Karolinska Research Articles

COLLABORATIVE INTERNATIONAL EXPERIENTIAL LEARNING IN GERONTOLOGY: AGING GLOBALLY INITIATIVE

Abstract Population aging is greatly impacting future generations of healthcare providers tasked with improving the healthcare systems they are inheriting. In this presentation, we introduce an innovative example of how students, researchers, educators and community partners from Canada and Scandinavia came together to comparatively explore models of health, social care, and welfare to advance global health. Collaborative international experiential learning in gerontology is an approach that broadens the application of academic theory outside classroom in an international context. It includes authentic reflection, develops transferable skills and strengthens employability. Our network supports future generations of healthcare professionals in becoming global-ready graduates. We highlight a collaborative course called Aging Globally: Lessons from Scandinavia, initiated at Western University, Canada in 2018, and delivered in partnership with OsloMet University (Norway), Karolinska Institutet (Sweden) and seven non-academic partners, such as Socialstyrelsen and Silviahemmet (Sweden) and Cycling without Age (Denmark). Over the past seven years, the course involved 425 students and 24 professors from Health Studies, Occupational Therapy, Physiotherapy, Nursing, and Technology, Science and Design programs. Student outcomes include expended knowledge, cultural competencies, and transferable skills. The course was a catalyst for three curriculum development grants totaling CAD $2 million, enrichment of the curriculum with 57 international internships and 13 exchanges, 12 summer courses, and new research partnerships, lifting international education in gerontology to a new level. Presenters will share experiences, evidence of impact on students, and describe joint efforts to inspire social change and sustainability of improved quality of life and well-being for older adults everywhere.

Self-Guided vs Clinician-Guided Online Cognitive Behavioral Therapy for Atopic Dermatitis

Clinician-guided online self-help based on cognitive behavioral therapy (CBT) has been shown to be effective at decreasing symptom severity for people with atopic dermatitis (AD). A brief online self-guided CBT intervention could be more cost-effective and allow for easy implementation and broader outreach compared with more comprehensive clinician-guided interventions. To investigate whether a brief online self-guided CBT intervention is noninferior to a comprehensive online clinician-guided CBT treatment. This single-blind randomized clinical noninferiority trial was conducted at Karolinska Institutet, Stockholm, Sweden. Adult individuals with AD were enrolled from November 2022 to April 2023. The last postintervention data were collected in December 2023. Participants randomized to the self-guided group had access to a self-guided online CBT intervention for 12 weeks without clinician support. Participants randomized to the clinician-guided group received online CBT for 12 weeks. The primary outcome was change in score from baseline to postintervention to 12-week follow-up on the self-reported Patient-Oriented Eczema Measure (POEM). The predefined noninferiority margin was 3 points on POEM. Of 168 randomized participants, 142 (84.5%) were female, and the mean (SD) age was 39 (10.5) years. A total of 86 participants were randomized to the self-guided group and 82 were randomized to the clinician-guided group. A total of 151 (90.0%) completed the main outcome postintervention assessment. Postintervention, the clinician-guided group had improved 4.20 points (95% CI, 1.94-6.05) on POEM and the self-guided group improved 4.60 points (95% CI, 2.57-6.64), corresponding to an estimated mean difference in change of 0.36 points (1-sided 97.5% CI, -∞ to 1.75), which was below the noninferiority margin of 3 points. No serious adverse events were reported. In the clinician-guided group, clinicians spent a mean (SD) of 36.0 (33.3) minutes (95% CI, 29.2-41.7) on treatment guidance and 14.0 (6.0) minutes (95% CI, 12.9-15.6) on assessments compared to 15.8 (6.4) minutes on assessments in the self-guided group. In this randomized clinical noninferiority trial, a brief self-guided CBT intervention was noninferior to clinician-guided CBT. Given the limited clinical resources required to deliver self-guided CBT, this treatment might be a promising means to disseminate evidence-based psychological treatment for patients with AD. ClinicalTrials.gov Identifier: NCT05517850.

Cross-border collaboration, communication, and research frontiers on biologics in chronic rhinosinusitis from 2004 to 2023.

Biologics are considered as a promising novel treatment option for patients with chronic rhinosinusitis who failed with the standard of care (medical therapy and surgical interventions). This bibliometric analysis was performed to explore cross-border collaboration, communication, and research frontiers on biologics in chronic rhinosinusitis. Original research publications on biologics in chronic rhinosinusitis were retrieved from the Science Citation Index-Expanded (SCI-E) database in the Web of Science Core Collection between 2004 and 2023. Using CiteSpace and R software, the country/region, author, institution, journal, reference, and keywords were extracted to analyze the research focus and global trends in this field. Research articles exhibited a consistent rising trend from 2004 to 2023, especially the period between 2020 and 2023. Most articles were published by authors from the USA. The USA was the most cited country, enjoying the most active cooperation with other countries/regions. Bachert C owned the most publications and collaborations. Ghent University and Karolinska Institute had the most collaborations with other institutions. Journal of Allergy and Clinical Immunology and Allergy published the most articles and were the most co-cited journals. Research frontiers on biologics in chronic rhinosinusitis would focus on efficacy, quality of life, safety, children, management, etc. This bibliometric analysis displayed the overall situation and global trend on biologics in chronic rhinosinusitis. The visualization analysis of publications could assist researchers rapidly in understanding the hotspots and trends. Further research is warranted to determine the long-term effects and side effects of biologics in chronic rhinosinusitis.

Sensitivity and specificity of a seed amplification assay for diagnosis of multiple system atrophy: a multicentre cohort study

The pathological hallmarks of multiple system atrophy and Parkinson's disease are, respectively, misfolded-α-synuclein-laden glial cytoplasmic inclusions and Lewy bodies. CSF-soluble misfolded α-synuclein aggregates (seeds) are readily detected in people with Parkinson's disease by α-synuclein seed amplification assay (synSAA), but identification of seeds associated with multiple system atrophy for diagnostic purposes has proven elusive. We aimed to assess whether a novel synSAA could reliably distinguish seeds from Lewy bodies and glial cytoplasmic inclusions. In this multicentre cohort study, a novel synSAA that multiplies and detects seeds by fluorescence was used to analyse masked CSF and brain samples from participants with either clinically diagnosed or pathology-confirmed multiple system atrophy, Parkinson's disease, dementia with Lewy bodies, isolated rapid eye movement sleep behaviour disorder (IRBD), disorders that were not synucleinopathies, or healthy controls. Participants were from eight available cohorts from seven medical centres in four countries: New York Brain Bank, New York, USA (NYBB); University of Pennsylvania, Philadelphia, PA, USA (UPENN); Paracelsus-Elena-Klinik, Kassel, Germany (DeNoPa and KAMSA); Hospital Clinic Barcelona, Spain (BARMSA); Universität Tübingen, Tübingen, Germany (EKUT); Göteborgs Universitet, Göteborgs, Sweden (UGOT); and Karolinska Institutet, Stockholm, Sweden (KIMSA). Clinical cohorts were classified for expected diagnostic accuracy as either research (longitudinal follow-up visits) or real-life (single visit). Sensitivity and specificity were estimated according to pathological (gold standard) and clinical (reference standard) diagnoses. In 23 brain samples (from the NYBB cohort), those containing Lewy bodies were synSAA-positive and produced high fluorescence amplification patterns (defined as type 1); those containing glial cytoplasmic inclusions were synSAA-positive and produced intermediate fluorescence (defined as type 2); and those without α-synuclein pathology produced below-threshold fluorescence and were synSAA-negative. In 21 pathology-confirmed CSF samples (from the UPENN cohort), those with Lewy bodies were synSAA-positive type 1; those with glial cytoplasmic inclusions were synSAA-positive type 2; and those with four-repeat tauopathy were synSAA-negative. In the DeNoPa research cohort (which had no samples from people with multiple system atrophy), the novel synSAA had sensitivities of 95% (95% CI 88-99) for 80 participants with Parkinson's disease and 95% (76-100) for 21 participants with IRBD, and a specificity of 95% (86-99) for 60 healthy controls. Overall (combining BARMSA, EKUT, KAMSA, UGOT, and KIMSA cohorts that were enriched for cases of multiple system atrophy), the novel synSAA had 87% sensitivity for multiple system atrophy (95% CI 80-93) and specificity for type 2 seeds was 77% (67-85). For participants with multiple system atrophy just in research cohorts (BARMSA and EKUT), the novel synSAA had a sensitivity of 84% (95% CI 71-92) and a specificity for type 2 seeds of 87% (74-95), whereas cases from real-life cohorts (KAMSA, KIMSA, and UGOT) had a sensitivity of 91% (95% CI 80-97) but a decreased specificity for type 2 seeds of 68% (53-81). The novel synSAA produced amplification patterns that enabled the identification of underlying α-synuclein pathology, showing two levels of fluorescence that corresponded with different pathological hallmarks of synucleinopathy. The synSAA might be useful for early diagnosis of synucleinopathies in clinical trials, and potentially for clinical use, but additional formal validation work is needed. Michael J Fox Foundation for Parkinson's Research, Amprion.

Disentangling relationships between Alzheimer's disease plasma biomarkers and established biomarkers in patients of tertiary memory clinics.

Several plasma biomarkers for Alzheimer's disease (AD) have demonstrated diagnostic and analytical robustness. Yet, contradictory results have been obtained regarding their association with standard diagnostic markers of AD. This study aims to investigate the specific relationship between the AD biomarkers currently used in clinical practice and the plasma biomarkers. In a memory clinic cohort, we analysed plasma pTau181, pTau217, pTau231, respectively, GFAP, NfL, CSF pTau181, Aβ-PET scans, and MRI/CT visual read of atrophy. We utilized methods based on multiple linear regression to evaluate the specific associations between clinically used and recently developed plasma biomarkers, while also considering demographic variables such as age and sex. Although plasma pTau181, pTau217, pTau231, and GFAP were significantly associated with both Aβ-PET and CSF pTau181, Aβ-PET explained more variance in the levels of these biomarkers. The effect of CSF pTau181 on plasma GFAP and pTau181 was completely attenuated by Aβ-PET, whereas pTau231 and pTau217 were affected by both Aβ-PET and CSF pTau181 levels. Unlike these biomarkers, increased NfL was rather indicative of brain atrophy and older age. Based on the effect sizes, plasma pTau217 emerged as highly effective in distinguishing between A+ and A-, and T+ and T- individuals, with 60% of variance in plasma pTau217 explained by clinical AD biomarkers. Amyloid burden primarily drives the changes in plasma pTau181, pTau217, pTau231, and GFAP. In contrast to plasma pTau217, a significant portion of variance in plasma pTau181, pTau231, GFAP, NfL remains unexplained by clinical AD biomarkers. This research is supported by the Swedish Research CouncilVR: 2017-06086, 2020-4-3018, 2024-2027; Swedish Brain Foundation, Swedish Alzhzeimer Foundation, CIMED Region Stockholm/Karolinska Institutet;the Region Stockholm - Karolinska Institutet regional agreement on medical training and clinical research (ALF), Fondation Recherche sur Alzheimer (France).

Factors Influencing the Quality of Undergraduate Students' Degree Projects: From Student and Supervisor Perspectives.

Degree projects are part of most professional study programmes and correspond to professional and academic requirements. Therefore, this study aimed to investigate factors that influence the quality of student degree projects from a supervisor and student perspective. Semi-structured interviews were performed with eight supervisors from the study programme in dentistry at Karolinska Institutet. The interviews were transcribed. The first part was summarised and described, and the second part was analysed thematically. Also, a questionnaire was completed by 45 students in their 7th and 9th semesters of the study programme. Student responses were summarised and described. The main findings indicate a convergence of expectations and perspectives between supervisors and students regarding the factors that influence the quality of the degree project. They emphasise the importance of realistic expectations, feasibility and adherence to academic standards for a high-quality outcome. Effective supervision involves the supervisor being readily available, responsive to student inquiries and supportive in time-management. Conversely, students are expected to demonstrate motivation, engagement and increasing autonomy. Additionally, both agree that the project should be engaging, relevant to the supervisor's expertise and the student's interests, contribute to personal and academic growth and ideally result in a publication. Taken together, supervisors and students share grounds for the degree project work, which is an important condition for ensuring a qualitatively sound degree project. Sharing expectations and perspectives in the beginning and having a continuously open dialogue concerning this issue during the degree project work benefits a sustainable collaboration and ensures quality.

Anyone can cook, but only the fearless can be a great chef.

Role models play a crucial role in inspiring and guiding careers in science, offering tangible examples of success and resilience. Reflecting on my journey from a small town in southern Chile to leading a lab at Karolinska Institutet, I've learned that relatable role models are particularly impactful for overcoming imposter syndrome and fostering a sense of belonging in academia. Early in my career, I drew inspiration from peers and mentors, gradually building my confidence and embracing my strengths. Later, exposure to interdisciplinary role models expanded my horizons and shaped my approach to science. Now, as a PI, I see my role as both a coach and mentor, fostering a team dynamic that amplifies individual strengths. Success in science often stems from fearlessness, adaptability and a willingness to seize opportunities, even when the outcome is uncertain. My journey demonstrates that good scientists can come from anywhere, including a small town in southern Chile.

Current status and prospects of congenital adrenal hyperplasia: A bibliometric and visualization study.

Congenital adrenal hyperplasia (CAH) is increasingly prevalent, leading to a surge in related research. To pinpoint emerging trends and recommend future directions, a bibliometric analysis of relevant CAH literature was performed. From January 1, 2000, to October 1, 2023, we searched the Web of Science Core Collection for CAH literature. For the bibliometric analysis, tools such as VOSviewer, CiteSpace, and the R package "bibliometrix" were employed. The United States and England are at the forefront among 113 countries, contributing 5034 papers to CAH research. However, there is a need for more extensive global collaboration across institutions in this field. The number of publications on CAH is increasing annually. Leading research institutions include the University of Michigan, University of California, San Francisco, Karolinska Institutet, and Karolinska University Hospital. The Journal of Clinical Endocrinology & Metabolism is the most cited in this area. The most prolific author is Falhammar H, with 88 publications, 2568 co-citations, and a significant overall contribution. Key research areas include diagnostic methods and therapeutic strategies for CAH. Emerging research hotspots are identified by keywords such as "disorders of sex development," "21-hydroxylase deficiency," "ambiguous genitalia," "testosterone" and "adrenal insufficiency." Research on CAH is expected to expand globally. Future studies will primarily focus on exploring CAH's diagnostic aspects and developing new therapies. This paper will help scholars better understand the dynamic evolution of the CAH and point out the direction for future research.

Proteome integral solubility alteration via label-free DIA approach (PISA-DIA), game changer in drug target deconvolution.

Drug protein-target identification in past decades required screening compound libraries against known proteins to determine drugs binding to specific protein. Protein targets used in drug-target screening were selected predominantly used laborious genetic manipulation assays. In 2013, a team led by Pär Nordlund from Karolinska Institutet(Stockholm, Sweden) developed Cellular Thermal Shift Assay (CETSA), a method which, for the first time, enabled the possibility of drug protein-target identification in the complex cellular proteome. High throughput, quantitative mass spectrometry (MS) proteomics appeared as a compatible analytical method of choice to complement CETSA, aka Thermal Protein Profiling assay (TPP). Since the seminal CETSA-MS/ TPP-MS publications, different protein-target deconvolution strategies emerged including Proteome Integral Solubility Alteration (PISA). The work of Emery-Corbin etal.(Proteomics2024,2300644), titled Proteome Integral Solubility Alteration via label-free DIA approach (PISA-DIA), introduces Data-Independent Acquisition (DIA) as a quantification method, opening new avenues in drug target-deconvolution field. Application of DIA for target deconvolution offers attractive alternative to widely used data dependent methodology.

6.O. Scientific session: The unmet needs of LGBTQ+ persons and communities: perspectives from across the globe

Abstract Lesbian, gay, bisexual, transgender and queer persons suffer from rising anti-LGBTQ+ stigma. Such stigma entails laws that punish being LGBTQ+ such as in Uganda, Russia, Ghana, Iran, etc. The stigmatizing contexts have numerous health-harming effects, including perpetrating mental health harms and creating environments that hamper access & quality of services. Rising global anti-LGBTQ+ stigma and the adverse health impacts require more data on the topic to adequately dispel LGBTQ+ mis- and dis-information. This workshop will give examples of studies that examine LGBTQ+ disparities and inequities in health across different social and cultural contexts, drawing from research in Czechia, Kenya, Rwanda, and Sweden. The workshop will first outline the relevant social and cultural contexts of LGBTQ+ persons in various countries, such as attitudes, beliefs, and values. The workshop will then discuss LGBTQ+ inequities and disparities that arise from health-harming attitudes, beliefs, and values. Afterward, the workshop will discuss public health-oriented solutions & policy directions, including using data for interpretation and advocacy labs and efforts, enhancing data collection, improving knowledge and attitudes, and other implications for public health practice and policy. The workshop will open a session that will situate LGBTQ+ public health for the audience. The first study will be by Andreas Malm from the Karolinska Institute, Sweden, examining LGBTQ+ differences in mental health and treatment disparities in Sweden. This will be followed by Luis Roxo from the Karolinska Institute and Universidade NOVA de Lisboa, Portugal, discussing stressors and symptoms that shape inequalities in mental health service use. Then, Michal Pitonák from the National Institute of Mental Health, Czechia, will present treatment and outcome gaps in the mental health of LGBTQ+ persons in Czechia. Lastly, Emmy Kageha Igonya from the African Population Health Research Center, Kenya, will showcase work from a mixed-methods study with LGBTQ+ people in Rwanda and Kenya, examining access to and use of healthcare services. After the individual presentations, which will each last 7-8 minutes, the audience will be invited to a moderated 20-25-minute open discussion on the papers & how the findings can help inform public health practice & policy to address the unmet needs of LGBTQ+ populations globally. The continuing rise in anti-LGBTQ+ sentiments across the globe is problematic from a public health standpoint, given the severe health-harming effects across numerous physical and mental health states and domains. Our workshop aims to facilitate a conversation on understanding the structural situations that shape LGBTQ+ health and identifying strategies to reduce gaps in services and needs that disproportionately burden LGBTQ+ persons. Key messages • LGBTQ+ people across the globe are experiencing rising stigma and discrimination. • Rising anti-LGBTQ+ backlash disproportionately harms LGBTQ+ physical and mental health and creates gaps in care.

1.O. Scientific session: Trans & Gender-Diverse Individuals’ Mental & Behavioral Health Risks & Intervention Needs

Abstract Transgender and gender-diverse (TGD) individuals are at a greater risk for various poor mental and behavioral health outcomes than cisgender individuals, including higher rates of suicide, psychiatric diagnoses, and behavioral health problems. For example, research has documented a seven-fold increased risk for lifetime suicide attempts among young TGD people, compared with the general population. Less is known about the age of onset of such mental and behavioral health disparities and how these disparities may vary across other intersectional socio-demographic variables. It has been well-documented that trans and gender-diverse individuals often encounter discrimination and transphobia across various social, educational, professional, administrative, and healthcare settings. This discrimination, as highlighted in the literature, frequently poses obstacles to accessing both general and trans-specific healthcare services due to experiences of discrimination (e.g., misgendering, refusal of care, lack of adequate services). The right and ability to self-determine and the accessibility to gender-affirming care without discrimination are key to closing the gap in TGD individuals’ mental and behavioral health outcomes, and for them to live authentically and thrive. Tailored and affirming mental and behavioral health interventions to reduce these health inequities are pivotal for TGD individuals to achieve the highest attainable standard of physical and mental health: a key fundamental human right. Considerable gaps in the literature remain concerning the onset and determinants of gender identity-based health disparities and healthcare approaches that are respectful, inclusive, non-pathologizing, and grounded in human rights principles for TGD individuals. This workshop intends to address these knowledge gaps by delving into the mental and behavioral health needs of TGD individuals. The workshop seeks to further foster dialogue on strategies to overcome resistance to implementing approaches that uphold the human rights and well-being of these communities. Dr. Richard Bränström (Karolinska Institutet) will present a study that explores the age at which gender identity-based disparities in psychiatric diagnoses and treatment can be first identified. Dr. Gonzales (Vanderbilt University) will examine disparities in mental health and social determinants of health among TGD individuals with private insurance. Dr. Moleiro (Lisbon University Institute) will review TGD persons’ ways of identifying with the choices and trajectories in social, legal, and affirmative healthcare processes in Portugal. Dr. Lelutiu-Weinberger (Columbia University School of Nursing) will present findings from a study that assessed tobacco use and cessation attitudes, facilitators, and barriers to quitting, and intervention components and delivery modality acceptability among TGD individuals, as well as sexual minority individuals, in Romania to inform a tailored and affirming smoking cessation intervention. Key messages • Transgender and gender-diverse are at increased risk for a variety of poor mental and behavioral health compared with the general public. • There is a critical need to foster healthcare services for transgender and gender-diverse individuals that are tailored and affirming.

Empowering Educators: Integrating Sustainable Health in Healthcare Professionals’ Training

Abstract Despite efforts to realize Agenda 2030, the sustainable development goals (SDGs) may not be achieved. This already now impacts public health and healthcare, including the training of providers. “Sustainable health” addresses this urgency by emphasizing health as key to achieving the SDGs. While the UN developed a competency framework for teachers in 2011, the specific competencies needed to train in sustainable health remain unclear. Transformative learning (TL) is crucial to integrating sustainable development in higher education (HE), yet its application in the education of health professionals is limited. TL entails a profound transformative journey that reshapes perceptions and experiences, necessitating a shift in the educator’s role from information provider to facilitator of transformative processes. According to a 2019 literature review on TL for healthcare students, teachers need detailed and practical guidelines on how to implement TL. We aimed to develop an evidence-based matrix outlining a) the educational strategies needed to ensure that students develop sustainable health competencies, and b) the competencies teachers need to use these strategies in a quality-assured way. We conducted a literature review to identify key dimensions of teacher competencies and educational strategies for sustainable health. We surveyed teachers at Karolinska Institutet to assess the relevance of these competencies and teachers’ confidence in using them. Focus group discussions were conducted, to explore barriers and enablers to develop competencies and use educational strategies. We present a competency framework for HE teachers, accompanied by recommended educational strategies and self-assessment tools to gauge further training needs. To be used by teachers and educational developers, it will be openly accessible in Swedish and English. This study contributes to enhancing competencies in training health professionals to contribute to achieving sustainable health for all. Key messages • Educators need to be equipped with competencies to lead transformative learning processes to enable future generations of health professionals to achieve sustainable health for all. • Educators need to be supported to transform their role and practice to provide relevant training for future health care providers.

2.Q. Skills building seminar: Publishing and disseminating your research: How to get published, and what then?

Abstract Getting your public health research published can be a real challenge, and the publishing process is not always clear. Often it takes a lot of time, effort and perseverance. In this skills building workshop, participants will be able to learn the ropes from the Editor-in-Chief and the Publisher (OUP) of the European Journal of Public Health (EJPH), EUPHA’s scientific Journal. The EJPH is a well-established multidisciplinary, Open Access journal that covers a broad scope of public health topics. It’s current impact factor is 4.4. The workshop will have the format of an interactive clinic and will start with short presentations by the Editor-in-Chief of the EJPH and the Publisher on how to write, how to disseminate your findings, and tools the publisher has for helping promote your research for the best impact. The Editor-in-Chief will focus on what makes manuscripts attractive to editors and reviewers, while the publisher will give an overview of the publishing process, important aspects of the wider publishing industry (including how to publish your work Open Access) and give authors tips of how to promote their articles post-publication. After that, there will be ample time for participants to ask their questions to the panellists. This skills-building workshop will be of interest to anyone who would like to increase their chances of getting published and who would like to learn more about creating impact with their publications. The session should in particular be helpful for young researchers who do not have a lot of publishing experience yet. Key messages • Think about relevance to public health, and what your research adds to science and policy. • Think about what tools you can use to disseminate your findings. Speakers/Panelists Peter Allebeck Karolinska Institute, Department of Global Public Health, Stockholm, Sweden Rachel Moriarty Oxford University Press, Oxford, UK

The 75-Year Anniversary of the Department of Physiology and Pharmacology at Karolinska Institutet-Examples of Recent Accomplishments and Future Perspectives.

Karolinska Institutet is a medical university encompassing 21 departments distributed across three departmental or campus groups. Pharmacological research has a long and successful tradition at the institute with a multitude of seminal findings in the areas of neuronal control of vasodilatation, cardiovascular pharmacology, neuropsychopharmacology, receptor pharmacology, and pharmacogenomics that resulted in, among many other recognitions, two Nobel prizes in Physiology and Medicine, one in 1970 to Ulf von Euler for his discovery of the processes involved in storage, release, and inactivation of neurotransmitters and the other in 1982 to Sune Bergström and Bengt Samuelsson for their work on prostaglandins and the discovery of leukotrienes. Pharmacology at Karolinska Institutet has over the last decade been ranked globally among the top 10 according to the QS World University Ranking. With the Department of Physiology and Pharmacology now celebrating its 75-year anniversary, we wanted to take this as an opportunity to showcase recent research achievements and how they paved the way for current activities at the department. We emphasize examples from preclinical and clinical research where the dpartment's integrative environment and robust infrastructure have successfully facilitated the translation of findings into clinical applications and patient benefits. The close collaboration between preclinical scientists and clinical researchers across various disciplines, along with a strong network of partnerships within the department and beyond, positions us to continue leading world-class pharmacological research at the Department of Physiology and Pharmacology for decades to come. SIGNIFICANCE STATEMENT: Pharmacological research at Karolinska Institutet has a long and successful history. Given the 75-year anniversary of the Department of Physiology and Pharmacology, this perspective provides an overview of recent departmental achievements and future trajectories. For these developments, interdisciplinary and intersectoral collaborations and a clear focus on result translation are key elements to continue its legacy of world-leading pharmacological research.

Enhancing clinical reasoning skills for medical students: a qualitative comparison of LLM-powered social robotic versus computer-based virtual patients within rheumatology

Virtual patients (VPs) are increasingly used in medical education to train clinical reasoning (CR) skills. However, optimal VP design for enhancing interactivity and authenticity remains unclear. Novel interactive modalities, such as large language model (LLM)-enhanced social robotic VPs might increase interactivity and authenticity in CR skill practice. To evaluate medical students’ perceptions of CR training using an LLM-enhanced social robotic VP platform compared with a conventional computer-based VP platform. A qualitative study involved 23 third-year medical students from Karolinska Institutet, who completed VP cases on an LLM-enhanced social robotic platform and a computer-based semi-linear platform. In-depth interviews assessed students’ self-perceived acquirement of CR skills using the two platforms. Thematic analysis was employed to identify themes and sub-themes. Three main themes were identified: authenticity, VP application, and strengths and limitations. Students found the social robotic platform more authentic and engaging. It enabled highly interactive communication and expressed emotions, collectively offering a realistic experience. It facilitated active learning, hypothesis generation, and adaptive thinking. Limitations included lack of physical examination options and, occasionally, mechanical dialogue. The LLM-enhanced social robotic VP platform offers a more authentic and interactive learning experience compared to the conventional computer-based platform. Despite some limitations, it shows promise in training CR skills, communication, and adaptive thinking. Social robotic VPs may prove useful and safe learning environments for exposing medical students to diverse, highly interactive patient simulations.

Sex differences in clinically diagnosed psychiatric disorders over the lifespan: a nationwide register-based study in Sweden

Limited studies exist on sex differences in incidence rates of psychiatric disorders across the lifespan. This study aims to analyze sex differences in the incidence rates of clinically diagnosed psychiatric disorders over the lifespan. We conducted a nationwide register-based cohort study, including all individuals who were born in Sweden and lived in Sweden between 2003 and 2019, including 4,818,071 females and 4,837,829 males. We calculated sex- and age-specific standardized incidence rates for any and 10 major types of psychiatric disorders. Multivariable-adjusted incidence rate differences (IRDs) for diagnosed psychiatric disorders between females and males were estimated. During a follow-up of 119,420,908 person-years, males showed a higher incidence rate of any diagnosed psychiatric disorder than females at age 5-9 (IRD=-8.93; 95% CI:-9.08 to-8.79; per 1000 person-years), whereas females showed a higher rate than males at age 15-19 (IRD=9.33; 95% CI: 9.12-9.54) and onwards (except age 60-69). Specifically, among females, excess rates were apparent for depressive, anxiety, eating, stress-related and bipolar disorders at age 10-54, whereas among males, excess rates were pronounced for autism and attention deficit hyperactivity disorders before age 14, drug use disorders at age 15-54, and alcohol use disorders in adulthood. For schizophrenia, the male excess at age 15-49 shifted to female excess at age 60-79. The magnitude of IRDs were greater in recent years and individuals with lower socioeconomic status. Knowledge about the lifespan and socioeconomic variations in the sex differences in rates of diagnosed psychiatric disorders may inform targeted screening/intervention strategies. Vetenskapsrådet, FORTE, Karolinska Institutet Strategic Research Area in Epidemiology and Biostatistics, and Icelandic Research Fund.

Effects of yoga compared with health promotion on health-related quality of life in adults with post-COVID-19 condition: protocol for a randomised controlled trial

IntroductionPost-COVID-19 condition (post COVID, also known as long COVID) is a global public health issue estimated to affect over 100 million people. Common symptoms include fatigue, dyspnoea and cognitive dysfunction...

Revolutionising Neurodegenerative Disease Treatment: Immunotherapy and Advanced Stem Cell Techniques

What drives the progression of neurodegenerative diseases like ALS, Alzheimer’s, and MS? Unraveling the mechanisms of neuroinflammation is at the heart of Prof. Bob Harris’s research at the Karolinska Institutet. His team is pioneering new therapeutic approaches by targeting microglial activity and harnessing advanced stem cell techniques. Their goal is to transform treatment strategies for these debilitating conditions.

Novel Immunotherapies for Neurodegenerative Diseases

What drives the progression of neurodegenerative diseases like ALS, Alzheimer’s, and MS? Unraveling the mechanisms of neuroinflammation is at the heart of Prof. Bob Harris’s research at the Karolinska Institutet. His team is pioneering new therapeutic approaches by targeting microglial activity and harnessing advanced stem cell techniques. Their goal is to transform treatment strategies for these debilitating conditions.

Earnings and work loss after colon and rectal cancer: a Swedish nationwide matched cohort study

Colorectal cancer is common and prognosis is improving. The conditions of survivors of treatment, including financial consequences, are thus important. The aim of this study was to quantify loss of earnings and work loss in working-age patients with colon and rectal cancer relative to matched comparators. The study utilised data from the CRCBaSe database that is generated from the nationwide Swedish ColoRectal Cancer Register and includes data from several Swedish nationwide registers. The study period was 1995-2020 for rectal cancer patients and 2007-2020 for colon cancer patients. A retrospective population-based nationwide cohort study on earnings, disposable income, and work loss, in survivors of stage I-III colorectal cancer treatment was undertaken. Median regression was used to analyse earnings and disposable income, and logistic regression to analyse the probability of work loss. A cohort of 8863 colorectal cancer survivors diagnosed before 2017 and 52,514 comparators matched on birth year, legal sex, and county of residence, was analysed. There was a clear reduction in earnings between the calendar year prior to and the calendar year after diagnosis, from € 31,319 to € 23,924 for colon cancer patients and from € 32,636 to € 22,647 for rectal cancer patients, and earnings never fully recovered during the 5-year follow-up. Disposable income was practically unaltered. The probability of work loss increased in the calendar year of diagnosis, from 29.8% to 25.3% the previous year to 83.3% and 84.4% for colon and rectal cancer patients respectively, and never fully recovered. The probability of work loss was similar between colon and rectal cancer survivors, but was higher among patients with rectal cancer who had received neoadjuvant therapy. This study shows that despite an extensive welfare system providing maintained disposable income, there is a financial burden in the form of increased risk of work loss and a reduction in earnings among survivors of colorectal cancer. The study was supported by the Swedish Cancer Society, the Swedish Cancer and Allergy Foundation, and the Stockholm Cancer Society, and supported by grants provided by the Regional Agreement on Medical Training and Clinical Research (ALF) between the Stockholm County Council and Karolinska Institutet.