Integrative Molecular Phenotyping
INTEGRATIVE MOLECULAR
PHENOTYPING
WHEELOCK LABORATORY
DEPARTMENT OF MEDICAL
BIOCHEMISTRY AND BIOPHYSICS
WHEELOCK LABORATORY
DEPARTMENT OF MEDICAL
BIOCHEMISTRY AND BIOPHYSICS
WHEELOCK LABORATORY
DEPARTMENT OF MEDICAL
BIOCHEMISTRY AND BIOPHYSICS
WHEELOCK LABORATORY
DEPARTMENT OF MEDICAL
BIOCHEMISTRY AND BIOPHYSICS
WHEELOCK LABORATORY
DEPARTMENT OF MEDICAL
BIOCHEMISTRY AND BIOPHYSICS
WHEELOCK LABORATORY

KI News

Updated: 1 hour 27 min ago

Grandparental support helps reduce the risk of child obesity

Mon, 22/06/2015 - 10:10
According to an English saying, it takes a whole village to raise a child. A new study from Karolinska Institutet has shown how important the support from grandparents could be. According to the study, which is being published in Pediatric Obesity, emotional support from grandparents has a protective effect against child obesity, even with the presence of other risk factors. Previous studies have shown that the parents' socioeconomic status affects the risk of children developing obesity. But the effect of other family-related aspects on this risk has not been investigated to the same extent. Researchers from Karolinska Institutet and researchers in social anthropology at Oxford University have jointly investigated the importance of grandparental support in this context. The study included 39 preschool-aged children from Stockholm County who had received treatment for obesity. Both the mother and father of the children answered detailed questionnaires in which socio-economic status was measured by education and income levels, work and domestic situation and by how much money they had left at the end of the month. After this, they answered questions about the kinds of support – and how much – they received from their own parents, i.e. the children's grandparents. The questions aimed to establish the extent to which grandparents contributed daily support, e.g. help with washing and cleaning, financial support and emotional support, which could create a sense of being seen and understood. Received emotional support It transpired that when the parents received emotional support from their own parents, it had a protective effect against obesity in their children. Parental income is in itself linked to the BMI, Body Mass Index, in children. But the children of parents with a low income and a low level of emotional support had a higher degree of obesity than children whose parents had a low income but a high level of emotional support. “Our study shows that emotional support from grandparents may have a preventive effect against child obesity, which is a serious disease. These findings could, for instance, be incorporated into the planning of public health programmes that are aimed at reducing obesity in children. Greater social support for families with small children could help alleviate stress in parents, who will thereby be in a better position to make better food choices,” says Paulina Nowicka, Associate Professor at the Department of Clinical Science, Intervention and Technology at Karolinska Institutet. The study in question is funded by Karolinska Institutet, the Vinnmer Marie Curie International Qualification and the Princess Lovisa Foundation for Child Health Care. Publication Low grandparental social support combined with low parental socioeconomic status is closely associated with obesity in preschool-aged children: A pilot study Louise Lindberg, Anna Ek, Jonna Nyman, Claude Marcus, Stanley Ulijaszek, Paulina Nowicka Pediatric Obesity, article first published online 19 June 2015, doi: 10.1111/ijpo.12049

New mechanism for male infertility discovered

Thu, 18/06/2015 - 08:08
A new study led from Sweden’s Karolinska Institutet links male infertility to autoimmune prostatic inflammation. The findings are published in the journal Science Translational Medicine.   Involuntary childlessness is common, and in half of all cases attributable to infertility in the man. Although male infertility has many possible causes, it often remains unexplained. In the present study, the researchers have discovered a reason for reduced fertility in people with autoimmune polyendocrine syndrome type 1 (APS1), which increases the risk of developing autoimmune disease (caused by the immune system attacking and damaging healthy cells) and which is often used as a model for autoimmune disease in general. Infertility is common in people of both sexes with the disease. While infertility in women with APS1 is caused by autoimmune action against the ovaries, what gives rise to the corresponding infertility in men has never been ascertained. Keen to investigate whether male fertility could be explained by an autoimmune reaction against some part of the male reproductive organs, the researchers behind this new study examined the immune system of 93 men and women with APS1. “We found that the immune system in a large group of patients reacted to a protein formed only in the prostate, namely the enzyme transglutaminase 4,” says lead investigator Nils Landegren, MD, Doctoral student at Karolinska Institutet’s Department of Medicine in Solna. “What we found was that it was only men who reacted to transglutaminase 4 and that the immune reaction first appeared at the onset of puberty once the prostate gland had matured. Interestingly, previous studies on mice have shown that transglutaminase 4 plays an important part in male fertility.” Animal model for APS1 To better understand their findings, the team examined the animal model for APS1 (i.e. mice with the same genetic defect as human patients with the syndrome) and found that male mice spontaneously developed an inflammatory disease in their prostate glands – a so-called prostatitis – and reacted to transglutaminase 4. “The finds are important as they point to a new disease mechanism for male infertility, but more work needs to be done to understand the significance of autoimmune prostatitis to infertility in the male population at large,” says Dr Landegren. The researchers involved in the study were from Karolinska Institutet, SciLifeLab, Uppsala University, Stanford University and University of California San Francisco. Supervisor of the study has been Professor Olle Kämpe, MD, PhD, at the Department of Medicine, Solna, Karolinska Institutet. The study was financed with grants from the Swedish Research Council, the Torsten and Ragnar Söderberg Foundation, the Swedish Research Council Formas and the Novo Nordisk Foundation, the National Organization for Rare Disorders and the NIH. View our press release about this study Publication Transglutaminase 4 as a prostate autoantigen in male subfertility N. Landegren, D. Sharon, A. K. Shum, I. S. Khan, K. J. Fasano, Å. Hallgren, C. Kampf, E. Freyhult, B. Ardesjö-Lundgren, M. Alimohammadi, S. Rathsman, J. F. Ludvigsson, D. Lundh, R. Motrich, V. Rivero, L. Fong, A. Giwercman, J. Gustafsson, J. Perheentupa, E. S. Husebye, M. S. Anderson, M. Snyder, O. Kämpe Science Translational Medicine, Vol 7 Issue 292 292ra101 (2015), online 17 June 2015

Study identifies the epigenetic basis of immunodeficiency disorder

Wed, 17/06/2015 - 16:16
Researchers at Karolinska Institutet have in collaboration with Spanish colleagues identified epigenetic alterations in Common Variable Immunodeficiency (CVID), the most common primary immunodeficiency, using as a starting point genetically identical monozygotic twins discordant for the disease. The findings are being published in the journal Nature Communications, and may open a door to future research avenues for the diagnosis and treatment of patients with CVID. CVID is a disorder characterized by low levels of antibodies (serum immunoglobulins) and increased susceptibility to infections. Most patients with CVID are diagnosed initially after suffering recurrent infections that involve ears, sinuses, nose, bronchi and lungs. When the lung infections are severe and occur repeatedly, can cause permanent damage to the bronchi and become chronically affected. The exact cause of low levels of serum immunoglobulins is not known. Given the heterogeneous nature of CVID, there is not a clear pattern of inheritance, although in recent years geneticists have described mutations in several genes related to the biology of lymphocytes in patients with CVID. Still, for several patients there are no identified mutations and it is thought that other mechanisms also determine the onset of the disease; in fact, there are examples of genetically identical twins, which are discordant for the manifestation of this disease. The current study was conducted in collaboration by researchers of the Chromatin and Disease Group at the Bellvitge Biomedical Research Institute (IDIBELL) and La Paz Hospital (IDIPAZ) in Spain, and the Computational Medicine team at Karolinska Institutet’s Department of Medicine, Solna. By comparing the epigenetic marks in B cells of a pair of identical twins, discordant for CVID, the researchers were able to identify the existence of epigenetic alterations in the twin with the immunodeficiency that are not present in the healthy twin. In particular, they observed higher DNA methylation levels in the twin with CVID. DNA methylation is related to the ability of cells to allow their genes to be expressed. A group of genes According to the researchers, this analysis allowed the identification of a group of genes important for the proper functioning of B lymphocytes which were more methylated in the CVID twin. Subsequently, the same genes were investigated in a cohort of individuals with CVID, and compared with a series of healthy individuals. The analysis of methylation of these genes in cells in different stages of maturation also showed that patients with CVID have partially lost the ability of demethylating those genes during the process of generating mature lymphocytes. These results indicate that patients not only produce less CVID memory B cells (the mature form which produces antibodies) but these cells are altered and have not completed properly their maturation. This work was supported by the Spanish Ministry of Economy and Competitiveness, the Fundación Ramón Areces, and the EU FP7 306000 STATegra project. This news article is an abbrivation of a press release from the IDIBELL.  Publication Monozygotic Twins Discordant for Common Variable Immunodeficiency Reveal Impaired DNA Demethylation during Naïve-to-Memory B-Cell Transition Virginia C. Rodríguez-Cortez, Lucia del Pino-Molina, Javier Rodríguez-Ubreva, Laura Ciudad, David Gómez-Cabrero, Carlos Company, José M. Urquiza, Jesper Tegnér, Carlos Rodríguez-Gallego, Eduardo López-Granados and Esteban Ballestar Nature Communications, online 17 June 2015, DOI: 10.1038/ncomms8335

Most heart muscle cells formed during childhood

Fri, 12/06/2015 - 08:08
New human heart muscle cells can be formed, but this mainly happens during the first ten years of life, according to a new study from Karolinska Institutet in Sweden. Other cell types, however, are replaced more quickly. The study, which is published in the journal Cell, demonstrates that the heart muscle is regenerated throughout a person’s life, supporting the idea that it is possible to stimulate the rebuilding of lost heart tissue. During a heart attack, when parts of the heart muscle are starved of oxygen, many heart cells die and are replaced by scar tissue. As this impairs functionality, many researchers are interested in the possibility of stimulating the regeneration of lost heart muscle cells. But is it possible? This is one of the big questions of regenerative medicine, and scientists have long been trying to answer it, without arriving at a consensus. To examine the regeneration of human heart cells, the team behind this new study used a combination of methods. One such was to measure the radioactive isotope C-14, exploiting the sharp rise in atmospheric levels of carbon-14 in the 1950s and 60s caused by nuclear testing. Levels then declined, which means that cells that were formed after that period give lower C-14 readings than those formed during it. Thus by measuring the amount of C-14 in a cell’s DNA, the researchers were able to calculate its age. “We examined the heart tissue from 29 deceased individuals of various ages and found that even by one month after birth, the heart contains the same number of cells as it has in adults,” says Olaf Bergmann from the Department of Cell and Molecular Biology. Cells increase in size According to the study, the heart grows during childhood because its cells increase in size rather than in number; in other words, heart cells are generated on only a modest scale, and even during a long life, only forty per cent of muscle cells are replaced. The heart also contains other types of cell, such as endothelial cells and cells in the connective tissue that go under the collective name of mesenchymal cells. What the researchers found was that these cell populations change much more than the heart muscle cells. The endothelial cells have the shortest life-cycle, and in adults all such cells are exchanged over a six-year period. The mesenchymal cells are also replaced, but more slowly – twice during a lifetime estimate the researchers behind this new study. “Our study shows that endothelial cells, mesenchymal cells and heart muscle cells are renewed in the human heart throughout life, albeit at a different rate for different cells,” says study leader Jonas Frisén from the Department of Cell and Molecular Biology. “Our findings suggest that it can be rational and realistic to develop new therapeutic strategies for strengthening the body’s own regenerative capacity to treat heart diseases.” The study was financed with grants from the Swedish Research Council, the Heart-Lung Foundation, the Swedish Cancer Society, the Tobias Foundation, StratRegen at Karolinska Institutet, the Torsten Söderberg Foundation, and the Knut and Alice Wallenberg Foundation. View our press release about this study More about the Frisén lab View a video abstract on YouTube     Publication Dynamics of cell generation and turnover in the human heart Olaf Bergmann, Sofia Zdunek, Anastasia Felker, Mehran Salehpour, Kanar Alkass, Samuel Bernard, Staffan Sjöström, Mirosława Szewczykowska, Teresa Jackowska, Cris dos Remedios, Torsten Malm, Michaela Andrä, Shira Perl, John Tisdale, Ramadan Jashari,Jens R. Nyengaard, Göran Possert, Stefan Jovinge, Henrik Druid, and Jonas Frisén Cell June 18, 2015 issue, online first 11 June  2015, DOI: http://dx.doi.org/10.1016/j.cell.2015.05.026

Better career system discussed at symposium

Thu, 11/06/2015 - 11:11
What might attractive career systems that promote good research look like? This was the subject of the mini-symposium on “Excellent Academic Career Systems in Europe” held at KI on 3 June. The mini-symposium on career systems arranged by KI’s Junior Faculty, an interest organisation of researchers with a PhD but as yet no professorship, and the journal Nature Genetics attracted a great deal of interest. Speakers from Europe and the US were there to talk about different solutions and experiences gained from their own countries. Stina Gerdes Barriere from the Swedish Research Council talked about how academic career paths had changed over the past 20 years, during which time the number of people working with research and education has outstripped the research appropriations. The sharpest increase has occurred in the category of junior researcher, and according to the council’s own research, career advancement for recent graduates is much slower than for previous generations; in other words, it takes those who want to continue researching longer to obtain a tenured academic position. Speakers raised the tenure-track model That Swedish academia needs clearer career paths was something on which everyone attending the symposium agreed. But what can decent career systems look like, what are they to prioritise, and at what level are they to be organised and financed? Many of the afternoon’s speakers talked on the tenure-track system, with evaluations at fixed times and permanent job offers for researchers meeting expectations. Iain Cameron from Research Councils UK talked about how universities in the UK all have different systems. Recently, a couple of universities have implemented what they term a “tenure-track equivalent” programme. Germany is also without a general career system, noted Sven Diederichs from the German Cancer Research Center DKFZ and the Institute of Pathology at Heidelberg University. Many universities operate a tenure track, but they differ from place to place. “My main point is that the most important decision is the one taken at the start when recruiting a tenure-track researcher: do we really have the resources for giving them a permanent position, and do we believe that they have the potential to become a successful, independent researcher?” said Sven Diederichs, who also spoke about the importance of having a fair, transparent and well-balanced evaluation process in place in the system. Ideas for future career systems Thomas Bjørnholm, prorector of research and innovation at Copenhagen University, shared his own experiences of implementing a tenure-track system. The model is inspired by California’s Berkeley University and has brought about considerable changes in organisation and in attitudes to Copenhagen University. The positions are for six years, with evaluations after five. Six-year positions were also something that both the Junior Faculty and Dean of Research Hans-Gustaf Ljunggren saw as interesting alternatives when talking about their different ideas about what a future career system at KI might look like. After the presentations, the speakers engaged in a panel debate with representatives of the Young Academy of Sweden and the National Junior Faculty of Sweden on the difficulties of assessing a researcher’s potential so early as directly after a postdoc period. Interviews were mentioned as a way of obtaining some idea of a researcher’s independence. The applicant’s publication history and research programme were other criteria that the panel deemed important. There was also general agreement that the evaluation criteria had to be clearly defined from the start. Text: Karin Söderlund Leifler  

Swift intervention doubles survival rate from cardiac arrest

Thu, 11/06/2015 - 08:08
A team of Swedish researchers finds that early cardiopulmonary resuscitation more than doubles the chance of survival for patients suffering out-of-hospital cardiac arrest. The percentage of patients who receive life-saving resuscitation has also increased substantially thanks to so-called SMS Lifesavers. These results are published simultaneously in two studies in the highly reputed New England Journal of Medicine. The two studies were conducted by researchers at the Center for Resuscitation Science at Karolinska Institutet and Södersjukhuset (Stockholm South General Hospital) in collaboration with University of Borås, Danderyd Hospital and Sahlgrenska Academy, all in Sweden. “Both these studies clearly show that cardiopulmonary resuscitation is an effective, life-saving treatment, and that further encouragement must be given to respond swiftly on suspected cardiac arrest,” says Dr Jacob Hollenberg, Cardiologist and Head of Research at the Center for Resuscitation Science. In one of the two articles, the researchers have analysed over 30,000 cases of out-of-hospital cardiac arrest in Sweden. The results show that cardiopulmonary resuscitation performed before the arrival of the ambulance is associated with over a two-fold increase in the chance of survival. This powerful effect is independent of age, sex, place, cause, ECG pattern, and time period. According to the researchers, this study unique in several ways. Aside from its main results, is the number of cases analysed, the fact that data is reproducible for three decades and that the material was subjected to thorough correction for sources of error and bias. Dispatching CPR trained volunteers In the other article, the researchers have evaluated a new method of dispatching CPR trained volunteers, known as SMS Lifesavers to cardiac arrests. Their results show that these volunteers have caused a 30 % increase in the number of patients who receive cardiopulmonary resuscitation before the arrival of paramedics, the rescue services or the police. The study involved 10,000 civilian volunteers in Stockholm County who were alerted by mobile phone text message to the cardiac arrest in order to administer cardiopulmonary resuscitation if they were within a range of 500 metres. “Traditional methods such as mass public training, which are now used throughout the world, are important but have not shown any evidence of a similar increase,” says Dr Hollenberg. “The new mobile phone text-message alert system shows convincingly that new technology can be used to ensure that more people receive life-saving treatment as they wait for an ambulance.” This research was financed by grants from the Heart-Lung Foundation, Stockholm County Council, the Swedish Association of Local Authorities and Regions and the Laerdal Foundation for Acute Medicine in Norway. Facts about cardiac arrest: About 10,000 Swedes suffer out-of-hospital cardiac arrest every year. In the USA, more than 300 000 persons suffer out-of-hospital cardiac arrest each year. Only 1 in 10 victims survive. Cardiac arrest is often caused by acute myocardial infarction. The delay between onset and treatment in the form of cardiopulmonary resuscitation and defibrillation is decisive for survival. More than 3 Million Swedes (out of a population of 10 Million inhabitants) have been trained in CPR. More about SMS Lifesavers Our press release about this research Publications Early Cardiopulmonary Resuscitation in Out-of-Hospital Cardiac Arrest Ingela Hasselqvist-Ax, Gabriel Riva, Johan Herlitz, Marten Rosenqvist, Jacob Hollenberg, Per Nordberg, Mattias Ringh, Martin Jonsson, Christer Axelsson, Jonny Lindqvist, Thomas Karlsson, and Leif Svensson NEJM 2015; 372:2307-15, online 11 June 2015 Mobile-Phone Dispatch of Laypersons for CPR in Out-of- Hospital Cardiac Arrest Mattias Ringh, Mårten Rosenqvist, Jacob Hollenberg, Martin Jonsson, David Fredman, Per Nordberg, Hans Järnbert-Pettersson, Ingela Hasselqvist-Ax, Gabriel Riva, and Leif Svensson NEJM 2015; 372:2316-25, online 11 June 2015

Large age-gaps between parents increase risk of autism in children

Tue, 09/06/2015 - 10:10
A new multinational study of parental age and autism risk, published in the journal Molecular Psychiatry, found increased autism rates among children whose parents have relatively large gaps between their ages. The study also confirmed that older parents are at higher risk of having children with autism. The analysis, which is the largest-ever, included more than 5.7 million children in five countries. The study builds on the broader research of the International Collaboration for Autism Registry for Epidemiology (iCARE). The investigators looked at autism rates among 5,766,794 children – including more than 30,000 with autism – in Denmark, Israel, Norway, Sweden and Western Australia. The children were born between 1985 and 2004, and the researchers followed up on their development between 2004 and 2009, checking national health records for autism diagnosis. “By combining information across five countries, we have created a valuable base for research into autism”, says Christina Hultman, a Professor of Psychiatric Epidemiology at Karolinska Institutet and one of the initiators of the iCare collaboration. Previous studies have found links between parental age and increased risk of autism in children. However, many questions still remain. The goal of this new study was to determine whether advancing maternal or paternal ages independently increase autism risk – and to what extent each might do so. Researchers identified and controlled for other age-related influences that might affect autism risk. When separating the influence of mother’s versus father’s age, they also adjusted for the potential influence of the other parent’s age. “After finding that paternal age, maternal age and parental-age gaps all influence autism risk independently, we calculated which aspect was most important,” says Dr Sven Sandin,a statistician and epidemiologist at Karolinska Institutet, also affiliated to the Icahn School of Medicine at Mount Sinai in New York, US. “It turned out to be parental age, though age gaps also contribute significantly.”  Key findings: Autism rates were 66 percent higher among children born to dads over 50 years of age than among those born to dads in their 20s. Autism rates were 28 percent higher when dads were in their 40s versus 20s. Autism rates were 15 percent higher in children born to mothers in their 40s, compared to those born to moms in their 20s. Autism rates were 18 percent higher among children born to teen moms than among those born to moms in their 20s. Autism rates rose still higher when both parents were older, in line with what one would expect if each parent’s age contributed to risk. Autism rates also rose with widening gaps between two parents’ ages. These rates were highest when dads were between 35 and 44 and their partners were 10 or more years younger. Conversely, rates were high when moms were in their 30s and their partners were 10 or more years younger. The higher risk associated with fathers over 50 is consistent with the idea that genetic mutations in sperm increase with a man’s age and that these mutations can contribute to the development of autism spectrum disorders (ASD). By contrast, the risk factors associated with a mother’s age remain unexplained, as do those associated with a wide gap between a mother and father’s age. “These results suggest that multiple mechanisms are contributing to the association between parental age and ASD risk”, says Sven Sandin. “However, it is important to remember that the majority of children born to older or younger parents will develop normally.” Christina Hultman and Sven Sandin are both affiliated to the Department of Medical Epidemiology and Biostatistics at Karolinska Institutet. The study was funded Autism Speaks, which is the world’s leading autism science and advocacy organization. This news article is an edited version of a press release from Autism Speaks. Publication Autism risk associated with parental age and with increasing difference in age between the parents Sandin Sven, Schendel Diana, Magnusson Patrik, Hultman Christina, Surén Pål, Susser Ezra, Grønborg Therese, Gissler Mika, Gunnes Nina, Gross Raz, Henning Maria, Bresnahan Micki, Sourander Andre, Hornig Mady, Carter Kim, Francis Richard, Parner Erik, Leonard Helen, Rosanoff Michael, Stoltenberg Camilla, Reichenberg Abraham Molecular Psychiatry (2015) 1359-4184/15, online 9 June 2015

Max Planck establishes a new research laboratory at Karolinska Institutet

Tue, 09/06/2015 - 09:09
Karolinska Institutet and Max Planck Society, Germany, have signed an agreement on a new joint research laboratory at Karolinska Institutet specialising in congenital metabolic diseases. The new Max Planck Institute for Biology of Ageing – Karolinska Institutet Laboratory is to be established in the Department of Laboratory medicine on Karolinska Institutet’s Solna campus, and will deepen existing research into congenital metabolic diseases. “This initiative is part of Karolinska Institutet’s strategy to tie itself more closely to internationally leading research institutes,” says Karolinska Institutet vice-chancellor, Anders Hamsten. At the Max Planck Institute in Cologne (the partner organisation) this research has, to date, mostly been done using animal models, and a new laboratory at Karolinska Institutet will offer fresh opportunities to collaborate using, amongst other resources, the unique patient material to which Karolinska Institutet’s leading scientists have access. “Even if we’ll be collaborating on a small scale at first, it’s important to both parties,” says Hans-Gustaf Ljunggren, dean of research at Karolinska Institutet. “Together, we’ll advance our research in a way that would have been impossible had we been working alone.” The collaborative programme is due to commence in 2015, and will run for five years under a common research group leader and with researchers recruited from Karolinska Institutet in Stockholm and visiting researchers from the Max Planck Institute in Cologne. There is also provision in the programme for doctoral students and postdocs to join as visiting researchers in both cities. Karolinska Institutet and the Max Planck Institute are investing the equivalent of 8.5 million kronor each in the programme.

New mutational patterns in gastrointestinal tract cancers

Mon, 08/06/2015 - 17:17
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

Tanzanian president visits KI

Fri, 05/06/2015 - 16:16
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

Extensive study of five-year mortality risk

Thu, 04/06/2015 - 13:13
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

No scientific evidence of risks linked to smoking cessation drug

Wed, 03/06/2015 - 08:08
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

Indian president visits Karolinska Institutet

Tue, 02/06/2015 - 13:13
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  

Research institute in the name of Bengt Samuelsson founded in China

Mon, 01/06/2015 - 15:15
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”

Study analyses link between psychotropic drugs and homicide risk

Mon, 01/06/2015 - 09:09
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 widens infrastructure offer

Thu, 28/05/2015 - 11:11
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

Conceptual confusion among researchers of value-based health care

Wed, 27/05/2015 - 14:14
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

New doctors and honorary doctors graduate in Stockholm City Hall

Wed, 27/05/2015 - 09:09
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

Information on complaints concerning performed tracheal operations and their investigation

Wed, 27/05/2015 - 09:09
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.

Heart failure drugs beneficial even in presence of kidney disease

Sat, 23/05/2015 - 11:11
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

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