Colorectal carcinoma (CRC) ranks high in mortality and morbidity in most developed countries. Following theses focus on specific aspects of colorectal carcinoma pathogenesis including the issue of screening. The goal of the first study was assessment of expression of epithelial markers of colorectal carcinogenesis p53, COX-2, bcl-2. The study included patients with active ulcerative colitis (UCA), ulcerative colitis in remission (UCR), primary sclerosing cholangitis with ulcerative colitis (PSC-UC) (PSC), patients after liver transplantation for PSC (OLT) and a control group (N). We found significantly increased expression of tumour suppressor gene p53 in non-dysplastic mucosae in PSC-UC compared with UCA, UCR, OLT, and N, which may indicate higher neoplastic potential of PSC. Statistically significant correlation was found between PSC incidence and p53 expression. Surprisingly, OLT showed no p53 expression in non-dysplastic mucosa compared with PSC-UC. This indicates that PSC may contribute to increased expression of p53 and p53-induced colorectal carcinogenesis. Furthermore, a correlation between expression of p53 and COX-2 together with the increased expression of bcl-2 in UCA compared to N can support the role of inflammation in colorectal carcinogenesis. The goal of the second study was...

Background: Inflammatory Bowel Disease (IBD) is a chronic, relapsing, autoimmune disease, affecting one in every 150 Canadians. Failure to induce remission of IBD with pharmacotherapy can necessitate surgical interventions, such as the creation of an ostomy. Ostomy surgery can help manage severe IBD and thus improve quality of life; however, individuals living with IBD report the possibility of ostomy surgery as a top concern, which can lead them to refuse or delay this decision until the disease becomes life threatening. Research Objective: The aim of this study is to understand what factors influence the decision to have ostomy surgery in young women with IBD, how the perception of the surgery compares to the reality of living with an ostomy, and the role healthcare professionals play in this decision. Methods: Nine participants who (1) identify as female, (2) are between the ages of 19 and 30, and (3) are currently living with an ostomy to treat IBD were recruited for this study. Additionally, seven healthcare professionals who work with IBD patients were recruited. Participants were invited for an individual, semi-structured interview. Findings: Young adult women living with an ostomy to treat their IBD reflected on their initial fears and concerns about undergoing surgery. Due to the severity of their illness, the majority of participants had requested surgery after having some time to adjust to the idea. This request, however, was often met with resistance or obstacles in the healthcare system. Healthcare professionals share mixed perceptions of ostomy surgery, with some viewing it as a last resort and others perceiving it as a treatment option. Once surgery had been performed, young adult women describe some challenges adjusting to life with an ostomy; but the majority report experiencing an overall improvement in quality of life. Conclusion: Understanding the perceptions that influence how young women perceive ostomies prior to versus after surgery will help identify the factors that influence the decision-making process for ostomy surgery, such as gender, age and stigma. Challenging current beliefs and assumptions may allow more supportive conversations between healthcare professionals and patients and provide insight on the actual lived experience of young women living with an ostomy. / Graduate / 2023-01-13

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Bakgrund: IBD är en kronisk inflammatorisk tarmsjukdom som innefattar sjukdomarna ulcerös kolit och Crohns sjukdom. Sjukdomen har ökat kraftigt i förekomst de senaste tre decennierna, även i Sverige. En person som har en kronisk sjukdom får en påverkad tillvaro och behöver stöd utöver bara kunskap om sjukdomen för att kunna hantera den. Professionell attityd och empati är viktiga aspekter för att skapa ömsesidigt förtroende och respektfull vård för personer med IBD. Syfte: Litteraturstudiens syfte var att belysa personers (≥18 år) upplevelser av att leva med inflammatorisk tarmsjukdom (IBD). Metod: En litteraturstudie med kvalitativ ansats, som omfattade 11 vetenskapliga artiklar med kvalitativ metodik, genomfördes. Databaserna CINAHL och PubMed användes för databassökning. Analysen genomfördes som en stegvis process inspirerad av innehållsanalys. Resultat: Personernas upplevelse av att leva med IBD sammanställdes i två kategorier; ‘Upplevelser ur ett inre perspektiv’ och ‘Upplevelser ur ett relationellt perspektiv’. Kategorierna delades därefter in i nio subkategorier; ‘Oförutsägbarhet och kontrollförlust’, ‘Oro för framtiden’, ‘Kroppsbild och stigma’, ‘Fysiska påfrestningar’, ‘Optimism’, ‘Sociala situationer’, ‘Familj och partner’, ‘Arbete samt ‘Sjukvård’. Konklusion: Personer med IBD upplever både fysiska och psykiska påfrestningar som kräver en helhetssyn i omvårdnaden. En individanpassad omvårdnad är avgörande för att upprätthålla förtroendet för vården och främja positiva resultat för personens behandling och hälsa. Sjuksköterskor bör vara lyhörda för de individuella behoven och ta hänsyn till de psykiska påfrestningar som sjukdomen kan bidra till. Det är också viktigt att skapa en trygg miljö för personerna, då sjuksköterskan kan fungera som en stödjande faktor vid sociala problem. Litteraturstudien visar därmed att omvårdnad spelar en betydande och värdefull roll i personers upplevelser av att leva med IBD. / Background: IBD is a chronic inflammatory bowel disease that includes ulcerative colitis and Crohn disease. It has significantly increased in incidence over the past three decades, in Sweden as well. A person with chronic illness experiences an impacted life and requires support beyond just knowledge of the disease in order to be able to manage it. Professional attitude and empathy are important aspects to create mutual trust and respectful care for people with IBD. Aim: The aim was to illuminate people’s (≥18 years) experiences of living with inflammatory bowel disease (IBD). Method: A literature review with a qualitative approach, which included 11 scientific articles with qualitative methodology. The databases CINAHL and PubMed were used for the database searching. The analysis was conducted as a stepwise process inspired by content analysis. Results: The people’s experience of living with IBD was compiled into two categories; ‘Experiences from an inner perspective’ & ‘Experiences from a relational perspective’. The categories were then divided into 9 subcategories; ‘Unpredictability and loss of control’, ‘Anxiety about the future’, ‘Body image and stigma’, ‘Physical stress’, ‘Optimism’, ‘Social situations’, ‘Family and partner’, ‘Work’ and ‘Healthcare’. Conclusion: People with IBD experience both physical and psychological stress, which requires a holistic view in nursing. Individualized care is crucial to maintaining trust and promoting positive outcomes for a person's treatment and health. Nurses should be attentive to individual needs and consider the psychological impacts of the disease. Additionally, creating a safe environment is important, as nurses can act as a supportive factor in case of social problems. The literature review highlights the significant and valuable role of nursing care in the experiences of individuals living with IBD.

Introduction Inflammatory bowel disease (IBD) and its complications have been well-established. The literature shows an association between IBD and decreased bone mineral density in the adult population. However, most studies have reported an association between IBD and osteoporosis, while the risk of fractures has not been well-studied. The aim of this meta-analysis is to summarize the best available evidence regarding IBS and osteoporotic fractures. Methods A review of the literature using the MEDLINE and EMBASE databases was performed during November 2017. We included cross-sectional and cohort studies that reported the relative risks, odds ratios, and hazard ratios comparing the risk of developing osteoporotic fractures among patients with IBD patients, both ulcerative colitis (UC) and Crohn's disease (CD), versus patients without IBD as controls. The pooled odds ratio (OR) and 95% confidence interval (CI) were calculated using the generic inverse-variance method. Results After a review of the literature, seven studies fulfilled the eligibility criteria established during the analysis. A significant association was found between IBD and osteoporosis, with a pooled OR of 1.32 (95% CI, 1.2 - 1.4). Low heterogeneity among the studies was found, I=42.3. No publication bias was found using the Egger regression test p=0.18. Sensitivity analysis showed that the inclusion of data on children by Kappelman et al. (2007) did not change the results. Conclusion A significant association between IBD and the risk of developing osteoporotic fractures was observed in this study. There is a 32% increased risk, which is consistent with different cohort studies previously done.

Bakgrund: Inflammatoriska tarmsjukdomar är samlingsnamnet för Crohns sjukdom och Ulcerös kolit. Insjuknandet sker i 20–30 års ålder och sjukdomen är vanligast i västvärlden. Skillnaden mellan varianterna är lokalisation, symtom och riskfaktorer. Sjukdomen är kronisk och därför har omvårdnaden en särskilt betydelsefull roll främst för att skapa goda förutsättningar för att leva med och inte kämpa emot sjukdomen. Syfte: Att beskriva personers upplevelser av inflammatorisk tarmsjukdom. Metod: Metoden som har använts är en litteraturöversikt som är baserad på originalartiklar från kvalitativa studier funna ur databaserna Cinahl Complete och PubMed. Vetenskapliga artiklar som svarade på litteraturöversiktens syfte har analyserats och syntetiserats för att svara på syftet. Resultat: De 10 valda vetenskapliga artiklarna resulterade i fyra kategorier vilka är: Sociala begränsningar och isolering, Relationernas betydelse, Ändå en mening med livet och acceptans samt Arbets-och studierelaterade konsekvenser. Sammanfattning: Till följd av sjukdomen upplevde personer med IBD ett begränsat vardagligt liv, socialt liv och ekonomiska problem. Planering av vardagen har varit mycket tids- & energikrävande. Personerna upplevde inte enbart negativa konsekvenser utan sjukdomen medförde att de fick se livet på ett positivt sätt, hittade mening med livet och förbättrade sin livskvalitet. Sjuksköterskans stödjande roll har varit att skapa en god vårdrelation utifrån ett personcentrerat förhållningssätt och  tillgodose deras vårdbehov. / Background: Inflammatory bowel diseases are a term used to describe Crohns disease and ulcerative colitis. Patients who develop IBD are usually diagnosed between the age of 20 - 30 years old and it is most common in western countries. The difference between Crohns disease and ulcerative colitis are the location in the bowels, symptoms and risk factors. IBD is a chronic disease and should therefore be treated accordingly to relieve symptoms and prevent them from returning. Aim: To describe the experience of inflammatory bowel disease. Method: The method that has been used is based on a literature review from original  articles of qualitative studies found in Cinahl complete and PubMed databases. The scientifical articles also responded to the purpose of the literature review which has been analysed and incorporated to answer the purpose. Results: The 10 different scientific articles have been selected to be used and then divided into four different categories which are the following: social limitations and isolation, importance of relationships, meaning of life and acceptance, and work- and study related consequences. Conclusion: As a result of the disease, people with IBD experienced a limited everyday life, social life and financial problems. Planning everyday life has been very time and energy consuming. The people not only experienced negative consequences, but the disease meant that they got to see life in a positive way, found meaning in life and improved their quality of life. The nurse's supportive role has been to create a good care relationship based on a person-centered approach and meet their care needs.

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Commercial and homemade diets are currently used to treat many canine patients with acquired disorders of the colon. Clinically, the efficacy of diets has been found to be unpredictable. Only one study to date has evaluated the effect of diet on the colonic mucosa. This study showed that diet did not observably alter the colonic mucosa of normal dogs, when biopsy samples were evaluated by light microscopy. The effect of diet on colonic ultrastructure in the dog, using transmission electron microscopy, has not previously been investigated. To determine the effect of diet on colonic ultrastructure, cell height, cell area, microvillus height, number of microvilli/apex width and basement membrane width were measured. Ten cells per animal were evaluated. Six dogs were assigned to the control group and fed the control diet for the duration of the study. Six dogs were fed each of the three test diets at four week intervals. The test diets used included a high fiber diet, a hypoallergenic diet and a highly digestible diet. These diets were selected because they are the diets most often recommended for the canine patient with colonic disorders. The value for cell height for the highly digestible group was significantly greater than the other groups, as measured by ANOV A and Duncan's multiple comparison test. No other significant differences were found. The biological relevance of a significantly different value for cell height alone is difficult to evaluate, as other parameters that would indicate an alteration in maturation or proliferation of the colonic epithelial cells did not change. value for cell height alone is difficult to evaluate, as other parameters that would indicate an alteration in maturation or proliferation of the colonic epithelial cells did not change. Therefore, we conclude that commercial diets do not have an effect on the colonic ultrastructure of normal dogs. Although no effect of diet was found, this study does provide morphologic measurements that can be used as a basis for future ultrastructural studies of the colonic mucosa. / Master of Science

No / The interleukin-2-deficient (IL-2¿/¿) mouse model of ulcerative colitis was used to test the hypothesis that colonic epithelial cells (CEC) directly respond to bacterial antigens and that alterations in Toll-like receptor (TLR)-mediated signaling may occur during the development of colitis. TLR expression and activation of TLR-mediated signaling pathways in primary CEC of healthy animals was compared with CEC in IL-2¿/¿ mice during the development of colitis. In healthy animals, CEC expressed functional TLR, and in response to the TLR4 ligand LPS, proliferated and secreted the cytokines IL-6 and monocyte chemoattractant protein-1 (MCP-1). However, the TLR-responsiveness of CEC in IL-2¿/¿ mice was different with decreased TLR4 responsiveness and augmented TLR2 responses that result in IL-6 and MCP-1 secretion. TLR signaling in CEC did not involve NF-B (p65) activation with the inhibitory p50 form of NF-B predominating in CEC in both the healthy and inflamed colon. Development of colitis was, however, associated with the activation of MAPK family members and upregulation of MyD88-independent signaling pathways characterized by increased caspase-1 activity and IL-18 production. These findings identify changes in TLR expression and signaling during the development of colitis that may contribute to changes in the host response to bacterial antigens seen in colitis.

Doctor of Philosophy / In healthy individuals, the autoimmune system is the body's natural defense against foreign materials and organisms. The main tools utilized for this defense mechanism are immune cells. However, in patients suffering from autoimmune diseases, the autoimmune system is overactive resulting in its attack on healthy cells, which leads to reduced or eliminated function of the targeted organs. To suppress these overreactive immune responses, pharmaceutical intervention is needed. An integral part of autoimmune response is the lipid sphingosine-1-phosphate (S1P). Interactions of S1P with its response-inducing receptors prompts the release of immune cells, lymphocytes in particular, from lymph tissue to migrate and participate in the invoked immune response. The pharmaceutical industry has produced five FDA approved drugs that disrupt this S1P-receptor interaction by blocking the receptor to reduce the autoimmune response in patients suffering from autoimmune diseases such as multiple sclerosis and ulcerative colitis. However, these treatments had adverse side effects on the cardiovascular system due to the presence of S1P receptors in the heart. Due to this, there is attraction to target a different node of the S1P signaling pathway to avoid these side effects while still suppressing the immune response. A node that is a viable target for therapeutic target that has recently become the focus of medicinal chemistry campaigns is the transporter protein spinster homolog 2 (Spns2). This protein is responsible for the transport of S1P from intracellular space to extracellular space to interact with its receptors and induce the immune response. Recently, our group has developed several effective inhibitors of Spns2. In this dissertation, several improvements of previously reported inhibitors are revealed. The pinnacle of this work is the development of 4.22v that is optimized to have drug-like properties for testing in mice. Administration of 4.22v to mice resulted in reduced circulating lymphocytes and without showing signs of toxicity following chronic dosing for 14 days. These results suggest that 4.22v is a potential drug candidate and is currently undergoing further biological evaluation.