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 20 min ago

Oral bacteria in pancreas linked to more aggressive tumours

Thu, 14/03/2019 - 09:00
The presence of oral bacteria in so-called cystic pancreatic tumours is associated with the severity of the tumour, a study by researchers at Karolinska Institutet in Sweden published in the journal Gut reports. It is hoped that the results can help to improve diagnosis and treatment of pancreatic cancer. Pancreatic cancer is one of the most lethal cancers in the west. The disease is often discovered late, which means that in most cases the prognosis is poor. But not all pancreatic tumours are cancerous. For instance there are so-called cystic pancreatic tumours (pancreatic cysts), many of which are benign. A few can, however, become cancerous. It is currently difficult to differentiate between these tumours. To rule out cancer, many patients therefore undergo surgery, which puts a strain both on the patient and on the healthcare services. Now, however, researchers at Karolinska Institutet have found that the presence of bacteria inside the cystic tumours is linked to how severe the tumour is. “We find most bacteria at the stage where the cysts are starting to show signs of cancer,” says corresponding author Margaret Sällberg Chen, docent and senior lecturer at the Department of Dental Medicine. “What we hope is that this can be used as a biomarker for the early identification of the cancerous cysts that need to be surgically removed to cure cancer, this will in turn also reduce the amount of unnecessary surgery of benignant tumours. But first, studies will be needed to corroborate our findings.” The researchers examined the presence of bacterial DNA in fluid from pancreatic cysts in 105 patients and compared the type and severity of the tumours. Doing this they found that the fluid from the cysts with high-grade dysplasia and cancer contained much more bacterial DNA than that from benign cysts. To identify the bacteria, the researchers sequenced the DNA of 35 of the samples that had high amounts of bacterial DNA. They found large variations in the bacterial composition between different individuals, but also a greater presence of certain oral bacteria in fluid and tissue from cysts with high-grade dysplasia and cancer. “We were surprised to find oral bacteria in the pancreas, but it wasn’t totally unexpected,” says Dr Sällberg Chen. “The bacteria we identified has already been shown in an earlier, smaller study to be higher in the saliva of patients with pancreatic cancer.” The results can help to reappraise the role of bacteria in the development of pancreatic cysts, she notes. If further studies show that the bacteria actually affects the pathological process it could lead to new therapeutic strategies using antibacterial agents. The researchers also studied different factors that could conceivably affect the amount of bacterial DNA in the tumour fluid. They found that the presence of bacterial DNA was higher in patients who had undergone invasive pancreas endoscopy, a procedure that involves the insertion of a flexible tube into the mouth to examine and treat pancreatic conditions thus the possible transfer of oral bacteria into the pancreas. “The results were not completely unequivocal, so the endoscopy can’t be the whole answer to why the bacteria is there,” she continues. “But maybe we can reduce the risk of transferring oral bacteria to the pancreas by rinsing the mouth with an antibacterial agent and ensuring good oral hygiene prior to examination. That would be an interesting clinical study.” The study was conducted in collaboration with researchers at the Department of Clinical Science, Intervention and Technology, the Department of Laboratory Medicine at Karolinska Institutet and Science for Life Laboratory. It was financed by the Swedish Cancer Society, Stockholm County Council (ALF funding), Styrgruppen KI/SLL för Odontologisk Forskning (the KI/SLL steering group for dental research, SOF), KI KID-funding, and the Ruth and Richard Julin Foundation. Publication ”Enrichment of Oral Microbiota in Early Cystic Precursors to Invasive Pancreatic Cancer”. Rogier Aäron Gaiser, Asif Halimi, Hassan Alkharaan, Liyan Lu, Haleh Davanian, Katie Healy, Luisa W Hugerth, Zeeshan Ateeb, Roberto Valente, Carlos Férnandez Moro, Marco del Chiaro, Margaret Sällberg Chen. Gut, online 14 mars 2019.

KI participated in a delegation trip to India to strengthen health collaboration

Wed, 13/03/2019 - 14:16
A Swedish delegation led by H.E. Lena Hallengren, Minister for Health and Social Affairs, visited India in late February with the purpose to strengthen Swedish-Indian health collaboration. KI's Vice-Rector Anders Gustafsson was one of the participants in the delegation. “It was very valuable for Karolinska Institutet, as the only Swedish university, to accompany the Minister for Health and Social Affairs' delegation trip to India. Many new contacts were made and old contacts strengthened“, says Anders Gustafsson, Academic vice president of research at KI. Other participants were representatives from The National Board of Health and Welfare, the Public Health Agency of Sweden, the Swedish Medical Products Agency, Karolinska University Hospital, Region Uppsala and Swecare, which is a foundation that works for enhanced export and internationalization of Swedish health care and life science, with several of their member companies. Within KI, an annual KI-India seminar is held, where researchers who are involved in collaborative projects with colleagues in India gather, present ongoing projects and discuss future opportunities. Researchers, teachers, PhD students and interested are invited to this year's KI-India Seminar which takes place Tuesday 21 May 2019. 

Initiative to reduce the leadership gap in global health

Fri, 08/03/2019 - 15:39
PhD student Sara Causevic and researcher Helena Nordenstedt at the Department of Public Health Sciences and student Wiebke Mohr at the Department of Learning, Informatics, Management and Ethics started the Women in Global Health Sweden Chapter as a response to the Call to Action on Gender Equality. What is the Women in Global Health Sweden Chapter? This chapter aims to enhance the visibility of women working in global health in Sweden or that are coming from Sweden, intensify mutual support, advocate for gender equal representation on panels and conferences, establish mentoring programs, promote women's health and support further countries to start a WGH chapter. We came into contact with the global organization called Women in Global Health (WGH) and got support to organize a WGH chapter in Sweden through the Swedish Institute for Global Health Transformation (SIGHT) at the Royal Swedish Academy of Sciences. WGH in Europe consists of three chapters: Germany, Sweden, and Norway. Why did you take this initiative? The status of women in global health calls for improvement, especially in the field of global health governance where women have not been advancing in their roles or have not been present at all. There are significant gender disparities in career choices, such that women account for up to 75% of the health workforce in many countries. Much work is needed to reach gender parity in leadership across high-level positions in Global Health, academia, non-governmental institutions and private sector institutions related to global health. If we want to achieve the Sustainable Development Goals (SDGs), we need to have a diverse, gender-balanced leadership. Whom do you want to reach and influence? We want to influence the global health field where we can strengthen the position of human resources, and we can connect and advocate for gender equality within UN organizations, aid and development agencies, academia, public and private sectors. What results do you hope for? We hope this initiative will help reduce the pay gap, leadership gap and advance women's position in Sweden, but also offer opportunities to share the lessons learned abroad. What will happen next?  Actively spreading and distributing a recently produced booklet consisting of 100 biographies of women working in global health in Sweden and Swedish women working in global health abroad. This booklet is to help identify women for leadership positions in the field of global health, to connect existing female talent to conference circuits in Europe and worldwide and to propose them for conferences in different thematic areas where global health is also an issue enhancing multidisciplinary cooperation and knowledge transfer. We hope to develop a database for enhanced networking and support. Also, we plan to have open discussion thematic meetings on subjects that have been identified as national priorities, for example increasing opportunities for education and training and transforming unpaid care and informal work into decent jobs. Looking globally, we are collaborating with the other two chapters in Europe to support the development of a South Eastern Europe chapter, so we are going beyond our countries and region.

Digital examinations offer new opportunities

Wed, 06/03/2019 - 16:18
Karolinska Institutet now facilitates for all educational programs to use digital examinations. Digital examinations are legally secure and efficient as well as allows for new possibilties for teachers and course administrators to develop the education programs. Examinations are an incredibly important tool since it defines what students focus on in a course, says Annika Östman Wernerson, Academic vice president of education at KI. — To be able to conduct the examinations digitally opens the door to new possibilities, where questions can be put into a context, for example a clinical context, with the help of pictures, films or web-based tools. This makes the teachers’ jobs easier and in compliance with the rule of law.  — It can sometimes be difficult to interpret handwritten answers, and it becomes easier to provide comments and feedback. Some of the questions can also be corrected automatically, which gives the teachers more time to correct other questions. I hope that it will also stimulate the teachers to further develop the examinations. The system makes it easy to visualise and analyse the examination statistically, says Annika Östman Wernerson. Ultimately this will benefit the health care system. — If our students undergo exams in a way that stimulates understanding and in-depth learning it will benefit future patients, says Annika Östman Wernerson. Computer equipped examination rooms The examination rooms in BZ at Campus Solna and in Neo at Campus Flemingsberg have been equipped with 250 respectively 175 computers for examination, which opens the door to larger courses to take examinations. It is the result of a venture that has been ongoing since January 2018 in collaboration between several parts of KI, among others the university library, the facilities office, the IT department and the Committee for Education, which is also financing the project. The work has focused on two aspects: acquiring the correct equipment and creating the conditions needed in the rooms to be able to conduct digital examinations. to create a management organisation that can conduct digital examinations in the future with issues surrounding law, technology and pedagogy, an organisation that is under construction. The selection process of computers began with an investigation. — We rather quickly found that in order to guarantee legal security and uniform exams together with secure computer operations we needed permanently installed equipment owned by KI, explains the project leaders from the university library, Joakim Jedholt and Bodil Moberg. The computers have been equipped with software in order for digital examinations to be conducted at KI. — In an exam, only those who are taking the exam have access to the exam plus applications on the computer allowed for the exam, like for example a calculator or pharmaceutical information. The answers are stored in the cloud, not in the computer, so that if there is a power failure everything is saved, says Bodil Moberg Decreasing the risk of cheating Minimizing the risk of cheating has been a top priority — We have ensured that all computers are equipped with secrecy filters and confidentiality protection. The questions can be arranged in individual order in the program, so that everyone is not working on the same questions at the same time, which is considerably harder with traditional paper exams, says Joakim Jedholt. The project leaders have also studied how other universities work with digital examinations. — In particular, we have been impressed by the work done at Oslo University, where the number of e-exams have skyrocketed and there is an efficient organisation that manages all examinations. We have also conducted study visits at Stockholm, Uppsala and Gothenburg universities, says Joakim Jedholt. The first digital examination in the new examination rooms will be held in the end of February-beginning of March, with no lack of tension felt by the two project leaders. — It feels kind of like getting up on stage for the first time. But we are convinced that it is going to work out well, says Bodil Moberg. Three advantages to digital examinations Offers more opportunities for students to demonstrate their knowledge. ​The teachers can better assess the students’ answers and their own exams. Increased compliance with the rule of law since the risk of cheating and misinterpretations of answers decreases. Quality and the compliance to the rule of law — We teachers will be saving loads of time in correcting the exams, time that we can use to prepare questions and analyse the results.  It will also make it easier to keep track of examination data and store questions. It also feels good from a sustainability perspective to stop handing out stacks of paper to the enormous amount of students who are taking the examinations, says Marie Dahlin, Course Coordinator and moderator for Clinical Medicine with an emphasis on neurology, senses and psyche at the Medical Program KI.

Molecular puzzle reveals unknown stages of fetal development

Tue, 05/03/2019 - 17:00
By applying gene analysis to individual cells from early mouse embryos, researchers at Karolinska Institutet in Sweden have discovered previously unknown cellular stages of fetal development from fertilised egg to living being. The study is published in the scientific journal Cell Reports. All over the world, researchers are trying to find all the pieces of the puzzle describing how a fertilised egg develops into a healthy being, in order to gain a detailed understanding of the differentiation process from the totipotent stem cell. This knowledge is essential to understanding the mechanisms behind congenital diseases and fetal malformation, and eventually, how to treat diseases using stem cells. “Being able to follow the differentiation process of every cell is the Holy Grail of developmental biology.” says Qiaolin Deng, researcher at the Department of Physiology and Pharmacology, Karolinska Institutet, and Karolinska University Hospital, Sweden. Dr Deng has led the study, which has revealed new details of the critical phase between the attachment of the embryo to the uterus and the formation of the first anatomical axis, at which point the embryonic cells begin their journey towards creating a body, with a front and a back. “It’s a critical period when the whole anatomical plane is created,” she says. “If it doesn’t go smoothly, it can cause fetal malformation or death.” However, the developmental states of the cells that take part in the process is not always the same. In order to map what happens in individual cells, the researchers used single-cell RNA sequencing on a total of 1,724 cells from 28 mouse embryos in four early stages of development (5.25 to 6.5 days old). An average of 8,577 genes were expressed in each cell. Using bioinformatic analysis, the cells were then sorted into different cell types on the basis of which genes were active or inactive, allowing the researchers to see the order in which the genes were switched on. The result was a molecular road-map of the events that control cell differentiation. Previously unknown details “The study has revealed previously unknown details about what happens before the early embryo gains its first spatial orientation, and shown that the cells along the future head-tail axis have different differentiation potential,” says Dr Deng. At the same time as the anatomical axis starts to form, another process gets underway in the female embryo, which contains two X chromosomes, one from each biological parent. Previous studies on mice have shown that the paternal X chromosome is first switched off completely in the embryo so that female embryos do not have twice the genetic activity as male. The paternal X chromosome copy remains switched off in the cells that form the placenta and the yolk sack, but is reactivated in the embryo’s cells. Then a random inactivation of the maternal or paternal X chromosome occurs. Female embryos therefore comprise a “mosaic” of cells, in which either the maternal or paternal X chromosome is active. The new study shows that the first inactivation of the paternal X copy does not happen to the extent previously believed. “What’s interesting, molecule-wise, is that the paternal X chromosomes that are reactivated never have been completely switched off. The random inactivation also takes place at different rates in the embryo’s cells.” New light on the early development The results of the study shed new light on the early development of the embryo in animals, humans included. “Knowledge of the events and factors that govern the development of the early embryo is indispensable for understanding miscarriages and congenital disease,” says Dr Deng. “Around three in every 100 babies are born with fetal malformation caused by faulty cellular differentiation.” The study was conducted in collaboration with researchers at the University of Chinese Academy of Sciences, Shanghai Tech University, Tongji University (Shanghai) and the University of Sydney (Australia). It was financed with grants from the Swedish Research Council, SSMF, the Åke Wiberg foundation, the KID foundation, KI faculty-funded career grant and the Jeansson foundation. Publication “Single-cell RNA-seq reveals cellular heterogeneity of pluripotency transition and X-chromosome dynamics during early mouse development” Shangli Cheng, Yu Pei, Liqun He, Guangdun Peng, Björn Reinius, Patrick P L Tam, Naihe Jing, Qiaolin Deng Cell Reports, online 5 March 2019, doi: 10.1016/j.celrep.2019.02.031

New mechanism of bone growth discovered

Wed, 27/02/2019 - 19:00
In a paper published in the journal Nature, an international research team led by researchers at Karolinska Institutet in Sweden report that bone growth in mice takes place in accordance with the same principles as when new cells are constantly produced in blood, skin and other tissue. This contradicts the previous understanding that bone growth depends on a finite number of gradually consumed progenitor cells. If the new findings also apply to humans, they could make an important contribution to the treatment of children with growth disorders. The growth of children’s bones depends on growth plates (physes) situated close to the end of all long bones in the body. These plates consist of cartilage cells, chondrocytes, that form a kind of scaffold supporting the formation of new bone tissue, and that are themselves generated from stem-cell like progenitor cells called chondroprogenitors. For long bones to grow properly, chondrocytes must be generated constantly throughout the growth period. The general view in the field has been that there is a limited number of progenitor cells that are formed during embryonic development and then consumed for bone growth until they run out and we stop growing. In an attempt to ascertain whether or not this is true, researchers at Karolinska Institutet decided to study the formation of chondrocytes in mice. “What we found was that small ‘clones’ of cells were generated from the same progenitor cells during embryonic development, which is in line with the current view,” says research group leader Andrei Chagin, docent at the Department of Physiology and Pharmacology, Karolinska Institutet. “But after birth there were dramatic changes in cell dynamics and large, stable clones were formed that proved to be a consequence of how the chondroprogenitors had acquired the ability to regenerate.” Progenitor cell situated in stem cell niche Such progenitor cell behaviour is typical for tissue that constantly produces many new cells, such as skin, blood and intestine. For such tissue types, it has been shown that the progenitor cells are situated in a very specific micro-environment, a stem cell niche, which helps to generate the necessary cells (e.g. skin and blood cells) but also enables the progenitor cells to renew themselves. If the niche is disrupted or dysfunctional, the progenitor cells become depleted and the tissue is damaged. The researchers have now shown that there is a stem cell niche in growth plates too, at least in mice, and that bone growth ceases if this local micro-environment is disrupted, implying that bone growth follows a completely different principle to what was once thought. “If it turns out that humans also have this growth mechanism, it could lead to a significant reassessment of numerous therapeutic approaches used for children with growth disorders,” says Dr Chagin. “The mechanism could also explain some previously puzzling phenomena, such as the unlimited growth seen in patients with certain genetic mutations.” The study was financed by the Swedish Research Council, StratRegen (Karolinska Institutet), the King Gustaf V 80-year Foundation, the Swedish Cancer Society, the Swiss National Science Foundation, EMBO, the Frimurare Barnhuset (Masonic children’s home) Foundation, the Foundation for Child Care and the Grant Agency of the Czech Republic. Publication “A radical switch in clonality reveals a stem cell niche in the epiphyseal growth plate”. Phillip T Newton, Lei Li, Baoyi Zhou, Christoph Schweingruber, Maria Hovorakova, Meng Xie, Xiaoyan Sun, Lakshmi Sandhow, Artem V Artemov, Evgeny Ivashkin, Simon Suter, Vyacheslav Dyachuk, Maha El Shahawy, Amel Gritli-Linde, Thibault Bouderlique, Julian Petersen, Annelie Mollbrink, Joakim Lundeberg, Grigori Enikolopov, Hong Qian, Kaj Fried, Maria Kasper, Eva Hedlund, Igor Adameyko, Lars Sävendahl, Andrei S Chagin. Nature, online 27 February 2019, doi: 10.1038/s41586-019-0989-6.

New skeletal disease found and explained

Mon, 25/02/2019 - 17:00
Researchers at Karolinska Institutet in Sweden have discovered a new and rare skeletal disease. In a study published in the journal Nature Medicine they describe the molecular mechanism of the disease, in which small RNA molecules play a role that has never before been observed in a congenital human disease. The results are important for affected patients but can also help scientists to understand other rare diagnoses. The newly identified skeletal disease was first observed in a parent and a child from a Swedish family. “They came to my clinic,” says the study’s lead author Giedre Grigelioniene, physician and associate professor at the Department of Molecular Medicine and Surgery, Karolinska Institutet. “They’d received a different diagnosis previously, but it didn’t fit with what we were seeing in the X-rays. I was convinced that we were looking at a new diagnosis that had not been described before.” A long, arduous process then began to examine the finding further. The results of these efforts are now published in a study in Nature Medicine, in which Giedre Grigelioniene and her colleagues describe the new skeletal disease – a type of skeletal dysplasia – and its mechanism. Mutation identified Together with Fulya Taylan, assistant professor at the same department at Karolinska Institutet, the disease causing mutation in a gene called MIR140 was identified. The gene does not give rise to a protein but to a so-called micro-RNA (miR-140), a small RNA molecule that regulates other genes. Working alongside with Tatsuya Kobayashi, associate professor at Massachusetts General Hospital, Harvard Medical School in Boston, USA, the researchers produced a mouse model of the disease, using the CRISPR-Cas9 “molecular scissors” technique to create a strain carrying the identified mutation. They subsequently observed that the animals’ skeletons displayed the same aberrations as the three patients in the study. The researchers also show that the identified mutation leads to an abnormal expression of several important genes in the cartilaginous growth plates and the ends of the long tubular bones. These studies were done in collaboration with Hiroshi Suzuki, researcher at the Massachusetts Institute of Technology in the lab of Phillip Sharp, Nobel laureate in medicine. Some genes that are normally suppressed by miR-140 are expressed, while others are down-regulated. “This causes a change in skeletal growth, deformed joints and the delayed maturation of cartilage cells in the patients, who have short stature, small hands and feet and joint pain,” says Dr Grigelioniene. Normal function knocked out The identified mutation knocks out a normal function of the micro-RNA, which is replaced by a different function. The mechanism is called neomorphic and has never before been described involving small RNAs in human congenital disease. A similar mechanism in cancer cells was described last year in a paper in Nature Genetics by researchers who were also involved in the present study. According to Dr Grigelioniene, the results now published are important both for patients with the disease and for scientists interested in how small regulatory RNA molecules are involved in the development of human congenital disease. “We plan to examine whether similar mechanisms with mutations in small RNA genes are involved in the development of other rare congenital disorders,” she says. “As for patients who already have this disease, the results mean that they can choose to use prenatal fetal diagnostic, in order not to pass the disease on to their children”. The study was financed by grants from Stockholm County Council, the National Institutes of Health, the Swedish Research Council, the European Society for Paediatric Endocrinology (a programme financed by pharmaceutical company Eli Lilly), the Fernström Foundation, Karolinska Institutet, the Swedish Society of Medicine, the Promobilia Foundation, Frimurare Barnhuset (Masonic children’s home), the Samariten Foundation for Paediatric Research, the Uehara Memorial Foundation and the Osamu Hayaishi Memorial Scholarship. One of the co-authors works at Emedgene Technologies and one is a director of Syros Pharmaceuticals. Publication "Gain-of-function mutation of microRNA-140 in human skeletal dysplasia” Giedre Grigelioniene, Hiroshi I. Suzuki, Fulya Taylan, Fatemeh Mirzamohammadi, Zvi U. Borochowitz, Ugur M. Ayturk, Shay Tzur, Eva Horemuzova, Anna Lindstrand, Mary Ann Weis, Gintautas Grigelionis, Anna Hammarsjö, Elin Marsk, Ann Nordgren, Magnus Nordenskjöld, David R. Eyre, Matthew L. Warman, Gen Nishimura, Phillip A. Sharp, Tatsuya Kobayashi. Nature Medicine, online 25 February 2019

New research prize in memory of Professor Dan Grandér

Fri, 22/02/2019 - 13:18
This year, the Swedish medical university Karolinska Institutet for the forst time awards a research prize in memory of Professor Dan Grandér, who passed away in 2017. The receiver of the Dan Grandér Memorial Prize for best doctoral thesis in the area of cancer research at Karolinska Institutet is Dr Nicholas Valerie, Department of Oncology-Pathology. Nicholas Valerie defended his thesis titled “Roles of NUDT5 and NUDT15 beyond oxidized nucleotide sanitation and their potential as therapeutic targets” in April 2018. In this thesis, he demonstrates novel functions of the two enzymes NUDT5 and NUDT15 in oxidized nucleotide metabolism. Furthermore he shows that NUDT5 is an important regulator of hormone signalling, and that it could block thiopurine-based chemotherapies to reduce their efficacy as cancer therapeutic agents. This led to the development of targeted NUDT5 inhibitors which might be used to potentiate cancer therapy. Professor Dan Grandér was a prominent researcher and physician in the field of cancer, and at the time for his death also Head at the Department of Oncology-Pathology at Karolinska Institutet. He passed away in 2017 at the age of 53 years, himself the victim of cancer disease. The research prize in his memory is awarded on Friday, 22 February 2019 at the BioClinicum Cancer Research Meeting in Stockholm, Sweden. The awardee receives SEK 50,000 and a diploma.

Combination therapy might be beneficial in schizophrenia

Wed, 20/02/2019 - 17:00
Combining certain types of two antipsychotic agents in the maintenance treatment of schizophrenia is associated with a lower risk of relapse than using monotherapy. This is suggested in a paper published by researchers at Karolinska Institutet in the journal JAMA Psychiatry. The current treatment guidelines should modify their categorical recommendations discouraging all antipsychotic polypharmacy, according to the researchers. The effectiveness of antipsychotic combination therapy in schizophrenia relapse prevention is controversial, and use of multiple agents is generally believed to impair physical well-being. But the evidence for this is weak and antipsychotic polypharmacy is widely used. Now researchers at Karolinska Institutet in Sweden have conducted a large registry based study to see if there is any difference in the risk of relapse in schizophrenia when patients use antipsychotic polypharmacy compared to monotherapy. Studied 62,000 patients The study was based on more than 62,000 patients; all persons with schizophrenia treated in the inpatient setting during 1972-2014 in Finland. The researchers then followed the patients to see to what extent they were rehospitalised for psychiatric care, which was used as a marker for relapse. The median follow-up time was 14.1 years and to avoid bias each patient was used as his or her own control (so called within-individual analysis). The results show that antipsychotic polypharmacy in general was associated with a slightly lower risk of psychiatric rehospitalisation than monotherapy. They do however not indicate that all types of polypharmacy are beneficial. Combining aripiprazole with clozapine was associated with the best outcome, with a 14-23 per cent lower risk of rehospitalisation compared to clozapine alone; which was the monotherapy associated with the best outcomes. Possible update of treatment guidelines Current treatment guidelines state that antipsychotic monotherapy should be preferred and polypharmacy should be avoided if possible. This study should change that view, according to first author of the study, Jari Tiihonen, specialist doctor and professor at Karolinska Institutet’s Department of Clinical Neuroscience. ”Our results indicate that the current treatment guidelines should tone down their categorical recommendations discouraging all antipsychotic polypharmacy. The evidence of superiority of polypharmacy might be sparse, and should be replicated in other countries, but there is no evidence at all on superiority of monotherapy over polypharmacy in the maintenance treatment of schizophrenia”, says Jari Tiihonen. Researchers affiliated to the University of Eastern Finland, Niuvanniemi Hospital, EPID research Oy, Hofstra Northwell School of Medicine, The Zucker Hillside Hospital, Charité Universitätsmedizin and National Institute for Health and Welfare, Finland, also contributed to the study. The study was funded by the Finnish Ministry of Social Affairs and the Academy of Finland. No company has financed this study, but several of the authors have previously received funding/fees from pharmaceutical companies in different contexts. Two of the authors are employed by the contract research organisation EPID Research. The scientific article provides more detailed information about potential conflicts of interest. Publication Association of Antipsychotic Polypharmacy vs Monotherapy With Psychiatric Rehospitalization Among Adults With Schizophrenia Jari Tiihonen, Heidi Taipale, Juha Mehtälä, Pia Vattulainen, Christoph U. Correll and Antti Tanskanen JAMA Psychiatry, online Februari 20, 2019, doi:10.1001/jamapsychiatry.2018.4320

Study on regenerative angiogenesis in humans shows encouraging results

Wed, 20/02/2019 - 11:05
An international team of researchers from academia and the biopharma industry has published a Phase 1a/b study, showing the therapeutic potential of mRNA encoding for vascular endothelial growth factor A (VEGF-A) for regenerative angiogenesis in humans. The goal of this potential novel treatment is to generate new blood vessels and improve blood flow in tissues where it is otherwise restricted. Partners in this randomized, double blind, placebo-controlled study in men with type 2 diabetes were AstraZeneca, Moderna Inc., Karolinska Institutet, and the Sahlgrenska Academy of Gothenburg University. The findings have been published in the scientific journal Nature Communications. VEGF-A mRNA was delivered to the study participants in a saline solution and was administered by intradermal injection into forearm skin in single ascending doses. The trial met its primary objectives of describing safety and tolerability and secondary objectives of protein production and changes in local blood flow post injection. The study showed that the VEGF-A protein, post injection of mRNA, had increased. At each sampling time, mean VEGF­A protein levels, across all mRNA-treated sites from patients across all cohorts, were higher than that of placebo up to the 24-26 hour time point in the study. The bioactivity of the VEGF-A protein post injection was also observed by an increase in blood flow at injection sites, up to seven days following a single injection, and the treatment was overall well tolerated. An important milestone “I believe this an important milestone in the field of mRNA therapeutics as it starts to address many questions regarding delivery of mRNA to human tissues, the duration and level of the protein that can be expressed and the ability of the technology to have a physiologic, measurable function over a prolonged period of time”, said study co-author Dr. Kenneth Chien, a professor of Karolinska Institutet and scientific co-founder of Moderna, in a press release. “Based on these early data, this approach may provide benefit to patients where proper blood flow is compromised in areas such as heart disease and diabetes as well as for other vascular complications.” AstraZeneca is now leading a Phase 2a study with patients receiving epicardial injections of VEGF-A mRNA during coronary artery bypass grafting surgery. The recent study was funded by AstraZeneca. This news article is a re-write of a press release from Moderna, Inc., which is a Nasdaq listed company. Publication Intradermal Delivery of Modified mRNA Encoding VEGF-A is Well Tolerated and Transiently Enhances Basal Skin Blood Flow in Patients with Type 2 Diabetes Li-Ming Gan, Maria Lagerström-Fermér, Leif G Carlsson, Cecilia Arfvidsson, Ann-Charlotte Egnell, Anna Rudvik, Magnus Kjaer, Anna Collén, James D Thompson, John Joyal, Ligia Chialda, Thomas Koernicke, Rainard Fuhr, Kenneth R Chien, Regina Fritsche-Danielson Nature Communications, online 20 January 2019, doi: 10.1038/s41467-019-08852-4

“One in five had completely avoided sexual relations after their diagnosis”

Mon, 18/02/2019 - 14:20
Hello, Galit Andersson, who recently defended a doctoral thesis at the Department of Public Health Sciences, Karolinska Institutet. For your thesis you conducted large surveys of transgender people and people living with HIV in Sweden to assay their quality of life. What were your most interesting results? “People living with HIV generally rate their quality of life rather high. But many of them still feel that there’s a stigma related to negative attitudes towards people living with HIV, and that this creates a negative self-image that undermines their wellbeing. Mental health is an important health issue for many people and in our research we found high rates of hopelessness.” “In our study of transgender people, we found that quality of life and self-rated health were lower in those who’d encountered ignorance or prejudice when dealing with healthcare professionals. People who wanted to change legal gender but who, for whatever reason, hadn’t done so, also had poorer health and quality of life.” What surprised you? “That one in five participants of the HIV study had completely avoided sexual relations after their diagnosis out of fear of being rejected or shamed. This despite the fact that most of them had known about their HIV for 10 – 15 years and that over 95 per cent of all people living with known HIV-infection in Sweden are under very effective treatment and cannot transmit the virus.” What do you think should be done, given your results? “We must continue to inform the public about what it’s like to live with HIV today – that the treatment is so effective that people can generally live a long, quality life. This will help reduce the stigma that comes from ignorance and hopefully improve wellbeing among people living with HIV. It’s also important that the health services can meet the group’s need for psychological support and sexual health information.” “Since the number of people seeking change of legal gender or gender-affirming medical interventions has increased, the same holds true for transgender people. It’s vital that the public are well-informed and that medical staff treat them with respect. I also think that the possibility of making it easier to change legal gender should be looked into. At the moment the process is a long one and linked to which gender-affirming treatments someone is undergoing. Maybe it would help matters if it was a purely legal process.” How did you get into this research field? “Before becoming a doctoral student, I was a research assistant at KI, and that piqued my interest. The Global and Sexual Health research group was working with HIV and sexual health and I had the opportunity to work on a large survey of transgender people’s health. Both groups have seen many improvements, in terms of both policy and medical treatment, so I became interested in what their health looks like today and what factors influence it.” What will you do now? “I’m now an investigator at the Public Health Agency at a unit that works with HIV prevention and LGBT health. It’s great that I can continue with the same kind of issues that I did my thesis on.”

Brain pathways of aversion identified

Thu, 14/02/2019 - 14:38
What happens in the brain when we feel discomfort? Researchers at Karolinska Institutet in Sweden are now one step closer to finding the answer. In a new study published in the journal Molecular Psychiatry they identify which pathways in the mouse brain control behaviour associated with aversion. Scientists have long been interested in how the brain creates signals associated with negative emotions in order to better understand how imbalances in the same system can lead to affective disorders such as depression and anxiety. The amygdala has long been the most commonly studied brain structure for understanding fear, whereas for rewards and positive signals the focus has been on the neurotransmitter dopamine. But when it comes to areas of the brain that control feelings of discomfort and aversion, much less is known. Brain structure controlling emotions In the past few years, research has indicated that a brain structure called the habenula controls positive and negative emotions in animal models. Moreover, clinical cases have been conducted with patients suffering from depression where deep brain stimulation of the habenula has been beneficial. The habenula controls both dopamine and the neurotransmitter serotonin, which is thought to play a significant part in the sense of wellbeing. However, it has not been known how the habenula is regulated. Researchers at Karolinska Institutet have now mapped which networks in the mouse brain control the habenula, and what role they play in aversion. “We’ve discovered a specific pathway that goes between the hypothalamus and the habenula, and that can be modulated using optogenetics to control the feeling of aversion,” says study leader docent Dinos Meletis at the Department of Neuroscience. “Our hope is that this can lead to the development of new treatments that can rebalance the brain’s networks in for example depression or anxiety disorders.” Using light to activate neurons Using optogenetics and other advanced methods, the group were able to identify the identity of the nerve cells and map their interconnections. Optogenetics is a method that uses light to activate specific neurons in order to study how the activation of different networks affects behaviour. “This methodological revolution in brain research has made it possible to functionally study how different types of nerve cell and pathways actually control different types of behaviour, something that was impossible to do only a decade ago,” says Dr Meletis. The study was supported by grants from the Swedish Research Council, the Swedish Foundation for Strategic Research, the Swedish Brain Foundation and Karolinska Institutet. Publication “A hypothalamus-habenula circuit controls aversion” Iakovos Lazaridis, Ourania Tzortzi, Moritz Weglage, Antje Märtin, Yang Xuan, Marc Parent, Yvonne Johansson, Janos Fuzik, Daniel Fürth, Lief E. Fenno, Charu Ramakrishnan, Gilad Silberberg, Karl Deisseroth, Marie Carlén, Konstantinos Meletis Molecular Psychiatry, online 12 February 2019, doi: 10.1038/s41380-019-0369-5

Social threat learning influences our decisions

Thu, 14/02/2019 - 11:02
Learning what is dangerous by watching a video or being told (known as social learning) has just as strong an effect on our decision-making as first-hand experience of danger, researchers at Karolinska Institutet in Sweden report. The results of the study, which is published in the journal PNAS (Proceedings of the National Academy of Sciences), can help to explain why we take irrational decisions. It is easy nowadays to be exposed to unpleasant and threatening information, with accidents, terrorist attacks and natural disasters appearing, for instance, on TV, digital news sources and social media. Previous research has shown that individuals who have long exposure to news reports of a terrorist attack can develop psychological problems as serious as those afflicting people who experienced it first-hand. However, just how our actual behaviour is affected by such indirect learning of danger has remained unknown.  This has now been laboratory tested in a study conducted by researchers at Karolinska Institutet, University of Amsterdam and University of Zurich. The study shows that threat learning via video or orally can affect human behaviour just as strongly as personal experience. New study with 120 participants In the study, three groups of participants, totalling 120 individuals, initially learnt which of two neutral images was “dangerous”. The first group learnt through direct experience of an electric shock, the second by watching a film of someone receiving electric shock when looking at the image, and the third by being given oral instructions on which image to associate with an electric shock. In other words, the participants in the social learning groups (observation and oral instruction) suffered no actual physical discomfort. The participants were then asked to repeatedly choose between the two images. Their choice could result in an electric shock, their task being to receive as few shocks as possible. For half of the participants, the choice of image that was “dangerous” during the first part of the experiment entailed the highest risk of electric shock. This meant that their previous learning was relevant to their decisions. For the other half, the choice of image that was not “dangerous” in the initial stage entailed the highest risk of shock. This meant that their previous learning was wrong. Strong impact on decision-making What the researchers found was indirect social learning (watching a film and oral information) had just as strong an effect on the participants’ decisions as learning by first-hand experience. Participants who had learnt that a certain image was “dangerous” continued to avoid it, even though their choice resulted more often in an electric shock. “The study suggests that these social ways of obtaining information can strongly influence our decision-making, even to our own detriment”, says lead author Björn Lindström, researcher at Amsterdam University and the Department of Clinical Neuroscience, Karolinska Institutet. “The results can help us understand why people behave irrationally”, says research group leader Andreas Olsson, senior lecturer at the Department of Clinical Neuroscience, Karolinska Institutet. “They indicate that it can depend on something we’ve learnt by watching a video clip or listening to a rumour that’s misleading for the environment in which we find ourselves.” The researchers also used computational models to show that the two types of social learning influence behaviour through different learning mechanisms, possibly reflecting differences in underlying brain systems. Brain activity was not measured in the study, however. The study was financed by the Knut and Alice Wallenberg Foundation, the Bank of Sweden Tercentenary Foundation, the European Research Council, the Swedish Research Council for Health, Working Life and Welfare (Forte), the Swedish Research Council and the Swiss National Science Foundation. Publication ”Social threat learning transfers to decision-making in humans”. Björn Lindström, Armita Golkar, Simon Jangard, Philippe Tobler och Andreas Olsson PNAS, online 13 februari 2019, doi: 10.1073/pnas.1810180116

Newly discovered disease opens for future diabetes treatment

Tue, 12/02/2019 - 11:01
Knowledge of a newly discovered genetic disorder, which means that a person cannot produce the protein TXNIP (thioredoxin interacting protein) in their cells, can open for the development of new diabetes drugs. This is shown in a study from Karolinska Institutet published in the journal Diabetes. With modern techniques more and more previously unknown genetic diseases are being discovered, which can lead to new knowledge about human biology and contribute to the development of new drugs. Researchers at Karolinska Institutet have recently been using gene sequencing (genome analysis) to investigate a family in which three of the children had excessively high levels of lactate (lactic acid) and simultaneously low levels of the amino acid methionine in the blood, which is an unusual symptom picture. If left untreated, elevated lactate levels can cause tissue damage, respiratory effects and even fatal outcome, but the children are being given continuous medical treatment and are otherwise well. "We discovered that the children's symptoms were due to a mutation in the gene that encodes the protein TXNIP (thioredoxin interacting protein), which had never previously been described in humans. Based on the results in animal models, this protein has been suggested as a possible target for new diabetes drugs, since overexpressing TXNIP in mice induces diabetes, while a lack of TXNIP protects against diabetes,” says Anna Wedell, consultant and professor at the Department of Molecular Medicine and Surgery at Karolinska Institutet and SciLifeLab. The cells thioredoxin system were analysed TXNIP is active in the thioredoxin system, which is found in all living cells. The system is of great importance in terms of the ability to make new DNA (genetic material) and to protect cells from reactive radicals. In the current study, the researchers examined cells from the children using more detailed methods and analyses of both the thioredoxin system and sugar metabolism. They also investigated how the mitochondria, which are the cells’ energy factories, functioned. "We found that the TXNIP protein was completely absent from the cells from these patients. The result is that the mitochondria are unable to use pyruvate resulting from the break-down of glucose, as is usually the case when cells use sugar to make energy. Instead, they only produced lactate from pyruvate. However, the cells were able to use another substance as fuel for the mitochondria - malate. This can explain much of the patients’ symptoms, and also shows that a complete absence of TXNIP is compatible with human life,” says Elias Arnér, professor at the Department of Medical Biochemistry and Biophysics, Karolinska Institutet, who led the study together with Anna Wedell and Alfredo Giménez-Cassina at the Universidad Autónoma de Madrid. TXNIP potential target for drug treatment in diabetes It has not previously been known what happens in humans if TXNIP is absent. The results of the new study provide important insights into the significance of TXNIP and strengthen the hypothesis for TXNIP being a potential target for drug treatment in diabetes, provided that any high lactate levels as a result of such treatment can be managed. "Studying patients in whom this protein is entirely absent can give some idea of the potential effects of a drug that inhibits the protein, though more studies are needed because these children do not have diabetes," says Elias Arnér. The researchers now want to conduct further research in order to understand why the children also have low levels of methionine in their blood, and how the metabolism of methionine might be linked to sugar metabolism. The study was funded with the support of Karolinska Institutet, the Swedish Research Council, the Swedish Cancer Society, the Knut and Alice Wallenberg Foundation, Region Stockholm, the Spanish Ministry of Economy and Competitiveness, the Ramón y Cajal Fellowship, the Swedish Diabetes Fund, the Alicia Koplowitz Foundation and the Ragnar Söderberg Foundation. Publication ”Absence of TXNIP in human gives lactic acidosis and low serum methionine linked to deficient respiration on pyruvate” Yurika Katsu-Jiménez, Carmela Vázquez-Calvo, Camilla Maffezzini, Maria Halldin, Xiaoxiao Peng, Christoph Freyer, Anna Wredenberg, Alfredo Giménez-Cassina, Anna Wedell and Elias S.J. Arnér. Diabetes, online 12 February, 2019, doi: 10.2337/db18-0557

Low physical fitness in adolescence linked to higher risk of disability pension later in life

Tue, 12/02/2019 - 09:55
Obesity or low physical fitness during adolescence is strongly associated with disability pension later in life. This is shown in a study of more than one million Swedish men, published in Annals of Internal Medicine by researchers at Karolinska Institutet. In many countries, disability pensions are granted to working-aged persons who are likely to never work full-time again because of a chronic disease or injury diagnosed by a physician.  In addition to serving as an important indicator of chronic disease, disability pensions are associated with high societal costs. Researchers from Karolinska Institutet in Sweden and University of Granada in Spain led a study assessing cardiorespiratory fitness and weight for more than 1 million men between the ages of 16 and 19. Data from the Swedish military service conscription registry was used. The researchers then reviewed who would later in life go on to receive a medical disability pension.  Over a median follow-up of 28.3 years, the data showed that low cardiorespiratory fitness was strongly associated with later receipt of a disability pension due to all causes. Obesity was also associated with a greater risk for disability pension, with the greatest risks observed for severe/morbid obesity.  Important marker regardless of body weight However, the researchers noted that compared with being unfit, being moderately or highly fit was associated with lower risk for disability, regardless of BMI. According to the researchers, this means that being physically fit is an important indicator of health irrespectively of body weight.  ”Our findings support the relevance of cardiorespiratory fitness and healthy body weight during adolescence as important markers of future health", said Pontus Henriksson, researcher at the Department of Biosciences and Nutrition, Karolinska Institutet, and first author of the study. This news article is based on a press release from Annals of Internal Medicine. The research was funded mainly by Karolinska Institutet, the Henning and Johan Throne-Holst Foundation, the Swedish Society of Medicine, Region Östergötland, National Institute on Aging, the European Union and the University of Granada. Publication ”Fitness and Body Mass Index During Adolescence and Disability Later in Life” Pontus Henriksson, Hanna Henriksson, Per Tynelius, Daniel Berglind, Marie Löf, I-Min Lee, Eric J. Shiroma and Francisco B. Ortega, Annals of Internal Medicine, online 12 February 2019, doi: 10.7326/M18-1861.

DNA puzzle uncovers rare chromosome defects

Mon, 11/02/2019 - 11:10
Using puzzle pieces from four different DNA analyses, researchers at Karolinska Institutet have been able to map three extremely complex chromosome aberrations. This has given families answers about the cause of their children’s serious symptoms. The study was published in the scientific journal PLOS Genetics and the goal is to produce a test to be used in the clinic. One in 500 people carries a balanced chromosome aberration. It means having all the genetic make-up but not in the right place. It does not necessarily cause any medical problems, depending on where the aberrations are located. However, healthy carriers may face fertility problems or an increased risk of having children with rare genetic disorders. Anna Lindstrand, clinically active researcher at Karolinska Institutet and Karolinska University Hospital, leads a research group specialised in studying the genetic background of rare diagnoses. This includes diseases caused by complex chromosome aberrations. For the past two years, she and her colleagues have used the latest technology to find genetic causes for the severe symptoms experienced by three persons since they were little. Neither studying the chromosomes under a microscope nor whole genome sequencing using the standard “short read” technique had been able to identify the exact cause of the problems. “We knew that they were carrying one or more irregular chromosomes, but we did not know what they looked like on a detailed level,” says Anna Lindstrand, Docent at the Department of Molecular Medicine and Surgery at Karolinska Institutet. The knowledge is important both in order to give the appropriate care, and to allow for prenatal screening in cases where parents want more children. The researchers chose to study the subjects’ genetic make-up with newer whole genome sequencing techniques. This allows them to study longer DNA molecules and also take high resolution images of the chromosomes. “Combining the results helped us solve the puzzle. We managed to piece together the complete altered chromosome in one patient and the chromosomes involved in the two other cases.” The results show that the chromosome aberrations in the three teenagers are each so rare that they can be considered unique. “It’s not even possible to calculate the probability that another person in the world would have the exact same 36 breakpoints on chromosome 1 that one of our patients had,” says Anna Lindstrand. She establishes that the message of the study is that there is a value in continuing with more whole genome sequencing when this type of deviation is found in clinical environments. “There is great clinical interest in developing better methods which allow us to describe in detail what is wrong.” Researchers now want to move on to studying the method on hundreds of people with different types of complicated chromosome aberrations. The goal is to create a test which can be used in clinics. “Perhaps in the future it will be possible to use this method directly when you have a sick child and don’t know why. I think this could be reality in just a couple of years. But today the method is more of a follow-up analysis.” The study was conducted in collaboration with researchers from KTH, Stockholm University and the Baylor College of Medicine in Houston, USA. The research project was funded by grants from SciLifeLab, the Swedish Research Council, the Swedish Society for Medical Research, Hjärnfonden, Riksbankens Jubileumsfond/Erik Rönnberg’s Donations and Stockholm County Council. Publication “Comprehensive structural variation genome map of individuals carrying complex chromosomal rearrangements”. Jesper Eisfeldt, Maria Pettersson, Francesco Vezzi, Josephine Wincent, Max Käller, Joel Gruselius, Daniel Nilsson, Elisabeth Syk Lundberg, Claudia M.B. Carvalho, Anna Lindstrand. PLOS Genetics, online 8 February 2019, doi: 10.1371/journal.pgen.1007858

KI signs agreement with the International Union of Basic and Clinical Pharmacology

Mon, 11/02/2019 - 09:48
KI has now formalised its collaboration with the International Union of Basic and Clinical Pharmacology (IUPHAR) in the interests of promoting sustainable drug development and rational drug use. The agreement applies to both research and education. A memorandum of understanding was signed by Michael Spedding, secretary general of the IUPHAR and KI president Ole Petter Ottersen at the end of January. Two collaborative projects are already underway on enhancing the capacity of low and middle-income countries as regards academic drug development and rational drug use. From KI, the projects are being led by, respectively, Per Arvidsson and Lars L Gustafsson. The IUPHAR is a not-for-profit pharmacology organisation that was formed in 1959 and that works for greater international cooperation in the field. One of its main contributions is to provide access to information on drugs through pubic databases such as the Guide to Pharmacology. The memorandum was signed at a workshop organised by KI and the Swedish Institute for Drug Informatics, an organisation offering scientific and evidence-based information on drugs and drug therapies.

New insight into cell receptors opens the way for tailored cancer drugs

Fri, 08/02/2019 - 14:37
New research on how cancer mutations influence a certain type of receptor on the cell membrane opens the way for the development of tailored drugs for certain cancers, such as rectal cancer and lung cancer. This according to researchers at Karolinska Institutet and Uppsala University, who have been collaborating with researchers in the UK and USA. The results of their work, which concerns a group of G protein-coupled receptors called Class Frizzled (Class F), are published in the journal Nature Communications. “Class F receptor dysfunction can be linked to different forms of cancer,” says Gunnar Schulte, study leader and professor at Karolinska Institutet’s Department of Physiology and Pharmacology. “We can now describe in molecular detail how the receptors are activated and try to find drugs that stop this activation to prevent tumour growth.” The receptors on the cell membrane are activated by hormones or messenger molecules, which trigger a cascade of processes within. G protein-coupled receptors are one of the largest protein families in the body and are already an established drug target for a whole range of diseases. An important subgroup of G protein-coupled receptors are the so-called Class F receptors, but to date they have not constituted a therapeutic target to any great extent. In this present study, the researchers used newly developed methods to compare the mutation frequency of Class F receptors in tumours with the normal population. In linking cancer mutations to receptor function in this way, they claim to have opened up new opportunities for mechanism-based drug discovery. The study describes for the first time how regions of the Class F receptor act as a kind of switch for receptor activation, and how mutations in the receptor molecules can drive tumour development. Target individual receptors According to Professor Schulte, there are indications that other diseases, such as fibrosis, can also be linked to Class F receptor dysfunction. The researchers are currently working with the Swedish national research facility SciLifeLab to develop their ideas and explore potential new drugs. “Drugs targeting receptors in this group have been unspecific,” Professor Schulte says. “We hope that it will now be possible to develop more effective drugs that can target individual receptors, drugs for cancers such as rectal, cervical and lung cancer.” This publication is the product of five years’ work, in which Shane Wright and Pawel Kozielewicz from Professor Schulte’s research group also played a significant part. The other research leaders were Jens Carlsson (Uppsala University), M Madan Babu (MRC Laboratory of Molecular Biology, UK) and Nevin Lambert (Augusta University, USA).  The study was financed by several bodies, including Karolinska Institutet, the Knut and Alice Wallenberg Foundation, the Swedish Research Council, the Swedish Cancer Society, the Novo Nordisk Foundation, the Olle Engkvist Byggmästare Foundation, and the Emil and Wera Cornell Foundation. Publication A conserved molecular switch in Class F receptors regulates receptor activation and pathway selection Shane C. Wright, Paweł Kozielewicz, Maria Kowalski-Jahn, Julian Petersen, Carl-Fredrik Bowin, Greg Slodkowicz, Maria Marti-Solano, David Rodríguez, Belma Hot, Najeah Okashah, Katerina Strakova, Jana Valnohova, M. Madan Babu, Nevin A. Lambert, Jens Carlsson and Gunnar Schulte Nature Communications, online 8 February 2019, doi: 10.1038/s41467-019-08630-2

Young people with Hodgkin lymphoma have low relapse risk

Fri, 08/02/2019 - 13:42
The treatment of Hodgkin lymphoma is now so effective that young patients who do not have a relapse within two years of therapy have a life expectancy similar to that of their healthy peers. This according to a new study published in The Journal of Clinical Oncology by researchers at Karolinska Institutet and their colleagues at Aalborg University Hospital in Denmark and Radiumhospitalet in Oslo. Hodgkin lymphoma is a cancer of the lymph system that mainly affects people in their twenties. While the disease is fatal if left untreated, most sufferers are cured. The researchers behind the present study analysed data from over 2,500 patients in Sweden, Norway and Denmark between the ages of 18 and 49 to ascertain the magnitude of the relapse risk. At present, these patients are being monitored for up to five years after treatment. The results of the study show, however, that even after two years the patients have, on average, the same life expectancy as individuals of the same age and gender without Hodgkin lymphoma, and that the risk of relapse averages out at only about 4 per cent. “Bearing in mind the good survival rate and low risk of relapse after two years, the frequency of check-ups for detecting relapse could be greatly reduced after this time,” says joint last author Karin Ekström Smedby, researcher at Karolinska Institutet’s Department of Medicine in Solna. “That said, further checks are needed at a later stage to find and treat delayed adverse reactions to the treatment.” The study was financed by the Danish and Swedish cancer societies. Publication “Relapse risk and loss of lifetime after modern combined modality treatment for young Hodgkin lymphoma patients: A Nordic Lymphoma Epidemiology Group study”. Jorne Lionel Biccler, Ingrid Glimelius, Sandra Eloranta, Knut B. Smeland, Peter de Nully Brown, Lasse Hjort Jakobsen, Henrik Frederiksen, Mats Jerkeman, Alexander Fosså, Therese M.L. Andersson, Harald Holte, Martin Bøgsted, Tarec Christoffer El-Galaly and Karin E. Smedby. Journal of Clinical Oncology, online 6 February 2019, doi: 10.1200/JCO.18.01652.

Jumping and jiving with Prince Daniel at public health professor’s farewell lecture

Thu, 07/02/2019 - 16:39
Mai-Lis Hellénius, popularly known as Karolinska Institutet’s lifestyle professor, held her farewell lecture in Aula Medica, Solna, on 1 February. The lecture, How diet and exercise can prevent cardiovascular disease, attracted some 700 people. One of these was Prince Daniel. “I’m overwhelmed and stunned!” So said Mai-Lis Hellénius, professor at the Department of Medicine, Solna, her arms full of flowers after her farewell lecture in Karolinska Institutet’s Aula Medica. The lecture was held to mark Mai-Lis Hellénius’ retirement from her post as professor and senior physician. It attracted some 700 people. One of these was His Royal Highness Prince Daniel of Sweden. Welcoming Mai-Lis Hellénius to the stage at the start of the lecture, Cecilia Linde, professor at the Department of Medicine, Solna, used the word “megasuccess”. Cecilia Linde also spoke about the “lifestyle centre” started on Mai-Lis Hellénius’ initiative at the Cardiology Clinic, Karolinska University Hospital, Solna, in 2007. “This resulted in dissertations, scientific articles and the evidence necessary for lifestyle to make it onto the agenda and be included in the treatment guidelines for heart diseases,” commented Cecilia, who was the head of the Cardiology Clinic at that time. Squats and dancercise on the programme Focusing on diet and physical activity, the lecture highlighted the importance of lifestyle in preventing cardiovascular diseases. It included not only examples from Mai-Lis Hellénius’ own research in this area, but also international perspectives. “Time for a Kiruna! Stand up everyone!” As is only right when the speaker knows the importance of not sitting down for too long, Mai-Lis Hellénius interrupted her lecture for the squat series now known as a “Kiruna” (after the town of the female originator) and some dancercise. Mai-Lis Hellénius also gave details of a project she helped to start in Sollentuna in the middle of the 1980s. In this, healthcare centre visitors were offered free health checks and a prevention programme with individual lifestyle counselling, presentations and group activities. Now, over 20 years later, around 5,700 participants have been followed up and matched to reference people outside Sollentuna. These latter form a control group. “Those who have taken part in the programme are at less risk of having a heart attack and also show reduced all-cause mortality. Thanks to the programme, around 175 people have enjoyed longer lives. We’re very pleased with those results,” states Mai-Lis Hellénius. Popular educator and inspiration Mai-Lis additionally emphasised the importance of universities’ public and science outreach, i.e. sharing their knowledge. After a comprehensive thank you, she left the stage with a summary. “Take the risks of being sedentary seriously. However, remember that every movement counts. Trust the science-based advice about good diet and lifestyle. Furthermore, let everyone in on this knowledge.” Ole Petter Ottersen, president at Karolinska Institutet, thanked Mai-Lis Hellénius for her contributions as researcher, doctor and teacher. He stressed the importance of information from researchers being evidence-based and held out, not least, Mai-Lis Hellénius’ role as public educator and inspiration. “Your energy, your commitment and your know-how in communicating with the general public are exemplary. Thank you for your initiatives and your great impact.” Mai-Lis Hellénius is to continue as an affiliate of Karolinska Institutet.

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