation for exocrine pancreatic failure were included. Each patient was scanned two times on a GE Logiq E9 scanner, by two different observers, and once on a Philips IU22 scanner, after a bolus of 1.5 ml Sonovue. A 60 second recording of contrast enhancement was performed before the burst and the scan continued for another 30 seconds for reperfusion. Data-analysis was performed using MATLAB-based DCE-US software (http://www.isibrno.cz/perfusion/). An artery in the same depth as the region of interest (ROI) was used for scaling. The measurements were compared using the intraclass correlation coefficient (ICC) and Bland Altman plots. Results: There was excellent interobserver agreement on the Logiq E9 for MTT (ICC=0.83, confidence interval (CI) 0.46-0.96). Between the Logiq E9- and the IU22 there was poor agreement for MTT (ICC=-0.084, CI -0.68-0.58). The overall agreement for blood volume measurements was excellent (ICC=0.86, CI 0.50-0.98). Conclusion: Interobserver agreement was excellent using the same scanner for both parameters and between scanners for BV, but the comparison between two scanners did not yield acceptable agreement for MTT. This was probably due to incomplete bursting of bubbles in some of the recordings on the IU22. 29 Mortality, physical performance & quality of life of patients treated within the standardized patient care Fast-track hip fractures – a prospective cohort study Runde, Henrik Alexander; Johnsen, Lars G.; Basso, Trude; Foss, Olav. Introduction/background: Elderly patients with hip fractures are especially vulnerable as a patient group. From the total 9-10.000 of Norwegians that break their hip per year, one out of four will die within one year. Less than half recover to the level of function they had before the fracture and therefore many loose their ability to live an independent life. Hip fracture is one of the most expensive diagnoses for the Norwegian health care and one hip fracture alone costs half a million NOK only the first year. One of the main targets for “Fast-track hip fractures” is to reduce the time before operation, which is shown to have a connection with postoperative morbidity and mortality. The introduction of “Fast-track hip fractures” at St. Olavs hospital in 2011 gave a reduction in the length of a hospital stay from 11 to 8 days. A new Swedish register study with data from 116.000 patients found that for each day shorter hospital stay than the threshold value of 10 days, the risk of dying within 30 days increased by 16 %. To improve the outcome after a hip fracture it is necessary to constantly evaluate and improve the process chain and further produce new knowledge about factors that can affect patients’ morbidity after the fracture. Objectives/aims: The study will follow a group of 120 patients with hip fractures treated at the Department of Orthopaedic Surgery, St. Olavs hospital from admission to one year after the fracture. The purpose is to evaluate how the effective Fast-track process affects mortality and further identify factors that may be of importance for physical performance and independence in the patient group. Methods: The study is organized within the frame of two tasks. In the first task we will evaluate the effect of the days of hospitalization on early mortality for patients treated within the Fast-track patient care. In the second task we will evaluate how change in the hip’s biomechanics affects physical performance and independence after a hip fracture with Short Physical Performance Battery scores and life quality with EuroQol EQ-5D-5L. We will do the latter by studying X-rays of the hip and examining the gait pattern in a laboratory at a one-year control. 30 Complications and discomfort of bronchoscopy; a systematic review. 1 1 1 Elise Orvedal Leiten , Einar Marius Hjellestad Martinsen , Per Sigvald Bakke , Tomas 1,2 2 Mikal Lind Eagan , and Rune Grønseth 1 Department of Clinical Science, University of Bergen, Norway 2 Department of Thoracic Medicine, Haukeland University Hospital, N-5021 Bergen, Norway Background: Bronchoscopy is a cornerstone of respiratory medicine. We depend on diagnostic bronchoscopy in the diagnosis of several conditions of the lung, and the procedure is considered as safe. However, no current systematic review on the safety aspects of bronchoscopy exists. Objective: To identify complications and discomfort, meaningful complication rates, and predictors related to diagnostic bronchoscopy. Method: We conducted a systematic literature search in PubMed on February th 8 2016, using a search strategy including the PICO model, on complications and discomfort related to bronchoscopy and related sampling techniques. Results: The search yielded 1707 hits, of which 45 publications were eligible for full review. Rates of mortality and severe complications were low. Other complications, for instance hypoxaemia, bleeding, pneumothorax and fever, were usually not related to patient characteristics or aspects of the procedure, and complication rates showed considerate ranges. Measures of patient discomfort differed considerably, and results were difficult to compare between different study populations. Conclusion: More research on safety aspects of bronchoscopy is needed to conclude on complication rates and patient and procedure-related predictors of complication and discomfort. 31 Abstracts in basal research and genetics Solvin, Åshild Øksnevad NTNU [email protected] Willems, Aron UiB [email protected] Schanche, Torstein UiT [email protected] Johansen, Silje Susanne Pettersen UiT [email protected] Schanche, Torstein UiT [email protected] Myklebust Ernø, Inger Thea UiO [email protected] Radunovic, Matej UiB [email protected] Krogh Aarebrot, Anders UiB [email protected] Bakken, Rasmus UiB [email protected] Hoel, Fredrik UiB [email protected] Hjøllo, Torunn UiB [email protected] Kristiansen, Elise UiO [email protected] Korkosh, Mohammed Bayar UiO [email protected] Klæstad, Elise NTNU [email protected] 32 Establishing a biobank for gene expression studies of psoriasis 1 1 1,2 1,2 Åshild Øksnevad Solvin , Ellen Heilmann Modalsli , Ingrid Snekvik , Maiken Elvestad 1 1 2,3 1 1,2 Gabrielsen , Oddgeir Lingaas Holmen , Marit Saunes , Kristian Hveem , Mari Løset 2 Department of Public Health and General Practice, DMF, NTNU; Department of Dermatology, St. 3 Olavs Hospital, Trondheim; Department of Cancer Research and Molecular Medicine, DMF, NTNU Introduction: Psoriasis is a chronic inflammatory disease of the skin that results from an interplay between multiple genetic and environmental factors. Several genes have been identified to affect the disease, however, much of the genetic contribution to psoriasis remains to be explained. Global gene expression studies are proven as powerful strategies for identification of disease-related genes and pathways, and studies of psoriatic skin have contributed to an increased understanding of psoriasis pathology. However, the sample sizes are often limited (<18 samples) and no large transcriptional studies have been performed on Norwegian samples. Objectives: Our overall goal is to carefully collect and store skin biopsies and blood samples from 50 psoriatic cases and 50 non-psoriatic controls and perform investigations on gene expression through RT-PCR and/or RNA sequencing of 150 skin biopsies (50 cases, both affected and unaffected skin, and 50 controls). Further, we will investigate protein levels and cellular localization of the most central differentially expressed transcripts identified by western blot and immunohistochemistry. Materials and Methods: All participants will be asked to fill out a questionnaire concerning their health status, and anthropometric traits will be recorded. We will have skin biopsies taken from the psoriatic cases and from the nonpsoriatic controls for RNA- and protein studies. All biopsies will be snap frozen in liquid nitrogen and stored in -80°C. The biopsies for immunohistochemistry will be placed in a container with formalin and further prepared for analysis. A blood sample will be taken from all participants, opening for additional analysis in future studies. Results/Conclusion: We have obtained preliminary RNA extraction data on four skin biopsies that show high-quality RNA, and similar RNA extraction procedures will be followed in the study. We have studied slide sections from four participants, which show that the morphology of the skin is well preserved, and this makes a good starting point for future immunohistochemical analysis. We hope that our psoriasis biobank will give us the opportunity to gain new insight in the genetic basis of psoriasis, which further have the potential to identify new drug targets for treatment and prevention. 33 SLC7A10 - A Novel Transcription Factor in the Understanding of Obesity-Related Pathogenesis 1,2 ,2,3 1,2,3 1,2 Willems A , Fernø J1 , Sagen JV , Mellgren G 2 Department of Clinical Science, University of Bergen; Hormone Laboratory, Haukeland 3 University Hospital, Bergen; and KG Jebsen Center for Diabetes Research, University of Bergen 1 Background: Obesity (BMI > 30) is increasing worldwide. Although related to a number of diseases, it remains unclear why the individual risk of developing disease varies so greatly. Genetic variation is believed to be important in understanding the relationship between obesity and obesityrelated diseases. Waist-to-hip ratio (WHR) has been used as an indicator of health, and the risk of developing disease. This is also reflected by the stronger correlation between visceral fat and development of obesityrelated diseases. The candidate gene SLC7A10 has been selected from micro-array studies of adipose tissue taken from patients who have undergone bariatric surgery. SLC7A10 strongly correlates with WHR. The gene is also correlated with metabolic parameters, such as triglyceride/HDL-serum levels and parameters of mitochondrial function. It has been selected due to high adipocyte-specific expression, and little known role in adipocyte function. Aims and Objectives: The aim for the project is to examine the effects of SLC7A10 in adipocyte function (both in cultured murine adipocytes and in primary adipocytes from humans). SLC7A10 will be silenced using siRNA, and subsequent down-stream effects on genetic expression, differentiation and adipocyte function will be measured. The ultimate goal is to uncover and characterize SLC7A10s role in obesity and development of obesityrelated diseases. Materials and Methods: Human preadipocytes isolated from liposuction material, in addition to cultured murine adipocytes (3T3-L1), is the primary material. This will be used as in vitro cell models for investigation of the function of SLC7A10. siRNA/shRNA – small interfering – and small hairpin RNA will be used to knock down the gene. qCR (quantative polymerase chans reaction) will be used for validation of changes in genetic up- or downregulation. Changes in global genetic expression will be measured using micro array studies of silenced primary human adipocytes 34 Platelet function during hypothermia and rewarming in an intact pig model 1 1 1 1 Torstein Schanche , Timofei Kondratiev , Magnus Torstensson , Hans Husum , Bjarne 2,3 1,4 Østerud , Torkjel Tveita 1. Anesthesia and Critical Care Research Group, Department of Clinical Medicine, UiT, The Arctic University of Norway, Tromsø, Norway 2. Molecular Inflammation Research Group, Department of Medical Biology, UiT, The Arctic University of Norway, Tromsø, Norway 3. K. G. Jebsen TREC – Thrombosis Research and Expertise Center, Department of Clinical Medicine, UiT, The Arctic University of Norway, Tromsø, Norway 4. Division of Surgical Medicine and Intensive Care, University Hospital of North Norway, Tromsø, Norway Introduction: Due to functional alteration of blood platelets and coagulation enzymes at low temperatures, excess bleeding is a wellrecognized complication in victims of accidental hypothermia. Thus, bleeding in the hypothermic multi-trauma patient is a great clinical challenge. The aim of this study was to investigate platelet function after rewarming from hypothermia using an experimental intact porcine model. Methods: The animals were randomized to cooling and rewarming (n=9), or to serve as normothermic, time-matched controls (n=3). Animals in the hypothermic group were immersion cooled in ice water to 25°C, maintained at 25°C for one hour, and rewarmed to 38°C (normal Tp in pigs) using warm (40°C) water. Platelet function was assessed indirectly at different temperatures during cooling and rewarming using a whole blood coagulometer (ReoRox®4, Medirox AB, Nyköping, Sweden), which measures clotting time of blood without adding anticoagulant at 38°C. Results: After rewarming from hypothermia, clotting time was significantly shortened compared to pre-hypothermic control values. Also, platelet count was significantly increased. Conclusion: A reduction in clotting time after rewarming from hypothermia was observed. This may indicate that rewarming from severe hypothermia induces a hypercoagulable state, in which thrombus formation is more likely to occur. The contribution of platelet activation to the observed decrease in clotting time is a subject for future studies. 35 Mesenchymal stromal cells from human umbilical cords display poor chondrogenic potential in scaffold-free three dimensional cultures A. Islam, A.K. Hansen, C. Mennan and I. Martinez-Zubiaurre Background: The question of whether or not stromal cells harvested from foetal tissue is suitable for allogenic cell transplantation therapies or tissue engineering. Objective: In this study, we have investigated the chondrogenic potential of mesenchymal stromal cells (MSCs) isolated from whole sections of human umbilical cord or mixed cord (UCSCs-MC), and compared them with cells isolated from synovial membrane (SMSCs), Hoffa’s fat pad (HFPSCs) and cartilage. All MSCs were positive for surface markers including CD73, CD90, CD105, CD44, CD146 and CD166, but negative for CD11b, CD19, CD34, CD45 and HLA-DR in addition to CD106 and CD271. Method: Chondrogenic potential of all cell sources was studied using 3D pellet cultures incubated in the presence of different combinations of anabolic substances such as dexamethasone, IGF-1, TGF-β1, TGF-β3, BMP-2 and BMP7. Results: BMP-2 and dexamethasone in combination with TGF-β1 or TGF-β3 excelled at inducing chondrogenesis on SMSCs, HFPSCs and chondrocytes, as measured by glycosaminoglycans and collagen type II staining of pellets, quantitative glycosaminoglycan expression, quantitative PCR of cartilage signature genes and electron microscopy. In contrast, none of the tested growth factor combinations was sufficient to induce chondrogenesis on UCSCs-MC. Moreover, incubation of UCSCs-MC spheroids in the presence of cartilage pieces or synovial cells in co-cultures did not aid chondrogenic induction. Conclusion: We show that in comparison with MSCs harvested from adult joint tissues, UCSCs-MC display poor chondrogenic abilities. This observation should alert researchers at the time of considering UCSCs-MC as cartilage forming cells in tissue engineering or repair strategies. 36 Colloid prime increases blood volume and improves organ blood flow in extracorporeal rewarming from deep hypothermic circulatory arrest in rats 1 1. 1 Torstein Schanche , Timofei Kondratiev , Torkjel Tveita 1,2 Anesthesia and Critical Care Research Group, Department of Clinical Medicine, UiT, The Arctic University of Norway, Tromsø, Norway 2. Division of Surgical Medicine and Intensive Care, University Hospital of North Norway, Tromsø, Norway Introduction: Severe accidental hypothermia (core temperature ≤ 28°C) is frequently accompanied by cardiac instability. Although recommended treatment include rewarming by extracorporeal circulation (ECC), scientific data on how to manage hypothermic patients on ECC is limited. Hypothermia, along with initiation of ECC introduces major changes to fluid homeostasis and blood flow. No current guidelines exists concerning choice of priming fluid for the extracorporeal circuit. This study aimed to investigate effects of two different fluid protocols on fluid balance, regional blood flow and hemodynamics during rewarming from severe hypothermia with cardiac arrest. Methods: A rat model of conduction cooling and extracorporeal rewarming was used. All rats were cooled to hypothermic cardiac arrest, and rewarmed by ECC. During cooling, rats were randomized to two groups: (1) extracorporeal circuit was primed with saline, or (2) hydroxyethyl starch (HES). Plasma volume (PV), organ blood flow (OBF), tissue water content and blood gases was measured. Circulating blood volume (CBV) and tissue oxygenation was calculated, whereas hemodynamics were continuously recorded during experiments. Results: During and after rewarming, pump flow rate, mean arterial pressure, pulse pressure, PV and CBV was significantly higher in HES treated compared to saline treated rats. After rewarming, the HES group had significantly increased OBF to brain, cerebellum and both kidneys compared to the saline group. Tissue water content in HES treated rats was significantly lower in both kidneys, skeletal muscle and lung. Conclusion: Compared to a crystalloid priming solution, the use of an isooncotic colloid prime significantly increases PV and CBV, as well as OBF to vital organs during and after rewarming. Animals receiving HES also demonstrated a more favorable fluid balance and improved hemodynamics compared to saline priming 37 Transportation of cultured oral mucosal epithelial sheets for worldwide treatment of limbal stem cell deficiency 1 1 1 Inger Thea Myklebust Ernø , Mohammed Bayar Korkosh , Ngoc Ky Cuong Khuu , Linda 1 2 1,3 1 Hildegard Bergersen , Zina Kristiansen , Tor Paaske Utheim and Amer Sehic 1 Department of Oral Biology, Faculty of Dentistry, University of Oslo, Norway 2 Homansbyen Dental Office, Oscars gate 20, 0353 Oslo, Norway 3 Department of Medical Biochemistry, Oslo University Hospital, Norway The cornea is critical for normal vision by allowing light transmission to the retina. The corneal epithelium is renewed by limbal epithelial cells (LEC), which are located in the periphery of the cornea, the limbus. Damage or disease involving LEC may lead to various clinical presentations of limbal stem cell deficiency (LSCD). Both severe pain and blindness may result. Transplantation of cultured oral mucosal epithelial cells (OMEC) represents the first use of a cultured non-limbal autologous cell types to treat this disease. Most of the patients suffering from this eye disease live in developing countries such as India where about 1.5 million people are affected. The necessary expertise however, is mainly found in the industrialized countries, including Norway. Furthermore, the optimal culture method and substrate for OMEC is not established. The importance of establishing good culture methods and methods for transportation has been highlighted following the recent European Medicine Agency`s (EMA) recommendation of approving LEC therapy in Europe. This decision is a major step for regenerative medicine in Europe and limbal regenerative therapy in particular as it represents the first recommendation by EMA for any stem cell therapy in Europe. The decision also reflects that corneal regenerative medicine is in the forefront of regenerative medicine. Despite numerous reports on the various aspects of storage of cultured OMEC, there are hitherto no full reports on the feasibility of transportation of cultured OMEC. Thus, this study aims to bridge the current gap of knowledge between culture, storage, and transplantation of OMEC, by investigating different culture additives and by simulating transportation of cultured OMEC in sealed storage containers. Research group PhD Ngoc Ky Cuong Khuu, PhD Catherine Jackson, Professor, MD PhD Tor Paaske Utheim, Professor, PhD Julie Daniels, DDS Zina Kristiansen, Professor, PhD May Griffith, Professor, PhD Darlene A. Dartt, Professor, PhD Majlinda Lako, Student Inger Thea Myklebust, Student Mohammed Bayar Korkosh, Associate Professor, PhD Amer Sehic 38 Identifying genetic variation in two potential vaccine candidates against Giardia Lamblia Radunovic M, Saghaug C, Langeland N, Hanevik K Klinisk institutt 2, University of Bergen Background: Giardia lamblia is the most commonly identified intestinal parasite in the world. It causes giardiasis, a disease characterized by nausea, vomiting, watery diarrhea and epigastric pain. Commonly found in day-care centers, the parasite is now more prevalent due to increased traveling to endemic areas. There is no known human vaccine against this parasite to date. Recently there have been studies showing that Giardia proteins Alpha-1 Giardin and Cyst Wall Protein 2 can act as potentially protective vaccine candidates in mice. However, these studies have not taken into account the genomic variation of Giardia. There are eight (A-H) different genotypes, or assemblages, of Giardia and several assemblages are further divided into subgroups. Assemblages A and B are known to infect humans. Genomic differences between assemblages are well known and locating potential antigens with conserved sequences across assemblages will help to pinpoint good vaccine candidates. Aim of the study: We wish to identify the genomic variation of two antigenic proteins, Alpha-1 Giardin (α-1-g) and Cyst Wall Protein-2 (CWP2) in Giardia isolates from infected humans. Methods: We have gathered stool samples from Giardia-infected patients in Norway. The samples have been processed with sucrose flotation in order to isolate Giardia cysts. Cyst isolates were then typed in to assemblage A or B. By using PCR, and custom made primers for α-1g and CWP2 sequences, we will amplify these genes and sequence them. A sequence alignment software (Geneious) will then be used to align the genes and locate single nucleotide polymorphisms (SNPs) between isolates and also reference sequences. Investigation of these SNPs will be done and divided into synonymous or non-synonymous SNPs. This will provide insight into the degree of sequence and amino acid variability between assemblages, and thereby the suitability of these proteins as antigens. We have so far managed to successfully amplify and sequence α-1-g in 12 out of 20 isolates. Further sequencing is ongoing and we will present data from α-1g and CWP2 at the conference. 39 Phospho-specific flow cytometry for analysis of TNF signaling 1 1,2 1 1 Anders Krogh Aarebrot , Silje Michelsen Solberg , Richard Davies , Marianne Eidsheim , 1 3 3 1,4 1 Kjerstin Jakobsen , Lucius Bader , Sonia Gavasso , Yenan Bryceson , Tim D. Holmes , Lene 2,5 1,3 1 Frøyen Sandvik , Roland Jonsson , Silke Appel 1 Broegelmann Research Laboratory, Department of Clinical Science, University of Bergen, Norway 2 Department of Dermatology, Haukeland University Hospital, Bergen, Norway 3 Department of Rheumatology, Haukeland University Hospital, Bergen, Norway 4 Centre for Hematology and Regenerative Medicine, Department of Medicine, Karolinska Institutet, Karolinska University Hospital Huddinge, Stockholm, Sweden 5 Department of Clinical Medicine, University of Bergen, Norway Background: Flow cytometry is a laser-based technology used to analyze characteristics of cells and particles on a single cell basis. It is a widely used method for analyzing the expression of cell surface proteins, by measuring fluorescence intensity produced by fluorescent-labeled antibodies. By staining the phosphorylated state of intracellular proteins, we can use the fluorescence intensity to measure their activation. Thus, flow cytometry can be used to measure the activation of intracellular signaling cascades. Aims: Develop a robust assay for measuring phosphorylated proteins mediated by tumor necrosis factor (TNF), in T-cells, B-cells, monocytes and NK-cells. Methods: We isolated and cryopreserved peripheral blood mononuclear cells (PBMCs) from 25 psoriasis patients and 19 healthy controls. The cells were stimulated with TNF, fixed with 1,5% PFA and permeabilized with 100% methanol. After permeabilization we added fluorochrome-coupled antibodies specific for surface antigens (CD3, CD20 and CD56) and phosphorylated NF-kB (pNF-kB), before analyzing the median fluorescence intensity (MFI) of pNF-kB in the different cell populations using flow cytometry. Results:TNF stimulation increased MFI of pNF-kB in T-cells, monocytes and NKcells. This reflects the increased level of phosphorylated NF-kB in cells stimulated with TNF. Thus, phosphoflow can be used to measure relative activity of NF-kB. Conclusions: Phospho-specific flow cytometry can be used to robustly analyze phosphorylation levels of NF-kB in PBMC. 40 Transcription profiling of a novel TB vaccine-induced responses in a Phase I Clinical Trial in India 1 1 2 Rasmus Bakken , Dhanasekaran Sivakumaran , Christian Ritz , and Harleen MS 1,3 Grewal 1 Authors’ Affiliations: Department of Clinical Science, Faculty of Medicine and Dentistry, 2 University of Bergen, Norway. Department of Nutrition, Exercise and Sports, University of 3 Copenhagen, Denmark. Department of Microbiology, Haukeland university hospital, University of Bergen, Norway. Introduction/background Tuberculosis (TB) remains a leading cause of morbidity and mortality globally, with an estimated incidence of 9.6 million people and causing 1.5 million mortalities in 2014. No new effective vaccine has been brought to marked since the introduction of the BacilleCalmette-Guérin (BCG) in 1921, and 2012 saw the first novel TB drug approved in 40 years. With the rise of multi drug resistant (MDR) strains, despite good BCG vaccination coverage, much effort is put into the development of new vaccines and drugs, as well as improved diagnostic and prognostic tools to improve the efficiency of TB detection and treatment. The AERAS-402, a recombinant, replication-deficient Ad35, which expressing the mycobacterial antigens Ag85A, Ag85B, and TB10.4, is one such candidate TB vaccine. AERAS-402 underwent a phase I clinical trial in Bangalore, India, in 2012. Objectives/aims: Nested within a phase I clinical trial of evaluating the safety of the AERAS-402 vaccine, the present study aimed to look at transcriptional markers of vaccine immunogenicity, by comparing RNA expression between vaccinated and placebo subjects to genes known to play a role in anti-mycobacterial immunity. Methods Peripheral blood mononuclear cells (PBMCs) were collected from the twelve study participants (2:1 ratio active vaccine and placebo injections) at study days 0, 7, 14, 28, 35, 42, 56, and 182. From these samples RNA for dual colour Reverse Transcription Multiplex Ligation Probe Amplification (dcRT-MLPA) was obtained. Gene by gene comparisons of expression of these biomarkers between the intervention groups and evaluation of potential biosignatures combining several markers were undertaken using publically available packages in R statistics. Results and Conclusion: The results will be presented for the first time during the conference. 41 A study on mitochondrial dysfunction in cell models of neurodegenerative disease 1 2 2,3 Fredrik Hoel , Jui-Chih Chan , Chin-San Liu , Karl J. Tronstad 1 1 Department of Biomedicine, University of Bergen, Norway Vascular and Genomic Center, Changhua Christian Hospital, Changhua, Taiwan 3 Department of Neurology, Changhua Christian Hospital, Changhua, Taiwan 2 Background: The mitochondria are the site of oxidative phosphorylation (OXPHOS), a process that is responsible for the bulk of the cellular ATP production. Impaired mitochondrial function results in aberrant ROS production, insufficient supply of ATP, cellular damage and cell death. Cell models have indicated the central role of mitochondrial function in the development of neurodegenerative diseases. Mitochondrial toxins have been used to model pathological mechanisms of neurodegenerative diseases such as Parkinson’s Disease (PD). Expression of mutated Ataxin-3 causes mitochondrial dysfunction in SCA3, while an mtDNA mutation recapitulates the MELAS cell pathology. There are limited options for interventions aimed at restoring mitochondrial function, and novel therapeutic approaches are in high demand. Far-infrared radiation (FIR) and peptide-mediated mitochondrial delivery (PMD) are two novel approaches that have shown beneficial effects in cell studies. Aims: This project aims to explore the mechanisms linking mitochondrial defects to degenerative diseases. Furthermore, we will investigate the potential of FIR and PMD in restoring mitochondrial dysfunction in cell models of SCA3 and MELAS, and the associated effects on mitochondrial function. Methods: Mechanisms of mitochondrial toxins were studied in SH-SY5Y neuroblastoma cells. Potential rescuing effects of FIR and PMD on mitochondrial function were investigated in cell models SCA3 and MELAS, respectively. Results: Mitochondrial dysfunction caused by electron transport chain inhibitors caused changes in gene expression in SH-SY5Y cells compatible with metabolic stress response. FIR protected cell viability via autophagy and improved mitochondrial function in a SCA3 cell model. PMD had rescuing effects on mitochondrial function and cell stress tolerance in MELAS cybrid cells. Conclusion: Mitochondrial toxins induce mechanisms of metabolic stress that may present in neurodegenerative diseases such as PD. FIR and PMD was found to improve aspects of mitochondrial function in cell models of degenerative disorders. Further studies are required to evaluate the therapeutic potential of these interventions. 42 Giardia lamblia variant-specific surface proteins, a longitudinal study of Immunoglobulin A and G responses Torunn Hjøllo, Eirik Bratland, Matej Radunovic, Nina Langeland and Kurt Hanevik Department of Clinical Science, University of Bergen Center for Tropical Infectious Diseases, Department of Medicine, Haukeland University Hospital, Bergen, Norway Introduction/Aims: Giardia lamblia is an intestinal parasite that causes giardiasis, and the duration of the antibody responses after natural infection is not well described. The aim of this study was to evaluate the longitudinally Immunoglobulin A and G (IgA and IgG) responses towards conserved Giardia specific surface proteins and the effect of the duration of infection on the response. Methods: We set up two enzyme linked immunosorbent assays (ELISAs) measuring Giardia specific IgA and IgG based on two recombinant antigens from G. lamblia, variant-specific surface proteins 3 and 5 (VSP3 and VSP5). We included serum samples from travellers returning to Norway with confirmed positive giardiasis by PCR of stool. Samples were collected in the acute phase, and then at 6 weeks, 6 and 12 months after effective treatment, and were compared to a group of Norwegians with a low risk of ever having had giardiasis. Results: Serum levels of VSP5 IgA and IgG and VSP3 IgG in exposed individuals were significantly higher than the low risk group in the acute giardiasis phase, 6 weeks and 6 months. The general trend is different for IgG and IgA, with levels of IgG stably elevated at the acute phase and 6 weeks, decreased at 6 months and normalized at 12 months. IgA levels declined rapidly after the acute phase. A short duration of infection (≤8 weeks) gives a significantly higher value for the VSP5 assay for IgA, but not for the other assays. Conclusion: IgG antibody levels against Giardia in serum can be detected until about 6 months after infection, while IgA declines within 6 weeks but is still detectable. A short duration gives higher values in one of the assays. 43 The oxidation resistance gene protects against apoptosis and tissue loss after hypoxic ischemia in brain Kristiansen ES, Yang M, Xiaolin L, Rolseth V, Wang W, Bjørge M, Eide L, Bjørås M Introduction: Every second our cells are exposed to oxidative stress from internal metabolic processes. The cells have several defense mechanisms to prevent and repair damage caused by oxidative stress. Disturbances in these processes make us vulnerable to many diseases, including cancer, diabetes and major neurological diseases. The Oxidation Resistance gene 1 (Oxr1) encodes for a mitochondrial protein protecting the mitochondrial DNA against oxidative stress. The Oxr1 protein has several known isoforms, among them Oxr1A. This isoform is only expressed in the brain. In this study we induce cerebral hypoxic ischemia in mouse pubs to investigate the function of Oxr1A under these circumstances. We aim to examine the role of Oxr1A for protection against stroke-induced cell death, tissue loss and regeneration. Methods: Generated black 6 Oxr1A knock outs and wild type mice are used. We operated the pubs (P9) ligating their common left carotid artery before placing them in a low oxygen chamber. This treatment induces a stroke in the left hemisphere. After recovery, the mice were euthanized at different time points (3 hours, 1 day, 7 days and 42 days). For immunohistochemistry, their brains were fixated and embedded in paraffin before sectioning. To quantify apoptotic cell death, we used a TUNEL kit and counterstained the nucleus with DAPI. To study the differences between the groups, we measured the average number of cell death in each area and performed a student T-test to test for significance. To study tissue loss after one day, sections were stained with tetrazoliumchloride (TTC). We also looked at nevrogenesis and regeneration in the brains. To do this we used markers for neuronal progenitors as well as markers for mature neurons and astrocytes. We also measured tissue loss 42 days post injury, when the regeneration is complete. Results: In three different brain regions, there was a significant increase of apoptotic cell death in the Oxr1A knock-out mice (n=4) compared to the wild type (n=6). Two of these areas are in the ischemia-susceptible hippocampus; dentate gyrus and Ca3 (P=0,020 and P=0,012, respectively). The third area is in the thalamus (P=0,002). TTC staining showed significantly increased tissue loss 1 day after ischemia. After 3 and 7 days we have more neuronal progenitors in the knock-outs compared to the wild types. There is however no difference in mature neurons or astrocytes in the genotypes. After 42 days, there is increased tissue loss in the knock-out mice compared to the wild types. Conclusion: Oxr1A protects the brain from tissue loss and apoptosis after hypoxic-ischemia in P9 mice and also when the regeneration is completed. Oxr1A also has a role in nevrogenesis after brain damage. 44 Optimizing The Storage of Stem cell for Treatment of Limbal stem cell deficiency Korkosh, Mohammed Bayar, UiO Limbal stem cell deficiency (LSCD) is a disease that affects millions of people all around the world. The disease manifest itself by damaging the limbus, an area in the eye that renews the cells in the Cornea. Chemical burns, infections, and autoimmune diseases can cause LSCD. LSCD might affect both or one of the eyes, and cause blindness and great pain. The treatment of LSCD has been known for a while now, and it is used in the developed part of the world. With a biopsy from the mouth of the affected patient, one can culture the stem cells in a lab and then transplant the stem cells in the Limbus area in the eye. The treatment has a high success rate of removing the pain and restoring the vision. The problem is that most people with LSCD are in third world countries, where treatment is limited. If we can optimize the storage time and standardize the cultivation of the stem cells, one can open a new door where we can use the western labs to culture the cells. So, by taking the biopsies from the affected patient and flying them to labs that have the ability to culture the stem cells beforehand, we can fly them back and then use it for treatment for LSCD. By expanding the storage time without affecting the cells quality and morphology, we can start treating the disease worldwide. Research group: Amer Sehic (hovedveileder), Tor Paaske Utheim (medveileder), Linda Bergersen (medveileder), Ngoc Ky Cuong Khuu, Inger Thea Myklebust Ernø, Mohammed Bayar Korkosh 45 The interplay between DNA-repair and epigenetics Elise Klæstad, Geir Slupphaug and Bodil Kavli. Department of Cancer Research and Molecular Medicine, Norwegian University of Science and Technology, Abstract: Epigenetic regulations and DNA-repair are two fundamental biological processes essential for normal human development and health. Epigenetic modifications in DNA and DNA –binding histones control gene expression, and thereby the organism’s phenotype, whilst DNA-repair removes damaged DNA to prevent mutations and apoptosis. New research indicates that there could be a link between the two processes. Understanding how epigenetic modifications in DNA affect processing of DNA-damage and vice versa could open up for new fields in medical diagnostics and treatment. The aim of the project is to examine how the epigenetic modification 5-meC in the presence of the aberrant base uracil (U) in DNA affects DNA-repair. The task will be implemented by examining synthetically prepared oligodeoxynucleotides containing 5-meC and uracil, separate and together, in distinct locations relative to each other and in specific sequences. DNA-metabolizing enzymes often recognize distinct primary structures in the DNA. The same has been shown for enzymes metabolizing DNA uracil and 5-meC. We hypothesize that each of these factors could affect the enzymatic binding involved in induction and/or processing of the other in a position dependent manner. The project is early on in the process and has yet to generate enough results to draw any conclusions. Any generated results will be presented at Frampeik 2016. 46 Abstracts in cancer research Skjefstad, Kaja UiT [email protected] Barua, Imon UiO [email protected] Jacobsen, Martha Rolland UiB [email protected] Grindstad, Thea UiT [email protected] Knutsen, Christina NTNU [email protected] Svanøe, Amalie Abrahamsen UiB [email protected] Yi, Dag UiB [email protected] 47 Prognostic Relevance of Estrogen Receptor α, β and Aromatase expression in Non-small cell lung cancer 1,* 1 1 Kaja Skjefstad , Thea Grindstad , Mehrdad Rakaee Khanehkenari , Elin 1,2 3,4 2,4 3,4 Richardsen , Tom Donnem , Thomas Kilvaer , Sigve Andersen , Roy M. 3,4 1,2 1,2 Bremnes , Lill-Tove Busund , Samer Al-Saad 1 Department of Medical Biology, UiT – The Arctic University of Norway, Department of Clinical Pathology, University Hospital of North Norway, 3 Department of Clinical Medicine, UiT – The Arctic University of Norway, 4 Department of Oncology, University Hospital of North Norway, 2 Translational research group, UiT – The Arctic University of Tromsø Introduction/background: Sex steroids and their receptors are important in the fetal development of normal lung tissue. In addition emerging evidence reveals their significance in lung cancer pathogenesis. This encourages the exploitation of hormone receptors as treatment targets in lung cancer, as it has been successfully used in breast cancer. Objectives: This study investigates the prognostic impact of estrogen receptor (ER) α and β and the aromatase (AR) enzyme in non-small cell lung cancer (NSCLC) patients. Methods: Tumor tissue from 335 NSCLC patients was collected and tissue microarrays (TMAs) were constructed. Immunohistochemical analyses were performed to evaluate the expression of ERα, ERβ and AR in the cytoplasme and nuclei of cells in the tumor epithelial and stromal compartment. By use of survival statistics we investigated the markers impact on disease-specific survival (DSS). Results: Nuclear ERβ expression in tumor epithelial cells in female patients (HR 3.03; 95% CI 1.39-6.61) and tumor cell AR expression in all patients (HR 1.55; 95% CI 1.08-2.23) were significant negative prognostic markers of diseasespecific survival in our cohort. Conclusions: High ERβ expression correlates with worse outcome in female patients. Further, patients with high AR expression had an unfavorable prognostic outcome compared with patients expressing low AR levels. These results emphasize the importance of sex steroids role in NSCLC, and, as antihormonal drugs are widely available, could lead to the development of novel palliative or even adjuvant treatment strategies in this patient population. 48 Histone deacetylase inhibitors in combined-modality cancer treatment – experimental studies of normal tissue effects 1,2 1 2 2 1,2 2 Barua IS , Kalanxhi E , Risberg K , Ree AH , Redalen KR Institute of Clinical Medicine, Campus AHUS, University of Oslo 2 Department of Oncology, Akershus University Hospital Background: In combined-modality cancer treatment, molecularly targeted agents may be combined with radiotherapy to increase therapeutic efficacy. One example is histone deacetylase (HDAC) inhibitors, and in our Pelvic Radiation and Vorinostat (PRAVO) study we investigated the combination of radiation with the HDAC inhibitor vorinostat ((suberoylanilide hydroxamic acid (SAHA)) in gastrointestinal carcinoma. Although such a combination treatment may result in improved therapeutic efficacy, it may also increase treatment toxicity, such as diarrhea, and lead to undesired treatment interruptions or dose limitations. HDAC inhibitors have been regarded as tumor specific, however, their influence on relevant normal tissues remain poorly investigated. Aim: To investigate potential treatment toxicity in experimental normal tissue models treated with the HDAC inhibitor SAHA. Methods: Two normal tissue models (rat IEC-6 intestinal epithelial cells and human BJ fibroblasts) and two colorectal cancer cell lines (HCT116 and HT29) were exposed to SAHA for 24 hours before mechanisms of cell death were analyzed with flow cytometry, western blot analysis and immunofluorescent imaging. Results: By flow cytometry (annexin V and propidium iodide) and western blot analysis we found that SAHA induced cell death in HCT116 and HT29 cells, but not in the BJ fibroblasts, and that induction of apoptosis was a main mechanism of cell death. Intriguingly, the intestinal epithelial IEC-6 cells responded similarly as the cancer cells to SAHA. In addition to apoptosis we also found that SAHA induced autophagy, both in the cancer cell lines and the IEC-6 cells, as reflected by increased expression of autophagy proteins (LC3-II and p62) on western blot and as visualized by immunofluorescent imaging of SAHA-treated cells. Conclusion: Treatment with the HDAC inhibitor SAHA resulted in cell death through induction of apoptosis and autophagy in a patient-relevant experimental normal tissue model. The results may contribute to explain normal tissue adverse events, such as intestinal toxicity, in patients treated with HDAC inhibitors as part of combined-modality cancer treatment. 49 Estrogen receptors α and β and aromatase as independent predictors for prostate cancer outcome Grindstad T 1, Skjefstad K 1, Andersen S 2,3, Ness N 1, Nordby Y 2, Al-Saad S 1,4, Fismen S 4, Donnem T 2,3, Khanehkenari MR 1, Busund LT 1,4, Bremnes RM 1,2, Richardsen E 1,4 1 Dept. of Medical Biology, UiT The Arctic University of Norway, Tromso, Norway. 2 Dept. of Clinical Medicine, UiT The Arctic University of Norway, Tromso, Norway. 3 Dept. of Oncology, University Hospital of North Norway, Tromso, Norway. 4 Dept. of Clinical Pathology, University Hospital of North Norway, Tromso, Norway Background Androgens are considered important in normal prostate physiology and prostate cancer (PCa) pathogenesis. However, androgen-targeted treatment preventing PCa recurrence is still lacking. This indicates additional mediators contributing to cancer development. Aim We sought to determine the prognostic significance of estrogen receptors, ERα and -β, and the aromatase enzyme in PCa. Methods Tissue microarrays were created from 535 PCa patients treated with radical prostatectomy. Expression of ERα, ERβ and aromatase were evaluated using immunohistochemistry. Representative tumor epithelial (TE) and tumor stromal (TS) areas were investigated separately. Survival analyses were used to evaluate the markers correlation to PCa outcome. Results In univariate analyses, ERα in TS was associated with delayed time to clinical failure (CF) (p=0.042) and PCa death (p = 0.019), while ERβ was associated with reduced time to biochemical failure (BF) (p = 0.002). Aromatase in TS and TE was associated with increased time to BF and CF respectively (p = 0.016, p = 0.046). Multivariate analyses supported these observations, indicating an independent prognostic impact of all markers. When stratifying the analysis according to different surgical centers the results were unchanged. Conclusion In conclusion, significant prognostic roles of ERα, ERβ and aromatase were discovered in the in PCa specimens of our large multicenter cohort. 50 Targeting cancer metabolism to prevent metastasis Knutsen, Christina, NTNU Objective: The objective of this project is to explore the relationship between metabolic characteristics and metastatic potential in breast cancer cell lines of metastatic and non-metastatic origin. The project is aiming to clarify how metabolism supports the metastatic process and to evaluate the potential for preventing metastasis by inhibiting key metabolic pathways. Background: Breast cancer accounts for approximately 3500 new cancer diagnoses in Norway each year (Cancer in Norway ref). Although the prognosis is favourable for many patient groups, there are still as many as 650 breast cancer deaths in Norway each year. Despite a national screening programme and significant improvements in surgical and pharmacological treatment of the primary tumors, a lot of women experience recurrence of their disease and eventually succumb to distant metastases. It has been suggested that the risk of recurrence is higher in women with triple negative breast cancer (TNBC), which accounts for approximately 15-20% of breast cancers, with a higher incidence in patients younger than 40 years old (1). There is a high therapeutic potential for breast cancer patients of several subtypes if we can identify metabolic targets for novel cancer treatment. Preliminary studies have shown that the isogenic cell lines 67NR and 4T1 has different metabolic profiles, despite their nearly identical genetic background. In conclusion, the current knowledge about the 4T1 model system for metastatic cancer suggests that metastatic cells may be sensitive to drugs that either inhibit anaplerosis or increase the intracellular oxidative stress. We will therefore target these mechanisms using clinically relevant drugs; aiming to confirm the hypothesis that cancer metastasis depends on extracellular acidification, high citric acid cycle turnover, anaplerosis and/or protection against oxidative stress. Methods: Cancer cell cultures grown in the laboratory will be used to put up a XTT Trans-Well Assay where different enzyme inhibitors will be added. To take the complexity of tumor/host interaction into account, the efficacy of metabolic inhibitors must be evaluated in vivo, as animal models will be set up for spring 2018 (forskertermin 3). In vitro studies: 96 well plate trans-well assay Drugs: CB-839: Glutaminase Inhibitor (Phase I trials). Dichloroacetate: Pyruvat dehydrogenase kinase inhibitor (Generic drug) AZD-3965: Monocarboxylate transporter 1-inhibitor (AstraZeneca) 51 Animal model: 4T1-model system established at NTNU by Research Scientist Tonje Steigedal (IKM). Exome sequencing performed by prof. Geir Bjørkøy (CEMIR) to evaluate genetic heterogeneity. HR-MAS-MRS performed on cell extracts will be used to measure metabolic responses to treatment. We will aim to use both 1H and 13C MR-spectroscopy to analyse polar cell extracts. Biochemical assays will be used to measure levels of metabolic stress (ROS). SeaHorse will be used to measure extracellular acidification. Hypotheses: In vitro studies: ”4T1 cancer cells are more sensitive than 67NR cells to drugs that contribute to oxidative stress by blocking glutamine consumption” Animal model studies: ”Metastatic spread of 4T1 tumors can be inhibited in vivo by drugs that alter tumor microenvironment or reduce their redox tolerance” Results and conclusions will be left blank as there are no data to demonstrate. 52 Age-related characteristics in breast cancer 1 1,2 1,2 1 Amalie A. Svanøe , Gøril Knutsvik , Ingunn Stefansson , Kristi Krüger , Monica 1 1 3 3 1,2 1, 2 Mannelqvist , Sura Aziz , Benedicte Davidsen , Turid Aas , Lars A. Akslen , Elisabeth Wik ¹Centre for Cancer Biomarkers CCBIO, Department of Clinical Medicine, University of Bergen, Bergen, Norway. ²Department of Pathology, Haukeland University Hospital, Bergen, Norway. 3 Department of Surgery, Haukeland University Hospital, Bergen, Norway Background: Breast cancer is the most common cancer, and the second most common cause of cancer related deaths among women in Norway. On average 5,7% of women diagnosed with breast cancer between 2009-2013 were 15-49 years old at the time of diagnosis, and these are referred to as “adolescent and young adults” (AYAs). Previous studies have shown that this is a group associated with particularly aggressive subtypes of breast cancer. Materials and methods: Tumor tissue and patient data from journals were collected from a population based breast cancer AYA group (n=378). A previously described population based breast cancer series of patients aged 5069 years old (n=546), was analyzed for comparison (Knutsvik et al, PLoS One 2013). Data from the Cancer Registry and the Cause of Death Registry were linked to the data and used for survival analyses. A dataset from The Cancer Genome Atlas (TCGA, n=520), including gene expression and clinico-pathologic data, was used for further analyses. The AYA group associated with more aggressive tumor features, such as ER negativity, high histologic grade, larger tumor size, lymph node metastases and locally advanced disease (all p<0.0005). Patients in the AYA group experienced shorter disease specific survival compared to older patients (p=0.001). TCGAdata showed a higher proportion of the basal-like subtype and BRCA1 germline mutations in the AYA group (both p=0.002). Genes differentially expressed between AYAs and patients ≥ 50 years identified one cluster within the AYA cases, that associated with BRCA1 germline mutations (p=0.03) and ER/PR negative tumors (p<0.0005). All basal-like cases were included in this subcluster. Gene expression patterns reflecting ER loss, stem cell profiles and hereditary breast cancer, were enriched in this cluster. Conclusions: In this large, population based cohort, we confirm aggressive tumors in AYA breast cancer. A subgroup of the AYA cases is characterized by the basal-like phenotype and gene expression programs reflecting low ER, stem cell features and hereditary breast cancer. 53 Monocyte derived dendritic cells stimulated with OK432, TLR 7/8 agonist and PGE2 show mature phenotype with chemotaxis towards CCR7, secretion of IL-12p70 and strong T-cell stimulatory capacity. Dag H. Yi, Silke Appel Dendritic cells (DC) are powerful antigen presenting cells that can promote both immunogenic and tolerogenic responses from the immune system(1). Ever since the discovery of DC(2), immunotherapeutic uses of these cells against cancer have been researched on(3-5). While DC based immunotherapy has been proven successful in animal models(6-8), it has been disappointing in clinical trials (9). The aim of this study is to find possible ways to improve upon current protocols for DC generation from monocytes for immunotherapeutic purposes. OK432, manufactured under the name Picibanil, is a streptococcal preparation against cancer that has been used for decades in Japan. It was discovered that DC co-cultured with OK432 expressed a mature phenotype as well as an inflammatory cytokine profile (10-13). The stimulation was shown to be in a TLR-3 dependent manner (14). Thus our cocktail consists of OK-432, a TLR2 7/8 agonist to in theory further improve stimulation as well as PGE to improve CCR7 expression. The cocktail matured DCs had their immunostimulatory and chemotactic motility compared to the gold standard (15). DCs were generated by culturing monocytes isolated by plastic adherence with IL-4 and GM-CSF and subsequently stimulated with the two different cocktails. Flow cytometry was used for phenotyping, autologous mixed lymphocyte reaction with tuberculin as recall antigen was used to measure T-cell stimulatory capacity, and chemotaxis was measured using semi permeable membrane chemotaxis towards CLL19. A 25-plex Luminex assay was used to determine cytokine secretion profile. The results shows that the DCs stimulated by the experimental cocktail yielded mature DCs with higher expression of CCR7, chemotactic motility as well as increased secretion of IL-12p70. T-cell stimulatory capacity appeared to be similar to the gold standard. Thus a cocktail consisting of OK432, TLR7/8 2 agonist and PGE appears to be a suitable alternative for maturing DC in immunotherapy. (Referances for abstract is in the digital version at frampeik.no) 54 Abstracts in epidemiology Madsen, Anders UiB [email protected] Ellingsen, Trygve Sølberg UiT [email protected] Mclean, Emily UiB [email protected] Pannu, Mehma UiB [email protected] Tran, Long NTNU [email protected] Warlo, Ellen Mathea Kirsch UiO [email protected] 55 Dissecting the hemagglutinin-specific antibody response after pandemic 2009 influenza vaccination 1 1 1 1,2 1 Anders Madsen* , Linda Azimi* , Sarah Tete , Rebecca Cox , Åsne Jul-Larsen *Equal contributors 1 Influenza Centre, Department of Clinical Science, University of Bergen, Norway 2 Department of Research & Development, Haukeland University Hospital, Bergen, Norway Background: Influenza is a contagious respiratory infection caused by the influenza virus. It occurs as seasonal epidemics and occasional pandemics. A pandemic arises when a novel virus causes worldwide diseases in mainly immunologically naïve human population. Interestingly, pandemics are known to have a higher mortality rate among people of younger age, in contrast to seasonal epidemics. Frequent mutations on the viral surface protein “hemagglutinin” (HA) is an important factor for the virus ability to evade hos immunity and reappear annually. In 2009, parallel to the ongoing “swine-flu”, 250 healthcare workers at Haukeland University Hospital were recruited to a clinical trial as they were vaccinated with the pandemic influenza vaccine. Aim: To investigate how an individual’s previous encounter with different influenza subtypes influences the humoral response after pandemic vaccination in 2009. Methods: Participants were retrospectively chosen, and grouped, based on their year of birth (reflecting which influenza subtype they were first exposed to during childhood). We investigated antibodies to the surface protein, HA, and looked specifically at antibodies binding to the conserved parts of this protein. Serum samples were analyzed using hemagglutination inhibition (HI) assay, microneutralization (MN) assay, and Enzyme-Linked Immunosorbent Assay (ELISA). These serological assays are designed to measure the quantity and quality of influenza-specific antibodies. Results: Antibody-levels increased significantly after vaccination. Older subjects had a higher level of preexisting antibodies to conserved parts of HA, whereas the younger subjects obtained a higher level of strain-specific antibodies directed to the more variable regions of the HA. Younger subjects also experienced an overall strong antibody-boost after vaccination. Conclusion: Our data shows how previous exposure to different influenza subtypes can affect the immune response to a novel influenza virus. We found that the more antigenically experienced individuals, who had a broader antibody repertoire towards novel viruses, obtained higher pre-vaccination antibody-levels. This was most prominent towards the conserved parts of HA. On the other hand, the least antigenically experienced individuals achieved the highest antibody boost in response to vaccination. 56 The association between red cell distribution width and risk of venous thromboembolism is not mediated by myocardial infarction, stroke or cancer – a cause-specific analysis 1 1 1,2 Trygve S. Ellingsen , Jostein Lappegård , Tove Skjelbakken , Ellisiv B. Mathiesen 1,5 1,2 1,2 Njølstad , Sigrid K. Brækkan and John-Bjarne Hansen 1,3,4 , Inger 1 K. G. Jebsen – Thrombosis Research and Expertise Center (TREC), Department of Clinical Medicine, UiT - The Arctic University of Norway, Tromsø, Norway 2 Division of Internal Medicine, University Hospital of North Norway, Tromsø, Norway 3 Brain and Circulation Research Group, Department of Clinical Medicine, UiT - The Arctic University of Norway, Tromsø, Norway 4 Department of Neurology and Neurophysiology, University Hospital of North Norway, Tromsø, Norway. 5 Department of Community Medicine, UiT - The Arctic University of Norway, Tromsø, Norway Correspondence to: Trygve S. Ellingsen, K.G. Jebsen Thrombosis Research and Expertise Center, Hematological research group (HERG), Department of Clinical Medicine, University of Tromsø, N9037 Tromsø, Norway e-mail: [email protected] telephone: +47 958 73 223 Background: Red cell distribution width (RDW) is a risk marker of venous thromboembolism, myocardial infarction (MI), stroke and cancer. Due to the established interrelations between these diseases, the apparent association between RDW and VTE may be mediated by MI, stroke or cancer. Aims: To investigate whether the effect of RDW on VTE was mediated by MI, stroke or cancer. Methods: RDW was measured in 24363 participants of the Tromsø Study in 1994-95. Incident VTE, MI, stroke and cancer were registered until December 31, 2010. Person-time was calculated from inclusion to the date of an incident outcome, migration, death, or study end, whichever came first. Conventional and cause-specific Cox-regression models were used to estimate hazard ratios (HR) for VTE with 95% confidence intervals (CI). Results: There were 502 first VTEs during a median of 16 years of follow-up. In conventional Cox regression analysis, RDW in the highest quartile was associated with a 71% higher risk (HR 1.71, 95% CI 1.09-2.67) and 27% higher risk (HR 1.27, 95% CI 0.88-1.85) of VTE in men and women, respectively, compared to subjects in the lowest quartiles. The risk of VTE by the highest quartile of RDW was similar for men and women of postmenopausal age. In cause-specific analysis, where each individual contributed with person-time until the first occurring event only, the risk estimates were essentially similar to those of the conventional Cox-regression analysis. Conclusion: Our findings imply that the association between RDW and future risk of VTE is not mediated by MI, stroke or cancer. 57 Working on the edge of the law: a qualitative study of ethical dilemmas faced by abortion providers in Addis Ababa, Ethiopia. Emily McLean, Ingrid Miljeteig, Astrid Blystad and Dawit Desalegn Introduction and Objectives: In 2005 Ethiopia changed its abortion law in order to curb the high maternal mortality. Abortion is now legal if the pregnancy is a result of rape or incest, if the woman's health is in danger or the foetus has an incurable and serious deformity, and if she suffers from physical or mental deficiency including if she is under 18. A twist in the law is that the word of the woman is sufficient to qualify for safe abortion services. The objective of this study is to enhance the understanding of how abortion providers in Ethiopia interpret the law, perceive their role as gatekeepers of the law and experiences potential ethical dilemmas Method: This is a qualitative study. Data collection took place from March to May 2016 in Addis Ababa at different health clinics providing abortion services. 24 in-depth interviews and 3 focus group discussions were conducted with nurses, midwifes and physicians providing abortion services in governmental and non-governmental clinics. Systematic text condensation has been employed in the analysis. Results: In the interaction with patients seeking abortions the health workers describe conflicting concerns, a burdensome responsibility and ambiguity concerning how to interpret the law. They describe efforts to balance their religious faith and values against their professional obligations and concern for woman´s health. This negotiation is particularly present in care for women who fall outside the laws indicators. They usually have to handle these ethical dilemmas and the decision-makings alone without guidance. Many face stigma from fellow colleges not performing abortions and keep their job a secret from family and friends. Conclusion: The study reveals how health workers in Ethiopia experiencing a moral workload by balancing on a difficult line trying to manoeuvring between the abortion law, their personal values and their genuine concerns for woman´s health. 58 Equality impact analysis of Post Malaria Chemoprevention delivery mechanisms trial (PMC) in Malawian children under five Mehmajeet Kaur Pannu, Bjarne Robberstad 1 Department of Global Public Health and Primary Care, The Research Council of Norway, Global Health and Vaccination Research (GLOBVAC). Project id.: 234487. College of Medicine (CoM), University of Malawi, Private Bag 360, Blantyre, Malawi Universitetet i Bergen, Bergen, Norge. Severe anemia is a leading cause of hospital admissions in Africa contributing substantially to pediatric mortality. Recent case control study in Malawian children indicated that children aged <5y admitted with severe anemia are not only at high risk of dying during the acute phase in-hospital (6%) but also for several months after they leave hospital: 8% had died by 6 months’ discharge, which is nine times higher than the mortality in community-based, age matched children with mild anemia. Similar rates are seen in western Kenya and in Uganda. (c.john et al, unpublished data). Hospitalized children with severe anemia are particular at risk within the first 3 months post-discharge, likely due to a combination of environmental, behavioral, nutritional and generic risk factors. PMC, or Post Malaria Chemoprevention is the administration of a full treatment course (Dihydroartemisinin-Piperaquine) of long-acting antimalarials at pre-defined time intervals (2, 6 & 10 weeks after discharge) irrespective of a patient’s malaria status. The main objective is to determine the uptake, effectiveness, cost-effectiveness, acceptability, feasibility and equity/equality of two different mechanisms for delivering IPTpd: facility vs community-based approaches and examining the added role of mobile phone text message reminders. This is an effort to incorporate equity into cost-effectiveness, and will be valuable input to decision makers when considering new policies. We will use a household asset index to differentiate the study population in quintiles, to examine the differences in a thorough way to answer questions as Does delivery mechanism affect compliance based on different socioeconomic variables? Is a specific mechanism superior for a specific part of the population depending on socioeconomic factors or positions? Study ongoing, no results yet. 59 The effect of red blood cell transfusion on long-term mortality in adult patients undergoing isolated coronary artery bypass grafting 1 1 2,3 2,4 2,5 2,3 1,6 Tran L. , Greiff G. , Pleym H. , Wahba A. , Stenseth R. , and Videm V. Corresponding author e-mail: [email protected] Department of Laboratory Medicine, Children’s and Women’s Health, NTNU, 7491 Trondheim. 2 Department of Circulation and Medical Imaging, NTNU, 7491 Trondheim. 3 Department of Cardiothoracic Anaesthesia and Intensive Care, St. Olavs Hospital, 7006 Trondheim. 4 Clinic of Anaesthesia and Intensive Care, St. Olavs Hospital, 7006 Trondheim. 5 Clinic of Cardiothoracic Surgery, St. Olavs Hospital, 7006 Trondheim. 6 Department of Immunology and Transfusion Medicine, St. Olavs Hospital, 7006 Trondheim. Introduction & Aim: Studies have shown a correlation between transfusion of as little as 1 unit of red blood cell (RBC) and long-term mortality in patients undergoing CABG[1]. Because the patients receiving transfusion have more preoperative risk factors, long-term effect of RBC transfusion itself is difficult to evaluate. We hypothesized that the increased risk is due to pre- and postoperative morbidity. Our aim was to investigate whether there was a difference in long-term mortality in a group of patients with fewer confounders for our primary outcome. Methods: The study is a part of the Cardiac Surgery Outcome Study at St. Olavs Hospital. Patient data are collected prospectively in a local database now consisting of adults undergoing cardiac surgery from 2000 through 2014. We included patients undergoing primary isolated CABG, excluding those with preoperative anemia, large intra- or postoperative blood loss and 30-day mortality. We compared mortality from 1 month postoperatively between patients receiving transfusion of at least 1 unit of RBC and patients who did not. We performed multivariate Cox regression analysis and sensitivity analysis using propensity score matching between RBC transfused and non-transfused patients. Results: Of 3550 included patients, 731 (20.6%) received transfusion of at least 1 unit of RBC and 188 (25.7%) died between 1 month and 15 years postoperatively. In an unadjusted Cox regression model, the hazard ratio (HR) for long-term mortality was 2.01 (1.69-2.38, p < 0.01). When adjusting for preand intraoperative variables, the HR was 1.28 (1.03-1.59, p = 0.03). With adjustment also for postoperative complications, RBC transfusion was no longer significant (HR: 1.15, 0.92-1.43, p = 0.22). These results were supported in the propensity score-matched patients. Conclusions: Our study indicated that the association between RBC transfusion and long-term mortality following CABG was due to confounding, especially from postoperative complications. The study does not support a restrictive transfusion policy as a method to reduce long-term mortality in this patient group. 60 Reduced levels of ADAMTS13 are associated with high on-aspirin residual platelet reactivity in patients with stable coronary artery disease. 1 Warlo, E.M.K. 1,2,3 , Seljeflot, I. 1,2,3 , Arnesen, H. 1,2,3 , Pettersen, A-Å. 1,3,4 Center for Clinical Heart Research, Department of Cardiology, Oslo University Hospital, Ullevaal, Oslo, Norway 2 Faculty of Medicine, University of Oslo, Oslo, Norway 3 Center for Heart Failure Research, University of Oslo, Norway 4 Department of Medicine, Vestre Viken HF, Ringerike Hospital, Hønefoss, Norway Introduction: The mechanisms behind residual platelet reactivity (RPR) despite aspirin treatment are not established. It has been shown that coronary artery disease (CAD) patients with high on-aspirin RPR have elevated levels of von Willebrand factor (vWF). ADAMTS13 is a metalloprotease cleaving ultra large vWF multimers into less active fragments. Our aim was to investigate whether ADAMTS13 and vWF/ADAMTS13 ratio were associated with high RPR, and further with clinical endpoints after 2 years. Materials and methods: Stable aspirin-treated CAD patients (n=1000) from the ASCET trial. RPR was assessed by PFA-100. ADAMTS13 antigen and activity were analysed using chromogenic assays. Endpoints were a composite of acute myocardial infarction, stroke and death. Results: The number of patients with high RPR was 258 (25.8%). Their serum thromboxane B2 (TxB2) levels were low, indicating inhibition of COX-1. They had significantly lower levels of ADAMTS13 antigen compared to patients with low RPR (517 vs 544ng/mL, p=0.001) and significantly lower ADAMTS13 activity (0.99 vs 1.04IU/mL, p=0.020). The differences were more pronounced when relating RPR to ratios of vWF/ADAMTS13 antigen and vWF/ADAMTS13 activity (p<0.001, both). We found an inverse correlation between vWF and ADAMTS13 antigen (r=-0.14, p<0.001) and ADAMTS13 activity (r=-0.11, p<0.001). No correlations between TxB2 and ADAMTS13 antigen or activity, were observed, implying that ADAMTS13 is not involved in TxB2 production. Patients who experienced endpoints (n=73) had higher vWF level (113 vs 105%, p=0.032) and vWF/ADAMTS13 antigen ratio (0.23 vs 0.20, p=0.012) compared to patients without. When dichotomizing vWF/ADAMTS13 antigen at median level we observed that patients above median had higher risk for suffering endpoints, with an adjusted OR of 1.86 (95% CI 1.45, 2.82). Conclusion: These results indicate that ADAMTS13 is of importance for RPR, and that it in combination with vWF also is associated with clinical endpoints in stable CAD patients on aspirin. 61 Poster presentations Abstracts not included in the following section is presented in the corresponding section for the topic above. Shreeram Akerkar [email protected] Clinical medicine Einarsen, Eigir [email protected] Clinical medicine Giriteka, Lionel [email protected] Clinical medicine Larsen, Christopher Storm [email protected] Clinical medicine Gulliksen, Håkon [email protected] Clinical medicine Bakken, Rasmus [email protected] Duus, Inger Hødnebø [email protected] Basal research and genetics Basal research and genetics Amundsen, Vivian S. [email protected] o [email protected] o.no Clinical medicine Stautland, Andrea [email protected] Neuroscience Tony Elvegaard [email protected] Clinical medicine Bergsmark, Camilla Basal research and genetics 62 Olanzapine-induced metabolic effects in female mice 1,2 1,2 1,2 1,2 Duus IH , Ersland KM , Skrede S , Steen VM . 1. Dr. Einar Martens Research Group for Biological Psychiatry, Center for Medical Genetics and Molecular Medicine, Haukeland University Hospital, 5021 Bergen, Norway. 2. K.G. Jebsen Center for Psychosis Research, and the Norwegian Center for Mental Disorders Research (NORMENT), Department of Clinical Science, University of Bergen, 5021 Bergen Norway. Introduction/background: Schizophrenia is a debilitating mental disorder associated with great personal suffering and economic burden. The use of antipsychotics is essential in relieving the symptoms, and today atypical antipsychotics are in widespread use. Unfortunately, these drugs also have a tendency to induce severe metabolic side effects, such as weight gain, dyslipidaemia and deranged glucose metabolism. The molecular mechanisms underlying these adverse effects are to a large extent unknown. In order to investigate the biological basis further, the development of an animal model is important. However, in several rat studies a continuous problem has been the failure to achieve antipsychotic-induced weight gain. Further studies on the potential effect of antipsychotics in mice are therefore worth pursuing. Objectives/aim: We want to investigate the effects of olanzapine depot formulation in mice, hopefully increasing our knowledge of the underlying molecular mechanisms contributing to weight gain. Methods: In an initial experiment, female mice received intramuscular injections of olanzapine depot formulation of 25 mg/kg, 50 mg/kg or vehicle solution. They were fed standard chow. Weight gain and chow intake were then measured daily for 15 consecutive days. In a second experiment, female mice received 50 mg/kg olanzapine long-acting injections and were fed a high fat diet, one group with ad libitum access to food, another group being pair fed. Weight gain and chow intake were measured as previously described. In both experiments, the mice received a second injection on day 9 and they were sacrificed on day 15. Plasma lipid and olanzapine concentrations were measured, as well as lipogenic gene expression in liver and periovarial fat using real-time PCR. Results/conclusion: The results of both experiments are not completely analysed. Preliminary results show significant weight gain in the 50 mg/kg group fed standard chow. Also, both experiments induced significant lipogenic upregulation in liver and periovarial fat. 63 Reduced Serum Lipid Levels in Patients Receiving ECT – Preliminary Findings Andrea Stautland (1), Ute Kessler (2), Leif Oltedal (1,3), Jan Haavik (2,4), Ketil J Ødegaard (1,2) (1) Department of Clinical Medicine, University of Bergen, Norway, (2) Division of Psychiatry, Haukeland University Hospital, Bergen, Norway, (3) Department of Radiology, Haukeland University Hospital, Bergen, Norway, (4) K.G. Jebsen Centre for Neuropsychiatric Disorders; Department of Biomedicine, University of Bergen, Norway. Introduction: Major depressive disorder (MDD) is a highly prevalent and debilitating mental illness. There is evidence for an altered lipid metabolism in MDD. Electroconvulsive therapy (ECT) is perhaps the most effective acute treatment of MDD. The mechanisms of action of ECT are not fully understood, but might include changes in lipid metabolism. Objectives: The aim of the study was to assess changes in serum lipid concentrations in MDD patients undergoing ECT. The study is part of a larger, multidisciplinary trial investigating the mechanisms of ECT. Methods: Serum lipid levels were measured in 16 patients suffering from treatment resistant MDD using a non-targeted lipidomics approach. Blood samples were obtained before first treatment and approximately one week after the completed treatment series. Ultrahigh performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) technology was used to detect lipid metabolites. A matched pairs t-test was used to compare pre and post-treatment samples. Results: In total, 399 lipid metabolites were detected, of which 69 were significantly altered after ECT. Post-treatment samples showed reduction of serum concentration in several classes of lipid metabolites, especially free fatty acids (FFA). Significant decreases were found in nearly all of the detected monoacylglycerol species, within several diacylglycerol species, several lysolipids and other phospholipid breakdown products and a number of fatty acid dicarboxylates. The observed changes in lipid levels can be mediated by different processes, including changes in biosynthesis and breakdown rates of FFAs. This can be related to altered levels of exercise, distribution and storage of lipids or dietary changes. More investigations are needed to explore the contributions of these processes. Conclusions: The study contributes to elucidate the role of lipid metabolism in MDD and the effects of ECT. Further investigations in larger samples should be performed to confirm these results and evaluate the clinical significance of the findings 64 Asymmetric septal hypertrophy as a prognostic indicator during progression of aortic valve stenosis 1 2 1 3 4 Einarsen E. , Cramariuc D. , Lonnebakken M.T. , Boman K. , Gohlke-Bärwolf C. , 5 1 Chambers J.B. , Gerdts E. From 1 University of Bergen, Bergen, Norway; 2Haukeland University 3 4 Hospital, Bergen, Norway; University of Umeaa, Skelefteaa, Sweden; Herz-Zentrum Bad 5 Krozingen, Germany; St. Thomas Hospital, London, United Kingdom. Objective: Asymmetric septal hypertrophy (ASH) in patients with severe aortic stenosis (AS) has been associated with increased perioperative morbidity and mortality in smaller studies with severe aortic stenosis (AS). This association has not been tested in a large, longitudinal study. Methods: Clinical, echocardiographic and outcome data from 1730 patients with asymptomatic AS, participated in the Simvastatin Ezetimibe in Aortic Stenosis study (SEAS), a randomized placebo controlled study evaluating the effect of lipid lowering medications on progression of AS, were used. ASH was considered present if interventricular septal/posterior wall thickness ratio exceeded 1.5. The association of ASH with rate of major cardiovascular (CV) events was tested in time-dependent cox-regression analysis. Results: During a median of 4.3 years follow-up, ASH developed in 17.0 % of patients, and was associated with higher left ventricular mass (LVM) and body mass index (BMI) compared to non-ASH patients (all p<0.05). In timevarying Cox regression analysis, ASH predicted a 50% greater incidence of ischemic CV events (ICE), a 63% greater incidence in the need for coronary artery bypass grafting (CABG) at the time of aortic valve replacement, and a 2fold higher incidence of hospitalization for heart failure due to progression of AS (CHFAS) independent of important confounders (all p<0.05) (Table). Conclusions: Development of ASH during progression of AS was a strong predictor of major CV events in patients participating in the SEAS-study. Table. Results are presented as Hazard ratio (95% Confidence Interval). ICE(n=322) CABG (n=165) CHFAS(n=47) Asymmetric septal hypertrophy 1.44(1-11-1.88)* 1.63 (1.13-2.32)* 2.26(1.21-4.22)* Aortic valvular velocity (m/sec) 1.25(1.08-1-44)* 1.74(1.44-2.14)ƚ 1.92(1.33-2.78)* Simvastatin/Ezetimibe treatment 0.77(0.62-0.96)* 0.66(0.46-0.90)* 1.03(0.58-1.82) Left ventricular mass (g) 1.00(1.00-1.00)* 1.00(0.99-1.00) Hypertension 1.95(1.36-2.81)ƚ 2.13(1.26-3.64)* P-value: *<0.05, ƚ <0.001 65 Actigraph-measured Daytime Sleep and Activity of Daily Living in Norwegian Nursing Home patients. The COSMOS Study (2013-2016) 1 1 1 T. Elvegaard , B.S. Husebo , E. Flo (poster presentation) Centre for Elderly and Nursing Home Medicine, and Research Group of General Practice, Department of Global Public Health and Primary Care, University of Bergen, Norway. 1 Background: More than 90% of Nursing Home (NH) patients with dementia develop neuropsychiatric symptoms (NPS) including agitation, depression, anxiety, and sleep problems during the course of the disease. Lack of activities has been associated with reduced mental and physical functioning and Quality of Life. Contrariwise, structured activities are shown to reduce NPS in NHs. Aims: To compare the physical activity and circadian rhythms of NH patients registered with actigraphs with the Proxy-Rater scores of the activity of daily living (ADL), neuropsychiatric inventory (NPI) and patient-specific activity logs. Methods: COSMOS is a 4-month effectiveness implementation-hybrid trial with follow-up at month 9 (data are collected at month 0, 4 and 9). The trial includes 520 patients from 64 NH units across Norway. The intervention consists of a 2-day educational program. Guidelines, patient-logs, and flashcards, as well as telephone support and a 2-month evaluation ensure implementation. The control group continues with current best practice. Outcome measures include actigraphy, patient-specific activity logs, NPI and ADL. The patient wears an actigraph on their dominant arm for 7 days at months 0 and 4. The actigraph objectively records both night- and daytime activity, yielding data on sleep-wake rhythms and movement. Baseline data investigate the association between proxy-rated activity, function, NPS and objective measures of activity by ADL, NPI and actigraphy. Discussion: Lack of educated staff, and high turnover may lead to a less systematic activity schedule. The comparison of objective measures of activities and proxy rating of patient function and activity provides important insight to the provision of activities in NHs. 66 Monomers Are Released After Orthodontic Bonding Håkon Gulliksen1, Marit Midtbø1, Inger Kleiven2, Hanne Wellendorf2, Nils R. Gjerdet1 1 Department of Clinical Dentistry, Faculty of Medicine and Dentistry, University of Bergen, 2 Norway and Nordic Institute of Dental Materials, Oslo, Norway Objective: The aim of this study was to estimate the release to saliva of monomers associated with bonding of fixed orthodontic appliances. Materal and methods: The study group constituted 30 children (mean age 13 years) scheduled for orthodontic treatment at the University Clinic, Bergen, Norway. Following rinsing with ultrapure water, unstimulated saliva was collected for 5min immediately before (A-samples), after bonding of brackets (B-samples), and at 3-6 weeks (C-samples). Brackets precoated with adhesive (TransbondPlus, 3M-Unitek) were used with the corresponding self-etch primer. Following the B-sample NiTi-type of achwires and elastomeric ligatures were placed. Most patients had molar bands cemented with glass-ionomer cement (Multi-Cure GIC, 3M-Unitek). The saliva samples were analysed by as chromatography/mass spectrometry (GC/MS) and liquid chromatography/ mass spectrometry (LC/MS) for different monomers (HEMA, TEGDMA, Poly-EGDMA, BMAEPH and Bis-GMA). Stata 13.1 was used for statistics. The clinical study was approved by the Regional Committee for Research Ethics. Results: Salivary levels of Poly-EGDMA, BMAEPH and HEMA were detectable in the B-samples at 42.1µg/m, 10.00µg/ml, and 30.0µg/ml, respectively. These monomers were not detectable in the A- or C-samples. TEGDMA and Bis-GMA were not detected in any of the samples. Conclusion: The release of monomers to saliva from bonded brackets and molar bands is transient, returning to below detectable amounts for GC/MS and LC/MS within 3-6 weeks. 67 Saksliste til generalforsamling Tidspunkt: søndag 23.oktober 2016, kl. 13.00-14.00 Sted: Odontologibygget, Bergen Sak 01-16 Sak 02-16 Sak 03-16 Sak 04-16 Sak 05-16 Godkjenning av innkalling. Valg av referent og ordstyrer. Årsmelding Regnskap Valg av vertsby for Frampeik 2017 Eventuelt Vel møtt til Generalforsamling! Frampeik-komiteen 2016 V/Tony Elvegaard Leder 68 Participants Akerkar Amundsen Arctander Rosenlund Bakken Barua Bergsmark Boland Bremnes Borge Coucheron Derouiche Duus Einarsen Ellingsen Elvegaard Engebretsen Fagerholt Frugård Habiger Giriteka Gjerde Grindstad Gullhav Hansen Gulliksen Hjøllo Hoel Hosar Høigaard Isaksen Jacobsen Johansen Shreeram Vivian S. Ingrid UiB UiO UiT Rasmus Imon Camilla Solveig Thomas Hanne Tina Sonja Inger Hødnebø Eigir Trygve Sølberg Tony Anja Susanne Oda Helen Eck Torstein Lionel Christiane Helgestad Thea Lisa Håkon Torunn Fredrik Rannei Maria Sylvia Hetlelid Martha Rolland Silje Susanne Pettersen Simon UiB UiO UiO UiB UiT UiB UiT UiT UiB UiB UiT UiB NTNU UiB UiB UiB UiB UiT UiT UiB UiB UiB NTNU NTNU NTNU UiB Tromsø UiT 69 Kildal Klæstad Knutsen Koppen Korkosh Kristiansen Krogh Aarebrot Lappegård Larsen Leiten Lund Løvik Madsen Mclean Myklebust Myklebust Ernø Mynarek Nypan Næss Olsen Pannu Paulsen Raa Radunovic Runde Schanche Skille Skjefstad Skjold Småbrekke Solvin Stangeland Staniszewski Stautland Elise Christina Elias Mohammed Bayar Elise Anders Jostein Christopher Storm Elise Orvedal Anders Katja Anders Emily Ivar Inger Thea Maren Erik Morten Svendsen Eirik Birkelund Mehma Benedikte Anette Matej Henrik Alexander Torstein Hanne Kaja Anneli Silje Åshild Øksnevad Marcus Kordian Andrea Åsta NTNU NTNU NTNU UiO UiO UiB UiT UiO UiB UiB UiB UiB UiB NTNU UiO NTNU NTNU UiT UiT UiB UiT UiB UiB NTNU UiT UiT UiT UiB UiT NTNU UiB UiB UiB UiB 70 Sulen Svanøe Svendsen Taraldsen Tislevoll Tran Uhlving Larsen Warlo Willassen Willems Xu Yi Amalie Abrahamsen Tuva Maria Dalen Benedicte Sjo Long Anette Ellen Mathea Kirsch Lisa Aron Linda Zi Yan Dag UiB UiT NTNU UiB NTNU UiT UiO UiB UiB UiB UiB 71 72 Sponsors 2016 73 74