| 1. |
- Falk Erhag, Hanna, et al.
(författare)
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A Multidisciplinary Approach to Capability in Age and Ageing
- 2022
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Bok (övrigt vetenskapligt/konstnärligt)abstract
- This open access book provides insight on how to interpret capability in ageing – one’s individual ability to perform actions in order to reach goals one has reason to value – from a multidisciplinary approach. With for the first time in history there being more people in the world aged 60 years and over than there are children below the age of 5, the book describes this demographic trends as well as the large global challenges and important societal implications this will have such as a worldwide increase in the number of persons affected with dementia, and in the ratio of retired persons to those still in the labor market. Through contributions from many different research areas, it discussed how capability depends on interactions between the individual (e.g. health, genetics, personality, intellectual capacity), environment (e.g. family, friends, home, work place), and society (e.g. political decisions, ageism, historical period). The final chapter by the editors summarizes the differences and similarities in these contributions. As such this book provides an interesting read for students, teachers and researchers at different levels and from different fields interested in capability and multidisciplinary research.
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| 2. |
- Bauzá-Thorbrügge, Marco, et al.
(författare)
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NRF2 is essential for adaptative browning of white adipocytes.
- 2023
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Ingår i: Redox biology. - : Elsevier. - 2213-2317. ; 68
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Tidskriftsartikel (refereegranskat)abstract
- White adipose tissue browning, defined by accelerated mitochondrial metabolism and biogenesis, is considered a promising mean to treat or prevent obesity-associated metabolic disturbances. We hypothesize that redox stress acutely leads to increased production of reactive oxygen species (ROS), which activate electrophile sensor nuclear factor erythroid 2-Related Factor 2 (NRF2) that over time results in an adaptive adipose tissue browning process. To test this, we have exploited adipocyte-specific NRF2 knockout mice and cultured adipocytes and analyzed time- and dose-dependent effect of NAC and lactate treatment on antioxidant expression and browning-like processes. We found that short-term antioxidant treatment with N-acetylcysteine (NAC) induced reductive stress as evident from increased intracellular NADH levels, increased ROS-production, reduced oxygen consumption rate (OCR), and increased NRF2 levels in white adipocytes. In contrast, and in line with our hypothesis, longer-term NAC treatment led to a NRF2-dependent browning response. Lactate treatment elicited similar effects as NAC, and mechanistically, these NRF2-dependent adipocyte browning responses in vitro were mediated by increased heme oxygenase-1 (HMOX1) activity. Moreover, this NRF2-HMOX1 axis was also important for β3-adrenergic receptor activation-induced adipose tissue browning in vivo. In conclusion, our findings show that administration of exogenous antioxidants can affect biological function not solely through ROS neutralization, but also through reductive stress. We also demonstrate that NRF2 is essential for white adipose tissue browning processes.
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| 3. |
- Molinaro, Angela, et al.
(författare)
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Insulin-Driven PI3K-AKT Signaling in the Hepatocyte Is Mediated by Redundant PI3Kα and PI3Kβ Activities and Is Promoted by RAS.
- 2019
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Ingår i: Cell Metabolism. - : Elsevier BV. - 1550-4131 .- 1932-7420. ; 29:6, s. 1400-
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Tidskriftsartikel (refereegranskat)abstract
- Phosphatidylinositol-3-kinase (PI3K) activity is aberrant in tumors, and PI3K inhibitors are investigated as cancer therapeutics. PI3K signaling mediates insulin action in metabolism, but the role of PI3K isoforms in insulin signaling remains unresolved. Defining the role of PI3K isoforms in insulin signaling is necessary for a mechanistic understanding of insulin action and to develop PI3K inhibitors with optimal therapeutic index. We show that insulin-driven PI3K-AKT signaling depends on redundant PI3Kα and PI3Kβ activities, whereas PI3Kδ and PI3Kγ are largely dispensable. We have also found that RAS activity promotes AKT phosphorylation in insulin-stimulated hepatocytes and that promotion of insulin-driven AKT phosphorylation by RAS depends on PI3Kα. These findings reveal the detailed mechanism by which insulin activates AKT, providing an improved mechanistic understanding of insulin signaling. This improved model for insulin signaling predicts that isoform-selective PI3K inhibitors discriminating between PI3Kα and PI3Kβ should be dosed below their hyperglycemic threshold to achieve isoform selectivity.
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| 4. |
- Andersson, Christin, et al.
(författare)
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Increasing CSF phospho-tau levels during cognitive decline and progression to dementia
- 2008
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Ingår i: Neurobiology of Aging. - : Elsevier BV. - 0197-4580 .- 1558-1497. ; 29:10, s. 1466-1473
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Little is known about longitudinal changes of cerebrospinal fluid (CSF) biomarkers during cognitive decline in neurodegenerative disease progression. OBJECTIVE: To investigate longitudinal changes in CSF biomarkers--total-tau (T-tau), phospho-tau (P-tau) and beta-amyloid (Abeta42)--during cognitive decline. METHODS: Forty memory clinic patients (47.5% females), aged 61.3+/-7.6 (S.D.) years, non-demented at baseline, underwent lumbar puncture and neuropsychological testing at two occasions. Baseline mean MMSE-score was 28.3+/-1.8. Patients were divided into three groups based on baseline memory functioning; severely impaired (SIM), moderately impaired (MIM) and no impairment (NIM). RESULTS: There was a significant increase in P-tau in the SIM-group during follow-up, while P-tau in MIM and NIM did not change. Eighty-three percent of the SIM-patients converted to dementia (80% AD), while most MIM- and NIM-patients remained non-demented. T-tau- and Abeta42-levels did not change in any of the memory groups during follow-up. CONCLUSION: Increasing P-tau levels during cognitive decline and conversion to dementia suggest that P-tau may be useful as a longitudinal marker of the neurodegenerative process.
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| 5. |
- Crommert, Martin Eriksson, 1974-, et al.
(författare)
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Trunk muscle activation at the initiation and braking of bilateral shoulder flexion movements of different amplitudes
- 2015
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Ingår i: PLOS ONE. - : PUBLIC LIBRARY SCIENCE. - 1932-6203. ; 10:11
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Tidskriftsartikel (refereegranskat)abstract
- The aim of this study was to investigate if trunk muscle activation patterns during rapid bilateral shoulder flexions are affected by movement amplitude. Eleven healthy males performed shoulder flexion movements starting from a position with arms along sides (0°) to either 45°, 90° or 180°. EMG was measured bilaterally from transversus abdominis (TrA), obliquus internus (OI) with intra-muscular electrodes, and from rectus abdominis (RA), erector spinae (ES) and deltoideus with surface electrodes. 3D kinematics was recorded and inverse dynamics was used to calculate the reactive linear forces and torque about the shoulders and the linear and angular impulses. The sequencing of trunk muscle onsets at the initiation of arm movements was the same across movement amplitudes with ES as the first muscle activated, followed by TrA, RA and OI. All arm movements induced a flexion angular impulse about the shoulders during acceleration that was reversed during deceleration. Increased movement amplitude led to shortened onset latencies of the abdominal muscles and increased level of activation in TrA and ES. The activation magnitude of TrA was similar in acceleration and deceleration where the other muscles were specific to acceleration or deceleration. The findings show that arm movements need to be standardized when used as a method to evaluate trunk muscle activation patterns and that inclusion of the deceleration of the arms in the analysis allow the study of the relationship between trunk muscle activation and direction of perturbing torque during one and the same arm movement.
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| 6. |
- Ruiz, Jonatan R., et al.
(författare)
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Homocysteine levels in children and adolescents are associated with the methylenetetrahydrofolate reductase 677C>T genotype, but not with physical activity, fitness or fatness : the European Youth Heart Study
- 2007
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Ingår i: British Journal of Nutrition. - Cambridge : Cambridge university press. - 0007-1145 .- 1475-2662. ; 97:2, s. 255-262
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Tidskriftsartikel (refereegranskat)abstract
- To examine the associations of total plasma homocysteine (tHcy) with physical activity, cardiorespiratory fitness and fatness in children and adolescents, a cross-sectional study of 301 children (9–10 years old) and 379 adolescents (15–16 years old) was conducted. Physical activity was measured by accelerometry. Cardiorespiratory fitness was measured with a maximal ergometer bike test. Body fat was derived from the sum of five skinfold thicknesses. Genotyping for the methylenetetrahydrofolate reductase (MTHFR) 677C>T polymorphism was done by DNA sequencing. Fasting tHcy level was the outcome variable. Multiple regressions were used to determine the degree to which variance in tHcy was explained by physical activity, cardiorespiratory fitness and body fat, after controlling for potential confounders including MTHFR 677C>T genotype. tHcy levels were neither associated with any measure of level and pattern of physical activity nor with data on cardiorespiratory fitness, or body fat, in any age group after controlling for potential confounders including MTHFR 677C>T and even when subgroups 677TT and 677CC+CT were analysed separately. Mean values of tHcy were significantly higher in the TT subgroup compared with CC and CT subgroups in children (TT 7·4 μmol/l, CC 6·3 μmol/l, CT 6·6 μmol/l, P < 0·001 and P = 0·019, respectively) and adolescents (TT 16·9 μmol/l, CC 8·3 μmol/l, CT 9·0 μmol/l, both P < 0·001). The results suggest that physical activity, fitness and body fat are not associated with tHcy levels in children and adolescents, even after controlling for presence of the MTHFR 677C>T genotype, the main influence on tHcy levels in these subjects.
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| 7. |
- Khoshnood, Ardavan
(författare)
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Prehospital Diagnosis and Oxygen Treatment in ST Elevation Myocardial Infarction
- 2017
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- IntroductionPaper I: An Artificial Neural Network (ANN) was constructed to identify ST Elevation Myocardial Infarction (STEMI) and predict the need for Percutaneous Coronary Intervention (PCI). Paper II, III and IV: Studies suggest that O2 therapy may be harmful in STEMI patients. We therefore conducted the SOCCER study to evaluate the effects of O2 therapy in STEMI patients.MethodsPaper I: 560 ambulance ECGs sent to the Cardiac Care Unit (CCU), was together with the CCU physicians interpretation and decision of conducting an acute PCI or not collected, and compared with the interpretation and PCI decision of the ANN. Paper II, III, IV: Normoxic (≥94%) STEMI patients accepted for acute PCI were in the ambulance randomized to standard care with 10 L/min O2 or room air. A subset of the patients underwent echocardiography for determination of the Left Ventricular Ejection Fraction (LVEF) and the Wall Motion Score Index (WMSI). All patients had a Cardiac Magnetic Resonance Imaging (CMRI) to evaluate Myocardial area at Risk (MaR), Infarct Size (IS) and Myocardial Salvage Index (MSI).ResultsPaper I: The area under the ANN’s receiver operating characteristics curve for STEMI detection as well as predicting the need of acute PCI were very good.Paper II, III, IV: No significant differences could be shown in discussing MaR, MSI or IS between the O2 group (n=46) and the air group (n=49). Neither could any differences be shown for LVEF and WMSI at the index visit as well after six months between the O2 group (n=46) and the air group (n=41)ConclusionsPaper I: The results indicate that the number of ECGs sent to the CCU could be reduced with 2/3 as the ANN would safely identify ECGs not being STEMI.Paper II, III, IV: The results suggest that it is safe to withhold O2 therapy in normoxic, stable STEMI patients.
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| 8. |
- Elcadi, Guilherme H., 1966-, et al.
(författare)
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Shoulder and forearm oxygenation and myoelectric activity in patients with work related muscle pain and healthy subjects
- 2013
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Ingår i: European Journal of Applied Physiology. - New York : Springer. - 1439-6319 .- 1439-6327. ; 113:5, s. 1103-1115
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Tidskriftsartikel (refereegranskat)abstract
- We tested hypotheses of (i) reduced oxygen usage, oxygen recovery, blood flow and oxygen consumption; and (ii) increased muscle activity for patients diagnosed with work related muscle pain in comparison to healthy controls. Oxygenation was measured with near infrared spectroscopy (NIRS), and muscle activity with EMG for the extensor carpi radialis (ECR) and trapezius descendens (TD) muscles. Eighteen patients with diffuse neck-shoulder-arm pain and seventeen controls (matched in age and sex) were equipped with NIRS and EMG probes. After determining an individual’s maximum voluntary contraction (MVC) force, short term (20 sec) isometric contractions for the ECR and TD of 10%, 30%, 50% and 70% MVC generated ∆StO2% and StO2% recovery (Rslope) from NIRS, and RMS%max from EMG signals. In addition, upper arm venous (VO) and arterial (AO) occlusions generated slopes of total hemoglobin (HbTslope) and deoxyhemoglobin (HHbslope) for the resting ECR as surrogates of blood flow and oxygen consumption, respectively. Mixed Model analyses, t-tests, and Mann-Whitney test were used to assess differences between groups. There was no significant difference in MVC between groups for either muscle. Also, ∆StO2%, Rslope for either muscle, and ECR-HbTslope were not different between groups, thus our hypotheses of reduced oxygen use, recovery, and blood flow for patients were not confirmed. However, patients had a significantly lower ECR-HHbslope confirming our hypothesis of reduced consumption. Further, there was no difference in RMS%max during contractions meaning that the hypothesis of increased activity for patients was not confirmed. When taking into account the number of NIRS variables studied, differences we found between our patient group and healthy controls (i.e. in forearm oxygen consumption and shoulder oxygen saturation level) may be considered modest. Overall our findings may have been impacted by the fact that our patients and controls were similar in muscle strength, which is in contrast to previous studies.
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| 9. |
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| 10. |
- Fransén, Karin, 1973-, et al.
(författare)
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CRP levels are significantly associated with CRP genotype and estrogen use in The Lifestyle, Biomarker and Atherosclerosis (LBA) study
- 2022
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Ingår i: BMC Cardiovascular Disorders. - : BioMed Central. - 1471-2261 .- 1471-2261. ; 22:1
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Tidskriftsartikel (refereegranskat)abstract
- Background: The C‑reactive protein (CRP) is an important biomarker for atherosclerosis and single nucleotide poly‑morphisms (SNPs) in the CRP locus have been associated with altered CRP levels and associated with risk for cardio‑vascular disease. However, the association between genetic variations in the CRP gene, estrogen use and CRP levels orearly signs of atherosclerosis in young healthy individuals is not fully characterized. We aimed to evaluate the influ‑ence of five genetic variants on both plasma CRP levels and carotid intima‑media thickness (cIMT) values, includingaspects on estrogen containing contraceptive use in females.Methods: Genotyping was performed with TaqMan real time PCR and compared with high sensitivity CRP serumlevels in 780 Swedish young, self‑reported healthy individuals. Haplotypes of the SNPs were estimated with the PHASEv 2.1. The cIMT was measured by 12 MHz ultrasound. The contraceptive use was self‑reported.Results: Strong associations between CRP and genotype were observed for rs3091244, rs1800947, rs1130864, andrs1205 in women (all p < 0.001). In men, only rs1800947 was associated with CRP (p = 0.029). The independent effectof genotypes on CRP remained significant also after adjustment for established risk factors. Female carriers of the H1/ATGTG haplotype had higher CRP than non‑carriers. This was specifically pronounced in the estrogen‑using group(p < 0.001), and they had also higher cIMT (p = 0.002) than non‑carriers but with a small cIMT difference between thehaplotype groups (0.02 mm). In parallel, a significant correlation between CRP and cIMT in the estrogen using groupwas observed (r = 0.194; p = 0.026).Conclusions: Estrogen use, genotypes and haplotypes in the CRP locus are significantly associated with CRP levels.Based on an observed interaction effect between sex/estrogen use and the H1/ATGTG haplotype on CRP, and amarginally thicker cIMT in the estrogen using group, our data suggest that both genotypes and estrogen usage couldbe involved in arterial wall structural differences. The causality between CRP levels and cIMT remains unclear, and theobserved difference in cIMT is not clinically relevant in the present state. Future larger and longitudinal studies mayshed further light on the role of more long‑term estrogen use and early atherosclerosis.
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