| 1. |
- Mishra, A., et al.
(författare)
-
Stroke genetics informs drug discovery and risk prediction across ancestries
- 2022
-
Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 611, s. 115-123
-
Tidskriftsartikel (refereegranskat)abstract
- Previous genome-wide association studies (GWASs) of stroke - the second leading cause of death worldwide - were conducted predominantly in populations of European ancestry(1,2). Here, in cross-ancestry GWAS meta-analyses of 110,182 patients who have had a stroke (five ancestries, 33% non-European) and 1,503,898 control individuals, we identify association signals for stroke and its subtypes at 89 (61 new) independent loci: 60 in primary inverse-variance-weighted analyses and 29 in secondary meta-regression and multitrait analyses. On the basis of internal cross-ancestry validation and an independent follow-up in 89,084 additional cases of stroke (30% non-European) and 1,013,843 control individuals, 87% of the primary stroke risk loci and 60% of the secondary stroke risk loci were replicated (P < 0.05). Effect sizes were highly correlated across ancestries. Cross-ancestry fine-mapping, in silico mutagenesis analysis(3), and transcriptome-wide and proteome-wide association analyses revealed putative causal genes (such as SH3PXD2A and FURIN) and variants (such as at GRK5 and NOS3). Using a three-pronged approach(4), we provide genetic evidence for putative drug effects, highlighting F11, KLKB1, PROC, GP1BA, LAMC2 and VCAM1 as possible targets, with drugs already under investigation for stroke for F11 and PROC. A polygenic score integrating cross-ancestry and ancestry-specific stroke GWASs with vascular-risk factor GWASs (integrative polygenic scores) strongly predicted ischaemic stroke in populations of European, East Asian and African ancestry(5). Stroke genetic risk scores were predictive of ischaemic stroke independent of clinical risk factors in 52,600 clinical-trial participants with cardiometabolic disease. Our results provide insights to inform biology, reveal potential drug targets and derive genetic risk prediction tools across ancestries.
|
|
| 2. |
- Wightman, D. P., et al.
(författare)
-
A genome-wide association study with 1,126,563 individuals identifies new risk loci for Alzheimer’s disease
- 2021
-
Ingår i: Nature Genetics. - : Springer Nature. - 1061-4036 .- 1546-1718. ; 53:9, s. 1276-1282
-
Tidskriftsartikel (refereegranskat)abstract
- Late-onset Alzheimer’s disease is a prevalent age-related polygenic disease that accounts for 50–70% of dementia cases. Currently, only a fraction of the genetic variants underlying Alzheimer’s disease have been identified. Here we show that increased sample sizes allowed identification of seven previously unidentified genetic loci contributing to Alzheimer’s disease. This study highlights microglia, immune cells and protein catabolism as relevant to late-onset Alzheimer’s disease, while identifying and prioritizing previously unidentified genes of potential interest. We anticipate that these results can be included in larger meta-analyses of Alzheimer’s disease to identify further genetic variants that contribute to Alzheimer’s pathology.
|
|
| 3. |
|
|
| 4. |
|
|
| 5. |
|
|
| 6. |
|
|
| 7. |
- Farioli, A, et al.
(författare)
-
Occupational exposure to asbestos and risk of cholangiocarcinoma: a population-based case-control study in four Nordic countries
- 2018
-
Ingår i: Occupational and environmental medicine. - : BMJ. - 1470-7926 .- 1351-0711. ; 75:3, s. 191-198
-
Tidskriftsartikel (refereegranskat)abstract
- To assess the association between occupational exposure to asbestos and the risk of cholangiocarcinoma (CC).MethodsWe conducted a case–control study nested in the Nordic Occupational Cancer (NOCCA) cohort. We studied 1458 intrahepatic CC (ICC) and 3972 extrahepatic CC (ECC) cases occurring among subjects born in 1920 or later in Finland, Iceland, Norway and Sweden. Each case was individually matched by birth year, gender and country to five population controls. The cumulative exposure to asbestos (measured in fibres (f)/ml × years) was assessed by applying the NOCCA job-exposure matrix to data on occupations collected during national population censuses (conducted in 1960, 1970, 1980/81 and 1990). Odds ratios (OR) and 95% CI were estimated using conditional logistic regression models adjusted by printing industry work.ResultsWe observed an increasing risk of ICC with cumulative exposure to asbestos: never exposed, OR 1.0 (reference category); 0.1–4.9 f/mL × years, OR 1.1 (95% CI 0.9 to 1.3); 5.0–9.9 f/mL × years, OR 1.3 (95% CI 0.9 to 2.1); 10.0–14.9 f/mL × years, OR 1.6 (95% CI 1.0 to 2.5); ≥15.0 f/mL × years, OR 1.7 (95% CI 1.1 to 2.6). We did not observe an association between cumulative asbestos exposure and ECC.ConclusionsOur study provides evidence that exposure to asbestos might be a risk factor for ICC. Our findings also suggest that the association between ECC and asbestos is null or weaker than that observed for ICC. Further studies based on large industrial cohorts of asbestos workers and possibly accounting for personal characteristics and clinical history are needed.
|
|
| 8. |
|
|
| 9. |
|
|
| 10. |
|
|
| 11. |
|
|
| 12. |
- Hadkhale, K, et al.
(författare)
-
Occupational variation in incidence of bladder cancer: a comparison of population-representative cohorts from Nordic countries and Canada
- 2017
-
Ingår i: BMJ open. - : BMJ. - 2044-6055. ; 7:8, s. e016538-
-
Tidskriftsartikel (refereegranskat)abstract
- The objective of this study was to compare occupational variation of the risk of bladder cancer in the Nordic countries and Canada.MethodsIn the Nordic Occupational Cancer study (NOCCA), 73 653 bladder cancer cases were observed during follow-up of 141.6 million person-years. In the Canadian Census Health and Environment Cohort (CanCHEC), 8170 cases were observed during the follow-up of 36.7 million person-years. Standardised incidence ratios with 95% CI were estimated for 53 occupations in the NOCCA cohort and HR with 95% CIs were estimated for 42 occupations in the CanCHEC.ResultsElevated risks of bladder cancer were observed among hairdressers, printers, sales workers, plumbers, painters, miners and laundry workers. Teachers and agricultural workers had reduced risk of bladder cancer in both cohorts. Chimney-sweeps, tobacco workers and waiters had about 1.5-fold risk in the Nordic countries; no risk estimates for these categories were given from the CanCHEC cohort.ConclusionWe observed different occupational patterns in risk of bladder cancer in Nordic countries and Canada. The only occupation with similarly increased risk was observed among sales workers. Differences in smoking across occupational groups may explain some, but not all, of this variation.
|
|
| 13. |
- Reijula, J, et al.
(författare)
-
Cancer incidence among waiters: 45 years of follow-up in five Nordic countries
- 2015
-
Ingår i: Scandinavian journal of public health. - : SAGE Publications. - 1651-1905 .- 1403-4948. ; 43:2, s. 204-211
-
Tidskriftsartikel (refereegranskat)abstract
- Aims: To study cancer risk patterns among waiters in the Nordic countries. Methods: We identified a cohort of 16,134 male and 81,838 female waiters from Denmark, Finland, Iceland, Norway and Sweden. During the follow-up period from 1961 to 2005, we found that 19,388 incident cancer cases were diagnosed. Standardised incidence ratio (SIR) was defined as the observed number of cancer cases divided by the expected number, based on national age, time period and gender-specific cancer incidence rates in the general population. Results: The SIR of all cancers in waiters, in the five countries combined, was 1.46 (95% CI 1.41–1.51) in men and 1.09 (1.07–1.11) in women. In male waiters, the SIR decreased from 1.79 (1.63–1.96) in 1961–1975, to 1.33 (1.26–1.40) in 1991–2005, but remained stable among women. The SIR among male waiters was highest for cancers in the pharynx (6.11; 95% CI 5.02–7.37), oral cavity (4.91; 95% CI 3.81–6.24) and tongue (4.36; 95% CI 3.13–5.92); and in female waiters, in the larynx (2.17; 95% CI 1.63–2.82), oral cavity (1.96; 95% CI 1.60–2.34) and lung (1.89; 95% CI 1.80–1.99). Conclusions: The risk of cancer among waiters was higher than in the general population. The elevated incidence in some cancer sites can likely be explained by higher alcohol consumption, the prevalence of smoking and occupational exposure to tobacco smoke. Hopefully, the incidence of cancer among waiters will decrease in the future, due to the banning of tobacco smoking in restaurants and bars in the Nordic countries.
|
|
| 14. |
- Sirevåg, K, et al.
(författare)
-
Physical EXercise Augmented COGnitive Behaviour Therapy for Older Adults with Generalised Anxiety Disorder (PEXACOG)
- 2018
-
Konferensbidrag (refereegranskat)abstract
- Generalised anxiety disorder (GAD) is the most prevalent severe anxiety disorder among older adults. The disorder has a pervasive influence on the lives of those affected, and is a risk factor for other severe disorders such as depression, dementia and coronary heart disease. Cognitive behaviour therapy (CBT) is the treatment of choice for this disorder, but older adults have shown reduced effect of treatment compared to working age adults. Physical exercise has been suggested as intervention to improve the effects of treatment for GAD, via its demonstrated positive effect on cognitive functioning, increased plasticity in the brain, and increased availability of neurotrophins important for extinction of fear associations. The aim of the current research project is to investigate whether augmenting CBT with physical exercise will lead to improved effects of CBT on GAD in older adults in a randomized controlled trial (RCT). Participants between 60-75 years of age with a primary diagnosis of GAD will be randomised to one of two treatment conditions. The effects of treatment will be assessed on outcome measures, biological, physiological and cognitive measures at pre- interim-, and post-treatment, and follow-up assessments at 6- and 12-months post intervention. Participants in both groups will receive five weeks of pre-treatment intervention consisting of either physical exercise or weekly telephone contact. Participants thereafter receive either ten weeks of manualised CBT for GAD combined with manualised physical exercise or ten weeks of manualised CBT for GAD combined with weekly telephone contact. We expect that the treatment effect of the physical exercise augmented CBT will be greater than that of CBT combined with weekly telephone contact, as measured by a reduction in GAD symptoms on the Penn State Worry Questionnaire and in the proportion of remitted patients. The study also aims to determining the possible beneficial and augmenting properties of physical exercise in combination with CBT, and our understanding of clinical characteristics of GAD and mechanisms involved in treatment effect. Treatment rationale, procedures and protocols will be presented in detail together with preliminary results from the initial feasibility study comprises eight participants
|
|
| 15. |
|
|
| 16. |
- Sirivåg, K, et al.
(författare)
-
Physical exercise augmented cognitive behaviour therapy for older adults with generalised anxiety disorder (PEXACOG) : Study protocol and feasibility results from a randomised controlled trial
- 2018
-
Konferensbidrag (refereegranskat)abstract
- Background. Generalised anxiety disorder (GAD) is prevalent among older adults. These patients exhibit impaired response to cognitive behaviour therapy (CBT), and physical exercise has been recommended as a potential add-on intervention to improve efficacy. The current study is a randomised clinical trial that will compare CBT augmented with physical exercise, or CBT combined with attention placebo, and the current study assessing the feasibility of testing procedures and the experimental combined treatment measures.Methods. 4 participants were included in the feasibility study, and feasibility was assessed trough completion and attendance rates of testing and treatment sessions. Primary outcome measures were remission as assessed by an independent clinical rater using the Anxiety Disorders Interview Schedule for DSM-IV, and by symptom reduction on Penn State Worry Questionnaire. Manipulation check was assessed by physical tests of change in aerobic capacity and strength. Participants were measured on clinical, biological, physiological and neuropsychological tests at pre-, interim and post-treatment.Results. Completed treatment protocol for the RCT will be presented. 3 of 4 participants completed the full protocol including testing and the experimental augmented treatment. Participants completed 100% and 80% of CBT and physical exercise content, respectively. The three completers had large improvements on primary outcome and on manipulation checks.Conclusion. The testing procedures and experimental augmented treatment appear to be feasible. The preliminary findings indicate that this combined intervention can be efficacious.
|
|
| 17. |
- Sirivåg, K, et al.
(författare)
-
Physical EXercise Augmented COGnitive Behaviour Therapy for Older Adults with Generalised Anxiety Disorder (PEXACOG)
- 2016
-
Konferensbidrag (refereegranskat)abstract
- Generalised anxiety disorder (GAD) is the most prevalent severe anxiety disorder among older adults. The disorder has a pervasive influence on the lives of those affected, and is a risk factor for other severe disorders such as depression, dementia and coronary heart disease. Cognitive behaviour therapy (CBT) is the treatment of choice for this disorder, but older adults have shown reduced effect of treatment compared to working age adults. Physical exercise has been suggested as intervention to improve the effects of treatment for GAD, via its demonstrated positive effect on cognitive functioning, increased plasticity in the brain, and increased availability of neurotrophins important for extinction of fear associations. The aim of the current research project is to investigate whether augmenting CBT with physical exercise will lead to improved effects of CBT on GAD in older adults in a randomized controlled trial (RCT). Participants between 60-75 years of age with a primary diagnosis of GAD will be randomised to one of two treatment conditions. The effects of treatment will be assessed on outcome measures, biological, physiological and cognitive measures at pre- interim-, and post-treatment, and follow-up assessments at 6- and 12-months post intervention. Participants in both groups will receive five weeks of pre-treatment intervention consisting of either physical exercise or weekly telephone contact. Participants thereafter receive either ten weeks of manualised CBT for GAD combined with manualised physical exercise or ten weeks of manualised CBT for GAD combined with weekly telephone contact. We expect that the treatment effect of the physical exercise augmented CBT will be greater than that of CBT combined with weekly telephone contact, as measured by a reduction in GAD symptoms on the Penn State Worry Questionnaire and in the proportion of remitted patients. The study also aims to determining the possible beneficial and augmenting properties of physical exercise in combination with CBT, and our understanding of clinical characteristics of GAD and mechanisms involved in treatment effect. Treatment rationale, procedures and protocols will be presented in detail together with preliminary results from the initial feasibility study comprises eight participants.
|
|
| 18. |
- Spokes, L., et al.
(författare)
-
MEAD: An interdisciplinary study of the marine effects of atmospheric deposition in the Kattegat
- 2006
-
Ingår i: Environmental Pollution. - : Elsevier BV. - 0269-7491. ; 140:3, s. 453-462
-
Tidskriftsartikel (refereegranskat)abstract
- This paper summarises the results of the EU funded MEAD project, an interdisciplinary study of the effects of atmospheric nitrogen deposition on the Kattegat Sea between Denmark and Sweden. The study considers emissions of reactive nitrogen gases, their transport, transformations, deposition and effects on algal growth together with management options to reduce these effects. We conclude that atmospheric deposition is an important source of fixed nitrogen to the region particularly in summer, when nitrogen is the limiting nutrient for phytoplankton growth, and contributes to the overall eutrophication pressures in this region. However, we also conclude that it is unlikely that atmospheric deposition can, on its own, induce algal blooms in this region. A reduction of atmospheric nitrogen loads to this region will require strategies to reduce emissions of ammonia from local agriculture and Europe wide reductions in nitrous oxide emissions. (c) 2005 Elsevier Ltd. All rights reserved.
|
|
| 19. |
|
|
| 20. |
|
|
| 21. |
|
|
| 22. |
|
|
| 23. |
|
|
| 24. |
|
|
| 25. |
- Bratland-Sanda, S., et al.
(författare)
-
Physical activity in treatment units for eating disorders : Clinical practice and attitudes
- 2009
-
Ingår i: Eating and Weight Disorders. - 1124-4909 .- 1590-1262. ; 14:2-3, s. E106-E112
-
Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: Physical activity (PA) in eating disorders (ED) may be harmful, but in a therapeutic setting also beneficial. The purpose of this survey was to examine these contradictory aspects of PA in ED specialist treatment settings. We examined whether 1) PA is assessed by the unit, 2) the units have guidelines for managing excessive PA, 3) the units have staff with higher education and special competence in PA and exercise science, 4) how units regard PA in ED, 5) whether regular PA is integrated in the treatment programs, and 6) how the units rate the role of PA in the treatment of ED compared with other mental disorders. METHODS: Of the 49 units located in Scandinavia and the United Kingdom, 41 (84%) responded to a questionnaire. RESULTS: In 28 units (68%) PA was assessed regularly. Excessive PA was considered a harmful symptom in ED, and most units reported guidelines to manage excessive PA. Thirty-two units included PA in their treatment programmes. Clinicians found PA most relevant in the treatment of obesity and, except for binge eating, less for ED. CONCLUSION: PA was more commonly integrated in treatment compared to previous studies. Future research should address how to manage excessive PA, and the potential beneficial role of PA in the treatment of ED. (Eating Weight Disord. 14: e106-e112, 2009). (C) 2009, Editrice Kurtis
|
|
| 26. |
|
|
| 27. |
|
|
| 28. |
- Cunha, André B., et al.
(författare)
-
Development of a Smart Wireless Multisensor Platform for an Optogenetic Brain Implant
- 2024
-
Ingår i: Sensors. - 1424-8220. ; 24:2
-
Tidskriftsartikel (refereegranskat)abstract
- Implantable cell replacement therapies promise to completely restore the function of neural structures, possibly changing how we currently perceive the onset of neurodegenerative diseases. One of the major clinical hurdles for the routine implementation of stem cell therapies is poor cell retention and survival, demanding the need to better understand these mechanisms while providing precise and scalable approaches to monitor these cell-based therapies in both pre-clinical and clinical scenarios. This poses significant multidisciplinary challenges regarding planning, defining the methodology and requirements, prototyping and different stages of testing. Aiming toward an optogenetic neural stem cell implant controlled by a smart wireless electronic frontend, we show how an iterative development methodology coupled with a modular design philosophy can mitigate some of these challenges. In this study, we present a miniaturized, wireless-controlled, modular multisensor platform with fully interfaced electronics featuring three different modules: an impedance analyzer, a potentiostat and an optical stimulator. We show the application of the platform for electrical impedance spectroscopy-based cell monitoring, optical stimulation to induce dopamine release from optogenetically modified neurons and a potentiostat for cyclic voltammetry and amperometric detection of dopamine release. The multisensor platform is designed to be used as an opto-electric headstage for future in vivo animal experiments.
|
|
| 29. |
|
|
| 30. |
|
|
| 31. |
|
|
| 32. |
- Håkansson, H., et al.
(författare)
-
In vivo and in vitro toxicity of fractionated fish lipids, with particular regard to their content of chlorinated organic compounds
- 1991
-
Ingår i: Pharmacology and Toxicology. - : Wiley. - 0901-9928 .- 1600-0773. ; 69:6, s. 459-471
-
Tidskriftsartikel (refereegranskat)abstract
- Six different lipid matrices (the intact lipid (IL), four lipid fractions with different polarity, and the free fatty acids (FFAs) obtained by hydrolysis of the triacylglycerol (TAG) containing fraction) were obtained from salmon (Salmo salar) and eel (Anguilla anguilla), each collected at a contaminated and a comparatively uncontaminated catch site along the coast of Scandinavia. The lipid matrices were studied in toxicological test systems representing various biological functions of different organ systems from several species and trophic levels. The results were evaluated with particular respect to the concentrations of extractable organically bound chlorine (EOCl) in the matrices tested. In some test systems, the specimens with a higher EOCl concentration appeared to be more toxic. For example, the TAG containing fraction (F2) from Idefjord eel, having a higher EOCl content than F2 from Oslofjord eel, reduced the number and hatchability of eggs laid by zebrafish. Both IL and F2 of Idefjord eel increased mortality and reduced the oxygen/nitrogen-ratio in blue mussels. Non-polar compounds (F1) from Bothnian Sea salmon induced 7-ethoxyresurofin O-deethylase (EROD) activity in rainbow trout hepatocytes, whereas F1 from Senja salmon did not. F1 from Bothnian Sea salmon also reduced the number of T-cells in foetal mouse thymus anlagen in vitro compared with the cell number in anlagen exposed to F1 from Senja salmon. A positive correlation between EOCl concentration and test response was found for EROD activity in rainbow trout hepatocytes and for ATP-leakage in Erlich ascites tumour cells when testing the phospolipid containing fraction (F4). However, in most test systems the fish oils, irrespective of EOCl content, were of low toxicity, and the observed effects need to be verified in future studies.
|
|
| 33. |
|
|
| 34. |
- Jorgensen, E. H., et al.
(författare)
-
Long-term fasting in the anadromous Arctic charr is associated with downregulation of metabolic enzyme activity and upregulation of leptin A1 and SOCS expression in the liver
- 2013
-
Ingår i: Journal of Experimental Biology. - : The Company of Biologists. - 0022-0949 .- 1477-9145. ; 216:17, s. 3222-3230
-
Tidskriftsartikel (refereegranskat)abstract
- The life strategy of the anadromous Arctic charr (Salvelinus alpinus) includes several months of voluntary fasting during overwintering in freshwater, leading to emaciation prior to seawater migration in spring. In this study we compared changes in condition, substrate utilization and liver metabolism between captive anadromous charr subjected to food deprivation during late winter and spring, and conspecifics fed in excess. In March, nine out of the 10 sampled fed fish had not eaten, indicating that they were in a voluntary anorexic state. In June, the fed fish were eating and all had higher body mass, condition factor and adiposity than in March. In fasted fish there were only small decreases in body mass, condition factor and adiposity between March and May, but all these parameters decreased markedly from May to June. The fasted fish were depleted in fat and glycogen in June, had suppressed activity of hepatic enzymes involved in lipid metabolism (G6PDH and HOAD) and seemed to rely on protein-derived glucose as a major energy source. This was associated with upregulated liver gene expression of leptin A1, leptin A2, SOCS1, SOCS2 and SOCS3, and reduced IGF-I expression. In an in vitro study with liver slices it was shown that recombinant rainbow trout leptin stimulated SOCS1 and SOCS3 expression, but not SOCS2, IGF-I or genes of enzymes involved in lipid (G6PDH) and amino acid (AspAT) metabolism. It is concluded that liver leptin interacts with SOCS in a paracrine fashion to suppress lipolytic pathways and depress metabolism when fat stores are depleted.
|
|
| 35. |
|
|
| 36. |
|
|
| 37. |
- Kjaerheim, K, et al.
(författare)
-
Variation in Nordic Work-Related Cancer Risks after Adjustment for Alcohol and Tobacco
- 2018
-
Ingår i: International journal of environmental research and public health. - : MDPI AG. - 1660-4601. ; 15:12
-
Tidskriftsartikel (refereegranskat)abstract
- Background: Alcohol and tobacco strongly increases the risk of cancers of the tongue, mouth, pharynx, larynx, and oesophagus, and are also established risk factors for cancer of the liver, colon, and rectum. It is well documented that these habits are unequally distributed among occupational groups. Most occupational cohort studies lack information on these potentially important confounders, and may therefore be prone to bias. Aim: The aim of the study is to present Nordic standardized incidence ratios (SIRs) for alcohol and tobacco related cancer by occupation, after adjustment for alcohol and tobacco, and to compare to the unadjusted SIRs. Material and Methods: The study is based on the Nordic Occupational Cancer (NOCCA) database. We used confirmatory factor analysis models for simultaneous analysis of the cancer sites related to alcohol and tobacco, to obtain factors that allow for computation of adjusted expected numbers from the reference rates. We then calculated adjusted SIRs for the relevant cancer sites for each occupation. Results: For some occupations and cancers, the changes of risk estimates were striking, from significantly high to significantly low and vice versa. Among Nordic farmers, unadjusted SIRs for cancer of the mouth and oesophagus were 0.56 (95% confidence interval (CI) 0.51–0.61) and 0.67 (CI 0.63–0.70), respectively. After adjustment, estimates changed to 1.10 (CI 1.01–1.21) and 1.16 (CI 1.10–1.22). Unadjusted SIR for pharynx cancer among wood workers was 0.83 (CI 0.75–0.91), adjusted SIR was 1.14 (CI 1.03–1.25). For larynx cancer, results in the opposite direction were seen: unadjusted SIR for economically inactive was 1.38 (CI 1.31–1.46) while the adjusted SIR was 0.91 (CI 0.86–0.96). Conclusions: Adjustment for the latent indicators of alcohol and tobacco consumption changed risk estimates for several occupations, gave a less confounded description of risk, and may guide in the identification of true risk factors.
|
|
| 38. |
- Kosek, Eva, et al.
(författare)
-
The translocator protein gene is associated with symptom severity and cerebral pain processing in fibromyalgia
- 2016
-
Ingår i: Brain Behavior and Immunity. - : Elsevier BV. - 0889-1591 .- 1090-2139. ; 58, s. 218-227
-
Tidskriftsartikel (refereegranskat)abstract
- The translocator protein (TSPO) is upregulated during glia activation in chronic pain patients. TSPO constitutes the rate-limiting step in neurosteroid synthesis, thus modulating synaptic transmission. Related serotonergic mechanisms influence if pro- or anti-nociceptive neurosteroids are produced. This study investigated the effects of a functional genetic polymorphism regulating the binding affinity to the TSPO, thus affecting symptom severity and cerebral pain processing in fibromyalgia patients. Gene-to-gene interactions with a functional polymorphism of the serotonin transporter gene were assessed. Fibromyalgia patients (n = 126) were genotyped regarding the polymorphisms of the TSPO (rs6971) and the serotonin transporter (5-HTTLPR/rs25531). Functional magnetic resonance imaging (n = 24) was used to study brain activation during individually calibrated pressure pain. Compared to mixed/low TSPO affinity binders, the high TSPO affinity binders rated more severe pain (p = 0.016) and fibromyalgia symptoms (p = 0.02). A significant interaction was found between the TSPO and the serotonin transporter polymorphisms regarding pain severity (p < 0.0001). Functional connectivity analyses revealed that the TSPO high affinity binding group had more pronounced pain-evoked functional connectivity in the right frontoparietal network, between the dorsolateral prefrontal area and the parietal cortex. In conclusion, fibromyalgia patients with the TSPO high affinity binding genotype reported a higher pain intensity and more severe fibromyalgia symptoms compared to mixed/low affinity binders, and this was modulated by interaction with the serotonin transporter gene. To our knowledge this is the first evidence of functional genetic polymorphisms affecting pain severity in FM and our findings are in line with proposed glia-related mechanisms. Furthermore, the functional magnetic resonance findings indicated an effect of translocator protein on the affective-motivational components of pain perception.
|
|
| 39. |
- Martinsen, Randi, et al.
(författare)
-
Self-reported competence among advanced practice nursing students in Denmark, Finland and Norway : a cross-sectional multicentre study
- 2024
-
Ingår i: BMC Nursing. - : BioMed Central (BMC). - 1472-6955. ; 23:1
-
Tidskriftsartikel (refereegranskat)abstract
- BackgroundThe health care systems in the Nordic countries and worldwide are under pressure due to increased longevity and a shortage of nurses. Providing nurses with a high level of education, such as advanced practice nursing, is of great importance to ensure effective, safe and high-quality care.AimThe aim of this study was to investigate self-reported competence using the Nurse Professional Competence Scale Short-Form for the first time among master’s students of advanced practice nursing in the Nordic countries and to relate the findings to age, work obligations, child-rearing responsibilities, level of education and clinical nursing experience.MethodsA multicentre, cross-sectional design was used in this study conducted at five universities in Denmark, Finland and Norway. The Nurse Professional Competence Scale Short-Form consisting of six competence areas was used with a maximum score of 7 per item for the analysis of single items and a transformed scale from 14.3 to 100 for analysing the competence areas (higher score equals higher self-reported competence). Descriptive and comparative statistics were used to analyse the data.ResultsThe highest mean score was found for the competence area ‘Value-based nursing care’. Students living with home-dwelling children (≤ 18 years) reported significantly higher competence in ‘Nursing care’, while students ≥33 years reported significantly higher competence in ‘Nursing care’ and ‘Value-based nursing care’. No significant differences were found between students working and those not working alongside their studies, between students with and without further nursing-related education, or between students with long and short experience as nurses.ConclusionsThe findings from this study might help to further develop curricula in advanced practice nursing master’s programmes to ensure high-quality nursing and sustainable health care in the future. Future high-quality master’s programmes might benefit from systematic collaboration between Nordic higher education institutions as also Sweden is planning master’s programme. Higher age, having children at home and working while studying should not be considered causes for concern.
|
|
| 40. |
|
|
| 41. |
|
|
| 42. |
|
|
| 43. |
|
|
| 44. |
|
|
| 45. |
|
|
| 46. |
|
|
| 47. |
|
|
| 48. |
|
|
| 49. |
|
|
| 50. |
- Sandström, A, et al.
(författare)
-
Altered cerebral pain processing of noxious stimuli from inflamed joints in rheumatoid arthritis : An event-related fMRI study.
- 2019
-
Ingår i: Brain, behavior, and immunity. - : Elsevier BV. - 0889-1591 .- 1090-2139. ; 81, s. 272-279
-
Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: To our knowledge, this is the first study assessing brain activation in response to painful stimulation over disease-relevant (finger joint) vs. neutral area (thumb nail) in patients suffering from rheumatoid arthritis (RA) compared to healthy controls (HC).METHOD: Thirty-one RA patients and 23 HC underwent functional magnetic resonance imaging (fMRI) while stimulated with subjectively calibrated painful pressures corresponding to a pain sensation of 50 mm on a 100 mm VAS scale (P50) at disease-affected finger joint and thumbnail (left hand), and corresponding sites in HC.RESULTS: Compared to controls, RA patients had significantly increased pain sensitivity (lower P50) at the inflamed joints but not at the thumbnail. RA patients exhibited significantly less activation in regions related to pain- and somatosensory processing (S1, M1, anterior insula, S2, SMG and MCC) during painful joint stimulation, compared to HC. No group difference in cerebral pain processing was found for the non-affected thumbnail. Within RA patients, significantly less brain activation was found in response to painful stimulation over disease-affected joint compared to non-affected thumbnail in bilateral S1, bilateral S2, and anterior insula. Further, RA patients exhibited a right-sided dlPFC deactivation, psycho-physiologically interacting (PPI) with the left dlPFC in response to painful stimulation at disease-affected joints.CONCLUSION: The results indicate normal pain sensitivity and cerebral pain processing in RA for non-affected sites, while the increased sensitivity at inflamed joints indicate peripheral/spinal sensitization. Brain imaging data suggest that disease-relevant pain processing in RA is marked by aberrations and a failed initiation of cortical top-down regulation.
|
|
