KI News

Researchers at Karolinska Institutet and the University of Helsinki have discovered previously uncharacterized mutational patterns in the human regulatory genome, in gastrointestinal tract and other cancers. The study is published in the journal Nature Genetics. Mutations that lead to cancer are not only occurring in the 2 percent of the DNA that encodes for proteins, but also in the non-coding regions.  These regions are determining when and where the genes are expressed. In the largest cancer genome study performed in the Nordic countries, researchers lead by Professors Lauri Aaltonen and Jussi Taipale, studied more than two hundred whole genomes from colorectal cancer samples. The scientists detected a distinct accumulation of mutations at sites where the proteins CTCF and cohesin bind to the DNA. Both CTCF and cohesin are transcription factors carrying out essential functions in the genome, including regulation of gene expression and chromatin structure. Hypermutated tumors According to the findings, in hypermutated tumors CTCF/cohesin sites appear to be protected from mutations. In contrast, in another group of tumors these sites are mutated with a higher frequency than protein coding cancer genes. Tumors with high CTCF site mutation load tend to have a greater frequency of certain types of mutations, distributed throughout their genome. The process producing these mutations is not fully understood and needs further investigation. “Until now the complete mutational pattern of colorectal cancer genomes has been poorly characterized”, says Jussi Taipale, Professor of medical systems biology at Karolinska Institutet’s Department of Biosciences and Nutrition. “Unraveling the underlying mechanisms of regulatory mutations in cancer remains a great challenge. These novel findings are significant and an important step towards understanding the cause and consequences of cancer-associated mutations.”    This project was supported by the Academy of Finland Centre of Excellence for Cancer Genetics, the EU FP7 project SYSCOL, the Jane and Aatos Erkko Foundation, the Finnish Cancer Society, ERC, the Sigrid Juselius Foundation, NIASC, NordForsk and State research funding of Kuopio University Hospital. Publication CTCF/cohesin-binding sites are frequently mutated in cancer Riku Katainen*, Kashyap Dave*, Esa Pitkänen*, Kimmo Palin*, Teemu Kivioja, Niko Välimäki, Alexandra E Gylfe, Heikki Ristolainen, Ulrika A Hänninen, Tatiana Cajuso, Johanna Kondelin, Tomas Tanskanen,  Jukka-Pekka Mecklin, Heikki Järvinen, Laura Renkonen-Sinisalo, Anna Lepistö, Eevi Kaasinen, Outi Kilpivaara, Sari Tuupanen, Martin Enge, Jussi Taipale & Lauri A Aaltonen Nature Genetics, published online 08 June 2015, doi: http://dx.doi.org/10.1038/ng.3335 ​* These authors contributed equally to the work

As part of a state visit to Sweden, the president of Tanzania, Jakaya Kikwete, stopped off at Karolinska Institutet, which has a long history of scientific collaboration with his country. The President’s visit to the university took him to a lab for malaria research. The Tanzanian president Jakaya Kikwete arrived in Sweden for his three-day visit on 3 June on the invitation of Prime Minister Stefan Löfven. The programme included a visit to Karolinska Institutet, which has had a long-standing and extensive scientific partnership with Tanzania centring mainly on women’s and children’s health, healthcare systems, malaria and HIV/Aids. The delegation was welcomed to Aula Medica by Deputy vice-chancellor for International Affairs Maria Masucci, pro-Vice-Chancellor Kerstin Tham and Dean of Doctoral Education Anders Gustafsson.  Since 2009, KI has had a cooperation agreement with Muhimbili University of Health and Allied Sciences (MUHAS) in Tanzania and together they have educated a great many doctoral students. KI has also had more joint publications with MUHAS than with any other African university. KI has also participated in Sida-financed projects between research institutions in Tanzania and Sweden. Helena Kopp Kallner, researcher at the Department of Women’s and Children’s Health, talked about how the work they were doing under the WHO’s collaborating centre on reproductive health has led, amongst other things, to new, safer emergency contraceptive pills and simpler medical abortions. Globally, unsafe abortions are a common cause of death amongst women of fertile age. The research done by the centre recently showed that the treatment of incomplete terminations with misoprostol can be effected just as safely by midwives in rural Uganda as by doctors. This has improved access to treatment and saved many women’s lives. Anders Björkman, professor of infection diseases, at the Department of Microbiology, Tumour and Cell biology and his departmental colleague docent Andreas Mårtensson, spoke of the over thirty-year collaboration between KI and Tanzania in malaria research. “We’ve built up an equal partnership in which both parties bring their own experiences to the table,” says Professor Björkman. “We get to share local knowledge about malaria and have been able to contribute new technologies. It’s been a fruitful relationship from both sides.” One of the concerns on which the partnership is currently focusing is combating malaria on the island of Zanzibar off the Tanzanian coast. The delegation then moved on to the Department of Microbiology, Tumour and Cell Biology, where Richard Mwaiswelo, doctoral student at MUHAS who is working on part of his project at KI, demonstrated some of the instruments he uses in his research on the effects of malaria drugs and the development of resistance to them. As president, Jakaya Kikwete has shown great interest in maternal and infant health. He was also recently made chairperson of the UN Secretary General’s High-Level Panel on Global Health Crises. The presidential visit also included an audience with the King of Sweden and talks with the Prime Minister and Minister for Foreign Affairs. Text: Sara Nilsson

Researchers from Uppsala University and Karolinska Institutet have studied the risk of dying over the next five years. They have developed a unique health-risk calculator by using one of the world’s largest study material, UK Biobank, containing data from nearly half a million people. The results are expected to have large areas of application both in the clinical setting, public health policy and in research. "We show that, using a few simple questions, one can predict the risk of dying within five years with greater reliability than in any other way we know today”, says Erik Ingelsson, a professor at Uppsala University who headed the study that has now been published in The Lancet. “We think our study and the associated risk calculator will become an important tool for a wide range of researchers, but also for doctors, decision-makers and the public.” UK Biobank contains data on as many as 655 variables collected from around half a million British people aged 40–70. Studies of the associations between one or a few risk factors and future mortality risk have been carried out previously in smaller studies, but none has been based on such extensive data material. By using a computer algorithm, Professor Ingelsson and his colleague Andrea Ganna at Karolinska Institutet were also able to pick out the combination of questionnaire items with the highest accuracy. The outcome was 13 questions for men and 11 for women, and on the basis of the replies to these questions a person’s ‘Ubble age’ can be calculated. If this is lower than the actual age, it means that the person’s risk of dying is lower than the average for people of the same sex and age, and vice versa. The researchers have also been working with web technicians and designers to develop a simple, user-friendly web tool for visualizing all results, and enabling five-year mortality risk and Ubble age to be calculated. This research was funded by the Knut and Alice Wallenberg Foundation and the Swedish Research Council. Read more in a press release from Uppsala University Publikation 5 year mortality predictors in 498 103 UK Biobank participants: a prospective population-based study Andrea Ganna, Erik Ingelsson The Lancet, published online 03 June 2015, DOI: http://dx.doi.org/10.1016/S0140-6736(15)60175-1

The smoking cessation drug varenicline has been reported to increased risks of suicidal behaviour, traffic accidents and violence, amongst other things. However, a new registry study from Karolinska Institutet and Oxford University now shows that there is no good scientific evidence for such adverse events due to the drug. The findings are being published in the BMJ. Varenicline (trade name Champix) was introduced to the market in 2006, and is today widely prescribed for the treatment of nicotine dependence. At the same time, reports that the drug may be linked with increased risks of suicidal behaviour, depression, psychoses and violence have led regulatory agencies in Europe and the US to issue warnings. Varenicline use has also been restricted or prohibited for several transportation industry professions, including pilots, air traffic controllers, truck and bus drivers, and certain military personnel, due to reports of increased traffic accidents. The current study is based on 69,757 individuals in Sweden aged 15 or above, who were prescribed varenicline between 2006 and 2009. The research team examined associations between the use of varenicline and a range of adverse outcomes, such as suicidal behaviours, depression, criminal offending, transport accidents, traffic-related offences, and psychoses. They adjusted carefully for known risk factors such as age, sex and pre-existing psychiatric disorders, and performed a novel analysis by examining rates of adverse outcomes in the same person during periods of medication and non-medication. National registers were used to collate information on criminal convictions, psychiatric conditions, suicidal behaviour, transport accidents and traffic offences, and substance abuse. Pre-existing psychiatric disorders The results show that varenicline was not associated with significant increases in suicidal behaviour, criminal offending, transport accidents, traffic offences, or psychoses. A small increased risk of mood and anxiety conditions during periods of medication was found, however, in individuals with pre-existing psychiatric disorders, which the authors say “requires confirmation using other study designs.” “Overall, our results suggest that previous reports linking the use of varenicline to several adverse events may not have taken full account of underlying risk factors, for example concurrent use of other drugs”, comments study co-author Dr Yasmina Molero at Karolinska Institutet’s Department of Medical Epidemiology and Biostatistics. “These findings may also be generalizable to other high income countries like the UK and USA, due to similar prescribing patterns and rates of these outcomes.” The study was funded with grants from Karolinska Institutet, the Swedish Research Council, FORTE (Swedish Research Council for Health, Working Life, and Welfare), and the Wellcome Trust. Participating investigators are affiliated to the Department of Medical Epidemiology and Biostatistics, and the Department of Clinical Neuroscience, Karolinska Instiutet, and to the Department of Psychiatry at University of Oxford, UK. This news article is an abbreviation of a press release from the BMJ. View an abstract movie about this research Publication Varenicline and risk of psychiatric conditions, suicidal behaviour, criminal offending, and transport accidents and offences: population based cohort study Yasmina Molero, Paul Lichtenstein, Johan Zetterqvist, Clara Hellner Gumpert, Seena Fazel BMJ 2015;350:h2388, online 2 June 2015, doi: 10.1136/bmj.h2388

The President of India is currently on a state visit, the first ever made by an Indian head of state to Sweden. During his time here, President Pranab Mukherjee visited Karolinska Institutet in the company of Their Royal Highnesses King Carl Gustaf and Queen Silvia. Helene Hellmark Knutsson, Minister for Higher Education and Research was also among the visitors. The visit commenced at the Nobel Forum, where Vice-Chancellor Anders Hamsten talked about Karolinska Institutet and its partnerships with India, and welcomed more Indian students to KI “because the ones we’ve had have been excellent”, he said. Professor Juleen R Zierath from the Department of Molecular Medicine and Surgery talked about new strategies and cooperation alliances for the treatment of diabetes, which still lacks a cure. She was followed by Dr Sven Hoffner, docent at the Department of Microbiology, Tumour and Cell Biology, who spoke about the production of the first new tuberculosis drug in 40 years, a project in which he has been actively involved, and about collaborations between researchers at KI and their Indian partners. A view of the changing landscape The delegation then moved on to Aula Medica, where Professor Hamsten showed his guests the model of the Solna campus and the buildings of the emerging new Hagastaden district, including the Biomedicum research laboratory, which he had mentioned in his presentation earlier. The hour-long visit concluded on the seventh floor of the auditorium, where the visitors could see with their own eyes how the local landscape is changing.  The visit to KI was a welcome item on the president’s state visit programme, says Banashri Bose Harrison, the Indian ambassador to Sweden, who was amongst the Indian VIPs.  “The Indian government is committed to making sure that its people receive top quality healthcare,” she said. “Karolinska Institutet is one of the world’s leading institutions for healthcare research and innovation and plays a key role in the partnership between India and Sweden in this vital field.”  Growing relationship between India and KI Last week, Ms Bose Harrison attended a seminar at KI on the growing relationship between India and KI, manifested, for example, in the increasing number of published scientific papers co-authored by researchers from India and KI, and the many doctoral students and postdoc researchers from India currently at the university. “It’s really exciting to have the president here,” says Professor Cecilia Stålsby Lundborg from the Department of Public Health Science and academic coordinator of KI’s partnership with India. “It feels wonderful to have the head of state of one of the biggest countries in the world not only visiting Sweden but also coming to KI! The scientific relationship between India and Sweden is active and this year and next we expect new funding announcements from Swedish and Indian research financiers.” This, the first ever official visit by an Indian head of state to Sweden, commenced on 31 May with a meeting with Prime Minister Stefan Löfven and members of the Riksdag, and is due to end today (2 June). The programme, with its focus on the themes of innovation, sustainable development and Life Science research, has also included a royal dinner and a visit to Uppsala University. Text: Sara Nilsson, Madeleine Svärd Huss Photo: Ulf Sirborn  

A research institute has been founded in China in the name of Bengt Samuelsson, Professor Emeritus and former Vice-Chancellor of Karolinska Institutet. The Bengt Samuelsson Institute of Life Science was inaugurated on April 22 in Jiangyin City, China. Bengt Samuelsson was awarded the Nobel Prize in Physiology or Medicine in 1982, together with Sune K Bergström and John R Vane, for his research on prostaglandins and related biologically active substances. In 2013, the governments of Wuxi Prefecture and Jiangyin City of Jiangsu Province, China, decided to support the foundation of a research institute in his name. The institute is located in Jiangyin National High-Tech Park. The institute will focus on the development and industrialisation of biomedical and pharmaceutical projects. One of the functions of the institute will be to transfer pharmaceutical and biomedical projects from Sweden to China. Initially, the projects and products will focus on anti-inflammatory proteins applicable to disorders of the skin, mucosa, and bone. Text: Karin Söderlund Leifler Read another article about Bengt Samuelsson on KI News: ”Celebrating a Nobel Prize Laureate – Professor Bengt Samuelsson”

A new study published in the journal World Psychiatry shows that the use of certain drugs that affect the central nervous system may be associated with an increased risk of committing a homicide. The greatest risk was recorded in the use of tranquillizing benzodiazepines and painkillers, while anti-depressants were associated only to a slightly elevated risk. In recent years, there has been plenty of debate over whether psychotropic drugs, and especially anti-depressants, can cause violent behaviour. In particular, this debate has been fuelled by massacres committed by young persons in schools and other public places in the US and other countries, too. To investigate this claimed link between certain drug use and crime, the international research team, led by Professor Jari Tiihonen at Karolinska Institutet’s Department of Clinical Neuroscience, analysed the use of prescription drugs of 959 persons convicted of a homicide in Finland during 2003 to 2011. The registers used were the Finnish Homicide Database of the Institute of Criminology and Legal Policy, and the Finnish Prescription Register of the Social Insurance Institution of Finland. After confounding factors were controlled for, the results show that the use of anti-psychotics was not associated with a significantly increased risk of committing a homicide, whereas the use of anti-depressants was associated with a slightly elevated risk, and the use of benzodiazepines (drugs used to treat anxiety and insomnia) with a significantly elevated risk. Anti-inflammatory painkillers Somewhat surprisingly, the study also found that the highest risk of committing a homicide was associated with opiate painkillers and anti-inflammatory painkillers. Although the use of intoxicants was present in the majority of the homicides, the differences between the drug groups could not be explained by simultaneous intoxicant use.  “In many cases, benzodiazepines had been prescribed in very high doses and for a long period of time”, says Dr Tiihonen. “Benzodiazepines can weaken impulse control, and earlier research has found that painkillers affect emotional processing. Caution is advisable in prescribing benzodiazepines and strong painkillers to people with a history of substance abuse.” The study was carried out in collaboration between Karolinska Institutet and several organisations in Finland; the University of Eastern Finland, Niuvanniemi Hospital, the National Institute for Health and Welfare, the National Research Institute of Legal Policy, Kuopio University Hospital, Helsinki University Hospital, the University of Helsinki, the Kela Research Department, and Epid Research Ltd. This news article is an abbreviation of a press release from University of Eastern Finland. More about Jari Tiihonen's research group Publication Psychotropic drugs and homicide: a prospective cohort study from Finland Tiihonen J, Lehti M, Aaltonen M, Kivivuori J, Kautiainen H, Virta L, Hoti F, Tanskanen A, Korhonen P World Psychiatry 2015, Epub June 1, 2015, doi: 10.1002/wps.20220  

SciLifeLab strengthens its available infrastructure and offers further support to Swedish researchers with activities at universities in Gothenburg, Linköping, Lund and Umeå. To widen the range of technologies and competences that are available for Swedish researchers within Science for Life Laboratory (SciLifeLab) the board has decided to integrate technology competences from other Swedish universities into the center. These technology laboratories will complement the current center infrastructure and will be integrated into the SciLifeLab technology platform organization. At the SciLifeLab board meeting April 13 it was decided that six such facilities will be financed and integrated in the center as of 2016. ”The expansion of SciLifeLab with complementary technologies means that researchers from all over Sweden get access to additional technologies and competences. It also facilitates collaboration between research groups at the involved universities and strengthens Swedish research and makes it more competitive internationally”, said Göran Sandberg, Chair of the SciLifeLab board.  Read more about this effort in a press release from SciLifeLab

A new study from Karolinska Institutet suggests that the management concept Value-Based Health Care (VBHC) is frequently misinterpreted and misunderstood by researchers. According to the study, which is being published in the journal BMJ Quality & Safety, this conceptual confusion may contribute to the carousel-like rapid replacement of management ideas in health care. Politicians and other decision-makers often apply different management theories to drive improvement projects in health and medical care. Six Sigma, Total Quality Management and Lean Management are just some examples that have found their way into health and medical care. Many theories are also linked to New Public Management (NPM), which has recently attracted considerable attention and criticism about the ways in which different management systems affect the public sector. ­­“One of the problems with these management concepts is that many are trend-driven. As soon as one health care organisation adopts a particular model, management decides that it's time to switch to the next. Many of these concepts essentially contain the same ideas but use different terminology. Research has labelled this phenomenon, which occurs in three- to five-year cycles, as Pseudo-Innovation,” says Carl Savage, senior researcher at Medical Management Centre, Karolinska Institutet. The most recent management concept to gain a foothold in health care is VBHC, which is aimed at measuring the effects of health care (rather than how much is produced) and comparing it with the costs. VBHC is currently being introduced at a number of hospitals in Sweden including the University Hospital in Uppsala and the Sahlgrenska University Hospital in Gothenburg. VBHC will also be a cornerstone at the future New Karolinska Solna Hospital. Identify a trend-starting article In the study, the researchers at the Medical Management Centre have scrutinised 199 scientific articles that reference VBHC. They have used a novel approach where they first identify a trend-starting article and then analyse how researchers cite that article. The results show that more than one-quarter of all researchers who cite the trend-starting VBHC article have failed to grasp the concept's key aspects. Furthermore, this understanding does not appear to have improved over time, which suggests that the researchers have not contributed to developing the concept. According to the researchers behind the study in question, this conceptual confusion among colleagues is cause for concern. If the supposed experts do not know what VBHC is, there is a big risk that neither will the decision-makers in health care. “A weak understanding of the implications of VBHC makes it difficult for decision-makers, supervisors and clinics to realise these ideas to their full potential. There is also a risk of resources going to waste if our dedication to improving health care is lost because we keep reaching for new trends instead of understanding, implementing and evaluating the management concepts to their fullest extent,” says Jens Jacob Fredriksson, MD, a PhD student and one of the researchers behind the study. The Medical Management Centre is part of the Department of Learning, Informatics, Management and Ethics at Karolinska Institutet. Publication Pseudo-understanding: an analysis of the dilution of value in healthcare Jens Jacob Fredriksson, David Ebbevi, Carl Savage  BMJ Quality & Safety, online 14 May 2015, doi:10.1136/bmjqs-2014-003803

Some 900 guests, supervisors and families along with the KI management and honoured guests gathered in the Blue Hall of the Stockholm City Hall on 22 May to celebrate the graduation of 126 new doctors and four honorary doctors. Present were the new honorary doctors of medicine Tak W Mak, professor at Toronto University, Canada; Bertil Hållsten, doctor of economics and founder of the Hållsten Research Foundation; Barry Everitt, professor of neurological behavioural science at the University of Cambridge, UK; and Mariam Claeson, director of Maternal, Newborn and Child Health at the Bill and Melinda Gates Foundation, USA. The four honorary doctors were presented with a hat and a diploma and honoured with a cannon salute from the City Hall quayside before the student ceremonial stewards led, in turn, each of the 126 new doctors by the arm to receive their own symbols of graduation, the hat and the diploma. Once the applause of the guests had faded amongst the spring flowers that decorated the hall, it was time to pass into the Golden Hall for the banquet. Tak W Mak held a speech on behalf of the honorary doctors and directed particular words of hope to the new doctors: “Thanks to you, beautiful blossoms are in the future”. Photo credit: Ulf Sirborn

An ongoing case in which Karolinska Institutet is investigating alleged scientific misconduct has attracted considerable attention in the Swedish and international media. There are two parts to the case. Firstly, there are the scientific papers that had been published following three operations involving the grafting of a synthetic trachea. It is the responsibility of Karolinska Institutet’s vice-chancellor to investigate suspicions of scientific misconduct. Secondly, there are the operations that were carried out at Karolinska University Hospital, which are the subject of an inquiry led by the Health and Social Care Inspectorate. The Swedish Medical Products Agency (LMV) has received a complaint regarding a possible breach of the pharmaceuticals legislation. LMV has filed a report with a prosecutor to ascertain the legal situation. Find information on complaints concerning previously performed tracheal operations and their investigation.

A novel study from Karolinska Institutesuggests that RAS-antagonists, common drugs for patients with heart failure, may benefit also patients who have concomitant kidney disease, a group previously not studied. These drugs have proven effect in heart failure, but patients with kidney disease were excluded from clinical trials due to fear of kidney complications. While kidney complications are still a potential concern, this new study, which is presented at the annual congress of the European Society of Cardiology Heart Failure Association, and published concurrently in the European Heart Journal, suggests that the net effect may be beneficial. In the current study, a Swedish team comprising researchers at Karolinska Institutet, Linköping University, Stockholm South General Hospital, and Karolinska University Hospital analysed data from 24,000 patients from the nationwide Swedish Heart Failure Registry (SwedeHF). Patients with heart failure and chronic kidney disease who were treated with RAS-antagonists (ACE-inhibitors or angiotensin receptor blockers) had better survival than un-treated patients. Reduction in mortality The difference persisted after adjustment for a large number of other factors, such as patient age and measures of general health, and the final decrease in mortality was 24 percent. The reduction in mortality was similar to that in patients without kidney disease which was in turn similar to that in randomized trials. “This study was large and rigorous but cannot prove that RAS-antagonists are beneficial”, says Dr Lars Lund at the Department of Medicine, Solna, who led the study. “It provides a rationale for performing large-scale randomized trials with this inexpensive category of drugs for the common combination of heart failure and kidney disease. Indeed, Swedish health care and national population registries provide an ideal setting for a novel concept, so called registry-randomized trials.” The work was financed by the Swedish Research Council, The Swedish Heart-Lung Foundation, the Stockholm County Council and the Swedish Association of Local Authorities and Regions. View our press release about this research Publication Association between renin-angiotensin system antagonist use and mortality in heart failure with severe renal insufficiency – a prospective propensity score-matched cohort study Lars H Lund, Lina Benson, Ulf Dahlström, Magnus Edner European Heart Journal, 23 May 2015

Karolinska Institute’s wholly owned company, Karolinska Institutet Holding AB, has signed an agreement with Johnson & Johnson Innovation. The collaboration aims to strengthen innovation at Karolinska Institute and integrate it into product and business development, and implementation of health care. At the same time a research collaboration is established between Karolinska Institutet and Janssen Pharmaceuticals. As part of the collaboration, Johnson & Johnson Innovation will establish a life science innovation hub at Karolinska Institutet to work with Karolinska Institutet Holding AB, to support and drive the growth of life science companies rooted in academic medical research. Promising projects in the Nordic life science industry should be supported to develop services and products to support patients and consumers. The collaboration benefits between Karolinska Institutet Holding AB and Johnson & Johnson Innovation serves to meet the needs of entrepreneurs in the pharmaceutical, medical technology and healthcare sectors. It will include knowledge sharing, establishment of coaching and scouting programs, investments in developing ideas into finished concepts, and funding for start-ups. “One of the main missions of Karolinska Institutet is to help develop medical discoveries into innovations and products for the benefit of patients”, said Professor Anders Hamsten, vice-chancellor of Karolinska Institutet. “An important part of our strategy for the years to come is to establish collaborations with industry so as to strengthen innovation at our university and support corporate development from new discoveries and the implementation in health care. The collaborations with Johnson & Johnson Innovation and Janssen are an important step in that direction.” While launching this Karolinska Institutet collaboration with the pharmaceutical company Janssen Pharmaceuticals NV, one of the Janssen Pharmaceutical Companies of  Johnson & Johnson, a number of research posts have been created for observational studies (Real World Evidence). The focus of this cooperation is the follow-up and effects of disease and treatment, using routine data from health care ("Real World Data") and how they relate to effects in clinical trials, all while social and economic factors will be evaluated. The research will initially focus on method development, depression, prostate cancer, psoriasis, and cancers of the immune-system. The collaboration between Karolinska Institutet and Janssen will be led by Johan Askling, professor at the Department of Medicine in Solna. “We will, among other things, study the relationship between data from randomized trials and observational data from clinical practice, in order to increase understanding of how these can be made comparable, and how observational data can be used as an adjunct to clinical trial data” said Johan Askling.

In a new study led from Karolinska Institutet, researchers report that people can be conditioned to associate images with particular pain responses – such as improved tolerance to pain – even when they are not consciously aware of the images.  The findings are being published in the journal PNAS. Previous studies have shown that a person’s pain experience can be increased or decreased by associating a specific cue, such as an image, with high or low intensity pain. However, until now it has been unclear if it is necessary to be consciously aware of the cue in order to learn the association. In this recent study, Dr. Karin Jensen and colleagues tested whether unconscious learning affected pain responses, by using subliminal images and training participants to associate a certain image with high pain and another image with low pain. The study involved 49 participants in all, randomly assigned into four experimental groups that would elucidate the impact of different levels of conscious awareness during the experiment. All participants were generally healthy, with no chronic illnesses or psychiatric diagnoses. None of the participants reported receiving any medication apart from hormonal contraceptives. In the experiment, images of different faces were presented on a computer screen. To some of the participants the images were shown so quickly that they could not be consciously recognized. For each image exposure, participants were subjected to pain stimulation and asked to rate the pain according to a specific scale. As each image was repeatedly associated with either high or low pain, it turned into a high pain cue or a low pain cue that would affect the participants’ expectations. Without conscious awareness The results suggest that pain cues could be learned without conscious awareness, as participants reported increased pain when shown the high pain image and reduced pain when shown the low pain image during identical levels of pain stimulation, regardless of whether or not the images were shown subliminally,  “These results demonstrate that pain responses can be shaped by learning that takes place outside conscious awareness, suggesting that unconscious learning may have an extensive effect on higher cognitive processes in general”, says Karin Jensen. This work was funded by the Osher Center for Integrative Medicine at Karolinska Institutet, and support was also provided by a NCCIH/NIH Grant. The study was conducted by researchers from the Osher Center at the Department of Clinical Neuroscience at Karolinska Institutet, Sweden and from Beth Israel Deaconess Medical Center and Harvard Medical School, USA. View our press release about this study Publication Classical conditioning of analgesic and hyperalgesic pain responses without conscious awareness Karin Jensen, Irving Kirsch, Sara Odmalm, Ted J. Kaptchuk, and Martin Ingvar PNAS, published ahead of print May 15, 2015, doi:10.1073/pnas.1504567112

As the only researcher active in Sweden out of a total 58, professor Thomas Helleday has been elected as a new member of EMBO 2015. EMBO – the European Molecular Biology Organization – is a very highly regarded European organisation which promotes quality in research in the field of life science. More than 1,700 leading researchers have been elected thus far, of which 50 are Swedish, and 24 of these from Karolinska Institutet. Read the press release from EMBO

A new study led from Karolinska Institutet shows that although individual components of a healthy so-called Nordic diet previously have been linked to beneficial effects on cardiovascular health, as well as to other health effects, there is no evidence of an association with cardiovascular events in a general population. The study, which was conducted in in over 40,000 Swedish women, is being published in the Journal of Internal Medicine. Cardiovascular disease, such as heart attack and stroke, is a leading cause of death worldwide, and it has long been known that dietary factors have an important influence on cardiovascular health. Previous studies have shown beneficial effects of a healthy Nordic diet – comprising whole grain bread and oatmeal, fruit (apples/pears), vegetables (root vegetables and cabbage) and fish – on short-term markers of cardiovascular health, for example lower blood pressure and weight loss. Several studies have also showed beneficial effects of individual components included in the Nordic diet on cardiovascular events. However, the current study is the first to investigate the overall, long-term association between a healthy Nordic diet and the incidence of cardiovascular disease in the general population. The study was conducted in 43,310 middle-aged Swedish women. The participants answered questions in 1991/92 about their food intake, and the incidence of cardiovascular disease was recorded through the Swedish registries over approximately 20 years until the end of 2012. During the follow-up period, nearly 20% of the women developed cardiovascular disease. However, unexpectedly given the results of previous studies, the beneficial effect of a healthy Nordic diet did not register when looking at the incidence of concrete, cardiovascular events in the general population. “The reason for this for this discrepancy could be that previous studies showing effect of a healthy Nordic diet were intervention trials, which means participants had a very high adherence to this particular diet and also were selected, high-risk persons in relation to developing cardiovascular disease, whereas the present study expected a lesser degree of adherence, and looked and a group of overall healthy women”, says first author Nina Roswall, PhD, at the Department of Medical Epidemiology and Biostatistics, Karolinska Institutet. Alcohol consumption or smoking An additional goal for the research team was to determine whether any relationship between the healthy Nordic diet and cardiovascular disease is modified by age, weight, alcohol consumption or smoking. Their results show that alcohol intake, weight (BMI) and age did not have any significant affect. “We did manage to show a beneficial effect of this diet among former smokers”, says Professor Elisabete Weiderpass, PhD, who supervised the study. “However, this may be due to the fact that smoking cessation is associated with dietary changes towards a healthier lifestyle, which may have affected the results. It is also important to point out that further investigation is required to confirm these findings.” Research organizations involved in this study, other than Karolinska Institutet, were the Danish Cancer Society Research Center, University of Auckland, New Zealand, Harvard School of Public Health, USA, Folkhälsan Research Center, Finland, The Cancer Registry of Norway, The Arctic University of Norway, and University of Tromsö, also in Norway. The investigation was supported by a grant from the Swedish Research Council. Publication No association between adherence to the healthy Nordic food index and cardiovascular disease among Swedish women – a cohort study Roswall Nina, Sandin Sven, Scragg Robert, Löf Marie, Skeie Guri, Olsen Anja, Adami Hans-Olov, Weiderpass Elisabete Journal of International Medicine, first published online 19 May 2015, DOI: 10.1111/joim.12378

“Now you can help to raise the life quality of these vulnerable patients and like flashing beacons spread your knowledge of dementia care,” said Karolinska Institutet’s vice-chancellor Anders Hamsten as he congratulated the first ever six doctors able to call themselves Silvia doctors. “I hope you all feel pride in what you’ve achieved.” Queen Silvia herself presented the diplomas to the six doctors who will now be bearing her name. The doctors have all taken a one-year’s Master’s programme in dementia care held jointly by Karolinska Institutet and the Silviahemmet Foundation, and received their diplomas at a degree ceremony at Drottningholm’s slottsteater. Also present was Minister for the Elderly, Åsa Regnér. In this unique 18th century theatre, with its orchestra in period garb and an audience from all over the world, the Queen talked of her own mother’s dementia and of how the difficulties giving and receiving proper care made her start the Silvia home, which has always trained Silvia sisters – nursing auxiliaries specialising in dementia – and Silvia nurses. Now there are also the first Silvia doctors, amongst them Moa Wibom, consultant and specialist in public health at Ängelholm Hospital. “These two years will be of benefit to us and our patients throughout our careers and our lives,” she says.   Text: Sara Nilsson Photo: Gustav Mårtensson

An international research team, led from Sweden’s Karolinska Institutet, have presented new knowledge about what happens when type 2 diabetes develops. By studying the insulin-producing beta cells in mice in real time, they have managed to identify a key part of the process that leads to the death of beta cells. The study is being published in the journal PNAS. Type 2 diabetes is characterised by two main events in the body. At the initial stage the cells become insulin-resistant, i.e. insensitive to insulin. At the next stage, the insulin-producing beta cells, which are located in the islets of Langerhans in the pancreas, die. Exactly how the disease develops is still unknown, but investigators at Karolinska Institutet and colleagues from Singapore and the USA have added another piece of the jigsaw. Ten years ago researchers at Karolinska Institutet discovered that blood levels of apolipoprotein CIII (apoCIII) become elevated in diabetes. This causes certain specific calcium channels in the beta cell wall to be overactivated which produces excessive calcium levels inside the beta cells. This has a toxic effect and results in beta cell death. However, the effect of apoCIII can be prevented by blocking the calcium channels. In the study in question, researchers have used insulin-resistant mice with type 2 diabetes. Because of the disease, the mice had elevated levels of apoCIII in their blood. This apoCIII was mainly produced in the liver although the islets themselves could also produce apoCIII as a consequence of local islet insulin resistance. Beta cell function and survival in real time The researchers then used a self-developed technique to transplant islets of Langerhans to the anterior eye chamber – a technique that makes it possible to study beta cell function and survival in real time. Normal islets of Langerhans which produce apoCIII were transplanted to one eye while genetically modified, non-apoCIII-producing islets were transplanted to the other eye. The researchers' main finding was that the beta cells reacted differently in each case. Despite the islets in both eyes being exposed to elevated levels of apoCIII circulating in the blood stream, only the apoCIII-producing islets showed an inflammatory reaction and, thereby, cell death. In the case of the genetically modified, non-apoCIII-producing islets, the beta cells survived. “This shows that local production of apoCIII has damaging effects on beta cells. Circulating apoCIII had no direct damaging effect on the beta cell under type 2 diabetic conditions,” says Lisa Juntti-Berggren, chief physician and professor at the Rolf Luft Research Center for Diabetes and Endocrinology, Department of Molecular Medicine and Surgery at Karolinska Institutet. Blocking the production of apoCIII locally The researchers are currently proceeding with animal studies to investigate the possibilities of blocking the production of apoCIII locally in islets of Langerhans. “Our goal is to develop a treatment strategy where you can prevent type 2 diabetes from developing in individuals with a high risk of the disease; people with insulin resistance, for example,” says Per-Olof Berggren, professor at the Rolf Luft Research Center for Diabetes and Endocrinology, Department of Molecular Medicine and Surgery at Karolinska Institutet. The study in question is funded by the Swedish Diabetes Association, Karolinska Institutet, Swedish Research Council, Novo Nordisk Foundation, Knut and Alice Wallenberg Foundation, Skandia insurance company, Diabetes Wellness Foundation, Bert von Kantzow Foundation, The Family Erling-Persson Foundation, The Swedish Diabetes Foundation, Lee Kong Chian School of Medicine, Nanyang Technological University Start-Up Grant, The Stichting af Jochnick Foundation and Diabetes Research Institute Foundation. Our press release about this study Publication Apolipoprotein CIII links islet insulin resistance to β-cell failure in diabetes Karin Åvall, Yusuf Ali, Ingo B. Leibiger, Barbara Leibiger, Tilo Moede, Meike Paschen, Andrea Dicker, Elisabetta Daré, Martin Köhler, Erwin Ilegems, Midhat H. Abdulreda, Mark Graham, Rosanne M. Crooke, Vanessa S. Y. Tay, Essam Refai, Stefan K. Nilsson, Stefan Jacob, Lars Selander, Per-Olof Berggren and Lisa Juntti-Berggren PNAS, 4 May 2015, doi: 10.1073/pnas.1423849112

KI’s pro-vice-chancellor, Kerstin Tham, has been put forward as the new vice-chancellor of Malmö University, the only candidate to be considered by the university board following recommendation by its selection committee.   Kerstin Tham, who was made professor of occupational therapy at the Department of Neurobiology, Care Sciences and Society in 2009 and Karolinska Institutet’s pro-vice-chancellor in January 2013, is the selection committee’s proposal for Malmö University’s new vice-chancellor. The consultative assembly and union representatives at the university both unanimously recommend Kerstin Tham out of the three final candidates to have been selected through interviews and tests from a starting field of 69. Malmö University will be holding an extraordinary board meeting to decide the matter on 22 May, after we go to press. It is then up to the government to consider the university’s proposal and officially announce the appointment, although no final date has been given for when this will happen. This means that after two and a half years as pro-vice-chancellor of KI, Professor Tham has to make a decision on taking up a new office and that KI will probably need to start looking for her replacement. “I’ve learnt an incredible amount in my 20-years and more at Karolinska Institutet and now feel that it’d be interesting to put my experience and knowledge to use in a new context,” she says. “Malmö University is really Sweden’s largest university college, and I’m convinced that my experience from KI will come in useful in its ambition to obtain full university status.” The incumbent vice-chancellor, Stefan Bengtsson, will be leaving in August to become president and CEO of Chalmers University in Gothenburg.

A new study from Karolinska Institutet shows that the effect of internet-based CBT (cognitive behavioural therapy) for people with people with obsessive-compulsive disorder (OCD) may be boosted with a drug called d-cycloserine, which has long been used to treat TB. According to the results, which are published in the journal JAMA Psychiatry, this enhancing effect is counteracted by antidepressants. “These types of drugs are sometimes called cognitive enhancers, as they affect specific brain processes that can speed up and boost the effects of psychotherapy,” says Dr Christian Rück, psychiatrist and researcher, who conducted the study with his colleagues at Karolinska Institutet’s Department of Clinical Neuroscience. “You could say that it’s to CBT what spinach is to Popeye.” The active therapeutic component of CBT is based on the concept of exposure or extinction, whereby the individual puts him/herself in feared situations that evoke feelings of discomfort or anxiety and remains there until the sensation wanes. D-cycloserine (DCS) is an old tuberculosis drug that also affects one of the brain’s most common receptors, the NMDA receptor. Previous studies have shown, for example, that DCS can amplify the effect of CBT if taken just prior to exposure to the fear-inducing stimulus. In the present study, the researchers tried adding DCS to online CBT for people with OCD. Previous research had shown that DCS can speed up the therapeutic effect of CBT for this disorder, but no study had been large enough to demonstrate lasting effects once the therapy has finished. The study randomly assigned 128 people with an OCD diagnosis to either a DCS or a placebo group. Also taking antidepressants The initial analysis indicated that while there was no difference between DCS and placebo, the effect of online CBT was considerable. In their subsequent analysis, the team therefore took into account whether the participants were also taking antidepressants. Doing so, they found that those not on antidepressants responded much better to DCS. “This tells us that the mechanism for DCS can be affected by antidepressants or vice versa and that it might one day be possible to use DCS and similar substances to boost the effect of CBT,” says Dr Rück. “Our study is the largest to date on DCS and OCD, but more research needs to be done to substantiate these positive effects and to fully understand and utilise the biological mechanisms behind effective CBT therapy.” The study’s first author is Erik Andersson, PhD. It was financed by grants obtained from the Swedish Research Council and through the ALF agreement between KI and the Stockholm County Council. More about the Rück lab Publication D-Cycloserine vs Placebo as Adjunct to Cognitive Behavioral Therapy for Obsessive-Compulsive Disorder and Interaction with Antidepressants; A Randomzed Clinical Trial Erik Andersson, Erik Hedman, Jesper Enander, Diana Radu Djurfeldt, Brjánn Ljótsson, Simon Cervenka, Josef Isung, Cecilia Svanborg, David Mataix-Cols, Viktor Kaldo, Gerhard Andersson, Nils Lindefors, Christian Rück JAMA Psychiatry, online 13 May 2015, doi: 10.1001/jamapsychiatry.2015.0546