KI News

Scientists from Karolinska Institutet and Hannover Medical School have published two studies that provide insights into how the immune system responds and helps to clear a hepatitis B infection after treatment interruption. The findings offer a framework for future tailored treatment strategies and are published in The Journal of Infectious Diseases and Journal of Hepatology. Chronic hepatitis B (CHB) caused by hepatitis B virus (HBV), affects 250 million individuals worldwide. The virus infects the liver and infected patients are at risk of developing liver cirrhosis and liver cancer. Nucleoside/nucleotide analogues (NAs) are the most commonly used drugs to treat CHB, but this treatment only suppresses the virus and rarely leads to eradication of the infection. Thus, for most patients this is a life-long treatment. The immune system recovers in some patients Because of this, new treatment strategies are continuously evaluated with the aim to achieve elimination of HBV. One involves doing a structured NA treatment interruption in patients that have been on the treatment for a couple of years. In 20-30 per cent of the CHB patients the immune system recovers from being exhausted by the chronic infection and gains the capacity to efficiently fight the virus when it starts to replicate after the treatment has been discontinued. In a clinical trial 15 patients with CHB underwent a structured treatment cessation. Before, during and after, the patients were closely monitored and biological samples were continuously collected for subsequent analysis using flow cytometry. The research focus was on the parts of the immune system that has the capacity to recognise and eliminate virus-infected liver cells. “Interruption of NA treatment significantly boosts the capacity of immune cells to kill HBV-infected cells and this activation was also associated with functional cure in the patients. For patients clearing the infection, we also found that the immune system was less exhausted and that immune cells specific for the virus expanded in vivo,” says PhD-student Christine Zimmer at the Department of Medicine, Huddinge, Karolinska Institutet.   Further studies neccessary Even though patient recruitment for this kind of clinical trial is extremely challenging, the findings need to be confirmed in larger studies. “Several questions still remain to be answered such as the identification of the exact component of the immune system needed to achieve a functional cure of CHB following NA interruption, and also identifying patients who will benefit from stopping NA treatment,” says Niklas Björkström, Physician and Associate Professor at the Department of Medicine Huddinge, Karolinska Institutet, one of the main authors. The studies were financed by the German Center for Infection Research (DZIF), the Swedish Research Council, the Swedish Cancer Society, the Swedish Foundation for Strategic Research, the Swedish Society for Medical Research, The Cancer Research Foundations of Radiumhemmet, Knut and Alice Wallenberg Foundation, the Novo Nordisk Foundation, Åke Wiberg´s Foundation, the Center for Innovative Medicine at Karolinska Institutet, the Stockholm County Council, and Karolinska Institutet. Some of the authors have received fees and/or grants from pharmaceutical companies. The scientific articles provide more detailed information about potential conflicts of interest. Publications “Increased NK cell function after cessation of long term nucleos(t)ide analogue treatment in chronic hepatis B is associated with liver damage and HBsAg loss” Christine L. Zimmer, Franziska Rinker, Christoph Höner zu Siederdissen, Michael P. Manns, Heiner Wedemeyer, Markus Cornberg and Niklas K. Björkström. The Journal of Infectious Diseases, online 23 April, 2018, doi: 10.1093/infdis/jiy097 “Modulation of Hepatitis B virus-specific T cell responses after nucleos(t)ide analogue therapy discontinuation in HBeAg negative chronic hepatitis B” Franziska Rinker, Christine L. Zimmer, Christoph Höner zu Siederdissen, Michael P. Manns, Anke R.M. Kraft, Heiner Wedemeyer, Niklas K. Björkström and Markus Cornberg. Journal of Hepatology, online 11 May, 2018, doi: 10.1016/j.jhep.2018.05.004

KI researcher Thomas Perlmann has been awarded the Torsten Söderberg Academy Professorial Chair in Medicine for his “groundbreaking research into the growth of dopamine-producing neurons”. The grant is for SEK 10 million over a five-year period. Is it possible to make the human brain grow new dopamine cells and thus repair itself from serious diseases such as Parkinson’s? This is one of the main questions being investigated by Professor Thomas Perlmann at the Department of Cell and Molecular Biology, who has just recently moved his research group into KI’s new Biomedicum research building in Solna. “This grant comes at a very good moment, just when we’re planning to take our research in partly new directions. It means a great deal and it will help us to make faster progress,” says Thomas Perlmann in a press release from the Royal Swedish Academy of Sciences. Loss of dopamine cells Thomas Perlmann’s research seeks to understand how nerve cells are formed in utero, and what it is that causes stem cells to become dopamine cells. The loss of dopamine cells is associated with many of the serious symptoms that affect patients with Parkinson’s disease. The dysfunction of dopamine cells is also linked with other serious conditions, such as schizophrenia, autism and drug addiction. “We want to understand why new cells of this type are not normally produced in humans, unlike in some other animal species,” he says. “This is an important fundamental question  in biology but it would also be very exciting if we could make the brain repair itself by re-activating the formation of new neurons. If we could manipulate this mechanism, it would enable us to work on ways to cure or at least improve the prognosis of people suffering from conditions such as Parkinson’s disease.” About the professorship The Torsten Söderberg Foundation awards grants for scientific research, primarily in the fields of medicine, economics and law. The Torsten Söderberg Academy’s Professorial Chair in Medicine is to promote internationally outstanding research in medicine by enabling the incumbent to devote his or her time to research for a five-year period at a Swedish medical faculty. The grant is prepared and decided by the Royal Swedish Academy of Sciences following a peer-review process.

Commentary: An article published in the journal Indian Journal of Medical Ethics, authored by an alleged "Lars Andersson, at the Department of Physiology and Pharmacology, Karolinska Institutet", claims that HPV vaccination could be behind an apparent increase in cervical cancer. Karolinska Institutet strongly rejects this study. The head at the Department of Physiology and Pharmacology Håkan Westerblad at Karolinska Institutet says in an interview published in the Swedish journal Läkartidningen (in Swedish only) that there is no such person as “Lars Andersson“ either employed or affiliated with the department. Karolinska Institutet has contacted the Indian journal, which has now removed the link to KI in the article.

Hello, Lill Hultman, doctoral student at the Department of Neurobiology, Care Sciences and Society. In your doctoral thesis you provide a more in-depth understanding of personal assistance from the perspective of both young assistance users and social workers. The new government directive was recently submitted to the LSS investigation, and it mentioned assistance compensation. What do you think this means for young assistance users and social workers? “The biggest difference is that the savings requirement for personal assistance has been removed, and that the end date for the investigation has been postponed until December. This is good news and feels like a step in the right direction, at the same time that there is still much to be done to put the LSS legislation back on its original footing. Sweden has approved the UN Convention on the Rights of Persons with Disabilities.” Can you describe some of the results produced by your thesis? “The results show that young people want the opportunity to do the same things and make the same choices as others of their age. For the young people taking part in this study, access to personal assistance was a prerequisite if this is to be achieved. The thesis also shows that young people would rather have skipped the needs assessment meetings because they find it offensive parading their disability in front of others and describing what they can’t do. Young people feel they have no influence on the structure or content of the meetings, nor on the decisions reached that have a huge impact on their circumstances in life.  I have also come to the conclusion that, in the absence of legal norms and case law, social workers turn to themselves and their own values.” Why did you choose to research this particular subject? “Research in personal assistance is a subject I consider important because assistance reform gives rise to dialogue on what we consider to be a good society. Being assured of the right to be able to live one’s life the way others do places huge demands on a functioning welfare state.” What are you going to do now? “After the public defence of my thesis I want to continue my research from a child and young adult perspective. Children and young people with disabilities are a heterogeneous group, and for that reason it is even more important to give them a voice so they can relate their individual experiences. Moreover, previous research shows that what children and young people think often differs from what adults believe children and young people think.” Doctoral thesis “Live life! Young people’s experience of living with personal assistance and social workers' experiences of handling LSS assessments from a child perspective” Lill Hultman, Karolinska Institutet (2018), ISBN: 978-91-7831-062-3 On 24 May Lill Hultman will publicly defend her doctoral thesis at Stockholms sjukhem in the Magnus Huss Aula.

4 May was an historic day for Karolinska Institutet. For the first time in its history, all the new honorary doctors celebrated in Stockholm City Hall, along with the university’s new PhDs, were women. Bringing science to the people is a passion they all have in common. The City Hall was at its most beautiful. The Blue Hall was bathed in sunlight and the gold in the Golden Hall sparkled as all the new doctors of medicine were saluted with cannon fire from the waterfront. The first ones to descend the marble stairs were the three new honorary doctors of medicine at Karolinska Institutet. Journalist Suzanne Axell, science writer Yvonne Enman and doctor Ingrid le Roux were all noticeably moved and clearly overwhelmed by the award. “Sometimes you do unsexy things – I had just emptied the cat’s litter tray when the call came,” says Suzanne Axell, presenter of the popular SVT programme ‘Fråga doktorn’ (Ask the Doctor). “It was a fantastic feeling.” “It was 4.30 in the afternoon and I had just closed and left the office, as I always do for security reasons, when Dean of Research Anders Gustafsson called,” says Ingrid le Roux, who works in South Africa. “It’s such an honour.” “It was a Friday afternoon and I was in the Coop foodstore,” says Yvonne Enman, who also teaches at Karolinska Institutet. “I wasn’t going to answer at first, but I saw it was a KI number so I did and what a surprise!” ”Bringing science closer to the general public” The ceremony kicked off with a formal address by KI Vice-President Karin Dahlman-Wright, who praised the important work done by the new honorary doctors in bringing science closer to the general public, stressing the value of patient-centred work and of reaching out comprehensively in a global world. “Our new honorary doctors are role models with it comes to reaching patients and involving the whole of society, and they are also role models for women for generations to come,” she said, and thanked them for all they had achieved. Professor Dahlman-Wright also talked about how important it is to protect scientific facts in a world in which information easilycan be distorted. Dean of Research Anders Gustafsson, who conferred the actual honorary titles at the ceremony, developed the theme: the importance of attaining a solid partnership between society and the healthcare sector and of global health work. A close to many years of doctoral study “It pleases me greatly that for the first time our new honorary doctors are women, all of whom have made a great difference to humanity and each of whom has her own way of bringing health issues to the fore. Suzanne Axell by presenting the latest medical research to a broad general public in ‘Fråga doktorn’; Yvonne Enman by working together with teachers, patients and researchers and using her own time as a patient to ensure that research is put to practical medical use – she really understands the patient experience; and Ingrid le Roux through her outstanding work for women and children in Africa.” The PhDs in medicine were conferred by the Dean of Doctoral Education, Marianne Schultzberg. One by one they received their doctoral hat and diploma. The conferment ceremony – the grandest of all academic ceremonies – brings to a close many years of doctoral study. The entertainment during the ceremony and subsequent banquet in the Golden Hall was provided by soprano Paulina Pfeiffer, baritone Karl Magnus Fredriksson and dance Lilly Zetterberg, accompanied by Roland Pöntinen on the piano. The ceremony was rounded off with an exit parade to the strains of Suite Gothique.  

From the 16th to the 18th of May, the international MEG Nord conference is being held at the Karolinska Institutet (KI). The venue is also the home of the organiser, NatMEG, the Swedish National Facility for Magnetoencephalography. Nordic brain researchers will be collaborating to jointly expand the boundaries of research into cerebral function.  The conference’s objective is to strengthen collaborations between Nordic brain researchers. It is hoped that their initiatives will lead to even higher resolution imaging of the brain’s work. This has the potential to increase the clinical benefit of examining epilepsy patients. It would also increase understanding of changes in brain activity patterns in neurodegenerative illnesses such as Parkinson’s and Alzheimer’s disease. By measuring the very small magnetic fields formed when brain cells are activated, magnetoencephalography (MEG) monitors brain activity with a unique richness of detail. The method can help researchers follow the rapid sequences of activity patterns when the brain is responding to thoughts, impressions or treatments. It is an unusual method and there is only one MEG laboratory in Sweden.    

The same kind of neurons can have completely different wiring diagrams in the rat and mouse, as mice lack intercellular molecular channels known as gap junctions, researchers at Karolinska Institutet report in the scientific journal eLIFE. The unexpected discovery gives the researchers a new model for studying the role of gap junctions in the brain. The brain consists of neuronal networks, which process and transfer information. Therefore, scientists need to understand how the links between the neurons work and to determine their interaction, in order to understand the workings of the healthy and unhealthy brain. The research group studied a cluster of neurons in the hypothalamus, the brain structure that governs basic survival functions such as appetite, reproduction and aggression. These so-termed TIDA (tuberoinfundibular dopamine) neurons control the release of hormones from the pituitary gland. Rat TIDA neurons also exhibit what are known as robust oscillations in their electrical activity that are perfectly synchronised between neurons, so that when a wave starts in one TIDA neuron, it also starts simultaneously in all the others. The cells also have exactly the same frequency, be it between different neurons or even different animals. Rat and mouse TIDA neurons behaved differently Unexpectedly, the researchers discovered that rat and mouse TIDA neurons behaved dramatically differently from each other. Unlike in the rat, the oscillations in the mice were irregular, faster and more varied in frequency from animal to animal and cell to cell. This turned out to be because mouse TIDA neurons lack “gap junctions”, which are a kind of protein tube found in the central nervous systems of mammals (including humans) that serve as molecular channels between nerve cells. The rat TIDA neurons, however, were connected by very strong channels. “We often assume that the brain is similarly organized between related species like rats and mice, but in this case they have fundamentally different wiring diagrams for similar groups of neurons,” says study leader Christian Broberger, senior researcher at the Department of Neuroscience, Karolinska Institutet. Gap junctions operate in parallel with the more classic, synaptic neuronal connections in the brain. This discovery gives the researchers a new model for studying the importance of gap junctions, since the same kind of neurons in rodents can now be studied in the absence of presence of these connections. Earlier methods were limited by, for instance, the fact that the chemical substances used to block receptors interact with many other proteins. The new model has enabled the researchers to show that the gap junctions are important not only for synchronising cells in one and the same oscillation, but also for determining the exact frequency of the oscillation. “The discovery is important since oscillations in neuronal activity are very common in many different parts of the brain,” says Dr Broberger. “They contribute to sleep, memory, the interpretation of sensory information and the regulation of hormone secretion, and are also observed in diseases such as epilepsy and Parkinson’s.” The study was financed with an ERC starting grant and grants from the Swedish Research Council, the Strategic Research Programme in Diabetes at KI, the Swedish Brain Fund, the Novo Nordisk Foundation and Karolinska Institutet’s foundations and funds. Publication ”Network Oscillation Rules Imposed by Species-Specific Electrical Coupling” Stefanos Stagkourakis*, Carolina Thörn Pérez, Arash Hellysaz, Rachida Ammari and Christian Broberger. eLIFE, online 3 May 2018, doi: 10.7554/eLife.33144

The day of the week on which a patient has a lung cancer operation has no significance for their survival. This has been demonstrated by researchers at Karolinska Institutet in a new study published in the journal Chest. The team of researchers wanted to find out if the day of the week on which a patient had a lung cancer operation has any importance as regards survival as earlier studies have pointed in different directions. One study for example showed that the weekday for heart surgery had no significance for survival while another showed a better prognosis for patients who underwent surgery for oesophageal cancer on a Monday or Tuesday than those who had operations at the end of the week. “We do not know why there are patient groups who have poorer survival the later in the week they have their operations. One possible explanation is that surgeons, who perform very demanding operations, are more tired at the end of the week and that fewer specialists and fewer staff at the weekend lead to poorer care,” says Veronica Jackson, thoracic surgeon at Karolinska University Hospital and post-doc at the Department of Molecular Medicine and Surgery at Karolinska Institutet, who led the study. Patient data for the present lung cancer study was taken from the Register for General Thoracic Surgery in Sweden (ThoR). The study included all patients in ThoR who had undergone an operation for lung cancer between 2009 and 2015. Of the approximately 4,500 patients, most, 25 per cent, had their operations on a Monday and the lowest number, 11 per cent, on a Friday. When in April 2017 the researchers followed up on whether the patients were still alive using the Swedish National Population Register, they found no connection or significant differences in long-term survival linked to the day of the week of the operation. “Our findings are important because they indicate that there is no reason to restructure the system so that more lung cancer operations are performed at the beginning of the working week. But it is still of course possible that the day of the week for other kinds of surgery in general has an impact on the prognosis. If such a connection exists, it can have sizable consequences for both patients and healthcare as regards planning operations and allocating resources,” says Ulrik Sartipy, thoracic surgeon at Karolinska University Hospital and associate professor at the Department of Molecular Medicine and Surgery at Karolinska Institutet, one of the researchers behind the study. The study lacks specific financing, but the researchers receive funding from The Swedish Heart-Lung Foundation, The Mats Kleberg Foundation, Karolinska Institutet Foundations and Funds, The Swedish Heart and Lung Association, The Åke Wiberg Foundation, The Magnus Bergvall Foundation and the regional ALF agreement between Stockholm County Council and Karolinska Institutet. Publication “Weekday and survival after pulmonary resections for lung cancer – a Swedish nationwide cohort study” Jackson V, AL-Ameri M, Sartipy U Chest, online 3 May 2018, doi: 10.1016/j.chest.2018.03.022

On 24 May, the new research building Neo will officially open on KI’s Campus Flemingsberg. However, researchers are already able to move in. “It feels wonderful! The potential here is enormous,” says Eva Hellström-Lindberg, professor of haematology and head of the newly relocated Center for Hematology and Regenerative Medicine (HERM). Located just across the road from the main entrance to Karolinska University Hospital in Huddinge, beside Novum, is Karolinska Institutet’s new research building, Neo. The officially opening will take place on 24 May, although almost all researchers have already moved into the building, among them researchers from the Center for Haematology and Regenerative Medicine (HERM), a unit of the Department of Medicine, Huddinge. “Until now, we have been somewhat isolated in terms of location. This move may lead to new collaborations and a more dynamic environment. It’s also a beautiful building; It inspires happiness whenever I enter,” says Eva Hellström-Lindberg. Neo has space for approximately 400 researchers. Members of four of KI’s departments will be relocating to the facility: the Department of Biosciences and Nutrition in its entirety, the HERM centre from the Department of Medicine, parts of the Department of Neurobiology, Care Sciences and Society, and a smaller part of the Department of Laboratory Medicine. Lennart Nilsson, professor of molecular modelling and deputy head of the Department of Biosciences and Nutrition, confirms the location of Neo’s laboratories at the centre of the building offers an invitation to spontaneous meetings and creates significantly increased proximity. “Everything is turned inwards towards the centre, so we see each other across the light garden,” he explains. In addition, research group leaders are gathered at the gable ends of each floor. The background to this is that previous staff surveys have shown that this group feels isolated and lacking in a sense of community. as Lennart Nilsson explains: “We have now placed group leaders together, further from their research groups but closer to one another. The idea is to attempt to create more lines of contact there as well,” he says. Collaboration and flexibility have been watchwords in planning the building. The facility has a common staff canteen and meeting rooms. In principle, the facilities belong to everyone – no department has preferential rights to any part of the building. The intention is that it should also be relatively easy to alter the nature of the various laboratory facilities. According to Lennart Nilsson, the challenge now is to encourage research groups to come together in a beneficial manner. A joint retreat was held at the end of last year and efforts are now underway to arrange joint seminar activities. “We also hope that, now we are in such close proximity, researchers will begin to attend one another’s seminars. Then, we need to attract greater numbers of skilled researchers. We have the building and now it’s up to us and our organisation to ensure that this is an attractive place to come,” says Lennart. For HERM, the relocation means an expansion phase and, even if the increased rent presents a temporary challenge, Eva Hellström-Lindberg is optimistic about the future. “Spaces are efficiently planned and, looking only a few years forward in time, the relocation will eventually offer us better value for money. In the end, renewal is inevitable, and it is important to KI in the long term that we have functional environments,” she says. Core facilities at NEO: Bioinformatics and Expression Analysis Cryo Electron Microscopy Live Cell Imaging facility Flow Cytometry Facility KI stem cell and tissue bank

Staffan Normark, senior professor at the Department of Microbiology, Tumor and Cell Biology at Karolinska Institutet, has been awarded the Robert Koch Gold Medal. He receives the medal for lifetime achievements as a biomedical researcher and mentor, and specifically for his research into microorganisms such as viruses, bacteria and fungi and their ability to cause disease. Professor Staffan Normark is a successful, prize-winning, leading international researcher in the field of molecular microbiology who has also worked tirelessly to support the activities and careers of young researchers so that they in turn can successfully initiate and conduct their own high-quality research. The medal will be presented at an official ceremony at the Berlin-Brandenburg Academy of Sciences and Humanities on 16 November 2018. In 1998, this same medal was awarded to Georg Klein, professor emeritus in tumour biology at Karolinska Institutet until his death in 2016. The Robert Koch Foundation is a non-profit foundation that supports research in the field of infectious diseases, as well as exemplary projects designed to address medical and hygienic problems. The medal is named after doctor and researcher Robert Koch (1843 – 1910) who laid the foundations for modern bacteriology, discovered the bacterium responsible for tuberculosis and was awarded the Nobel Prize in Physiology or Medicine in 1905.

The importance of collaboration was a recurring theme when the Swedish Global Health Research Conference was held at Karolinska Institutet on 18–19 April. Over the course of two days, the attendees investigated how their research and commitment to global health can contribute to achieving the goals of the 2030 Agenda for Sustainable Development. The aim of the conference is to reinforce interdisciplinary research into global health and Sweden and to show how Sweden is able to contribute to achieving the global sustainability goals stated in the UN 2030 Agenda. Karolinska Institutet’s Vice-Chancellor, Ole Petter Ottersen, opened the conference by emphasising the important role students – the leaders of the future – have to play in achieving the goals of the 2030 Agenda. He stated that universities are very important stakeholders in this work and that new study programmes are needed that meet the major challenges presented by the sustainable development goals. “Because the task is so complex, the universities must take particular responsibility. And the complexity must be reflected in our study programmes to a much greater degree than is presently the case,” says Ole Petter Ottersen. Aims to reach the general public with information from the UN The other opening speaker at the conference, Ola Rosling, who founded the Gapminder Foundation together with his father, Hans Rosling, professor of international health, who died last year, and his wife Anna Rosling. The foundation works to spread knowledge about the situation in the world by developing new tools with which to visualise statistics. In one project, Gapminder has asked questions about global development to the general public in fourteen countries. One of the questions is “What proportion of the world’s one-year-olds are vaccinated against any disease?”, with the responses available being 20, 50 or 80 per cent. In Sweden, 22 per cent of those asked answered correctly, which is a worse result than would have been generated by choosing randomly. “We see there is a lot of ignorance and are trying to find new ways to reach the general public with information from the UN,” says Ola Rosling. He noted that the correct answer is 80 per cent, and now even higher.   The questions were also asked to certain smaller groups, for example attendees at the World Health Summit in Berlin in 2017. Twenty-seven per cent of that group answered the vaccination question correctly. “These experts are therefore largely ignorant about the major successes achieved by vaccination programmes. Even fewer of the investors at one of the world’s largest banks answered correctly. In a world that is changing, these adults have an inaccurate world-view and don’t know what the world they are investing in looks like,” he says. At the conference at Karolinska Institutet, 84 per cent of attendees answered the vaccination question correctly. Research, data and expertise make decision making easier The conference’s first panel discussion covered the challenges and opportunities in the field of global health, with the 2030 Agenda forming the backdrop. Agnes Binagwaho, Vice-Chancellor of the University of Global Health Equity in Rwanda and the country’s former health minister, stated that all parts of the world can make a contribution to global health. She described how the African region has reduced infant mortality faster than other parts of the world, but that more is required and believes Sweden can contribute to the sustainable development goals by prioritising making research, data and expertise available in order to make it easier to introduce data-driven decision making. Ernest Aryeetey, General-Secretary of the African Research Universities Alliance, stated that global health is a global concern and must be treated as such, and also that collaboration between different scientific disciplines is required. “The future requires us to collaborate across disciplinary boundaries and between universities. No single discipline has all the answers – if we are to develop new treatments and demonstrate that they work as intended, collaboration is required between doctors, engineers, sociologists, economists and behavioural scientists, for example,” says Ernest Aryeetey. The importance of collaboration was emphasised by many speakers, for example in Wednesday’s panel discussion, which dealt with needs and opportunities for research within global health. It was observed that Sweden, as a small country, has a great deal of experience collaborating outside of the country and is able to build on this. "Sweden must dare to use its loud voice" Kristina Gemzell, professor of obstetrics and gynaecology at Karolinska Institutet, stated that Sweden has a loud voice internationally, which we must dare to use in order to achieve the sustainable development goals. “I work in an area that is often hidden away – women’s access to safe, high-quality abortions. Sweden must dare to use its loud voice when we talk about sexual and reproductive health. We must dare to mention abortions, support research in this area and bridge the gap between research and policy,” said Kristina Gemzell. The attendees were then divided into smaller groups in order to discuss tangible issues in a workshop setting. The second day of the conference was about making the move from research to implementation and discussed successful examples of this. This year’s edition was the third time the Swedish Global Health Research Conference has been held. It was organised by the Swedish Society of Medicine in partnership with representatives of all seven Swedish medical faculties, as well as Familjen Einhorns stiftelse, the Government Offices of Sweden and the Swedish Institute for Global Health Transformation (SIGHT). The conference was hosted by the Department of Public Health Sciences at Karolinska Institutet. Text: Sara Nilsson Foto: Erik Cronberg

Hello there Knut Lönnroth, professor at the Department of Public Health Sciences and director of KI’s new TB research centre ... why has KI set up a TB centre? “Tuberculosis is one of the most prevalent communicable diseases in the world and the new centre has been set up to contribute to the development of better diagnostics, vaccines and treatments. The centre will also conduct research in the fields of epidemiology and healthcare organisation and on how to design and provide social and financial support for patients. Sufficient social support is particularly important for people with TB, since most of them are poor." “We also want to strengthen the collaborative ties between the departments concerned as well as the university’s national and international standing in TB research. The global TB situation is only very slowly improving, and the death rate is still very high, with 5,000 deaths a day. KI’s new TB centre is also a response to the fact that the WHO has raised the bar for research to expedite this trend and attain the goals laid out in the UN’s Agenda 2030.” How is it being funded? “The centre has been set up by five KI departments, but its administrative base is the Department of Public Health Sciences. Each research group is separately financed but we also are very hopeful that we can apply for more funding jointly. So far, the centre has received SEK 50,000 in start-up grant from the Board of Research and as much again from the Department of Public Health Sciences.” How will it lead to advancement? “For many years we’ve had a great deal to offer at KI when it comes to TB-related research, in disciplines ranging from immunology, biochemistry and microbiology to public health and health economics. The centre will allow us to reinforce this research, to do more relevant research, tie together research teams, coordinate research training and encourage even stronger interest for collaboration with KI." “We also want to work with information and lobbying. Despite the global political support, many politicians need to be convinced to invest more. Another dilemma is that it’s hard from a market perspective to get investors to back research since poor people have a low payment capacity.” Text: Helena Mayer

A new study from Karolinska Institutet shows that imagined movements can change our perception in the same way as real, executed movements do. The research, which is presented in the scientific journal Nature Communications, contributes to an increased understanding of how mental training works and may be useful for patients with motor disabilities. “Mental training is very beneficial if you want to improve your motor performance – this is something elite athletes and professional musicians know very well. We wanted to find out the mechanisms behind this phenomenon,” says Dr. Konstantina Kilteni, lead author of the study and researcher at Karolinska Institutet’s Department of Neuroscience. Touch resulting from our voluntary movements, for example when we touch one hand with the other, feels less intense compared to when somebody else touches our hand with the exact same intensity. This is because our brain uses information about how we plan to move in order to predict how we will feel. These predictable sensations feel weaker. The brain predicts how we would feel “Our study shows that if we imagine the movement but we do not physically perform it, real touch will still feel less intense,” says Dr. Kilteni. “This implies that during imagining the movement the brain also predicts how we would feel if the imagined movements were executed. Taken together our findings suggest that imagined and real movements have very similar brain mechanisms, if not sharing the same one, which may explain the positive effects of mental training”. The study consists of three series of experiments where 36 healthy individuals were asked to either perform or imagine performing a movement. The experimenters recorded muscular activity to ensure that the participants were not moving while imagining. During imagination, the participants were told to imagine pressing their right index finger against the relaxed left index finger. At the same time, a touch was applied on their left index finger via specially designed equipment. Participants perceived this touch as less intense compared to when they were neither moving nor imagining suggesting that the brain had predicted how they would feel. In fact, their weakened perception during imagination was equivalent to that when they physically performed the movement. May be useful for some patient groups In addition to shedding new light on a classic question in psychology and neuroscience – whether the brain’s representation of imagined and executed movements are the same – the results can be useful for clinical research, especially for neurological patient groups with motor disabilities. “For example, stroke patients imagining performing the movement that they cannot physically perform could benefit their motor rehabilitation,” says principal investigator Dr. H. Henrik Ehrsson, professor at Karolinska Institutet’s Department of Neuroscience. “Another area of application concerns paralysed or amputated patients that use brain-computer interfaces to control artificial limbs through imagining moving them.” The study was funded by the European Commission, the Swedish Research Council, the Torsten Söderberg Foundation and Riksbankens Jubileumsfond. Publication “Motor imagery involves predicting the sensory consequences of the imagined movement” Konstantina Kilteni, Benjamin Jan Andersson, Christian Houborg and H. Henrik Ehrsson Nature Communications, online 24 April 2018, doi: 10.1038/s41467-018-03989-0

After surgery for breast cancer women who have undergone breast reconstruction using abdominal tissue do not have a higher risk of recurrence than women who do not undergo breast reconstruction. This has been shown by researchers at Karolinska Institutet in a study published in the British Journal of Surgery. In Sweden today, more than 90,000 women are living with a diagnosis of breast cancer, and each year almost 2,000 women die from the disease. More than 90 per cent undergo surgery for their breast cancer. Reconstruction can be performed if the entire breast is removed, using either an implant or tissue from the woman’s own body. Today, many women want to reconstruct their breast using tissue from themselves. This tissue can be taken from the abdomen and transplanted to the site of the breast that has been removed. This particular and common method is called DIEP flap reconstruction, which stands for deep inferior epigastric artery perforator flap reconstruction. Physical trauma “Discussions have been ongoing for some time as to whether this type of reconstruction is safe or whether it could contribute to a higher risk of recurrence. Previous studies had given conflicting results”, says Hannah Adam, PhD Candidate at the Department of Molecular Medicine and Surgery at Karolinska Institutet, and the first author of a new study that examines the risk of recurrence. The operation, which takes several hours, is a physical trauma that could theoretically result in an impaired immune system and reactivation of dormant micrometastases. The current study included 254 patients who all underwent surgery using the DIEP flap method at Karolinska University Hospital Solna 1999-2013. Each patient was matched with up to three patients in a control group including 729 patients, all of whom had removed a breast without any secondary reconstructive surgery. No increased risk The results revealed that slightly less than 20 per cent of the women in the DIEP group versus 24 per cent in the control group had recurrence of breast cancer at follow-up after seven or six years. The five-year survival rate after surgery was 92 per cent and slightly less than 90 per cent respectively. “Our study demonstrates that there is no increased risk of recurrence for women who undergo this type of reconstruction. Moreover, the survival rate was higher for the DIEP group than the control group”, says Hannah Adam. The study is financed by the Percy Falk Foundation, the Swedish Society for Medical Research, Stockholm County Council and the Karolinska Institutet. Publication “Risk of recurrence and death in patients with breast cancer after delayed deep inferior epigastric perforator flap reconstruction” H Adam, AC Docherty Skogh, Å Edsander Nord, I Schultz, J Gahm, P. Hall, J Frisell, M Halle and J de Boniface British Journal of Surgery, online 23 April 2018, doi:10.1002/bjs.10866

Difficult to treat and aggressive “triple-negative” breast cancer is chemoresistant even before chemotherapy begins, a new study by researchers from Karolinska Institutet and the University of Texas MD Anderson Cancer Center reports. The findings, which are published in the journal Cell, may lead to better and more personalised treatments for breast cancer. Breast cancer is the most common form of cancer in women and the most common cause of death in middle-aged women in Sweden. Triple-negative breast cancer (TNBC) is an aggressive and difficult to treat form of the disease that makes up about 15 per cent of all breast cancer cases. Chemotherapy is the cornerstone of treatment for TNBC, used either prior to surgery or prophylactically after surgery, as well as for treatment of metastatic disease. Even though several chemotherapy drugs are effective against TNBC, resistance to treatment is a common problem since it can ultimately lead to relapse and tumour growth. For many years researchers have been trying to understand why such resistance develops and to prevent or reverse it. Key question “A key question is whether the resistance develops because of the existence of resistant groups of cells, called clones, in the tumour from the start, or whether tumour cells develop new genetic changes (mutations) during the treatment that cause resistance,” says Theodoros Foukakis, Associate Professor at the Department of Oncology-Pathology, Karolinska Institutet, who co-led the study with Associate Professor Nicholas Navin at the University of Texas MD Anderson Cancer Center, Houston, USA. The researchers analysed tumour tissue from 20 patients with TNBC who received preoperative chemotherapy. The tissue was collected before the onset of therapy, after two courses of therapy and on surgery. The researchers used a technique called single-cell sequencing to examine the DNA and gene expression (RNA) of all genes in the individual tumour cells and thus ascertain the cells’ properties and kinship. “The DNA analyses revealed tumour clones remaining after treatment in half of the cases,” says Dr Foukakis. “When we studied them in detail at a single-cell level, we found that these same clones were present in the tumour before chemotherapy, often as a small minority of the tumour cell population.” Adapted their gene expression Single-cell RNA sequencing of thousands of cell nuclei showed that the remaining tumour clones had also adapted their gene expression during treatment to become even more chemoresistant. “All in all, the study shows that chemoresistance in TNBC is a complex process involving both a selection of resistant clones that existed in the tumour from the start as well as a reprogramming of their gene expression to ensure survival during therapy,” concludes Dr Foukakis. The results may provide a basis for future studies to identify therapy-resistant tumour clones and thus personalise treatment for breast cancer patients who respond poorly to chemotherapy and have a worse prognosis. The Swedish part of the study was financed by the Swedish Cancer Society, the Cancer Research Funds of Radiumhemmet and StratCan (KI-MDACC Collaborative Grants). The clinical study was part-financed by Roche, the Cancer Research Funds of Radiumhemmet and the Swedish Breast Cancer Association. Publication “Chemoresistance Evolution in Triple-Negative Breast Cancer Delineated by Single Cell Sequencing” Charissa Kim & Ruli Gao, Emi Sei, Rachel Brandt, Johan Hartman, Thomas Hatschek, Nicola Crosetto, Theodoros Foukakis and Nicholas Navin Cell, online 19 April 2018, doi: 10.1016/j.cell.2018.03.041

Ten researchers at Karolinska Institutet have been awarded grants in the Swedish Childhood Cancer Foundation’s latest call for funding, during which approximately SEK 62 million was allocated. Appropriations include a six-year researcher position and several postdoctoral positions. Karolinska Institutet researchers account for 11 of 26 successful applications. Financing for a six-year senior research position was awarded to Lisa Westerberg of the Department of Microbiology, Tumor and Cell Biology for a project studying the link between the ability of antibodies to move around and an increased risk for childhood cancer. The aim of the study is to better understand how an uncontrolled immune response leads to immunodeficiency diseases and tumours in children. Magdalini Lourda of the Department of Women’s and Children’s Health has been granted funding for a research assistant position relating to immunological and genetic studies of children suffering from the rare condition Langerhans cell histiocytosis. The call also resulted in a grant to five KI researchers for postdoctoral positions. These are Saeed Eshtad, Aida Rodriguez Garcia, Jenny Thorsell Cederberg, Johanna Viiliäinen and Arnika Wagner. Doctoral grants for clinicians were awarded to Susanna Ranta and Emma Tham. Funding for clinical research months – three months per year for three years – was awarded to Bianca Tesi and Emma Tham. In total, approximately SEK 62 million in grants were awarded. From a total of 107 applications, 26 were granted – 17 of which came from women and 9 from men. The Swedish Childhood Cancer Foundation awards grants three times a year.

The Swedish Government has appointed Mandus Frykman, researcher at Karolinska Institutet, as national coordinator for a well-functioning sick-leave process. This newly established function involves examining how sick leave can be developed from an individual perspective. “I am extremely pleased and proud to be given this assignment. It is incredibly exciting and an opportunity to participate in influencing matters on a large scale,” says Mandus Frykman, a researcher at Karolinska Institutet’s Department of Learning, Informatics, Management and Ethics (LIME). Focus on the individual On 12 April, the Swedish Government appointed Mandus Frykman as national coordinator for the sick-leave process, a newly established function. At the same time, an inquiry was set up into health insurance and both of these initiatives are part of the action programme for health insurance presented by the Swedish Government earlier this year. Mandus Frykman’s research deals with the impact of decisions at board-room level on occupational health and safety. He is a psychologist and economist and is also works in occupational healthcare. As national coordinator, Mandus Frykman will be examining how the sick-leave process works and how it can be developed from an individual perspective. According to the Government, this is a matter of taking the individual’s journey through health insurance as a starting point and placing it at the centre of the process. Several stakeholders in cooperation Because the sick-leave process involves a number of stakeholders – such as employers, healthcare and welfare services, the Swedish Social Insurance Agency and the Swedish Public Employment Service – cooperation is a central concept. “Cooperation between stakeholders in the sick-leave process has proved to be a challenge, and my task is to analyse the preconditions for and promote cooperation between them. I look forward to getting started on the assignment and establishing contacts with the stakeholders and other experts in the field,” says Mandus Frykman. According to Minister for Health and Social Affairs Annika Strandhäll, both Magnus Frykman and Claes Jansson, responsible for the inquiry into health insurance, have a clear mandate to drive development towards a secure and modernised national health insurance. Mandus Frykman is due to deliver an interim report on his assignment on 30 April 2019, with a final report to be published no later than 30 April 2020.

Sweden’s first occupational therapists and physiotherapists with a Master’s in Dementia Care will be awarded their diploma today in the presence of HM Queen Silvia at a ceremony at the Royal Palace in Stockholm. The Master's Courses in Dementia Care is part of the efforts being made to improve theoretical and practical competence in the field of dementia care. The Master's Courses in Dementia Care were created four years ago as a joint undertaking by Karolinska Institutet and Silviahemmet. It is the only education of its kind, and has recently been expanded to include occupational therapists and physiotherapists as well as physicians. “It’s extremely gratifying that the first intake of occupational therapists and physiotherapists have now taken their Master’s in Dementia Care and that they will be receiving a diploma as ‘Silvia Occupational Therapists’ and ‘Silvia Physiotherapists’,” says Maria Eriksdotter, head of the Department of Neurobiology, Care Sciences and Society, Karolinska Institutet. “Raising the educational bar for dementia diseases is in keeping with the recently updated national guidelines for dementia care and the government’s aims.” A total of fourteen participants have now completed this round of the Master's Courses in Dementia Care. Among the participants, one of the new degree recipients is the first physician from China to adopt the title of ‘Silvia Doctor’. The care of dementia sufferers has been in focus recently. At the end of last year, the National Board of Health and Welfare issued updated national guidelines for the health and social care of people with dementia, and in mid March this year, the government ringfenced additional funds for raising the quality of dementia care.

Children in sub-Saharan Africa with uncomplicated fever may be safely managed with conditional, rather than universal, 3-day follow-up with a community health worker, according to a randomised trial by researchers at Karolinska Institutet published in PLOS Medicine. The study suggests that current WHO guidelines for these children could be reconsidered. The WHO’s integrated community case management (iCCM) guidelines recommend that all children presenting with uncomplicated fever and no danger signs return for follow-up with a community health worker on day 3 following the initial consultation on day 1. Such fevers often resolve rapidly, however, and previous studies suggest that expectant home care for uncomplicated fever can be safely recommended. The trial was conducted in Ethiopia and included approximately 4,000 children under age five with uncomplicated fever, who were randomised to receive either conditional follow-up if symptoms remained or the recommended universal 3-day follow up. The results suggest that conditional follow-up is non-inferior to universal follow-up. More efficient use of resources  “Allowing community health workers to advise caregivers to bring children back only in case of continued symptoms might be a more efficient use of resources in these settings,” says first author Karin Källander, adjunct senior lecturer at Karolinska Institutet’s Department of Public Health Sciences. Another study from Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, United States, published at the same time in PLOS Medicine, shows similar results for children in the Democratic Republic of the Congo (DRC). Additional trials in other sub-Saharan African settings are needed to establish generalisability. However, taken together, the current results provide evidence relevant to formulation of WHO recommendations. The study involving researchers from Karolinska Institutet was made possible by the support of the U.S. President's Malaria Initiative under the United States Agency for International Development's Translating Research into Action (TRAction) Project. This news article is based on a press release from PLOS Medicine. Publication “Universal versus conditional day 3 follow-up for children with non-severe unclassified fever at the community level in Ethiopia: A cluster-randomised non-inferiority trial” Källander K, Alfvén T, Funk T, Abebe A, Hailemariam A, Getachew D, Petzold M, Steinhardt LC, Gutman JR PLOS Medicine, online 17 April 2018, doi: 10.1371/journal.pmed.1002553

Researchers at Karolinska Institutet have developed a new disease model for neurodegenerative diseases such as ALS and MS that can be used to develop new immunotherapies. The model is described in a publication in the scientific journal Nature Immunology. All of the body’s organs contain macrophages, which, as part of the immune system, consume bacteria and other foreign bodies. However, macrophages are also specialised according to the organ in which they operate; in the brain they are known as microglia, and researchers believe that this specialisation is controlled by the cytokine TGF-β, which is a kind of protein.  Involved in interneuronal communication In a healthy brain, microglia are involved in interneuronal communication and the renewal of myelin, the insulating sheaths enveloping axons of nerve cells that enable the transmission of nerve impulses. In diseases like MS and ALS, other immune cells called monocytes can enter the brain via the blood, be transformed into inflammatory cells and cause damage to the neurons and the myelin sheath. The researchers behind the current study had a hypothesis that TGF-β may program monocytes from being inflammatory cells to becoming microglia-like cells. “We already knew that TGF-β is produced in the brain and is important for giving microglia their specialised functions,” says first author Harald Lund, doctoral student at the Department of Clinical Neuroscience, Karolinska Institutet. “So we figured that monocytes should also respond to TGF-β when they enter the brain. We were curious to see what would happen if the monocytes lost the ability to respond to TGF-β.” Developed a disease similar to ALS To test this, the researchers first used a mouse model in which the animal’s own microglia could be removed. This lead to a rapid influx of monocytes into the brain and spinal cord, which gave rise to new microglia-like cells, and the mice displayed no pathological symptoms. But when the researchers then switched off the TGF-β receptors on the new microglia-like cells, they started to consume large parts of the myelin in the spinal cord. The mice quickly developed a deadly neurodegenerative disease, the symptoms of which were similar to those of ALS. The disease model can explain a mechanism that is active in neuroinflammatory and neurodegenerative diseases, and could be used to develop and test new immunotherapies. Today there are no effective treatments. Lack of experimental models “There are many deadly neurodegenerative diseases in humans, but a lack of experimental models for developing new immunotherapies,” says Professor Bob Harris at the Centre for Molecular Medicine, Karolinska University Hospital and the Department of Clinical Neuroscience, Karolinska Institutet. “This new disease model will be a valuable addition to our research programme and we hope that the next study will result in a new, effective therapy.” The study was financed by the Swedish Alzheimer’s Foundation, the Swedish Research Council, the Swedish Childhood Cancer Foundation, the Åke Wiberg Foundation, the Swedish MS Research Foundation, the NIH-NINDS, NIH-NIA, the National Multiple Sclerosis Society, the Amyotrophic Lateral Sclerosis Association, the Swedish Heart and Lung Foundation, the Novo Nordisk Foundation and the Margaretha af Ugglas Foundation. Publication “Fatal demyelinating disease is induced by monocyte-derived macrophages in the absence of TGF-β signaling” Lund H, Pieber M, Parsa R, Grommisch D, Ewing E, Kular L, Han J, Zhu K, Nijssen J, Hedlund E, Needhamsen M, Ruhrmann S, Ortlieb Guerreiro Cacais A, Berglund R, Forteza MJ, Ketelhuth DFJ, Butovsky O, Jagodic M, Zhang X-M, Harris RA Nature Immunology, online 16 April 2018, doi: 10.1038/s41590-018-0091-5