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Health effects of electronic cigarettes and alternative tobacco products with a focus on vascular function
No full textBackgroundHuman tobacco use is estimated to cause 8 million deaths worldwide and over 1,3 billion humans are estimated to be tobacco users. An estimated 50% of cigarette users die from complications to their tobacco habit. Besides different kinds of cancer, tobacco consumption is a major cause of cardiovascular disease and death. The adverse cardiovascular effects of tobacco use are known to be caused by endothelial dysfunction, inflammation, heightened platelet activity, procoagulant effects and DNA-damage.Due to all these adverse health effects, there is a growing trend worldwide both in public opinion and from governments to phase out cigarettes. During the last two decades nicotine consumption has begun to shift to alternative nicotine-delivery devices with less or no combustion. Electronic cigarettes (EC) are still growing in popularity despite warnings and indications of negative health effects and are more popular than ever - especially among the young. The use of ECs as means of smoking cessation tools is also debated with contradictory results of its efficiency. Also, there is limited data on long term respiratory health outcomes from use of these products. Heated tobacco products (HTP) are a newer form of tobacco delivery device with industry proven reduced exposure of toxic chemicals compared to cigarettes but with limited data on human health effects.Methods and resultsPaper I was a randomized double-blinded crossover study where twenty-two healthy young volunteers were subjected to brief EC exposure with either nicotine or without nicotine content. Microcirculation was assessed at baseline and 30 minutes postexposure with laser speckle contrast imaging on the forearm together with iontophoresis of acetylcholine and sodium nitroprusside to assess endothelium-dependent and independent vasodilatation. Moreover, thrombogenicity was evaluated with the Total-thrombus analysis system (T-TAS) by analyzing blood samples taken at baseline, 15- and 60 minutes postexposure. Exposure to nicotine-containing ECs, but not nicotine-free ECs, led to increased platelet thrombus formation and enhanced fibrin-rich thrombus formation. Moreover, no significant effects were seen following EC exposure with or without nicotine on endothelial independent or dependent perfusion capacity. However, skin temperature was decreased following both exposures.In Paper II a randomized cross-over study was conducted in which thirty-one healthy young adults were exposed to either HTP of the brand IQOS or ambient air (no exposure). The study evaluated the effects of HTP use on arterial stiffness at baseline, 20- and 90 minutes postexposure measured through pulse wave velocity and pulse wave analysis. Moreover, platelet thrombus formation and fibrin-rich thrombus formation was analyzed with the T-TAS at baseline and 5 minutes postexposure. Arterial stiffness and platelet thrombus formation increased immediately following HTP exposure. Fibrin-rich thrombus formation was not altered by either exposure.Paper III was a prospective population-based study with random samples of the population aged 16-69 years of age. The aim was to evaluate the role of EC use in relation to cigarette smoking and changes in respiratory symptoms. The study was conducted within the Obstructive Lung Disease in Northern Sweden (OLIN) study and West Sweden Asthma Study (WSAS). Both studies used identical validated postal questionnaires. Baseline was a questionnaire survey in 2006-2008 and follow-up was in 2016. A total of 17 325 individuals answered on both occasions. EC use was found to be most common in persistent smokers, and no association was observed between EC use and smoking cessation. Likewise, EC use did not correspond to a lower amount of cigarettes smoked per day among persistent smokers, nor was it linked to a reduction in respiratory symptoms in either former or persistent smokers.In Paper IV, twenty-two healthy young adults participated in a double-blind randomized crossover study, where each participant used EC with and without nicotine on separate occasions. Blood samples were collected at baseline, 30- and 105 minutes after exposure. Six extracellular vesicle-associated proteins linked to pulmonary inflammation were analyzed using flow cytometry, with conjugated antibodies targeting each marker. Following brief exposure to nicotine-containing aerosol, levels of angiotensin-converting enzyme (ACE), aldehyde dehydrogenase 3B1 (ALDH3B1), and palate, lung, and nasal epithelial clone (PLUNC)-positive vesicles were significantly increased, whereas no changes were observed after nicotine-free exposure. The elevations peaked at 105 minutes post exposure, suggesting an inflammatory response triggered by inhaled nicotine.ConclusionsEC use with nicotine but not without had several adverse effects in healthy young individuals, implicating inhaled nicotine as a mediator of the demonstrated effects. Platelet and fibrin-rich thrombus formation was significantly increased transiently indicating heightened thrombogenicity. Several markers of pulmonary inflammation; ACE, PLUNC and ALDH3B1, were increased suggesting potential initiation of disease pathways and toxicological effects of inhaled nicotine.Brief use of HTP had immediate adverse effects on platelet thrombogenicity similar to the effects observed in EC with nicotine. Further, arterial stiffness was transiently increased following HTP use. Both heightened platelet thrombogenicity and arterial stiffness are considered risk factors and associated with development of atherosclerotic- and cardiovascular disease.In the populated based cohort study, we showed that EC use was most common among persistent smokers who were less likely to quit smoking or reduce the number of cigarettes used compared to those who did not use EC. Finally, dual use of cigarettes and EC is linked with more respiratory symptoms than use of only cigarettes.List of scientific papersI. Gustaf Lyytinen, Amelie Brynedal, Erik Anesäter, Lukasz Antoniewicz, Anders Blomberg, Håkan Wallén, Jenny A. Bosson, Linnea Hedman, Fariborz Mobarrez, Sara Tehrani, Magnus Lundbäck. Electronic Cigarette Vaping with Nicotine Causes Increased Thrombogenicity and Impaired Microvascular Function in Healthy Volunteers: A Randomised Clinical Trial. Cardiovascular Toxicology, 2023, Volume 23:255-264. https://doi.org/10.1007/s12012-023-09802-9II. Gustaf Lyytinen, Georgy Melnikov, Amelie Brynedal, Erik Anesäter, Lukasz Antoniewicz, Anders Blomberg, Håkan Wallen, Jenny A. Bosson, Linnea Hedman, Sara Tehrani, Magnus Lundbäck. Use of heated tobacco products (IQOS) causes an acute increase in arterial stiffness and platelet thrombus formation. Atherosclerosis, 2023, Volume 390, 117335. https://doi.org/10.1016/j.atherosclerosis.2023.117335III. Linnea Hedman*+, Gustaf Lyytinen*, Helena Backman, Magnus Lundbäck, Caroline Stridsman, Anne Lindberg Hannu Kankaanranta, Lina Rönnebjerg, Eva Rönmark, Linda Ekerljung. Electronic cigarette use in relation to changes in smoking status and respiratory symptoms. Tobacco Induced Diseases, 2024;22(January):21. https://doi.org/10.18332/tid/176949IV. Mikael Kabéle, Gustaf Lyytinen, Jenny A. Bosson, Linnea Hedman, Lukasz Antoniewicz M.D, Magnus Lundbäck, Fariborz Mobarrez. Nicotine in E-cigarette aerosol may lead to pulmonary inflammation. Respiratory Medicine 2025; Volume 242:108101. https://doi.org/10.1016/j.rmed.2025.108101*Co-first authors</p
Mental health stigma and its consequences : a systematic scoping review of pathways to discrimination and adverse outcomes
No full textCurrent research evaluating the consequences of stigma towards people with mental illness is not nuanced in emphasizing the critical distinction between stigma as negative attitudes and discrimination as harmful behaviours that limit access to services, employment, and social inclusion. Understanding these distinctions is essential for designing targeted, evidence-based universal, targeted and indicated interventions to improve the quality of life and well-being. This review evaluates the evidence on the consequences of stigma towards people with mental illness. Using PRISMA guidelines, we analysed 448 studies (294 quantitative, 154 qualitative) investigating stigma's negative outcomes. Findings were categorized into health, service use, psychosocial, economic, and structural impacts. Although stigma is consistently associated with adverse outcomes across life domains, evidence of a causal link between negative attitudes and poorer outcomes for individuals with mental disorders remains limited. Furthermore, there is a striking scarcity of research from low- and middle-income countries, with significant regional gaps, and studies addressing structural stigma embedded in societal institutions are particularly rare. Efforts to combat stigma must distinguish between attitudes and behaviours, focusing on reducing discrimination while enhancing public mental health literacy and access to effective interventions. Tackling these challenges requires a comprehensive, evidence-informed approach to improving mental health outcomes for all.</p
Exercise-induced extracellular vesicles and their protective role against diabetes
No full textExercise is known for the positive effects on metabolic diseases, partly because of the release of circulating extracellular vesicles (EVs) that mediate intercellular communication and organ crosstalk. In this thesis, we explored the molecular composition and biofunction of exercise-induced EVs, focusing on their role in health benefits and pancreatic B -cell protection. At same time, we modified and engineered EVs to develop an efficient cellular delivery platform.In study I, we compared the systemic effects of circulating EVs induced by continuous aerobic training (CAT) and high-intensity interval training (HIIT) in healthy volunteers. Proteomic and miRNA profiling revealed that EVs from both two types of exercise modalities regulate neuronal signaling, autophagy, and cell fate, while CAT preferentially modulates cognitive function and substrate metabolism, and HIIT is associated with organ growth, cardiac function, and insulin signaling. Notably, the miR-379 cluster was specifically upregulated by HIIT, and EVs were traced to multiple tissues including metabolic, immune, and nervous systems, highlighting their role in organ crosstalk.Building on these findings, study II investigated the protective effects of exercise induced EVs on pancreatic B -cells. Exercise induced EVs alleviated endoplasmic reticulum stress-induced apoptosis in ß -cells, predominantly through miR-124-5p derived from the central nervous system. These findings reveal a novel brain-to-islet communication axis, providing molecular insight into how exercise improves ß -cell function and suggesting potential therapeutic strategies against diabetes.Finally, in study III, we took advantage of the nature of EVs, we modified and programed them to serve as efficient and customizable cellular delivery platforms by DNA nanotechnology. To enable real-time monitoring of EV-mediated miRNA dynamics, we developed a miRNA detection-amplification system (miRDAS) using extracellular vesicle-based spherical nucleic acids (EV-SNA). This system rapidly safely internalizes into cells and amplifies target miRNA signals in situ. As a proof- of-concept, miR-124-specific miRDAS was employed to track its expression during neuronal differentiation, demonstrating high sensitivity, specificity, and multiplexing capability.Collectively, this thesis provides mechanistic understanding of exercise- induced EVs, highlights their critical role in B -cell health, and introduces advanced tools for monitoring EV-mediated miRNA signaling, offering insights for both basic research and potential therapeutic applications.List of scientific papersI. Wang, Z .* , Ou, Y *. , Zhu, X., Zhou, Y., Zheng, X., Zhang, M., Li, S., Yang, S. N., Juntti-Berggren, L., Berggren, P. O., & Zheng, X. (2025). Differential Regulation of miRNA and Protein Profiles in Human Plasma-Derived Extracellular Vesicles via Continuous Aerobic and High-Intensity Interval Training. International journal of molecular sciences, 26(3), 1383. https://doi.org/10.3390/ijms26031383II. Wang, Z.*, Zhu, X.*, Zhou, Y., , Shi, Y., , Yang, S. N., Zheng, X.,Berggren, P. O Exercise-induced extracellular vesicles protect against islet ß cell failure and diabetes by delivering miR-124-5p [Manuscript]III. Wang, Z., Zhu, X., Zhou, Y., Zhang, T., Shi, Y., Zheng, X., Yang, S. N., Li, W., & Berggren, P. O. (2025). Target-Mediated EV-SNA Clustering as an Amplifier for In Situ miRNA Imaging in Living Cells. Nano letters, 25(31), 11860-11869. https://doi.org/10.1021/acs.nanolett.5c02256</p
Understanding and preventing sexual and gender-based violence among South African youth during public health crises
No full textThe COVID-19 pandemic has had far-reaching consequences beyond the immediate threat of infection, exacerbating existing social inequalities and vulnerabilities, particularly in low- and middle-income countries. Among these, the risk of sexual and gender-based violence (SGBV) among young people emerged as a critical public health concern. This doctoral thesis investigates the impact of the COVID-19 crisis on SGBV exposure among adolescents and young adults aged 10-24 in South Africa-a country with high baseline rates of SGBV and stringent lockdown policies during the pandemic.The thesis is structured around four sub-studies embedded within two overarching studies: a longitudinal mixed-methods cohort of young people with and without HIV (the BUDDY study (Sub-studies l-II)) and a cluster randomized controlled trial assessing the impact of an empowerment-based self-defense intervention for girls (the No Means No (NMN) evaluation (Sub-studies III-IV)). Using a combination of quantitative and qualitative methods, the research explores the trajectories of SGBV during and after lockdowns, the psychosocial and structural drivers of violence, and the potential of targeted interventions to mitigate violence in public health crisis contexts.Findings from Sub-study I highlights a complex pattern of violence exposure, with notable perceived increases in community and household violence during the initial lockdown period. Risk factors such as common mental disorder symptomology, unemployment/being out of school, and food insecurity were associated with higher exposure to SGBV among youth. Trajectory modeling revealed distinct subgroups of youth experiencing persistent or fluctuating patterns of violence, influenced by mental health, and socioeconomic factors (Sub-study II).The NMN evaluation demonstrated that an 8-hour, COVID-adapted Empowerment Self-Defense curriculum had a positive impact on self-defense knowledge, and perceived feelings of confidence and sources of support among adolescent girls. However, the trial did not find statistically significant differences in sexual violence exposure across arms at 12-month follow-up (Sub-study III). Qualitative findings suggest that contextual and implementation barriers-such as school disruptions and limited time for skill reinforcement-may have influenced outcomes (Sub-study IV).This research contributes new longitudinal and intervention-based evidence on youth SGBV during a global public health crisis. It underscores the importance of addressing mental health, and socioeconomic drivers of SGBV as part of prevention strategies. It also calls for trauma-informed, contextually grounded interventions that are responsive to specific risk factors exacerbated in times of widespread social instability. The findings hold important implications for public health policy, education systems, and SGBV prevention programming in South Africa and similar settings.List of scientific papersI. Hartmann, M., Giovenco, D., Zeebari, Z., Itzikowitz, G., Ekström, A.M., Nielsen, A., Pettifor, A., Bekker, L.G. and Kågesten, A.E., 2023. Associations between psychosocial wellbeing and experience of gender-based violence at community, household, and intimate- partner levels among a cross-sectional cohort of young people living with and without HIV during COVID-19 in Cape Town, South Africa. BMC public health, 23(1), p.2115. https://doi.org/10.1186/s12889-023-16945-5II. Hartmann, M., Stoner, M.C., Storey, S., Giovenco, D., Zondi, Y.Z., Qwabe, N., Ekström, A.M., Pettifor, A.E., Bekker, L.G. and Kågesten, A., 2025. Mixed-method longitudinal investigation of sexual and gender-based violence following COVID-19 in South Africa. BMJ public health, 3(1).https://doi.org/10.1136/bmjph-2024-001697III. Hartmann, M., Mutangabende, S., Nash, S., Browne, E.N., Hatcher, A., Kågesten, A.E. and Roberts, S.T., 2025. Effectiveness of an empowerment-based self-defense program among South African girls: results from a cluster-randomized control trial in schools. BMC Women's Health, 25(1), p.119. https://doi.org/10.1186/s12905-025-03647-wIV. Hartmann, M. Wallengren, E., Mutangabende, S., Goba, M., Hatcher, A., Roberts, S.T., and Kågesten, A. Adolescent girls' embodied experiences with an empowerment-based self-defense intervention for sexual violence prevention: a qualitative study in Gqeberha, South Africa. [Submitted]</p
Oxygen levels regulating embryonic genome activation
No full textInvoluntary infertility affects some 18% of the world's population. Assisted reproductive technologies (ART), including in vitro fertilization (IVF), are for many the only hope on their journey to have children. However, the success rate of IVF is still 33-42%, and one of the main bottlenecks in ART is that 45-50% of the fertilized oocytes stall in development and do not reach the blastocyst stage of embryo development. The stalling of in vitro embryos mostly happens around day 3 of development, which coincides with the embryonic genome activation (EGA) event in humans. Due to ethical concerns about using human embryos for research and the scarcity of the material, studying EGA in humans is challenging. Therefore, in this thesis, we tackled this problem by establishing bovine as a model for human embryogenesis for higher similarity than, e.g., mouse. We achieved this by developing a method to perform RNA sequencing using single cells/embryos with limited numbers of samples. STRT-N seq is a 5' end sequencing method, making it possible to distinguish between degrading maternal transcripts and novel embryonic transcripts (Paper I). Next, we applied this method to identify previously predicted but unconfirmed paired-like homeobox (PRDL) genes in bovine that are similar to those involved in human EGA. We provided evidence of the PRDL genes in bovine and cloned them from the specific embryo development stages, showing their involvement in bovine EGA. This confirms that bovine models are indeed useful for studying human embryogenesis, as many PRDL genes are absent from mice, rendering them unsuitable for such studies (Paper II). We then applied this knowledge to understand the impact that oxygen levels have on in vitro embryo development, especially on EGA and metabolism. We found that the highest blastocyst formation rate happened in hypoxic culture conditions that induced timely EGA and energy metabolism genes. On the contrary, normoxia slowed down maternal transcript degradation, which is necessary for the embryo to achieve totipotency and reprogramming. In addition, these embryos had several key metabolic pathways downregulated, making them less likely to be able to respond to the environment, and this might potentially be the reason why the embryos grown in normoxia have a lower success rate in IVF. Finally, we tested the hypothesis of a sequential hypoxia culture system by switching to ultrahypoxia after day 3 of development and showed that these embryos had a similar transcriptomic profile to hypoxia embryos, but a significantly lower number reached the blastocyst embryo stage (Paper III). Overall, this thesis introduced a new RNA sequencing technology applicable to various embryology studies and offered insights into EGA in bovine embryos. It also showed the impact of IVF culture conditions on EGA and the metabolism of in vitro embryos to improve embryo culturing protocols for ART.List of scientific papersThis thesis is based on the following original articles:I. Optimized single-cell RNA sequencing protocol to study early genome activation in mammalian preimplantation development. Nina Boskovic, Gamze Yazgeldi, Sini Ezer, Mari H. Tervaniemi, Jose Inzunza, Spyridon Panagiotis Deligiannis, Barış Yaşar, Tiina Skoog, Kaarel Krjutškov, Shintaro Katayama, Juha Kere. STAR Protocols. 2023 Volume 4, Issue 3, 102357. https://doi.org/10.1016/j.xpro.2023.102357II. Molecular cloning of PRD-like homeobox genes expressed in bovine oocytes and early IVF embryos. Barış Yaşar, Nina Boskovic, Marilin Ivask, Jere Weltner, Eeva-Mari Jouhilahti, Piibe Vill, Tiina Skoog, Ülle Jaakma, Juha Kere, Thomas R. Bürglin, Shintaro Katayama, Tõnis Org, Ants Kurg. BMC Genomics 25, 1048 (2024). https://doi.org/10.1186/s12864-024-10969-wIII. Oxygen level alters energy metabolism in bovine preimplantation embryos. Nina Boskovic, Marilin Ivask, Gamze Yazgeldi Gunaydin, Barış Yaşar, Shintaro Katayama, Andres Salumets, Tõnis Org, Ants Kurg, Karolina Lundin, Timo Tuuri, Carsten O. Daub, Juha Kere. Scientific Reports 15, 11327 (2025)https://doi.org/10.1038/s41598-025-95990-z</p
Bioinformatic characterization of structural variation in rare disease
No full textThe genome contains the blueprint for human development, health, and disease. Despite significant advances, the full implications of many regions of the genome remain poorly understood, leaving approximately 60% of patients referred for genetic analysis undiagnosed.Only about 2% of the genome consists of protein-coding exons, and the remaining 98% consists of non-coding regions, including regulatory elements, introns, and various types of repeat elements, such as transposable elements (TEs), low-copy repeats, and satellite sequences. These non-coding regions have often been neglected and remain understudied, despite their known association with structural variation. Only recently was the first complete human reference genome released, the telomere-to-telomere assembly (T2T-CHM13). This added over 200 megabase-pairs of previously missing or computed sequences, mainly composed of repetitive elements.Structural variant detection has historically been limited by short read lengths, which struggle with alignment and resolution across repetitive regions. However, with new techniques such as long-read sequencing and T2T-CHM13, it is now possible to increase coverage and resolution in these challenging areas. In this thesis, we developed workflows and applied new techniques to identify and characterize both simple and complex structural variants.In study I, we developed a pipeline to detect TE insertions in short-read genome sequencing data. The pipeline was applied to population genomic datasets to build databases for frequency annotation, and to patient genomes, where it identified two cases of disease-causing TE insertions. In study II, we developed STELLeR, a fast, sensitive, and precise tool for TE detection in long-read sequencing data that can easily be implemented into long-read workflows.In study III, we used long-read genome sequencing and multiple reference genomes to resolve and characterize large chromosomal inversions. Four of twelve cases could only be identified using the T2T-CHM13 assembly. We further explored regions present in T2T-CHM13 but absent from other human and primate reference genomes. In study IV, we applied similar strategies to investigate supernumerary marker chromosomes. We characterized and proposed formation mechanisms for nine out of ten cases, four of which could not have been resolved without T2T-CHM13. Methylation analysis also revealed the parental origin in one case and skewed X-inactivation in another.This thesis presents new tools and methodologies for detecting structural variants, including TEs, inversions, and supernumerary marker chromosomes. The work enhances our understanding of repetitive genomic regions and their implications in structural variant formation and detection. Furthermore, it highlights the need for longer reads and complete reference genomes for an accurate and comprehensive genome analysis.List of scientific papersI. Transposable element insertions in 1000 Swedish individuals. Bilgrav Saether K, Nilsson D, Thonberg H, Tham E, Ameur A, Eisfeldt J, Lindstrand A. PLoS One. 2023 Jul 28;18(7):e0289346. PMID: 37506127. https://doi.org/10.1371/journal.pone.0289346II. Detecting transposable elements in long read genomes using STELLER. Bilgrav Saether K, Eisfeldt J, Bioinformatics, 2024 Nov 18; btae68. PMID: 39558574. https://doi.org/10.1093/bioinformatics/btae686III. Leveraging the T2T-CHM13 assembly to resolve rare and pathogenic inversions in reference genome gaps. Bilgrav Saether K, Eisfeldt J, Bengtsson JD, Lun MY, Grochowski CM, Mahmoud M, Chao HT, Rosenfeld JA, Liu P, Ek M, Schuy J, Ameur A, Dai H; Undiagnosed Diseases Network; Hwang JP, Sedlazeck FJ, Bi W, Marom R, Wincent J, Nordgren A, Carvalho CMB, Lindstrand A. Genome Res. 2024 Nov 1;34(11):1785-1797. PMID: 39486878. https://doi.org/10.1101/gr.279346.124IV. Detailed resolution and methylation patterns of supernumerary marker chromosomes using long read genome sequencing Bilgrav Saether K, Marlene Ek, Maria Pettersson, Elisabeth Syk Lundberg, Christopher M. Grochowski, Claudia M. B. Carvalho, Jesper Eisfeldt, Anna Lindstrand [Manuscript]</p
Groin hernia surgery in women : outputs, factors, methods and cost-effectiveness
No full textThere is inequity in access to surgical treatment and quality of care globally and this is more pronounced in low-and middle-income countries (LMICs) especially among women. Prioritizing treatment of common surgical conditions like groin hernias in LMICs would improve this aspect.Aims. The present aims were to assess groin hernia surgery outputs and practices in Uganda, to evaluate the relationship between parity and the incidence rate of groin hernia repair among women born in Sweden between 1956 and 1983, to compare the safety and effectiveness of open anterior mesh repair for groin hernia in adult women in Uganda to modified open anterior mesh repair through which both the inguinal and the femoral canal can be accessed and covered with a mesh flap. A further aim was to assess the cost and cost-effectiveness of the open anterior mesh repair in comparison to the modified open anterior mesh repair.Methods. Studies I, III and IV were carried out in Uganda. Study II was carried out in Sweden. Study I was a hospital-based observational study to retrospectively review theatre records for groin hernia repairs in 2013 and 2014, and a questionnaire interview for the surgical providers. Study II was a population-based cohort study among women born in Sweden between 1956 and 1983 in which the Swedish Hernia Register, and the National Medical Birth Register were cross- matched to identify groin hernia repairs after childbirth. The follow up period was until 31st December 2022. Incidence rates and incidence rate ratios for inguinal and femoral hernia repairs were determined. Study III was a double- blinded randomized controlled trial among adult women in Uganda in which the safety and effectiveness of open anterior mesh repair were compared with those of modified open anterior mesh repair. Study IV was a cost-effectiveness study of the trial in Study III to compare the cost and cost-effectiveness of the two groin hernia repair methods.Results. Study I, found that 5518 groin hernia repairs were performed in 2013 and 2014, with an annual repair rate of 7/100, 000 population. Most of the repairs were performed by non- specialized surgeons using suture techniques and almost 16% of the repairs were performed in women. In Study II, the mean incidence of inguinal hernia repair was 10.7 per 100,000 person-year and 2.6 per 100,000 person-year for femoral hernia repairs. The incidence rate and the incidence rate ratios for both inguinal and femoral hernia repairs increased with the number of births. In Study III, altogether, 200 participants were included. Nearly 45% had a femoral hernia. At one-year follow-up, overall recurrence was 5.6% and overall wound complications at two weeks follow-up were 10.1%. In Study IV, the cost per DALY averted in the open anterior mesh repair was 292.0 (SD, 264.4) USD compared to 328.8 (SD, 284.2) USD in the modified open anterior mesh repair.In conclusion, groin hernia repair outputs in Uganda need to improve along with mesh-based methods. High parity levels may increase the risk of groin hernias. Opening of the transversalis fascia to inspect the femoral canal should be routinely done among women to detect femoral hernias. The modified open anterior mesh repair is an option to treat inguinal and femoral hernias in the absence of laparoscopy. While the open anterior mesh repair and its modified version are cost-effective, their application should depend on patient needs. However, the high possibility of femoral hernias among women in the study setting, calls for promotion of the modified open anterior mesh method.List of scientific papersI. Groin hernia Surgery in Uganda. Caseload and Practices at Hospitals Operating Within the Publicly Funded Health Care Sector. Alphonsus Matovu, Pär Nordin, Andreas Wladis, Mary Margaret Ajiko, Jenny Löfgren. World J.Surg (2020) 44:3277-3283. https://doi.org/10.1007/s00268-020-05633-9II. Incidence of groin hernia repairs in women and parity. A population - based cohort study among women born in Sweden between 1956 and 1983. A. Matovu, J. Lofgren, A. Wladis, P. Nordin, G. Sandblom, H.J. Pettersson. Hernia (2024) 28:1231-1238. https://doi.org/10.1007/s10029-024-03011-1III. Open anterior mesh repair versus modified open anterior mesh repair for groin hernia in women. A randomized clinical trial. Alphonsus Matovu, Par Nordin, Andreas Wladis, Gabriel Sandblom, Moses Elaju, Fredrik Lindmark, Olof Bladin, Jenny Löfgren. [Manuscript]IV. Cost-effectiveness of open anterior mesh repair compared to modified open anterior mesh repair for groin hernia repair in women in a low resource setting. A randomized clinical trial. Alphonsus Matovu, Zin Min Thet Lwin, Geoffrey Okello, Francis Lulu, Gabriel Sandblom, Moses Elaju, Olof Bladin, Filip Westling, Andreas Wladis, Pär Nordin, Jenny Löfgren. [Manuscript]</p
On the stability of dendritic architecture : roles of Nogo receptor 1 and sleep
No full textThe ability of the brain to rewire itself is central to its functioning. This plasticity must be tightly regulated to ensure the stability of memories and maintain normal levels of signalling. This thesis investigates two different systems contributing to the regulation of structural plasticity.Nogo receptor 1 (NgR1) is a potent negative regulator of plasticity. First characterised in the setting of central nervous system injury, it is emerging as an important regulator of memory formation as well. Understanding how this system functions and is regulated could offer novel avenues for treatment of common and severe brain diseases.In paper I we investigated how Nogo receptor 1 levels influence memory function and structural plasticity. Using transgenic mice, we found that constitutive overexpression of NgR1 impaired performance in the Morris water maze, while constitutive lack of NgR1 impaired novel object recognition. Further, overexpression of NgR1 limited the formation of dendritic spines. This paper adds to the growing evidence for a role for NgR1 in regulating memory formation and structural plasticity.Given that NgR1 is strongly expressed in highly plastic brain regions, we hypothesised that there must be ways to bypass the growth inhibition of NgR1 to allow for lasting memory formation. In paper IV we find that a chemical LTP protocol induces rapid downregulation of dendritic NgR1 protein. Conversely, a chemical LTD protocol rapidly upregulates dendritic NgR1 protein. These findings suggest novel ways in which NgR1 levels are dynamically regulated to permit or inhibit memory formation.Sleep is a well-conserved and costly behaviour, yet its function remains poorly understood. The synaptic homeostasis hypothesis is an influential theory that proposes that sleep serves to downscale synaptic weights, and several lines of evidence point to plastic changes in dendritic structure occurring during sleep. However, the evidence is conflicted regarding whether sleep results in a net growth or shrinkage of the dendritic tree. This is an important question to elucidate if we are to develop effective treatments for the ill effects of sleep loss.In paper II we investigated how CA1 dendritic structure is affected by sleep deprivation. We measured dendritic length and dendritic spine density after 5 h sleep deprivation by gentle handling, and did not find any significant effects. In paper III we looked at the same issue but through a systematic review and meta- analysis. We included 30 studies in the meta-analysis, which were individually small and with high variability We found that current evidence does not indicate an effect on CA1 dendritic structure after 24 h or less of sleep deprivation. Chronic sleep deprivation of 72 h or longer does reduce CA1 spine density and dendritic length, but it remains unclear if this is solely due to sleep loss or to stress associated with the method of sleep deprivation.Together, these studies advance our understanding of how structural plasticity is regulated.List of scientific papersI. Tobias E Karlsson, Gabriella Smedfors, Alvin TS Brodin, Elin Åberg, Anna Mattsson, Isabelle Högbeck, Katrin Wellfelt, Anna Josephson, Stefan Brené, Lars Olson. NgR1: A Tunable Sensor Regulating Memory Formation, Synaptic, and Dendritic Plasticity. Cereb Cortex. 2016 Apr;26(4):1804-17. https://doi.org/10.1093/cercor/bhw007II. Alvin TS Brodin, Sarolta Gabulya, Katrin Wellfelt, Tobias E Karlsson. Five Hours Total Sleep Deprivation Does Not Affect CA1 Dendritic Length or Spine Density. Front Synaptic Neurosci. 2022 Mar 14;14:854160. https://doi.org/10.3389/fnsyn.2022.854160III. Alvin TS Brodin, Franziska Liesecke, Julia Spielbauer, Tobias E Karlsson. Effects of sleep deprivation on dendritic architecture: A systematic review and meta-analysis of rodent studies. [Manuscript]IV. Alvin TS Brodin, Julia Spielbauer, Katrin Wellfelt, Lars Olson, Tobias E Karlsson. Localisation and regulation of Nogo-66 receptor 1 during chemical long term potentiation and depression. [Manuscript]</p
Complex paths of lifestyle change in stroke prevention : unveiling seeds and processes of engaging occupations
No full textLifestyle habits influence health, disease, and premature death. Addressing unhealthy habits such as physical inactivity, poor diet, alcohol and tobacco use, which are increasing globally, is urgent. Together with hypertension, overweight, dyslipidaemia, and type II diabetes, they are risk factors for cardiovascular disease, including stroke. Tackling these modifiable risk factors can significantly decrease stroke risk and yield substantial societal and economic benefits. Multifactorial approaches targeting multiple lifestyle aspects show promise; however, a sustainable change is a challenge. While meaningful and engaging occupations have shown to motivate change, an occupational perspective is often missing in prevention interventions.The studies in this thesis aimed to evaluate the effects and implementation strategies of the stroke prevention intervention, Make My Day. Moreover, to explore and describe mechanisms affecting the change process to provide knowledge into how occupations can serve as a means for change and sustainability in prevention interventions. The aim is also to identify and ideate refinements to the Make My Day intervention.Within this thesis, 122 persons at high risk for stroke were included and randomised to either the intervention group or the control group. Additionally, three primary healthcare clinics in Region Stockholm, Sweden, with 16 healthcare professionals, were included to implement the Make My Day intervention. To capture the complexity of lifestyle change and stroke risk reduction, a variety of methods utilising both quantitative and qualitative data, including the voices of stakeholders, were employed.The findings from Study I, a randomised controlled trial, revealed that participation in the Make My Day intervention reduced high stroke risk at 12 months and had a potential clinical effect on the predicted 10-year stroke risk compared to the controls. Additionally, a perceived improvement in occupational balance and quality of life was detected compared to baseline. Notably, both groups demonstrated within-group improvements in goal achievement and a reduction in risk factors such as physical inactivity and hypertension.Study II, a process evaluation, contributes to the knowledge that setting realistic individual goals, being part of the group, and engaging occupations were valuable mechanisms for the participants' change processes. However, the study revealed a dualistic role of several mechanisms of change, being both facilitators and barriers to the change process. For instance the complex nature of engaging occupations, having the potential of having both beneficial and harmful influences on health, and being both highly valued and hard to grap, was illustrated. The study also underscores the well-known challenge of reaching a population from low-socioeconomic areas.In Study III, collaborative workshops with stakeholders identified key components within Make My Day in need of refinement. Refinements, addressing the key components, were co-created. Refinements included a suggestion to expand the Make My Day education for healthcare professionals, as well as providing concrete strategies for the intervention sessions addressing core concepts of engaging occupations and individual goals.To conclude, this thesis contributes new knowledge on the potential of occupation-focused lifestyle interventions in stroke prevention. It highlights the power of engaging occupations and occupation-focused goals to change and sustain lifestyle habits, and reduce stroke risk, while exploring the complex mechanisms that influence change. These insights can contribute to future paths for the development of Make My Day and stroke prevention interventions. Moreover, it contributes to knowledge about the valuable role of stakeholder involvement in creating acceptable, relevant, and inclusive interventions, thereby bridging the gap between research and practice.This thesis illustrates that applying occupational science, occupational therapy theory, and empirical research about occupations is one way that occupational science can contribute new perspectives to significant public health dilemmas. As a result, this enhances the relevance of occupational therapy and occupational science to public and population health. In other words, the potential of Make My Day goes beyond stroke prevention to encompass the prevention and treatment of various other health issues.List of scientific papersI. Johnsson C, Asaba E, Guidetti S, Åkesson E, Hagströmer M, and Patomella A-H. Make My Day - stroke prevention grounded in engaging everyday activities in primary healthcare - a single- blinded randomised controlled trial. Journal of Primary Care and Community Health. 2025;16(1-19). https://doi.org/10.1177/21501319251385889II. Johnsson C, Asaba E, Guidetti S, Hagströmer M, and Patomella A-H. Performing lifestyle changes and reducing stroke risk - a process evaluation of the Make My Day Intervention grounded in engaging everyday activities. [Manuscript]III. Johnsson C, Jakobsson E, Hagströmer M, Guidetti S, Patomella A- H, Asaba E. Refining the Make My Day stroke prevention intervention for primary healthcare through co-creation with stakeholders. Research involvement and engagement. 2025;11(1). https://doi.org/10.1186/s40900-025-00676-5</p
First report of Escherichia albertii in Iran : a case study highlighting diagnostic challenges in pediatric gastroenteritis
No full textBackground: Escherichia albertii is a gram-negative, facultative anaerobic bacillus in the order Enterobacterales, family Enterobacteriaceae, increasingly recognized as an emerging enteropathogen. Initially isolated in 1991 from a child with diarrhea in Bangladesh and misclassified as Hafnia alvei, it was reclassified in 2003 and is now acknowledged as the second pathogenic species of the Escherichia genus, following Escherichia coli.Case Summary: This article reports the first documented case of E. albertii in Iran, infecting a 5-year-old girl who presented with profuse watery diarrhea. During a 7-month surveillance study at Akbar Children’s Hospital in Mashhad, stool samples from 231 children with diarrhea were analyzed, with this single case demonstrating infection by E. albertii. The strain was identified through pentaplex PCR but exhibited phenotypic traits highly similar to other enteropathogens and showed resistance to antibiotics, such as ampicillin and amoxicillin-clavulanate. Conclusion The study highlights the diagnostic challenges associated with the discrimination between E. coli and E. albertii, which is often misidentified when solely biochemical tests are used.Our findings and literature data suggest that E. albertii should be considered a significant cause of pediatric gastroenteritis, akin to Shigella and enteroinvasive E. coli. These observations emphasize the need for adequate diagnostic protocols, including PCR testing, to accurately identify E. albertii and inform appropriate clinical management strategies. Further research is necessary to deepen our understanding of this emerging pathogen and its implications for human health.</p