| 1. |
- Karamanis, Georgios
(författare)
-
Gender dysphoria : Insights on etiology and outcomes
- 2023
-
Licentiatavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Gender Dysphoria (GD) is defined as significant distress or impairment caused by the discrepancy between an individual's experienced gender and the sex assigned at birth. This work explores the etiology and outcomes of GD through two studies. The first assesses its prevalence in different twin categories, and the second examines the incidence of idiopathic intracranial hypertension (IIH) in individuals undergoing gonadotropin-releasing hormone analogue (GnRHa) treatment for GD.The first study utilizes a population-based approach to analyze the prevalence of GD in twins, using data from a Swedish population-based cohort collected over a 16-year period. The objective is to assess the influence of genetic and environmental factors on the development of GD by comparing its prevalence in different-sex twins, same-sex twins, and non-twin siblings. The results indicate a higher prevalence of GD in different-sex twins and suggest a potential influence of intrauterine factors in the development of GD, necessitating further examination of current genetic and environmental theories.The second study focuses on evaluating the occurrence of IIH in individuals undergoing treatment with GnRHa for GD in Sweden between 2006 and 2016. The study did not observe any cases of IIH within the studied cohort. While better-powered studies are needed to clarify any potential association between GnRHa and IIH, the study results do not present substantial evidence to support this association.
|
|
| 2. |
- Blomgren, Per-Ola
(författare)
-
Clean work, the pursuit of increased adherence to hand hygiene routines : a descriptive study
- 2022
-
Licentiatavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Healthcare-associated infections (HAI) are a problem in health care worldwide. In Sweden 7-8% of all patients treated in hospital suffer from an adverse event of varying severity, of which approximately 60,000 from a HAI. Proper hand hygiene is considered the single most important measure to reduce HAI. Despite the importance, adherence to correct hand hygiene routines are lacking among healthcare workers (HCWs). The World Health Organizations (WHO) multimodal promotion strategy promotes areas that need to be addressed in order to change the behaviour of individual HCWs to optimise adherence to hand hygiene and to improve patient safety. These areas include feedback, education, reminders at the workplace and institutional safety climate. The overall aim of this study was to examine the possibility of adherence to hand hygiene routines and to explore factors that might influence the HCWs adherence. The study used a descriptive research design made through qualitative method, with focus group interviews, and quantitative method, using a questionnaire survey. Eight focus group interviews were conducted with assistant nurses (n=18), nurses (n=15) and physicians (n=5) and analysed with abductive qualitative content analysis. The questionnaire survey was answered by nurses (n=84) and nursing students in their first semester (n=71) and last semester (n=46) and the data was statistically analysed.The main findings show that there are barriers to hand hygiene adherence and measures to improve these. HCWs highlighted discrepancies regarding how the organisation was supposed to give feedback and how it actually was at the workplace and expressed needs for more direct feedback to improve adherence. The study also found that hygienic knowledge gaps exists among nurses and nursing students regarding causes of HAI and how the risk of contamination of patients and HCWs can be minimized among others. Students at the beginning of the education had a lower level of knowledge than last semester students and registered nurses. The last semester students tended to have the highest level of hand hygiene knowledge. In conclusion, the key areas presented by WHO’s multimodal promotion strategy to improve adherence all lack the appropriate measures, in some extent. The use of an electronic reminder system could give the means to improve a behaviour as long as the individual integrity is protected and development of curriculums for nursing students and continuing education of nurses is needed to further develop and maintaining knowledge.
|
|
| 3. |
- Ersson, Lisa, 1985-
(författare)
-
β-N-methylamino-L-alanine (BMAA)-induced neurotoxicity : Studies in vitro and in vivo
- 2020
-
Licentiatavhandling (övrigt vetenskapligt/konstnärligt)abstract
- β-N-methylamino-L-alanine (BMAA) is a neurotoxic non-proteinogenic amino acid produced naturally by cyanobacteria, diatoms and dinoflagellates and it has been detected in samples from fresh and marine water from all over the world. It can bioaccumulate in fish and shellfish, and has a potential to biomagnify in a terrestrial food chain. BMAA was first discovered in the search for a neurotoxin related to the amyotrophic lateral sclerosis/Parkinsonism-dementia complex (ALS/PDC) found among the Chamorro people in Guam. This non-proteinogenic amino acid has also been suggested to contribute to sporadic neurodegenerative diseases such as amyotrophic lateral sclerosis (ALS), Parkinson's disease (PD) and Alzheimer's disease (AD). BMAA can induce neurotoxicity via multiple mechanisms. It can act as an excitotoxin by activating glutamate receptors and to induce oxidative stress. It has also been suggested to be misincorporated into proteins leading to misfolded protein aggregates. Previous studies have demonstrated a specific damage in the hippocampus, including intracellular fibril formation, in adult rats following neonatal exposure to BMAA. In this thesis both in vitro and in vivo models were used to characterize the uptake, transport and effects of BMAA in cultured cell lines and in neonatal rodent brain tissue. The uptake of radiolabeled BMAA, as well as the effects of various amino acids and transporter antagonists on the uptake were studied in human mammary epithelial cells, intestinal epithelial cells, glioblastoma and neuroblastoma cells. Based on the obtained results a potential human mother-to-infant transfer of BMAA was suggested. BMAA-induced metabolic changes in a differentiated human neuroblastoma cell line were also characterized. The results revealed a plentitude of altered metabolites, many of them involved in amino acid metabolism and the TCA cycle. Of special interest were the perturbations in alanine, aspartate and glutamate metabolism as this pathway is involved in neurotransmission. The results revealed that BMAA can interfere with fundamental metabolic and neurotransmission pathways. Finally, the levels of free and protein-associated BMAA in the brain and peripheral tissues in neonatal rats exposed to BMAA were analysed. The results revealed high levels of free BMAA in some brain regions, thus demonstrating that the neonatal brain is not protected from BMAA by the blood-brain barrier. The results also revealed a protein-association of BMAA in the neonatal hypothalamus and hippocampus. Although the total amount of BMAA in the hippocampus was not high compared to other brain regions, the percentage of protein-associated BMAA was significantly higher. The results suggest that the protein-association of BMAA may play a role in the long-term effects in the hippocampus following neonatal exposure to BMAA. The studies in this thesis have demonstrated 1) a potential transfer of BMAA via breast milk to the brain of the nursing infant, 2) BMAA-induced metabolic alterations related to neurotransmission in human neuroblastoma cells and 3) that both free and protein-associated BMAA can be detected in the neonatal rat brain.
|
|
| 4. |
- Lundberg, Stina
(författare)
-
Examining Female Resilience to Early Environmental Influences : Short- and long-term consequences on behaviour, HPA axis activity and alcohol intake after prolonged maternal separation
- 2017
-
Licentiatavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Early-life experiences are an important factor influencing further development of the individual. Adverse experiences early in life, such as various kinds of abuse or neglect, are types of early-life stress that can adversely affect an individuals health, as well as contribute to the development of an array of disorders later in life. Most prominent is the increased risk for psychiatric disorders, primarily depression, anxiety-related and substance use disorders. Many of the implicated disorders also exhibit sex-dependent differences in prevalence and severity. Thus, it is important to consider sex-dependent effects when modeling early-life stress and its consequences. A common animal model for early-life stress is prolonged maternal separation (MS). MS is an umbrella term for different manipulations of the early environment of rodent pups. In this thesis, a prolonged MS condition with separation of rat litters from their dams for six hours per day during the first three weeks of life (MS360) was used. In male offspring MS360 have been associated with early-life stress and negative effects apparent during both adolescence and adulthood. The literature regarding female offspring is not as substantial as for the males, but it seems that females’ exhibit less pronounced or no effect after prolonged MS independent of separation time. In addition, the studies that have examined female offspring have done so in adulthood and thus, short-term consequences of prolonged MS possibly present during adolescence have not been investigated. The aim of this thesis is to provide a broad investigation into the consequences of prolonged MS in female offspring, in both adolescence and adulthood. As stated above, MS360 was used as the adverse rearing condition in this thesis. As control, daily short MS (15 min; MS15) was used; this ensured that all animals were handled equally, except for the length of separation. Any detected differences are thus due to the length of separation only. Three categories of assessments were used to evaluate short- and long-term consequences: 1) hypothalamus-pituitary-adrenal (HPA) axis assessments, 2) behavioral assessments and 3) assessment of voluntary alcohol consumption. HPA axis reactivity was assessed in adolescent and adult offspring by blood sampling before and after challenge. HPA activity was also evaluated after long-term alcohol consumption by measurement of the fecal corticosterone content. Behavior was assessed in adolescence by registration of social play behavior and in adulthood by generation of behavioral profiles in the multivariate concentric square fieldTM (MCSF). Alcohol consumption was evaluated using the modified intermittent alcohol access schedule with the two- (20% alcohol) and three- bottle (5% and 20% alcohol) free-choice paradigms. Female offspring did not differ depending on rearing condition in HPA reactivity in adolescence or adulthood. However, after the long-term alcohol intake, MS360 females had increased levels of corticosterone in their feces compared to MS15 females. No difference was detected in adolescent social play among female offspring and only a minor alteration was detected in the adult behavioral profile, where MS360 females had increased risk assessment compared to MS15 females. No effect of rearing condition was seen during the two-bottle choice paradigm of alcohol intake, while whole- group differences over time were discovered. Alcohol intake and preference were highest the first week of access and directly after a two-week deprivation period, apart from those time-points, intake and preference were maintained on a stable level. In the three-bottle choice, an interaction with rearing condition was revealed for the total alcohol preference, however this only translated to a minor group-dependent difference. In conclusion, females reared under a prolonged MS paradigm exhibited no or only minor basal changes in HPA axis reactivity, behavior and alcohol consumption. However, after long-term alcohol intake females subjected to prolonged MS had increased corticosterone excretion into feces. That differences only emerge after long-term perturbation can be a sign that females have higher buffering capabilities than males after early-life adversity, as modeled through prolonged MS, and thus require additional challenges before consequences become apparent. This thesis highlights the importance of considering sex when studying the impact of early-life stress, and that the choice of animal model needs to be considered carefully in relation to the research question posed.
|
|
| 5. |
|
|
| 6. |
- Mohammad, Salahuddin
(författare)
-
Investigating mental health disorders in relation to job and living related factors
- 2023
-
Licentiatavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Job satisfaction plays an important role for life quality and health of working individuals. While studies have shown that self-reported mental health conditions such as stress, anxiety and depression are associated with job satisfaction, a large population-based study exploring and comparing self-reported physician posed diagnosed conditions and their association with job satisfaction and job tenure is missing. First study addresses the gap along with exploring the impact of the neurotic personality trait and other possible contributing factors.Individuals with autism spectrum disorder (ASD) experience lower well-being as demonstrated epidemiologically mostly for children and adolescents. Further etiological investigation of inclusive wellbeing, in terms of five wellbeing spectrum (5-WBS) traits including neuroticism, depression, loneliness, life satisfaction and positive affect, among adults with ASD may deepen the understanding. Seond study aims to investigate if a genetic predisposition for ASD is associated with 5-WBS traits using polygenic risk score (PRS) analysis.In the first study, sixteen mental health disorders diagnosed by physicians, categorized into four major groups were investigated in relation to employment status (108,711 participants) and in relation to job satisfaction and job tenure (34,808 participants). Analyses were performed using linear regression adjusted for age, sex, TDI, BMI, education, physical activity, work hours and neuroticism. In the second study, PRS for ASD were constructed in the UK Biobank (N = 337,423), based on the GWAS conducted by Psychiatric Genetics Consortium (18,381 cases, 27,969 comparisons) using PRSice-2. First study showed Neurotic & Stress Disorders, Eating Disorders and Other Mental Health Disorders were strongly associated with lower job satisfaction and shorter job tenure in both unadjusted and adjusted analyses. Neuroticism was strongly linked to job satisfaction but was not associated with job tenure. Second study showed, ASD PRS significantly predicted associations with all 5-WBS traits, showing a positive association with the negative WBS traits, neuroticism (max R2 = 0.04%, P < 1x10-4, AUC 0.51), depression (max R2 = 0.06%, P < 1x10-4, AUC 0.51), loneliness (max R2 = 0.04%, P < 1x10-4, AUC 0.51) and a negative association with the positive WBS traits, life satisfaction (max R2 = 0.08%, P < 1x10-4, AUC 0.56), positive affect (max R2 = 0.10%, P < 1x10-4, AUC 0.53).Findings of first study clarify the complex relationship of mental health with job satisfaction and job tenure which is very important to understand in designing measures to improve working life participation of individuals with mental health issues. The findings of second study suggest that adults carrying a high load of susceptible SNPs for ASD are more likely to show a decreased well-being.
|
|
| 7. |
|
|
| 8. |
- Lindgren, Anne
(författare)
-
Pregnancy-related low back and pelvic girdle pain : with reference to joint hypermobility and treatment
- 2020
-
Licentiatavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Objectives: To explore if joint mobility, as a measure of connective tissue quality, could be a predictor for pregnancy-related low back pain after pregnancy and to evaluate local corticosteroid injection treatment in women with persistent pelvic girdle pain long after childbirth.Material and methods: To investigate joint mobility in relation to pain, 200 women were examined repeatedly from early pregnancy until three months after delivery. Their mobility in left fourth finger abduction in early pregnancy was compared with clinically assessed low back and pelvic pain 3 months after delivery. To evaluate local corticosteroid injection treatment, 36 women with persistent PGP were included in a randomised controlled trial (RCT) and randomised to either corticosteroid injection or saline injection on one occasion at the ischial spine bilaterally, with a follow-up after four weeks. In both studies, the women were asked about obstetric history, to complete a pain drawing, estimate their level of pain on a visual analogue scale (0-100) and estimate how they manage their everyday activities on a questionnaire, Disability Rating Index (DRI). In the RCT, the 36 women also completed Short Form 36 (SF-36), a quality of life questionnaire, six-minute walk test (6MWT), and isometric trunk flexion and extension were examined.Results: Women with low back and pelvic pain three months after pregnancy had increased finger laxity in early pregnancy. The larger the finger angle and the more pregnancies, the greater the risk of low back and pelvic pain after pregnancy. In the RCT, at follow-up, the women who received corticosteroid injection treatment improved in walking ability, estimated physical ability and isometric trunk extension more than those who received saline injections.Conclusions: Increased joint mobility, as measured by finger joint mobility, together with the number of previous pregnancies, may be an indicator of low back and pelvic pain postpartum. One single corticosteroid injection treatment to intra-pelvic structures improved function in women with persistent PGP which may indicate a source of pain.
|
|
| 9. |
- Söderquist, Fanny, 1985-
(författare)
-
Melatonin and its receptors in the normal human gastrointestinal tract, pancreas and in small intestinal neuroendocrine tumours
- 2017
-
Licentiatavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Melatonin, “the hormone of darkness” is well known to regulate sleep and circadian rhythm. However, melatonin is also present in numerous peripheral tissues and the number of actions assigned to this neurohormone is growing steadily. Based on animal studies, it has been proposed that gastrointestinal melatonin is produced in enterochromaffin cells.The aims were to characterise the expression of melatonin and its receptors MT1 and MT2 in normal human gastrointestinal tract and pancreas as well as in tumours derived from enterochromaffin cells, small intestinal neuroendocrine tumours (SI-NET), using immunohistochemistry. Melatonin and receptor expression was furthermore compared to clinical symptoms, tumour prognostic factors and treatment response.In enterochromaffin cells from normal gastrointestinal tissue and in SI-NETs a strong immunoreactivity (IR) for melatonin and MT2 was found, while MT1 IR was low or absent. Melatonin, MT1 and MT2 IR was also seen in the large intestinal epithelium of normal gastrointestinal tract and in pancreatic islets, although the expression of MT1 in pancreatic tissue varied. Analyses of mRNA data confirmed the expression of the enzymes needed for melatonin synthesis as well as MT1 and MT2 in small intestine and pancreas.The intensity of melatonin IR in SI-NETs correlated to lower proliferation index and less symptoms of diarrhoea, which is well in line with the proposed actions of melatonin described in nimal studies. The intensity of MT2 IR was generally lower in metastases than in primary tumours. Plasma levels of melatonin in patients with SI-NETs and disease stabilisation/remission were reduced after treatment and higher levels were associated with nausea.In conclusion, melatonin and its receptors are present in the normal human gastrointestinal tract, pancreas and in SI-NETs. Melatonin IR intensity in tumours correlated significantly to less diarrhoea and to lower proliferation index. Plasma levels of melatonin in patients with SI-NETs were reduced with treatment response, indicating a possible tumour-derived origin of circulating melatonin levels.These results are in agreement with the suggested actions of melatonin on gastrointestinal motility and tumour growth.
|
|
| 10. |
- Thunander Sundbom, Lena, 1970-
(författare)
-
The influence of gender and psychological distress on adherence to prescribed medication
- 2014
-
Licentiatavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Background: The lack of adherence to drug therapy is a major problem; it can contribute to significant deterioration of disease and increased health-care costs. Improving medication adherence is a big challenge; there is no simple solution to the problem. It is thus essential to improve our knowledge of non-adherence (NA) and its causes.Aims: The aims of the thesis were to study the influence of gender and psychological distress on self-reported, intentional and unintentional non-adherent behaviour, and to investigate the reasons for NA.Methods: A population-based study that included a postal questionnaire was carried out in a cross-section of the general Swedish population (n=7,985, aged 18-84 years). The response rate was 61.1% (n=4,875) and current prescription drug use was reported by 2,802 participants. The questionnaire covered use of prescription drugs, NA to the drug regimens, reasons for NA, economic status, attitudes to drugs, and the presence of somatic or mental problems, and also included the Hospital Anxiety and Depression Scale questionnaire.Results: The results showed differences in various self-reported non-adherent behaviour patterns and reasons for NA between the genders. In most cases, these remained after controlling for confounders such as socioeconomic factors and attitudes to drugs that are known to differ between women and men. Associations were also found between symptoms of anxiety and/or depression and the presence of intentional or unintentional non-adherent behaviour (with a stronger average association for intentional NA), and between anxiety/depression and some of the reasons given for NA, e.g. adverse drug reactions (ADRs).Conclusions: Although it was not possible to confirm causal relationships, this thesis emphasises the effects of gender and psychological distress on NA. In summary, both gender and anxiety and/or depression influenced non-adherent behaviour and the reasons given for NA. For instance, ADRs seemed to influence the decision not to take the drug as prescribed, especially among women and participants under psychological distress. It is suggested that a deep understanding of the causes of NA and of the impact of gender and psychological distress on the outcomes would help those aiming to improve adherence to prescribed medication.
|
|
