| 1. |
- Brodkorb, A., et al.
(författare)
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INFOGEST static in vitro simulation of gastrointestinal food digestion
- 2019
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Ingår i: Nature Protocols. - : Springer Science and Business Media LLC. - 1754-2189 .- 1750-2799. ; 14:4, s. 991-1014
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Tidskriftsartikel (refereegranskat)abstract
- Developing a mechanistic understanding of the impact of food structure and composition on human health has increasingly involved simulating digestion in the upper gastrointestinal tract. These simulations have used a wide range of different conditions that often have very little physiological relevance, and this impedes the meaningful comparison of results. The standardized protocol presented here is based on an international consensus developed by the COST INFOGEST network. The method is designed to be used with standard laboratory equipment and requires limited experience to encourage a wide range of researchers to adopt it. It is a static digestion method that uses constant ratios of meal to digestive fluids and a constant pH for each step of digestion. This makes the method simple to use but not suitable for simulating digestion kinetics. Using this method, food samples are subjected to sequential oral, gastric and intestinal digestion while parameters such as electrolytes, enzymes, bile, dilution, pH and time of digestion are based on available physiological data. This amended and improved digestion method (INFOGEST 2.0) avoids challenges associated with the original method, such as the inclusion of the oral phase and the use of gastric lipase. The method can be used to assess the endpoints resulting from digestion of foods by analyzing the digestion products (e.g., peptides/amino acids, fatty acids, simple sugars) and evaluating the release of micronutrients from the food matrix. The whole protocol can be completed in ~7 d, including ~5 d required for the determination of enzyme activities.
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| 4. |
- Aaen, J., et al.
(författare)
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Clinical and MRI findings in lumbar spinal stenosis: baseline data from the NORDSTEN study
- 2022
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Ingår i: European Spine Journal. - : Springer Science and Business Media LLC. - 0940-6719 .- 1432-0932. ; 31:6, s. 1391-1398
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Tidskriftsartikel (refereegranskat)abstract
- Purpose The aim was to describe magnetic resonance imaging findings in patients planned for lumbar spinal stenosis surgery. Further, to describe possible associations between MRI findings and patient characteristics with patient reported disability or pain. Methods The NORDSTEN spinal stenosis trial included 437 patients planned for surgical decompression of LSS. The following MRI findings were evaluated before surgery: morphological (Schizas) and quantitative (cross-sectional area) grade of stenosis, disk degeneration (Pfirrmann), facet joint tropism and fatty infiltration of the multifidus muscle. Patients were dichotomized into a moderate or severe category for each radiological parameter classification. A multivariable linear regression analysis was performed to investigate the association between MRI findings and preoperative scores for Oswestry Disability Index, Zurich Claudication Questionnaire and Numeric rating scale for back and leg pain. The following patient characteristics were included in the analysis: gender, age, smoking and weight. Results The percentage of patients with severe scores was as follows: Schizas (C + D) 71.3%, cross-sectional area (< 75 mm(2)) 86.8%, Pfirrmann (4 + 5) 58.1%, tropism (>= 15 degrees) 11.9%, degeneration of multifidus muscle (2-4) 83.7%. Regression coefficients indicated minimal changes in severity of symptoms when comparing the groups with moderate and severe MRI findings. Only gender had a significant and clinically relevant association with ODI score. Conclusion In this cross-sectional study, the majority of the patients had MRI findings classified as severe LSS changes, but the findings had no clinically relevant association with patient reported disability and pain at baseline. Patient characteristics have a larger impact on disability and pain than radiological findings.
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| 5. |
- Aaen, J., et al.
(författare)
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Is the presence of foraminal stenosis associated with outcome in lumbar spinal stenosis patients treated with posterior microsurgical decompression
- 2023
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Ingår i: ACTA NEUROCHIRURGICA. - 0001-6268. ; 165, s. 2121-2129
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Tidskriftsartikel (refereegranskat)abstract
- Background We aim to investigate associations between preoperative radiological findings of lumbar foraminal stenosis with clinical outcomes after posterior microsurgical decompression in patients with predominantly central lumbar spinal stenosis (LSS). Methods The study was an additional analysis in the NORDSTEN Spinal Stenosis Trial. In total, 230 men and 207 women (mean age 66.8 ( SD 8.3)) were included. All patients underwent an MRI including T1- and T2-weighted sequences. Grade of foraminal stenosis was dichotomized into none to moderate (0-1) and severe (2-3) category using Lee's classification system. The Oswestry Disability Index (ODI), Zurich Claudication Questionnaire (ZCQ), and numeric rating scale (NRS) for back and leg pain were collected at baseline and at 2-year follow-up. Primary outcome was a reduction of 30% or more on the ODI score. Secondary outcomes included the mean improvement on the ODI, ZCQ, and NRS scores. We performed multivariable regression analyses with the radiological variates foraminal stenosis, Pfirrmann grade, Schizas score, dural sac cross-sectional area, and the possible plausible confounders: patients' gender, age, smoking status, and BMI. Results The cohort of 437 patients presented a high degree of degenerative changes at baseline. Of 414 patients with adequate imaging of potential foraminal stenosis, 402 were labeled in the none to moderate category and 12 in the severe category. Of the patients with none to moderate foraminal stenosis, 71% achieved at least 30% improvement in ODI. Among the patients with severe foraminal stenosis, 36% achieved at least 30% improvement in ODI. A significant association between severe foraminal stenosis and less chance of reaching the target of 30% improvement in the ODI score after surgery was detected: OR 0.22 (95% CI 0.06, 0.83), p=0.03. When investigating outcome as continuous variables, a similar association between severe foraminal stenosis and less improved ODI with a mean difference of 9.28 points (95%CI 0.47, 18.09; p=0.04) was found. Significant association between severe foraminal stenosis and less improved NRS pain in the lumbar region was also detected with a mean difference of 1.89 ( 95% CI 0.30, 3.49; p=0.02). No significant association was suggested between severe foraminal stenosis and ZCQ or NRS leg pain. Conclusion In patients operated with posterior microsurgical decompression for LSS, a preoperative severe lumbar foraminal stenosis was associated with higher proportion of patients with less than 30% improvement in ODI. Trial registration The study is registered at ClinicalTrials. gov (22.11.2013) under the identifier NCT02007083.
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| 6. |
- Aaen, J., et al.
(författare)
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The association between preoperative MRI findings and clinical improvement in patients included in the NORDSTEN spinal stenosis trial
- 2022
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Ingår i: European Spine Journal. - : Springer Science and Business Media LLC. - 0940-6719 .- 1432-0932. ; 31:10, s. 2777-2785
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Tidskriftsartikel (refereegranskat)abstract
- Purpose To investigate potential associations between preoperative MRI findings and patient reported outcome measures (PROMs) after surgery for lumbar spinal stenosis (LSS). Methods The NORDSTEN trial included 437 patients. We investigated the association between preoperative MRI findings such as morphological grade of stenosis (Schizas grade), quantitative grade of stenosis (dural sac cross-sectional area), disc degeneration (Pfirrmann score), facet joint tropism and fatty infiltration of the multifidus muscle, and improvement in patient reported outcome measures (PROMs) 2 years after surgery. We dichotomized each radiological parameter into a moderate or severe category. PROMs i.e., Oswestry Disability Index (ODI), Zurich Claudication Questionnaire (ZCQ) and Numeric rating scale (NRS) for back and leg pain were collected before surgery and at 2 year follow-up. In the primary analysis, we investigated the association between MRI findings and ODI score (dichotomized to >= 30% improvement or not). In the secondary analysis, we investigated the association between MRI findings and the mean improvement on the ODI-, ZCQ- and NRS scores. We used multivariable regression models adjusted for patients' gender, age, smoking status and BMI. Results The primary analysis showed that severe disc degeneration (Pfirrmann score 4-5) was significantly associated with less chance of achieving a 30% improvement on the ODI score (OR 0.54, 95% CI 0.34, 0.88). In the secondary analysis, we detected no clinical relevant associations. Conclusion Severe disc degeneration preoperatively suggest lesser chance of achieving 30% improvement in ODI score after surgery for LSS. Other preoperative MRI findings were not associated with patient reported outcome.
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| 7. |
- Aalto, K, et al.
(författare)
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Nerve growth factor in serum of children with systemic lupus erythematosus is correlated with disease activity
- 2002
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Ingår i: Cytokine. - : ACADEMIC PRESS LTD ELSEVIER SCIENCE LTD. - 1043-4666 .- 1096-0023. ; 20:3, s. 136-139
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Tidskriftsartikel (refereegranskat)abstract
- Nerve growth factor (NGF) is a neurotrophic factor, which is expressed both in the nervous system and in peripheral organs. NGF is also present in mast cells, and in B- and T-lymphocytes, and may play a role in the immune cell development and differentiation. Various cytokines have been shown to affect NGF expression, and NGF is elevated in inflammation and in some autoimmune diseases. Here we have studied NGF concentrations in serum of pediatric patients with systemic lupus erythematosus (SLE) using a two-site enzyme-linked immunosorbent assay (ELISA). We have further correlated the levels of NGF to the inflammatory state of the disease. The mean value of serum NGF in SLE patients was significantly increased compared with controls (3346 vs 627 pg/ml). There was a correlation between the activity of SLE and the levels of NGF. The results show that NGF is elevated in childhood SLE and that the levels are correlated with disease activity. The present results suggest that NGF may play a role in the pathogenesis of SLE and may have a prognostic value in evaluating the course of the disease and in outlining the medication. (C) 2002 Elsevier Science Ltd. All rights reserved.
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| 8. |
- Aamodt, A. H., et al.
(författare)
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Blood neurofilament light concentration at admittance: a potential prognostic marker in COVID-19
- 2021
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Ingår i: Journal of Neurology. - : Springer Science and Business Media LLC. - 0340-5354 .- 1432-1459. ; 268, s. 3574-3583
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Tidskriftsartikel (refereegranskat)abstract
- Objective To test the hypotheses that blood biomarkers for nervous system injury, serum concentrations of neurofilament light chain protein (NfL) and glial fibrillary acidic protein (GFAp) can serve as biomarkers for disease severity in COVID-19 patients. Methods Forty-seven inpatients with confirmed COVID-19 had blood samples drawn on admission for assessing serum biomarkers of CNS injury by Single molecule array (Simoa), NfL and GFAp. Concentrations of NfL and GFAp were analyzed in relation to symptoms, clinical signs, inflammatory biomarkers and clinical outcomes. We used multivariate linear models to test for differences in biomarker concentrations in the subgroups, accounting for confounding effects. Results In total, 21% (n = 10) of the patients were admitted to an intensive care unit, and the overall mortality rate was 13% (n = 6). Non-survivors had higher serum concentrations of NfL (p < 0.001) upon admission than patients who were discharged alive both in adjusted analyses (p = 2.6 x 10(-7)) and unadjusted analyses (p = 0.001). The concentrations of NfL in non-survivors increased over repeated measurements; whereas, the concentrations in survivors were stable. The GFAp concentration was also significantly higher in non-survivors than survivors (p = 0.02). Conclusion Increased concentrations of NfL and GFAp in COVID-19 patients on admission may indicate increased mortality risk. Measurement of blood biomarkers for nervous system injury can be useful to detect and monitor CNS injury in COVID-19.
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| 9. |
- Aare, Sudhakar Reddy, 1978-
(författare)
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Intensive Care Unit Muscle Wasting : Skeletal Muscle Phenotype and Underlying Molecular Mechanisms
- 2012
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Acute quadriplegic myopathy (AQM), or critical illness myopathy, is a common debilitating acquired disorder in critically ill intensive care unit (ICU) patients characterized by generalized muscle wasting and weakness of limb and trunk muscles. A preferential loss of the thick filament protein myosin is considered pathognomonic of this disorder, but the myosin loss is observed relatively late during the disease progression. In attempt to explore the potential role of factors considered triggering AQM in sedated mechanically ventilated (MV) ICU patients, we have studied the early effects, prior to the myosin loss, of neuromuscular blockade (NMB), corticosteroids (CS) and sepsis separate or in combination in a porcine experimental ICU model. Specific interest has been focused on skeletal muscle gene/protein expression and regulation of muscle contraction at the muscle fiber level. This project aims at improving our understanding of the molecular mechanisms underlying muscle specific differences in response to the ICU intervention and the role played by the different triggering factors.The sparing of masticatory muscle fiber function was coupled to an up-regulation of heat shock protein genes and down-regulation of myostatin are suggested to be key factors in the relative sparing of masticatory muscles. Up-regulation of chemokine activity genes and down-regulation of heat shock protein genes play a significant role in the limb muscle dysfunction associated with sepsis. The effects of corticosteroids in the development of limb muscle weakness reveals up-regulation of kinase activity and transcriptional regulation genes and the down-regulation of heat shock protein, sarcomeric, cytoskeletal and oxidative stress responsive genes. In contrast to limb and craniofacial muscles, the respiratory diaphragm muscle responded differently to the different triggering factors. MV itself appears to play a major role for the diaphragm muscle dysfunction. By targeting these genes, future experiments can give an insight into the development of innovative treatments expected at protecting muscle mass and function in critically ill ICU patients.
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| 10. |
- Aarnio, K., et al.
(författare)
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Cancer in Young Adults With Ischemic Stroke
- 2015
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Ingår i: Stroke. - : Ovid Technologies (Wolters Kluwer Health). - 0039-2499 .- 1524-4628. ; 46:6
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Tidskriftsartikel (refereegranskat)abstract
- Background and Purpose-Cancer is a risk factor for ischemic stroke. Little is known about cancer among young adults with ischemic stroke. We studied the frequency of cancer and its association with long-term risk of death among young patients with first-ever ischemic stroke. Methods-1002 patients aged 15 to 49 years, registered in the Helsinki Young Stroke Registry, and with a median follow-up of 10.0 years (interquartile range 6.5-13.8) after stroke were included. Historical and follow-up data were derived from the Finnish Care Register and Statistics Finland. Survival between groups was compared with the Kaplan-Meier life-table method, and Cox proportional hazard models were used to identify factors associated with mortality. Results-One or more cancer diagnosis was made in 77 (7.7%) patients, of whom 39 (3.9%) had cancer diagnosed prestroke. During the poststroke follow-up, 41 (53.2%) of the cancer patients died. Median time from prestroke cancer to stroke was 4.9 (1.0-9.5) years and from stroke to poststroke cancer was 6.7 (2.7-10.9) years. Poststroke cancer was associated with age >40 years, heavy drinking, and cigarette smoking. The cumulative mortality was significantly higher among the cancer patients (68.6%, 95% confidence interval 52.0%-85.3%) compared with patients without cancer (19.7%, 95% confidence interval 16.3%-23.2%). Active cancer at index stroke, melanoma, and lung/respiratory tract cancer had the strongest independent association with death during the follow-up when adjusted for known poststroke mortality prognosticators. Conclusions-Cancer, and especially active cancer and no other apparent cause for stroke, is associated with unfavorable survival among young stroke patients.
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