Integrative Molecular Phenotyping

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Preterm birth linked to higher risk of heart failure

Tue, 23/05/2017 - 08:59
Babies born preterm run a higher risk of heart failure during childhood and adolescence than those born at full term, researchers at Karolinska Institutet in Sweden report. The registry-based study is published in The Journal of the American College of Cardiology (JACC). More and more babies survive increasingly preterm births. Babies born prematurely are exposed to life outside the womb at a time when their organs are yet to fully mature and their bodies are not entirely prepared for the radical transition from fetus to neonate. In recent years, scientists have become all the more interested in the consequences of preterm birth on, amongst other things, cardiovascular health in young adults. Complementing previous studies indicating a higher risk of hypertension, stroke and fatal cardiovascular disease, researchers at Karolinska Institutet have now uncovered a hitherto unknown connection between preterm birth and heart failure in a registry study of 2.6 million individuals born between 1987 and 2012. “We found that the risk of heart failure was higher for individuals born preterm, and inversely correlated with duration of pregnancy, in that the earlier you’re born, the greater the risk,” explains lead author Hanna Carr, doctoral student at Karolinska Institutet’s Department of Medicine in Solna. The study shows that children born before the 28th week are 17 times more likely to suffer heart failure than those born at full term. Individuals born a little later – in weeks 28 to 31 – ran just over three times the risk. This correlation held when children with birth defects were excluded from the analysis and other possible determinants, such as birth weight, socioeconomic situation and parental heart conditions, were controlled for. The results corroborate earlier studies indicating abnormal development of the cardiovascular system in people born prematurely. The researchers point out, however, that heart failure is very rare in children and young adults, so the risk of developing the condition at a young age is very small, even for people born prematurely. “It could be the case that the higher risk of heart failure remains when they grow older, in which case more people will be affected as heart failure is much more common in older people,” says associate professor Anna-Karin Edstedt Bonamy, paediatrician, who led the project. “In general the risk of heart failure can be reduced by adopting a healthy lifestyle, including refraining from tobacco use, keeping physically active, minimising your alcohol consumption and occasionally checking your blood pressure.” The study was financed by Stockholm County Council Research Service, the Karolinska Institutet Clinical Scientist Training Programme and the Swedish Heart and Lung Foundation. Publication Preterm birth and risk of Heart Failure Up to Early Adulthood Hanna Carr, Sven Cnattingius, Fredrik Granath, Jonas F. Ludvigsson, Anna-Karin Edstedt Bonamy, Journal of the American College of Cardiology, online 22 May 2017.

New findings on formation and malformation of blood vessels

Tue, 23/05/2017 - 08:54
In diseases like cancer, diabetes, rheumatism and stroke, a disorder develops in the blood vessels that exacerbates the condition and obstructs treatment. Researchers at Karolinska Institutet now show how blood vessels can normally change their size to create a functional circulatory system and how vascular malformation during disease can occur. In the study, published in Nature Cell Biology, the researchers managed to treat vascular malformation in mice, a discovery of potential significance to numerous vascular diseases. A healthy body has a perfect balance of arteries, capillaries and veins that allow the blood to reach every cell in the body and that form what is called the “vascular tree”. New blood vessels are formed by endothelial cells, which normally coat the inside of blood vessels and which organise themselves into tubes and mature, along with other cells, into arteries, capillaries or veins. Throughout a person’s life, the vascular tree has to adapt its branches to the changing needs of body tissue, such as during growth, muscle building or wound healing. However, there are diseases that affect the endothelial cells in a way that throws the vascular tree out of balance, which exacerbates the disease and often causes haemorrhaging. In cancer, for example, it is known that the vessels leak and direct shunts form between arteries and veins, preventing drugs from reaching the tumour. To understand how arteries, veins and capillaries are created – and how the process malfunctions in the presence of disease – the researchers studied normal vascular formation and the inherited Osler-Weber-Rendu disease (HHT), which is characterised by vascular malformation and repeated haemorrhaging, with an increased risk of stroke. By switching signals on and off in the endothelial cells of genetically manipulated mice, the researchers could describe how the protein Endoglin controls vascular formation and malformation. They found that the protein acts like a sensor that detects blood flow and tells the endothelial cells to organise themselves into veins, capillaries or arteries as necessary. Cells that lacked the protein were less able to form arteries. The researchers were also able to reduce vascular malformation in the genetically manipulated mice. “Our findings contribute to the understanding of fundamental biological processes that explain how the vascular tree is formed and what causes vascular malformation,” says Lars Jakobsson, assistant professor at Karolinska Institutet’s Department of Medical Biochemistry and Biophysics. “Drugs with a similar effect as one of those we tested are currently used to treat patients with inherited vascular malformation but are still under evaluation. Now we have another candidate and a more nuanced idea of how it works. We are now in a better position to control the formation and malformation of blood vessels and thus their function, which can eventually lead to improved treatments for a number of diseases.” The researchers at Karolinska Institutet also contributed to a parallel study, published in the same issue of Nature Cell Biology, describing how blood flow influences endothelial cell size that in turn affects vessel identity and malformation. The studies were financed by several bodies, including the William K. Bowes, Jr. Foundation, the Swedish Research Council, the Swedish Cancer Society, Karolinska Institutet, the Jeansson Foundations and the Magnus Bergvall Foundation. Publications Endoglin prevents vascular malformation by regulating flow-induced cell migration and specification through VEGFR2 signalling. Yi Jin, LarsMuhl, Mikhail Burmakin, YixinWang, Anne-Claire Duchez, Christer Betsholtz, Helen M. Arthur and Lars Jakobsson. Nature Cell Biology, online 22 May 2017 Endoglin controls blood vessel diameter through endothelial cell shape changes in response to haemodynamic cues. Wade W. Sugden, RobertMeissner, Tinri Aegerter-Wilmsen, Roman Tsaryk, Elvin V. Leonard, Jeroen Bussmann, Mailin J. Hamm, Wiebke Herzog, Yi Jin, Lars Jakobsson, Cornelia Denz, Arndt F. Siekmann. Nature Cell Biology, online 22 May 2017

Preparing for the management transition

Mon, 22/05/2017 - 14:28
Karolinska Institutet’s vice-chancellor-elect, Ole Petter Ottersen, has held his first day of meetings with representatives of the organisation, including Acting Vice-Chancellor Karin Dahlman-Wright, the chair of the university board Mikael Odenberg, the deans and University Director Per Bengtsson. He also attended a scientific meeting in the Nobel Forum. Ole Petter Ottersen takes over as vice-chancellor on 1 August 2017, at which point Karin Dahlman-Wright resumes her ordinary role as pro-vice-chancellor. Amongst the issues they discussed during his visit, which took place on 19 May, were the responsibilities that fall to them and how they are to be shared. “I’m looking forward to being a pro-vice-chancellor again, which is the job I actually applied for,” says Karin Dahlman-Wright, who admits that it came as a surprise to everyone, not least to her, for her to end up after a couple of days in the middle of all the turmoil that led to her stepping in as acting vice-chancellor. After the then vice-chancellor resigned his office following the storm of criticism over the Macchiarini case, Karolinska Institutet has been engaged not only in investigations and remedial action plans but also in a recruitment process to find a new vice chancellor. In April, the government appointed Ole Petter Ottersen as vice-chancellor at Karolinska Institutet, the only final candidate that the University Board had put forward. Starts formally on 1 August Ole Petter Ottersen will be quitting the rectorate of Oslo University this summer, but stresses that he will not have any formal role at KI before 1 August 2017. “But I’m hoping for many discussions before that,” he says. “I’ve got a very sharp learning curve to follow, given all I need to know about – Swedish law, the academic sector and, not least, the culture. It’s incredibly inspiring.” “It’s also imperative for me that Karin knows the university so well and is continuing as pro-vice-chancellor. I’m looking forward very much to working with her.” As the newly appointed pro-vice-chancellor the idea for Karin Dahlman-Wright was to be in charge of infrastructure, but this year Stefan Eriksson was made the new vice-dean of infrastructure, so it is time for a revised job description. Whether her remit will be healthcare issues, which have often landed on the pro-vice-chancellor’s desk in the past, is a matter for further discussion. “The main thing for me is to engage in new issues with the new vice-chancellor, it’s really important to move on,” says Karin Dahlman-Wright, adding: “And I can’t wait to learn some Norwegian!” Ole Petter Ottersen has his own plans for that: “I’ll try to steer clear of the very hardest words, like utdanning and overflate and say utbildning (education) and yta (space) instead,” he says.    Text: Madeleine Svärd Huss Foto: Gustav Mårtensson

Respiratory infections in children often treated unnecessarily with antibiotics

Fri, 19/05/2017 - 18:01
Many childhood virus infections are mistaken for bacterial infection and risk being unnecessarily treated with antibiotics. A new thesis from Karolinska Institutet on respiratory infections in children shows that viruses are a more common cause of serious respiratory infection than previously believed. It is hoped that the research will help to reduce antibiotic use and contribute to new more effective drugs and diagnostic tests. By comparing the viral flora of healthy children at child health centres and children in care for serious respiratory infections, doctoral student Samuel Rhedin has found that viruses are a more common cause of respiratory infection than previously thought. He also charted the incidence of different types of virus, which can facilitate the development of more effective treatments for viral infections. “Our results suggest that we need better treatments for viruses,” says Samuel Rhedin, physician and doctoral student at Karolinska Institutet’s Department of Medicine in Solna. “They can help give the pharmaceutical industry the proper focus for the development of new antiviral drugs. Knowledge of which virus the child has can also give the parents better information on the condition’s prognosis and transmissibility.” Virus common cause of pneumonia Owing to the difficulty of differentiating between viral and bacterial infections, there is a risk that doctors will err on the side of caution and given the children antibiotics, which merely exacerbates the problem of antibiotic resistance. A total of around 1,300 children were studied from 23 child health centres, Sachs’ Children’s Hospital and Astrid Lindgren’s Children’s Hospital. The studies showed that viruses are the more common probable cause of respiratory infections in children, even in those with pneumonia, which has traditionally been considered a bacterial infection. The researchers used the routine diagnostic method PCR (polymerase chain reaction), which has revolutionised the ability to discover and isolate different viruses. The problem with PCR is that it can take days to get a result and that certain viruses are also found in healthy children. The solution to that problem was to take samples from healthy children at child health centres as controls. Evaluating a new blood test “I hope that our results will help to reduce the use of antibiotics and provide incentives to develop new diagnostic tests that are better at distinguishing between viruses and bacteria,” says Dr Rhedin. He and his research group will shortly be starting an evaluation of a new blood test that can diagnose viruses much more quickly. Samuel Rhedin defended his thesis on “Severe viral respiratory tract infections in children” on 12 May 2017. The individual studies have, however, already been frequently cited in the international scientific press.

The Axel Hirsch Prize awarded for research on the history of the Nobel Prize in Physiology or Medicine

Fri, 19/05/2017 - 10:25
Nils Hansson, researcher at Heinrich Heine University in Düsseldorf, is awarded the Axel Hirsch Prize 2017 for his research in Swedish and German archives on candidates for the Nobel Prize in Physiology or Medicine who were not awarded the prize. The award is made by decision of the Board of Research at Karolinska Institutet. Since 2014 Nils Hansson has written 17 articles on this theme, several of which have been published or are in press in recognised scientific journals. “This gratifying news reaches me in Berlin, where I am to give a talk at the Charité university hospital this evening – on the very topic of the history of the Nobel Prize. It’s an important recognition that will stimulate me to continue my research!,” Nils Hansson says. Nils Hansson received his PhD from Lund University in 2013, defending a thesis on medical contact between Sweden and Germany during the Nazi era.  The prize, worth SEK 50,000, will be presented during the installation ceremony on 12 October.

Eva Herweijer is awarded a scholarship for her thesis on HPV vaccination

Fri, 19/05/2017 - 10:18
This year’s recipient of the Sven Gard scholarship for best thesis in virology is Eva Herweijer of the Department of medical epidemiology and biostatistics, MEB. Eva Herweijer is awarded the scholarship, worth SEK 50,000, for her thesis entitled Register-Based Evaluation of HPV Vaccination Programs, where she combines information from various Swedish quality registers and thus contributes important bases for how HPV vaccinations can best be carried out. Because Eva Herweijer’s thesis shows that HPV vaccination is effective against preliminary stages of cervical cancer it will probably lead to greater acceptance of HPV vaccination.

Mechanisms behind sensory deficits in Parkinson’s disease

Thu, 18/05/2017 - 08:15
Although Parkinson’s disease is often associated with motor symptoms such as stiffness, poor balance and trembling, the first symptoms are often sensory and include a reduced sense of touch and smell. In a study on mice, researchers at Karolinska Institutet have now been able to identify neural circuits and mechanisms behind this loss of sensory perception. The study, which is published in the scientific journal Neuron, may open avenues to methods of earlier diagnosis. There are some 18,000 people with Parkinson’s disease in Sweden, and around 2,000 new diagnoses every year. The disease, which is one of our most common neurological conditions, is currently incurable, although its symptoms can be alleviated. When we think of Parkinson’s disease, we often focus on its motor symptoms, such as stiffness and trembling, which are caused by a gradual decrease in the dopamine supply to a brain area called the striatum, the primary input nucleus of the basal ganglia. Research on Parkinson’s disease has mainly focused on these motor impairments. However, patients are also affected by severe sensory problems, including an impaired sense of smell, touch and vision, and this area of research has remained relatively neglected. “Our study highlights the sensory aspects of basal ganglia function and presents a new approach to the mechanisms behind the sensory impairments seen in Parkinson’s disease,” says Gilad Silberberg, associate professor at Karolinska Institutet’s Department of Neuroscience. Is hoped to open the way for earlier diagnosis The researchers in the present study used a light puff of air to stimulate either the right or left whiskers of mice, some of which had an especially low number of dopamine cells, while using a new optogenetic tool called an optopatcher. Applying this technique, which enables the activity of neurons to be recorded during manipulation with light, they were able to see which neurons in the basal ganglia were active and when they transmitted signals. “By studying neuronal activity in the striatum, we found that the neurons in dopamine-depleted mice did not properly signal if it was the right or left whiskers that were being stimulated,” says Dr Silberberg. “But when we treated the mice with L-DOPA, the most commonly used Parkinson’s drug, they recovered their ability to distinguish between left and right.” It is hoped that the discovery will open the way for methods of earlier diagnosis. The study was financed by the ERC, the Knut and Alice Wallenberg Foundation, the Swedish Brain Fund, Karolinska Institutet and the Swedish Research Council.     Publication Dopamine Depletion Impairs Bilateral Sensory Processing in the Striatum in a Pathway-Dependent Manner Maya Ketzef, Giada Spigolon, Yvonne Johansson, Alessandra Bonito-Oliva, Gilberto Fisone and Gilad Silberberg, Neuron, online 17 May 2017

Karolinska Institutet returns indigenous remains to New Zealand

Wed, 17/05/2017 - 16:55
At a ceremony on 15 May, Karolinska Institutet returned the remains of three people from New Zealand’s indigenous population to a delegation from Te Papa Tongarewa museum. The procession entered the Hagströmer Library courtroom to the tones of a shell trumpet and traditional Maori song. Three student ushers bearing crates containing the remains were followed by representatives of Te Papa Tongarewa, Museum of New Zealand, and Karolinska Institutet. The crates were placed at the front and covered with Maori cloaks. Unit manager Eva Åhrén and docent Olof Ljungström from Karolinska Institutet’s Medical History and Heritage Unit gave a speech about the time when the remains were stolen from the indigenous people and about their efforts to repatriate them. Finally, the handover documents were signed and the Te Papa delegation invited the university’s representatives to join in a hongi, a traditional Maori greeting involving rubbing noses and foreheads. The crates were then removed and prepared for the journey home. Ceremonies are important According to Dr Olof Ljungström, it was important for KI to hold a repatriation ceremony. “It’s a tragic tale, not only in the very fact of assembling collections but also how medical science went about it. What’s done can’t be undone but we’re working hard to make what amends we can.” The Medical History and Heritage Unit was put in charge of the university’s collection of human remains in 2014, which had been stored outside KI since the 1960s. “It’s taken some detective work to identify the skulls so they could be returned,” says Dr Ljungström. Olof Ljungström and osteologist Ann Gustavsson are working on a database that will facilitate repatriation. There must be solid reasons for deciding which organisation to send human remains back to, and it is a job that requires a great deal of paperwork and a decision from the Ministry for Foreign Affairs.  One of the remains handed over at the ceremony on 15 May was a mummified head that had been presented to professor of anatomy Anders Retzius in 1862 by the British industrialist and collector  Henry Christy. The other skulls were brought to Sweden by hunter and zoologist Conrad Fristedt, who plundered a grave at Whangaroa on New Zealand’s north island in 1890. The Swedish Museum of Natural History then arranged contact with KI, which subsequently purchased the skulls. “Otherwise, direct purchases were rare and most of the material was acquired through trade with other institutions and individual scientists in the 1800s,” says Dr Ljungström. Resting place at the museum before burial When the remains arrive back in New Zealand, they will be given a temporary resting place in a consecrated space at the museum, Dr Arapata Hakiwai informs us. “We’ll then continue our investigations to ascertain where they come from so that we can give them a proper reburial.” It was Te Papa Tongarewa, Museum of New Zealand, that requested the skulls back, and the decision to do so was taken in December 2014, with ministerial approval coming the following January. “The fact that it has taken until May 2017 to effect the actual handover is because the delegation had coordinated it with other repatriations in Europe,” says Dr Ljungström. “That said, it did take too many years to make the decision. The first request from them came in 2008. They got in touch several times afterward but nothing happened. KI had an under-dimensioned registrar’s office and no clear strategy for how such cases should be handled.” Dr Hakiwai was grateful for the decision to let the ancestors return home. “It will allow healing and reconciliation,” he says. “What’s important is that they return to those who are alive today. We bear our ancestors within us. They’re part of us and our identity.”   Text: Ann Patmalnieks Photo: Erik Cronberg

New way of preventing pneumococcal brain invasion

Wed, 17/05/2017 - 16:13
An international team of researchers, led from Karolinska Institutet, has identified two receptors on the cells in the blood vessels of the brain that can be blocked and thereby prevent pneumococci from entering the brain. The study, which is published in The Journal of Experimental Medicine, shows that the use of antibodies that block the receptors can potentially be used as a new therapeutic strategy for pneumococcal meningitis. Pneumococci is the most common bacterial cause of infections in the airways and the most significant cause of meningitis in the world, a condition that affects an estimated 100,000 children under the age of 5 every year, many of them fatally. Despite antibiotic treatment, patients often develop chronic neurological complications. Bind to cerebral blood vessels In order to cause meningitis, pneumococcal bacteria have to make their way from the airways to the blood and then pass through the blood-brain barrier – the dense layer of cells surrounding the cerebral blood vessels. How the bacteria manage to penetrate this barrier has been hitherto unknown. In the present study the researchers found after examining brain tissue from patients who died from meningitis that 90–95 per cent of all pneumococci clustered around two receptors on the blood-brain barrier cells: PECAM-1 and pIgR. While it has been known that pneumococci can enter the brain, it has remained a mystery how they attach to the brain vascular cells and enter. This new paper shows how two important pneumococcal proteins, RrgA and PspC, are recognised by PECAM-1 and pIgR. “Our results suggest that these two receptors are most important for the ability of pneumococci to enter the brain,” says Birgitta Henriques-Normark, professor at Karolinska Institutet’s Department of Microbiology, Tumour and Cell Biology. The researchers then examined if antibody-mediated blocking of these two receptors could influence pneumococcal infections in mice, and found that the control group had several hundred times more bacteria in the brain than the antibody treated group. New treatment strategy The researchers also showed that antibiotics, which are the most common form of treatment, were much more efficacious when combined with antibodies – some mice were completely cured. This suggests that antibiotic-resistant bacteria might also be prevented from infecting the brain using antibodies. “We will now further study mechanisms that enable pneumococci to enter the brain via these receptors,” explains Professor Henriques-Normark. “Our findings suggest that we might be able to develop new strategies for treatment of these infections by stopping interactions between pneumococci and brain vascular cells.” The study was financed by the Knut & Alice Wallenberg Foundation, the Swedish Research Council, and the Swedish Foundation for Strategic Research, as well as through the ALF agreement with Stockholm County Council. Publication pIgR and PECAM-1 bind to pneumococcal adhesins RrgA and PspC mediating bacterial brain invasion Federico Iovino, Joo-Yeon Engelen-Lee, Matthijs Brouwer, Diederik van de Beek, Arie van der Ende, Merche Valls Seron, Peter Mellroth, Sandra Muschiol, J. Bergstrand, J. Widengren, Birgitta Henriques-Normark, The Journal of Experimental Medicine, online 17 May 2017

KI student presented with Global Swede award

Wed, 17/05/2017 - 15:19
Adina Khamitova, master’s student of Public Health Sciences at KI, has been honoured with the accolade Global Swede, which is awarded by the government and the Swedish Institute to international university students in Sweden for outstanding achievements in innovation and entrepreneurship. Adina Khamitova has combined her studies with the establishment of a Swedish-Kazakhstani partnership to give people in her home region access to clean water using a Swedish innovation. “Many of the global challenges we’re currently facing require a broad partnership,” says Minister of EU Affairs and Trade Ann Linde, who presented Adina Khamitova with the award at a ceremony at the Ministry for Foreign Affairs. “Not only do overseas students bring new knowledge and perspectives, but they are also a vital resource for building bridges between Sweden and the outside world.”

Seminar on healthcare of the future: Patients the source of development and research

Wed, 17/05/2017 - 11:38
Changes in the health and medical care landscape will impact Karolinska Institutet’s research and education. At a seminar on Solna Campus on 10 May, speakers described how specialist and emergency care in the future to a large extent will be carried out in primary care units. “That Karolinska Institutet is given good opportunities to conduct clinical research and education also in the healthcare of the future is not only a matter for the university but also for the health and medical care system as well as for society at large,” said acting Vice-Chancellor Karin Dahlman-Wright when she opened the seminar. The seminar background was that Karolinska Institutet believes that a highly specialised intensive emergency department at the new Karolinska University Hospital will affect both research projects and medical and nursing students’ prospects of getting sufficient training. KI has also criticised the Stockholm County Council for its lack of collaboration during the planning. “The fact that we were involved does not mean that we have always been listened to. The hope we all share is to establish a good dialogue on all levels,” Karin Dahlman-Wright continued. She pointed out that Karolinska Institutet, KI, needs health and medical care services for the students to be able to get good in-service training and enable researchers to conduct their research projects. “Have never had more resources” The remodeling at the new Karolinska University Hospital is part of the new national health and medical care landscape. Göran Stiernstedt, Associate Professor and member of Karolinska Institutet’s Board, spoke about this based on his position as the government investigator of effective care. There are many reasons to be proud of Swedish healthcare, Göran Stiernstedt stated. But there are problems. A small proportion of the population feel that healthcare works well compared to other countries. “What doesn't work is accessibility. We haven’t prioritised that aspect. The number of doctors and nurses is increasing and we have never had more resources, yet people nonetheless feel that there were more resources in the past. In the future there will be sicker patients outside the hospitals,” Göran Stiernstedt said and continued: “We’re poorly equipped for that. We need more primary care. The hospitals also need to be opened for this. Hospital healthcare needs to operate outside the hospital to a greater extent. The great potential for increased efficiency lies in the overall care of the most ill group of elderly people.” Education also in outpatient care Göran Stiernstedt emphasised that every encounter with patients is a source of development and research. Primary care must be available 24 hours a day and resources need to be transferred from specialist care. “Education must gradually become more located in outpatient care,” Göran Stiernstedt said. Stockholm County Council Chief Executive Malin Frenning spoke about the challenges Stockholm faces with among other things a substantial increase in population. The goal is a healthcare network with the individual's total needs in focus. “The care residents need must be as local and accessible as possible. We need a shift within the system so that people will go to their family doctor instead of to the emergency room. The local emergency departments will be strengthened and more spread out. Research is then more closely tied to healthcare and the endeavour will then be a more patient-oriented kind of research. But the system needs to be arranged so that we can conduct research on the patients we have even more," Malin Frenning said. Regarding prerequisites for education and research, Malin Frenning among other things points out in particular the prioritisation of 14 basic training programmes and clinical research in endemic diseases and diseases that cause great suffering, as well as the establishment of a specialist centre to support research in diabetes, neurology and rheumatological disorders. “In five years’ time I think we’ll have a cohesive structure where it is easy to access healthcare,” she said. Analysis completed by 31 May When the audience were invited to comment on what had been said during the seminar, many people had concerns about what will happen to the education and skills when specialist care is relocated. The consequences of such major relocations must be thoroughly investigated was one view. More specialist care centres were another suggestion. The seminar’s last item, KI’s opportunities and challenges in the healthcare of the future, was cancelled. Karin Dahlman-Wright said she instead would comment further on the subject after 31 May, by which time KI’s internal analysis of the consequences of an intensive emergency care department will have been completed. Text: Ann Patmalnieks

Singapore health minister visits Karolinska Institutet

Wed, 17/05/2017 - 10:01
Singapore’s minister of health, Mr Gan Kim Yong, visited Karolinska Institutet on Monday 15 May, along with a delegation that included representatives of the country’s healthcare organisation. During the visit, the delegation learnt more about Karolinska Institutet’s nursing programmes, ageing research and collaboration with the healthcare sector on research and education. The visit was a joint arrangement by Business Sweden and the Swedish Embassy in Singapore. Acting Vice-Chancellor Karin Dahlman-Wright received the delegation in Aula Medica in the company of acting pro-Vice Chancellor Anders Ekbom and Deputy Vice-Chancellor for International Affairs Maria Masucci. Also present were Gunnar Nilsson, pro-dean of higher education; Ann-Langius-Eklöf, head of the nursing division/nursing subject coordinator; and Chengxuan Qiu and Anna-Karin Welmer from the Aging Research Centre. KI collaborates with Singapore on research and on education at all three levels. Its first contact with Singapore in 1999 resulted in collaborations with the National University of Singapore, Nanyang Technological University and A*STAR. Some 20 doctoral students have graduated under joint programmes with departments in Singapore, and student exchange schemes are in place for numerous study programmes, including biomedicine, medicine and public health science.

Placebo effective despite intellectual disability

Tue, 16/05/2017 - 14:51
Contrary to earlier beliefs, people with severe congenital intellectual disability are sensitive to placebo-like effects, new research from Karolinska Institutet shows, published in the scientific journal Neurology. The results suggest that the influence of implicit social signals on expectancy effects has been underestimated. The placebo effect is an example of how the power of the mind may influence the functions of the body, such as when a simple sugar pill alleviates pain when the taker believes it to be a real analgesic. But placebo-like effects also occur when expectations influence the efficacy of real drugs. Until now, placebo researchers have presumed that this type of expectancy effect requires higher-order intellectual functions, such as reasoning, abstract thinking and predicting the future. But it now turns out to be more complex than that. “Our results challenge the existing ideas of how treatment expectations are formed and we can now propose other more intuitive processes as a possible basis of the placebo effect, such as the ability to internalise the expectations of the people around you,” says Karin Jensen, assistant professor at Karolinska Institutet’s Department of Clinical Neuroscience. Analysis of 24 medical studies She and her colleagues at Karolinska Institutet and Harvard Medical School analysed 24 published medical studies involving people with congenital intellectual disability (an IQ below 70), including diagnoses such as Down’s, fragile x or Prader-Willi syndrome. Half of the studies were so-called open-label, in which all participants received active drugs. The other type were placebo-controlled, in which the participants did not know whether they were being given a placebo or active drug. “We only compared the results from those who received real drugs, and found significant differences in treatment outcomes between the two groups – despite the fact that the patients had received exactly the same drugs,” says Dr Jensen. “The only difference between the groups was the likelihood of getting an active drug.” Subtle social cues could be important The conclusion is that implicit expectations conveyed by the people who administer the drugs, or who are otherwise involved in the treatment, are likely to influence the patients’ neurobiology and, ultimately, their response to treatment. In that sense, expectancy effects are not only the result of facts and suggestions but also the subtle social cues the patients pick up from the people around them. “This aspect of the placebo effect has been underestimated,” says Dr Jensen. “This means that the models we’ve created of how the placebo effect works should be revised so that the focus isn’t just on advanced cognitive functions, such as the patient’s ability to create abstract future scenarios.” The study was financed in part by the National Institutes of Health, USA. The researchers involved have no commercial stake in the results. Publication ”Certainty of genuine treatment increases drug responses among intellectually disabled patients” Karin B. Jensen, Irving Kirsch, Moa Pontén, Annelie Rosén, Kathy Yang, Randy L. Gollub, Vincent des Portes, Ted J. Kaptchuk, Aurore Curie Neurology, 16 May 2017, 88:1912-1918; published ahead of print 19 April 2017. doi: 10.1212/WNL.0000000000003934

Spread of tau protein measured in the brains of Alzheimer’s patients

Tue, 16/05/2017 - 10:11
In a new study presented in Molecular Psychiatry, researchers at Karolinska Institutet have measured how deposits of the pathological protein tau spread through the brain over the course of Alzheimer’s disease. Their results show that the size of the deposit and the speed of its spread differ from one individual to the next, and that large amounts of tau in the brain can be linked to episodic memory impairment. Already in a very early phase of Alzheimer’s disease there is an accumulation of tau in the brain cells, where its adverse effect on cell function causes memory impairment. It is therefore an attractive target for vaccine researchers. For the present study, Professor Agneta Nordberg at Karolinska Institutet’s Department of Neurobiology, Care Sciences and Society and her doctoral student Konstantinos Chiotis along with the rest of her team used PET brain imaging to measure the spread of tau deposits as well as the amyloid plaque associated with Alzheimer’s disease, and charted the energy metabolism of the brain cells. They then examined how these three parameters changed over the course of the disease. International race “There’s been an international race to measure tau spread, and we probably got there first,” says Professor Nordberg. “There are no previous reports on how tau deposits spread after 17 months into the disease. Our results can improve understanding of tau accumulation in Alzheimer’s disease, help ongoing research to quantify the effect of tau vaccines, and enable early diagnosis.” The study included 16 patients at different stages of Alzheimer’s disease from the memory unit at Karolinska Hospital in Huddinge. The patients were given a series of neurological memory tests and underwent PET scans at 17-month intervals. While all 16 participants had abundant amyloid plaque deposition in the brain, the size and speed of spread of their tau deposits differed significantly between individuals. Episodic memory impairment “We also saw a strong direct correlation between size of deposit and episodic memory impairment,” continues Professor Nordberg. “This could explain why the disease progresses at such a varying rate from one patient to the other. That said, tau doesn’t seem to have much of an effect on the global general memory, which is more reasonably related to brain metabolism.” The study was conducted in collaboration with Uppsala University, where the PET scans were performed. The study was financed by the Swedish Research Council, the Swedish Foundation for Strategic Research, Stockholm County Council (ALF funds), the Strategic Research Area in neuroscience at Karolinska Institutet, the Gamla Tjänarinnor Foundation, the Axel Linder Foundation, the Gun and Bertil Stohne Foundation, KI’s Funds, the Swedish Brain Fund, the Swedish Alzheimer’s Foundation, the Swedish Dementia Foundation, the Wenner-Gren Foundations, KTH – SCC research grants and the EU INMiND project. Publication 'Longitudinal changes of tau PET imaging in relation to hypometabolism in prodromal and Alzheimer’s disease dementia' K Chiotis, L Saint-Aubert, E Rodriguez-Vieitez, A Leuzy, O Almkvist, I Savitcheva, M Jonasson, M Lubberink, A Wall, G Antoni och A Nordberg Molecular Psychiatry, online 16 May 2017. Doi: 10.1038/MP.2017.108

JO investigation into KI dropped

Tue, 16/05/2017 - 09:06
The Parliamentary Ombudsman (JO) has dropped the inquiry that it launched last spring following the report filed by Paolo Macchiarini against Karolinska Institutet. In November 2016, Paolo Macchiarini reported KI to the Parliamentary Ombudsman, accusing the university of having made serious mistakes in its investigation into allegations of scientific misconduct concerning articles published in scientific journals, including Nature Communications and The Lancet. According to Macchiarini, this caused considerable damage to his and his co-authors’ professional reputation. The Parliamentary Ombudsman has now announced that he is closing the investigation after having obtained documents from KI and spoken to one of the university’s lawyers. “The facts as presented give me no reason to continue the investigation,” he writes.

Corticosteroid treatment increases survival of preterm infants within hours

Mon, 15/05/2017 - 18:00
The effects of corticosteroid treatments on pregnant women facing preterm delivery to prevent infant death and morbidity have been thought to develop gradually over days. However, a new study by researchers at Karolinska Institutet and colleagues in the European EPICE project – published in JAMA Pediatrics – suggests that survival and health gains for very preterm infants may occur within hours. Hundreds of thousands of pregnant women in Europe deliver preterm every year. Even if survival nowadays is the most probable outcome, preterm birth is still one of the major causes of death in children under the age of 5. To prepare the foetus for breathing air and increase chances of survival after birth, corticosteroid treatment is given to pregnant women at risk of preterm delivery. So far, the protective effect of corticosteroids before birth has been thought to develop gradually over days. A large European study provides new knowledge, however, indicating an immediate effect. Significant effect after 3 hours “Our study finds that antenatal (before birth) corticosteroids given to pregnant women only hours before delivery were associated with a survival advantage for their infants”, says Mikael Norman, lead author, neonatologist and professor at Karolinska Institutet’s Department of Clinical Science, Intervention and Technology in Stockholm, Sweden. Mikael Norman and colleagues on the EPICE (Effective Perinatal Intensive Care in Europe) research project have studied outcomes in over 4,500 very preterm infants, born at 24 to 31 weeks of gestation (excluding multiple pregnancies and severe congenital malformations) in 11 countries across Europe. In this cohort, 15 per cent of the pregnant women were not exposed to antenatal corticosteroids. 21 per cent of the unexposed infants died after birth. Infants born already 3 hours after corticosteroid administration to the mother had significantly lower mortality than those not exposed to the treatment, and corticosteroid administration 6 to 12 hours before birth was associated with halved risks of infant death. “Given the current concept of a slow effect, pregnant women at immediate risk of preterm delivery may not receive corticosteroid treatment because it is considered futile”, says Dr Norman. “Also our results can provide reassurance for clinicians or parents in situations where it is not possible to wait a day or two to reach the full effect of corticosteroid treatment because of the need for action to reduce or stop ongoing morbidity in the pregnant woman and her foetus”, he continues. Substantial survival and health gains In the study, antenatal corticosteroid treatment was also associated with a lower risk of severe neonatal morbidity such as bleedings in the brain. This reduction in the risk was associated with longer administration-to-birth intervals. “Our findings challenge current beliefs that very short exposures to antenatal steroids before delivery have no effect, and suggest that encouraging the administration of antenatal corticosteroids to pregnant women when delivery is very imminent could result in substantial survival and health gains for very preterm infants” says Jennifer Zeitlin, principal investigator of the EPICE study and researcher at Inserm (French National Institute of Health and Medical Research), Paris, France. The research received funding from the European Union's Seventh Framework Program, the French Institute of Public Health Research/Institute of Public Health and its partners, the National Research Agency through the French Equipex Program of Investments in the Future, the PremUp Foundation in France, the Polish Ministry of Science and Higher Education, regional agreement on medical training and clinical research (ALF) between Stockholm County Council and Karolinska Institutet, and Karolinska University Hospital in Sweden. Publication 'Association of short antenatal corticosteroid administration-to-birth intervals with survival and morbidity in very preterm infants – results from the EPICE cohort' Mikael Norman, Aurelie Piedvache, Klaus Børch, Lene Drasbek Huusom, Anna-Karin Edstedt Bonamy, Elizabeth A. Howell, Pierre-Henri Jarreau, Rolf F. Maier, Ole Pryds, Liis Toome, Heili Varendi, Tom Weber, Emilija Wilson, Arno VanHeijst, Marina Cuttini, Jan Mazela, Henrique Barros, Patrick Van Reempts, Elizabeth Draper, Jennifer Zeitlin on behalf of the EPICE Research Group JAMA Pediatrics, online 15 May 2017, doi:10.1001/jamapediatrics.2017.0602

Congratulations all new doctors!

Mon, 15/05/2017 - 14:53
With a nod to Norway, this year’s spring conferment ceremony took place in Stockholm City Hall on 12 May to the tune of “En liten Fuggel” sung by Adolf Fredrik’s boys’ choir. The doctors and honorary doctors then donned their hats to the canon salute from the City Hall waterfront. Karolinska Institutet’s vice-chancellor-elect Ole Petter Ottersen comes from Oslo University, and even though he did not attend the ceremony was welcomed in his absence by the choir and in the speeches. Acting Vice-Chancellor Karin Dahlman-Wright, who spoke for the last time in this capacity during a conferment ceremony, advised the new vice-chancellor that the student ushers, who make the ceremony run so smoothly, are a key to success. The ushers also guided each of the 150 new doctors, leading them to the marble stairway in the Blue Hall where the conferrer, Dean of Doctoral Education Marianne Schultzberg, had the privilege of presenting them with their hats and diplomas in celebration of their achievements in having successfully defended their theses. Tribute was also paid during the evening to the two new honorary doctors of medicine at Karolinska Institutet: Professor Francis L. Demonico, a champion of ethical organ donation and opponent of human donor trafficking; and doctor and researcher Margaret A. Liu, who was involved in fundamental discoveries in gene activity and the immune system that are important to the development of vaccines and immunotherapy. Their honorary doctorates were conferred by Dean of Research Anders Gustafsson. Soprano Saara Rauvala, mezzo Karin Osbeck, tenor Willian Davis Lind and baritone Caspar Engdahl accompanied by Majsan Dahling at the piano provided the entertainment during the ceremony and ensuing banquet in the Golden Hall. The ceremony concluded with a parade, with the assembled doctors and standard bearers exiting the hall to the tune of the Star Wars theme. Text: Madeleine Svärd Huss Translation: Neil Betteridge Photo: Ulf Sirborn and Stefan Zimmerman

Swedish snus can be as damaging to the fetus as smoking

Fri, 12/05/2017 - 11:12
While it is well known that smoking while pregnant can damage the fetus, the effects of using Swedish snus (oral moist snuff) have been more mooted. Now, a new thesis from Karolinska Institutet in Sweden shows that using snus while pregnant carries the same level of risk as smoking as regards to stillbirth, preterm birth, cleft lip and palate, and neonatal apnea. However, it pays off to quit using snus early in the pregnancy, before the first visit at the antenatal care, as doing so gives no observable increase in risk. Anna Gunnerbeck at Karolinska Institutet’s Department of Women’s and Children’s Health has recently defended her thesis on how the nicotine consumption of pregnant women affects their unborn babies. Cigarettes contain some 4,000 substances, while Swedish snus contains almost only nicotine. Basing research on women who use snus provides unique information about what kind of damage nicotine does to the fetus. Her doctoral thesis is based on data from the National Board of Health and Welfare’s Medical Birth Register, which provides information on the health of mother and baby for effectively all pregnancies in Sweden from the point of entry into antenatal care to a month after birth.  Not a healthier alternative Snus gives even higher doses of nicotine than cigarettes and can be taken more frequently. By charting the tobacco habits of pregnant women and the state of health of their babies, Anna Gunnerbeck’s research group found that using snus carried an equally high risk of stillbirth, preterm birth, cleft lip and palate and neonatal apnea. “Snus is often promoted as a healthier alternative to smoking, and it may be for adult users,” says Dr Gunnerbeck. “But the nicotine in the snus can damage fetuses. Young women who start using snus are unaware of the risk they subject their unborn babies to when they use snus while pregnant.” Important to reach out to young women Anna Gunnerbeck's research also shows that the health risk to the fetus is significantly reduced if the mother stops using snus very early in her pregnancy. “If you stop using snus as soon as you find out you’re pregnant, the risk of fetal damage doesn’t increase,” continues Dr Gunnerbeck. “So it’s important that we reach out with this health message to young people. Ideally before they start using tobacco, since the nicotine in snus, like that in cigarettes, is highly addictive and very hard to give up.” Sweden is uniquely placed to study the effects of nicotine in pregnancy given that snus has been in widespread use here for such a long time. The results are, however, of global interest since e-cigarettes and nicotine patches are often marketed as healthy alternatives to smoking, and the use of the former is increasing in many countries.   The research was financed by Karolinska Institutet and Stockholm County Council. Anna Gunnerbeck defended her thesis "Prenatal nicotine exposure and effects on the health of the newborn" on 21 April 2017.

Newly discovered malaria mechanism gives hope to pregnant women

Mon, 08/05/2017 - 17:00
Resistance to malaria drugs means that pregnant women are unable to overcome the anaemia caused by the malaria parasite – and their babies are born undersized. A study carried out at Karolinska Institutet, however, exposes the effects of malaria in pregnant women and shows how the PTEF protein is central to the infection. The study, which is published in the scientific journal Nature Microbiology, opens the way for new malaria drugs. Some 50 million pregnant women contract malaria every year. The most common and most dangerous parasite, “Plasmodium falciparum”, affects both female carriers of the malaria parasite and their unborn babies. The parasite retards fetal growth by consuming vital nutrients and the babies are born undersized. The women are also affected by anaemia when the parasite infects the placenta. When the parasite sends a 'glue protein' to the infected red blood membrane, tens, even hundreds of thousands of parasites can accumulate in the placental vessel wall and cause inflammation. First-time mothers, who have not built up immunity to the glue molecule, develop serious, chronic infections unless given prophylactic treatment. Due to growing resistance to modern malaria drugs, the treatments are not always that efficacious. An alternative to antibiotics The team behind the study found a certain protein in the parasite, PTEF, that is vital to the synthesis of the glue molecule to which the parasites attach themselves. The researchers show how PTEF binds direct to the cell’s protein-manufacturing ribosome, where it speeds up the production of new glue molecules. “However, we can now stop this happening, and will one day be able to develop drugs that prevent the accumulation of parasites in the placenta,” says Professor Mats Wahlgren at Karolinska Institutet’s Department of Microbiology, Tumor and Cell Biology who was involved in the study. “We think that it will be possible in the future to deliver small molecules rather than traditional antibiotics to prevent pregnant women and the babies they are carrying from contracting malaria.” The researchers also collaborated with Professor Suparna Sanyal at Uppsala University, who examined how the PTEF protein affected the ribosomes in E. coli bacteria models and found that it could stimulate protein synthesis in bacteria too. The study was financed by several bodies, including the Swedish Research Council, the Swedish Foundation for Strategic Research and the Torsten Söderberg Foundation. Publication 'Regulation of PfEMP1-VAR2CSA Translation by a Plasmodium Translation- Enhancing Factor' Sherwin Chan, Alejandra Frasch, Chandra Sekhar Mandava, Jun-Hong Ch’ng, Maria del Pilar Quintana, Mattias Vesterlund, Mehdi Ghorbal, Nicolas Joannin, Oscar Franzén, Jose-Juan Lopez-Rubio, Sonia Barbieri, Antonio Lanzavecchia, Suparna Sanyal and Mats Wahlgren Nature Microbiology, online 8 May 2017

Education needs representation

Mon, 08/05/2017 - 15:43
  “Student representation is the most important tool we have for influencing our education, our current study situation and our future as colleagues,” says Pontus Dannberg, deputy chair of the Medical Students’ Association in Stockholm (MF). MF and the Student Union of Odontology organised a joint meeting on Thursday to inform students about what student influence means, how to become a student representative and what such a position can give in return. “Apart from the influence aspect, it’s also a good way to get experience of board work and how meetings are structured and a plus on your CV,” says Pontus Dannberg. There are currently some 100 student representatives on many of KI’s various bodies, including the University Board (konsistoriet), the boards of Research, Doctoral Education and Higher Education, the Working Environment Committee and the Education Committee. “Some representatives are on more than one body, which means that at the moment we’re raising the student perspective in over 200 contexts at KI,” he continues. “We hope that today’s meeting will encourage even more people to get on board.”