Introduction: In recent years, robot-assisted surgery has taken over as a first option in rectal cancer treatment. The overall perception is that robot-assisted surgery is a method with good surgical outcomes. Many current studies have focused on comparing robot-assisted surgery to conventional laparoscopy. To our knowledge, few studies have been conducted to compare surgical outcomes in rectal cancer over time in robot-assisted surgery as training and knowledge increases in the field. Aim: To examine the two most commonly used robot-assisted surgical procedures in rectal cancer, to compare surgical outcomes of each procedure over a ten-year period. Method: A retrospective comparative study design was used. The national Swedish Colorectal Cancer Registry (SCRCR) was used to identify patients who underwent robot-assisted rectal cancer surgery at Örebro University Hospital between 2013 and 2022. Two surgical procedures were assessed: anterior resection and abdomino-perineal resection. Studied outcomes included: console-time, operation time, blood loss, hospital stay and conversion rate. Group comparisons were performed. Results: In total 202 patients were included and grouped into two periods (2013-2017; 2018-2022). A statistically significant reduction was observed in both procedures regarding blood loss in the later period. No other statistically significant differences were identified. Patients operated with APR in the later period were less fit. Conclusion: The surgical procedures showed comparable clinical outcomes in both periods. Our study showed that more complex cases in the group operated with APR were selected in the second period, which could imply that a higher degree of surgical proficiency was obtained over time.

Studien utgår ifrån behandlingspersonal på ett SiS LVM-hem och deras beskrivningar av sitt förhållningssätt gentemot kvinnor med samsjuklighet i form av missbruk och ätstörning, samt vilka utmaningar och möjligheter som de upplever i sitt arbete i förhållande till gruppen. Studien har en kvalitativ ansats med semi-strukturerade intervjuer som utförts med fem personer som arbetar som behandlingspersonal på ett SiS LVM-hem i Sverige. Den insamlade datan har framställts i en tematisk analys med fem identifierade huvudteman och 13 subteman som tolkats utifrån tolkningsramen, vilken inkluderar nationella regelverk och de teoretiska begreppen yrkeskompetens; relationskompetens och handlingskompetens samt teori om idealtypiska handlingar. Resultatet visar att det förekommer missbruk och ätstörning på LVM-hemmet och att behandlingspersonalen arbetar med det genom att förhålla sig lika till klienten oberoende dess problematik med viljan att hjälpa och anpassa strategier till problematiken, även om syftet med LVM inte är att behandla ätstörningar och det saknas förutsättningar på organisatoriskt plan. Resultatet visar även att behandlingspersonalen har fokus vid att arbeta relationsskapande för att nå klienterna och motivera dem. Studiens slutsatser är att det saknas kompetens om ätstörningar inom LVM-hemmet men att behandlingspersonalen bemöter missbruk och ätstörning genom att använda rutiner och begränsningar samt sin yrkes- och relationskompetens / The study is based on treatment workers at a SiS LVM-home and their descriptions of their approach to women with co-morbidity in the form of substance abuse and eating disorders, as well as the challenges and opportunities they experience in their work in relation to the group. The study has a qualitative approach with semi-structured interviews conducted with five treatment workers from one SiS LVM-home. The collected data have been represented in a thematic analysis with five identified main themes and 13 sub-themes interpreted based on our interpretive framework which includes the following theoretical concepts of professional competence; relational competence and action competence as well as the theory of four ideal actions. The result shows that there is substance abuse and eating disorders at the LVM-home and that the treatment staff works with it by treating the client equally regardless of their problem with the desire to help and adapt strategies to the problem, even if the purpose of LVM is not to treat eating disorders and that there are no prerequisites on an organizational level. The results also show that the treatment workers have a focus on relationship-building in order to reach the clients and motivate them. The study's conclusions are that there is a lack of expertise on eating disorders within the LVM-home, but that the treatment staff deal with addiction and eating disorders by using routines and restrictions as well as using their professional and relational skills

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Background: Cannabis use is highly prevalent among adolescents in Germany, and chronic cannabis use (CCU) during this developmental stage raises significant public health concerns due to its potential impact on neurodevelopment. Adolescents with CCU are at a major risk of developing Cannabis use Disorder (CUD), particularly when co-occurring psychiatric disorders are present, which can negatively affect treatment outcomes for CUD. Among these co-occurring disorders, psychotic and depressive disorders have frequently been associated with adolescent CCU. Moreover, CCU in adolescence is associated with cognitive impairment, with impaired verbal learning ability being a common manifestation. These cognitive impairments and co-occurring disorders are rooted in underlying neurobiological alterations that may disrupt normal brain development during adolescence. The psychoactive effects of cannabis primarily stem from Δ⁹-trans-Tetrahydrocannabinol, and it is suspected that cannabis use affects the signaling of the endocannabinoid system (ECS). The ECS, known for its regulatory role in various physiological systems such as stress and immune responses, has been implicated in the neurobiological processes underlying certain psychiatric disorders. In recent years, there has been a growing interest in understanding the factors contributing to neurobiological changes associated with psychiatric disorders. Epigenetic processes, which describe the interplay between environmental factors and genetic regulation of phenotypic expression, have gained particular attention. DNA methylation (DNAm), the most extensively studied epigenetic mechanism, has emerged as a central focus in identifying epigenetic changes that underlie the neurobiological processes involved in psychiatric disorders. The present dissertation aims to investigate the psychological, neurobiological, and epigenetic correlates associated with CCU in adolescent outpatients with CUD. By exploring these dimensions, this work seeks to enhance our understanding of the multifaceted factors contributing to CCU and its impact on adolescent mental health. Methods: This thesis consists of five studies presented in chapters 2 to 6. Chapter 2 provides a description of the sample of adolescent outpatients who sought treatment at the SUD outpatient center. The chapter focuses on the prevalence of cannabis and other substance use, the occurrence of cannabis and other substance use disorders (SUDs), and the presence of co-occurring psychiatric disorders. In chapter 3, a study examines the association between cannabis use, additional 3,4-methylenedioxymethamphetamine (MDMA) use and attenuated psychotic symptoms (APS). Chapter 4 presents a study that investigates the relationship between CCU and DNAm. Additionally, it explores the potential mediating effects of DNAm on the association between CCU and impaired cognitive performance. The focus of chapter 5 is on the relationship between depressive symptoms and DNAm in target genes related to depression. The study also examines the association between DNAm of depression-related genes and CCU, while exploring the mediating effects of DNAm on the relationship between CCU and depressive symptoms. Finally, in chapter 6, a study analyzes site-specific DNAm to estimate the proportions of circulating white blood cell types in adolescents with CCU compared to non-using controls (NCU). The study also investigates the DNAm profiles of selected immune cell markers and determines their gene expression levels. Results: In a first step, the prevalence of cannabis use and CUD among treatment seeking adolescents with suspected SUD was examined. Cannabis use and CUD was highly prevalent in the sample. The results indicated no effects of gender or age on cannabis use and CUD prevalence rates. Further, co-occurring conduct disorders, attention deficit hyperactivity disorders and depressive disorder were also highly prevalent in this sample. In chapter 3, the results did not indicate a relationship between APS and cannabis use, which was contrary to the predictions. MDMA use additional to cannabis however was associated with increased APS. However, as described in Chapter 4, CCU was associated with impairment in a verbal learning task. Furthermore, six CpG sites were identified whose DNAm levels showed a significant mediating effect on the relationship between CCU and verbal learning impairment. The results presented in Chapter 5 indicate that CCU is associated with increased depressive symptoms, and both depressive symptoms and CCU are associated with DNAm of one key gene in the stress system. Moreover, the findings in the last chapter, Chapter 6, suggest that CCU has immune-modulatory effects and affects the proportion of B-cells in adolescents with CCU, potentially acting through the alteration of DNAm of related genes. Discussion: The studies conducted in this thesis have produced several significant findings. Firstly, it was observed that cannabis use and CUD are highly prevalent among adolescents with SUDs. While there was no cross-sectional association between cannabis use and increased APS, it was associated with higher levels of depressive symptoms, poorer performance in verbal learning tasks, and a higher prevalence of co-occurring psychiatric disorders. Additionally, it was found that adolescent CCU may have an impact on the epigenome through alterations in DNAm. Specifically, these alterations may affect the regulation of cognitive processes by influencing neurogenerative processes. Adolescent CCU may also interfere with the stress axis through DNAm-related changes. Furthermore, there is evidence to suggest that adolescent CCU may impair parts of the immune system. However, it is important to note that the studies presented in this thesis are based on cross-sectional data, and therefore, causal interpretations cannot be made. The relationships discussed, which imply causality, are speculative and require examination in longitudinal studies.:Statement for a publication-based dissertation List of Tables List of Figures Important Abbreviations Abstract 1. General Introduction 1.1 Prevalence of Cannabis Use and Cannabis Use Disorder (CUD) 1.2 CCU associated cognitive and behavioral changes 1.3 Neurobiological changes associated with CCU in adolescence 1.4. Epigenetic regulations and DNA methylation 1.5 Research Aims and Hypotheses 1.6 Sample Population and Measurements 2. Prevalence of cannabis use and CUD in an outpatient clinic 2.1 Background 2.2 Methods 2.3 Results 2.4 Discussion 2.5 Conclusion 2.6 Acknowledgements, Funding, Conflicts of Interest 3. Cannabis use and psychotic symptoms 3.1 Background 3.2 Methods 3.3 Results 3.4 Discussion 3.5 Conclusion 3.6 Acknowledgements, Funding, Conflicts of Interest 4. CCU, cognitive impairment and shared epigenetic associations 4.1 Background 4.2 Methods 4.3 Results 4.4 Discussion 4.5 Conclusion 4.6 Acknowledgements, Funding, Conflicts of Interest 5. CCU, depressive symptoms and shared epigenetic associations 5.1 Background 5.2 Methods 5.3 Results 5.4 Discussion 5.5 Conclusion 5.6 Acknowledgements, Funding, Conflicts of Interest 6. Immunological alterations associated with CCU 6.1 Background 6.2 Methods 6.3 Results 6.4 Discussion 6.5 Conclusion 6.6 Acknowledgements, Funding, Conflicts of Interest 7. General Discussion 7.1 Summary 7.2. Implications for DNAm mediated disruption of cognitive systems due to adolescent CCU 7.3 Implications for DNAm mediated disruption of immunological systems and its interactions with depression in chronic cannabis users 7.4 Neurobiological and epigenetic alteration may be affected by CCU 7.5. Clinical Implications 7.6. Limitations & Future Research 8. References 9. Appendices 9.1 Appendix A (chapter 2) 9.2 Appendix B (chapter 3) 9.3 Appendix C (chapter 4) 9.4 Appendix D (chapter 5) 9.5 Appendix E (chapter 6) 10. Erklärung gemäß der Promotionsordnung

Little to no research has evaluated factors that explain the manifestation and maintenance of bipolar disorder-anxiety disorder (BD-AD) comorbidity. The literature has shown that disruption of social and circadian rhythms is associated with mood episode onset. This association is especially pronounced among individuals who have a sensitive behavioral approach system (BAS). Inasmuch as anxiety sensitivity and trait anxiety have been associated both with BD and social rhythm disruption, it is worth examining whether anxiety sensitivity and trait anxiety confer risk for mood episode onset. The aims of this project were to: 1) evaluate trait anxiety and anxiety sensitivity as predictors of social rhythm disruption and BD-AD comorbidity, 2) examine social rhythm disruption (SRD) as a mediator of the association between trait anxiety and anxiety sensitivity and BD-AD comorbidity status, and 3) explore behavioral approach system sensitivity in these processes as contributing to the vulnerability to BD-AD comorbidity. A sample of 156 young adults participated in a multi-wave study in which they completed diagnostic interviews, symptom measures, and life event interviews which assessed the occurrence of positive and negative life events and the degree of SRD following these events every six months. Partial support for the hypotheses was found. Initial anxiety sensitivity, but not trait anxiety, positively predicted SRD for rewarding life events and follow-up bipolar symptoms. Additionally, SRD following positive life events predicted increases in depressive symptoms, but not hypomanic symptoms. SRD mediated the relationship between anxiety sensitivity and depressive symptoms. Furthermore, this relationship was stronger for healthy controls than for those with a bipolar disorder (BD) diagnosis or at-risk for developing BD. Moreover, individuals with a comorbid BD-AD diagnosis tended to have greater social rhythm disruption following negative life events than BD only or healthy individuals. Unexpectedly, individuals with comorbid BD-AD did not exhibit greater anxiety sensitivity or trait anxiety. Overall, the results suggest that anxiety sensitivity is a factor that may help to identify individuals who are vulnerable to bipolar symptoms. Furthermore, SRD is a mechanism that may partially explain this relationship. / Psychology