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| 2. |
- Jersin, R. A., et al.
(författare)
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Role of the Neutral Amino Acid Transporter SLC7A10 in Adipocyte Lipid Storage, Obesity, and Insulin Resistance
- 2021
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Ingår i: Diabetes. - : American Diabetes Association. - 0012-1797 .- 1939-327X. ; 70:3, s. 680-695
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Tidskriftsartikel (refereegranskat)abstract
- Elucidation of mechanisms that govern lipid storage, oxidative stress, and insulin resistance may lead to improved therapeutic options for type 2 diabetes and other obesity-related diseases. Here, we find that adipose expression of the small neutral amino acid transporter SLC7A10, also known as alanine-serine-cysteine transporter-1 (ASC-1), shows strong inverse correlates with visceral adiposity, insulin resistance, and adipocyte hypertrophy across multiple cohorts. Concordantly, loss of Slc7a10 function in zebrafish in vivo accelerates diet-induced body weight gain and adipocyte enlargement. Mechanistically, SLC7A10 inhibition in human and murine adipocytes decreases adipocyte serine uptake and total glutathione levels and promotes reactive oxygen species (ROS) generation. Conversely, SLC7A10 overexpression decreases ROS generation and increases mitochondrial respiratory capacity. RNA sequencing revealed consistent changes in gene expression between human adipocytes and zebrafish visceral adipose tissue following loss of SLC7A10, e.g., upregulation of SCD (lipid storage) and downregulation of CPT1A (lipid oxidation). Interestingly, ROS scavenger reduced lipid accumulation and attenuated the lipid-storing effect of SLC7A10 inhibition. These data uncover adipocyte SLC7A10 as a novel important regulator of adipocyte resilience to nutrient and oxidative stress, in part by enhancing glutathione levels and mitochondrial respiration, conducive to decreased ROS generation, lipid accumulation, adipocyte hypertrophy, insulin resistance, and type 2 diabetes.
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| 3. |
- Beiske, A G, et al.
(författare)
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Health-related quality of life in secondary progressive multiple sclerosis.
- 2007
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Ingår i: Multiple sclerosis (Houndmills, Basingstoke, England). - : SAGE Publications. - 1352-4585 .- 1477-0970. ; 13:3, s. 386-92
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Tidskriftsartikel (refereegranskat)abstract
- Common disability scales in multiple sclerosis (MS) are often weighted towards physical disability. Non-motor symptoms such as depression, fatigue and pain substantially influence wellbeing in MS. Health-related quality of life (HRQoL) measures the broader impact of MS and might indicate less obvious disease burdens. We analysed HRQoL, using the Nottingham Health Profile Part I (NHP-I), among 345 secondary progressive MS (SPMS) patients participating in a randomized trial of interferon-beta1a (IFN-beta1a), 22 mug subcutaneously weekly, or matching placebo. The results did not reveal any beneficial effect of IFN-beta1a in any outcome measure. NHP-I sub- and sum scores were compared for 217 population controls and correlated with demographic and clinical disease variables. SPMS patients had lower NHP-I sum and all subscores than the controls. Patients experiencing disease progression reported worse NHP-I sum scores. Increased fatigue, Expanded Disability Status Scale (EDSS) and Arm Index scores were independently associated with reduction in several NHP-I subscores. SPMS patients had significantly lower HRQoL than controls and physical disability (EDSS and Arm Index), disease progression and fatigue strongly influenced this. MS.
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| 4. |
- Beiske, A. G., et al.
(författare)
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Health-related quality of life in secondary progressive multiple sclerosis
- 2007
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Ingår i: Multiple Sclerosis Journal. - : SAGE Publications. - 1477-0970 .- 1352-4585. ; 13:3, s. 386-392
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Tidskriftsartikel (refereegranskat)abstract
- Common disability scales in multiple sclerosis (MS) are often weighted towards physical disability. Non-motor symptoms such as depression, fatigue and pain substantially influence wellbeing in MS. Health-related quality of life (HRQoL) measures the broader impact of MS and might indicate less obvious disease burdens. We analysed HRQoL, using the Nottingham Health Profile Part I (NHP-I), among 345 secondary progressive MS (SPMS) patients participating in a randomized trial of interferon-beta 1a (IFN-beta 1a), 22 mu g subcutaneously weekly, or matching placebo. The results did not reveal any beneficial effect of IFN-beta 1a in any outcome measure. NHP-I sub- and sum scores were compared for 217 population controls and correlated with demographic and clinical disease variables. SPMS patients had lower NHP-I sum and all subscores than the controls. Patients experiencing disease progression reported worse NHP-I sum scores. Increased fatigue, Expanded Disability Status Scale (EDSS) and Arm Index scores were independently associated with reduction in several NHP-I subscores. SPMS patients had significantly lower HRQoL than controls and physical disability (EDSS and Arm Index), disease progression and fatigue strongly influenced this. MS influenced subdimensions such as pain, sleep and emotional reactions. Increased focus on optimizing symptomatic treatment and psychosocial patient care could improve patients' HRQoL.
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| 6. |
- Andersen, Oluf, 1941, et al.
(författare)
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Multicentre, randomised, double blind, placebo controlled, phase III study of weekly, low dose, subcutaneous interferon beta-1a in secondary progressive multiple sclerosis
- 2004
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Ingår i: JOURNAL OF NEUROLOGY NEUROSURGERY AND PSYCHIATRY. - : BMJ. - 0022-3050 .- 1468-330X. ; 75:5, s. 706-710
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Tidskriftsartikel (refereegranskat)
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| 7. |
- Claussnitzer, M., et al.
(författare)
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FTO Obesity Variant Circuitry and Adipocyte Browning in Humans
- 2015
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Ingår i: New England Journal of Medicine. - 0028-4793. ; 373:10, s. 895-907
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND Genomewide association studies can be used to identify disease-relevant genomic regions, but interpretation of the data is challenging. The FTO region harbors the strongest genetic association with obesity, yet the mechanistic basis of this association remains elusive. We examined epigenomic data, allelic activity, motif conservation, regulator expression, and gene coexpression patterns, with the aim of dissecting the regulatory circuitry and mechanistic basis of the association between the FTO region and obesity. We validated our predictions with the use of directed perturbations in samples from patients and from mice and with endogenous CRISPR-Cas9 genome editing in samples from patients. Our data indicate that the FTO allele associated with obesity represses mitochondrial thermogenesis in adipocyte precursor cells in a tissue-autonomous manner. The rs1421085 T-to-C single-nucleotide variant disrupts a conserved motif for the ARID5B repressor, which leads to derepression of a potent preadipocyte enhancer and a doubling of IRX3 and IRX5 expression during early adipocyte differentiation. This results in a cell-autonomous developmental shift from energy-dissipating beige (brite) adipocytes to energy-storing white adipocytes, with a reduction in mitochondrial thermogenesis by a factor of 5, as well as an increase in lipid storage. Inhibition of Irx3 in adipose tissue in mice reduced body weight and increased energy dissipation without a change in physical activity or appetite. Knockdown of IRX3 or IRX5 in primary adipocytes from participants with the risk allele restored thermogenesis, increasing it by a factor of 7, and overexpression of these genes had the opposite effect in adipocytes from nonrisk-allele carriers. Repair of the ARID5B motif by CRISPR-Cas9 editing of rs1421085 in primary adipocytes from a patient with the risk allele restored IRX3 and IRX5 repression, activated browning expression programs, and restored thermogenesis, increasing it by a factor of 7. Our results point to a pathway for adipocyte thermogenesis regulation involving ARID5B, rs1421085, IRX3, and IRX5, which, when manipulated, had pronounced pro-obesity and anti-obesity effects. (Funded by the German Research Center for Environmental Health and others.)
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| 8. |
- Moseholm, E., et al.
(författare)
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Psychosocial health in pregnancy and postpartum among women living with-and without HIV and non-pregnant women living with HIV living in the Nordic countries - Results from a longitudinal survey study
- 2022
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Ingår i: Bmc Pregnancy and Childbirth. - : Springer Science and Business Media LLC. - 1471-2393. ; 22:1
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Tidskriftsartikel (refereegranskat)abstract
- Background The success of antiretroviral therapy has normalized pregnancy among women living with HIV (WWH) with a very low risk of perinatal transmission of HIV. Despite these advances, WWH still face complex medical and psychosocial issues during pregnancy and postpartum. The aim of this study was to assess differences in psychosocial health outcomes between pregnant WWH, non-pregnant WWH, and pregnant women without HIV, and further identify factors associated with probable depression in the third trimester and postpartum. Methods In a longitudinal survey study, participants were included from sites in Denmark, Finland, and Sweden during 2019-2020. Data was collected in the 3rd trimester, 3 and 6 months postpartum using standardized questionnaires assessing depression, perceived stress, loneliness, and social support. Mixed regression models were used to assess changes over time within and between groups. Logistic regression models were used to identify factors associated with depression in pregnancy and postpartum. Results A total of 47 pregnant WWH, 75 non-pregnant WWH, and 147 pregnant women without HIV were included. The prevalence of depression was high among both pregnant and non-pregnant WWH. There was no significant difference between pregnant and non-pregnant WWH in depression scores, perceived stress scores, or social support scores at any time point. Compared to pregnant women without HIV, pregnant WWH reported worse outcomes on all psychosocial scales. Social support and loneliness were associated with an increased odds of depressive symptoms in the adjusted analysis. Conclusions A high burden of adverse psychosocial outcomes was observed in both pregnant and non-pregnant women living with HIV compared to pregnant women without HIV. Loneliness and inadequate social support were associated with increased odds of depression in pregnancy and should be a focus in future support interventions.
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| 9. |
- Moseholm, E., et al.
(författare)
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The experience of pregnancy among women living with HIV in Nordic countries: A qualitative narrative enquiry
- 2022
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Ingår i: Womens Health. - : SAGE Publications. - 1745-5057 .- 1745-5065. ; 18
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Tidskriftsartikel (refereegranskat)abstract
- Objective: The success of antiretroviral therapy has resulted in the normalization of pregnancy among women living with HIV and a very low risk of perinatal transmission of HIV. Despite these advances, women living with HIV still face complex medical and psychosocial issues during pregnancy. The purpose of this study is to describe experiences of pregnancy and the relevance of social support among women living with HIV in Nordic countries. Methods: This qualitative study examined data from pregnant women living with HIV from sites in Denmark, Sweden and Finland from 2019 to 2020. Data were collected in the third trimester via individual interviews using a hybrid, narrative/semistructured format. The transcribed interviews were analyzed using narrative thematic analysis. Results: In total, 31 women living with HIV were enrolled, of whom 61% originated from an African country and 29% from a Nordic country. The analysis generated four primary narrative themes: just a normal pregnancy, unique considerations and concerns, interactions with healthcare, and social support. Women living with HIV have a strong desire to have normal pregnancies and to be treated like any other pregnant woman. However, this normality is fragile, and being pregnant and living with HIV does come with unique considerations and concerns, such as fear of transmission, antiretroviral therapy, and the need for specialized care, which are fundamental to the women's experiences. Interactions with healthcare providers and social support influence their experiences in both positive and negative ways. Conclusion: The findings emphasize a sense of normality in pregnancy among women living with HIV. However, pregnancy does come with unique considerations and concerns, which highly influence the women's experience of pregnancy. Healthcare providers should focus on person-centered care, ensuring continuity and that women living with HIV do not feel discriminated against throughout their pregnancy.
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| 10. |
- Nebuchennykh, M., et al.
(författare)
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Quantitative sensory testing in patients with polyneuropathy and healthy individuals
- 2008
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Ingår i: Acta Neurologica Scandinavica, Supplementum. - : Hindawi Limited. - 0065-1427 .- 1600-5449 .- 0001-6314 .- 1600-0404. ; 117:188, s. 56-61
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Tidskriftsartikel (refereegranskat)abstract
- AIMS Elderly individuals and patients with polyneuropathy often feel heat pain or burning sensation on quantitative sensory testing (QST) of warm perception distally in the lower limbs. We therefore studied heat pain threshold (HPT), warm perception threshold (WPT) and the difference between heat pain and warm perception thresholds in 48 patients with symptoms and signs of polyneuropathy matched according to age and gender with 48 healthy persons. METHODS QST (using method of limits) was performed on the distal calf and the dorsal foot. RESULTS Particularly in the neuropathy group several individuals (58%) had an unpleasant feeling, often burning, when the thresholds according to the WPT algorithm were recorded. Difference between heat pain and warm perception thresholds in the lower calf of the patients was 3.9 +/- 3.5 and 5.8 +/- 3.4 degrees C in the controls (P = 0.012), and on the foot 3.8 +/- 2.8 vs 5.3 +/- 3.6 degrees C (P = 0.02). CONCLUSIONS When performing QST it is important to assess also quality features of warm perception, such as burning and heat pain sensation.
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