| 1. |
- Alonso, Fabiola, et al.
(författare)
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Investigation into Deep Brain Stimulation Lead Designs : A Patient-Specific Simulation Study
- 2016
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Ingår i: Brain Sciences. - : MDPI. - 2076-3425. ; 6:3, s. 1-16
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Tidskriftsartikel (refereegranskat)abstract
- New deep brain stimulation (DBS) electrode designs offer operation in voltage and current mode and capability to steer the electric field (EF). The aim of the study was to compare the EF distributions of four DBS leads at equivalent amplitudes (3 V and 3.4 mA). Finite element method (FEM) simulations (n = 38) around cylindrical contacts (leads 3389, 6148) or equivalent contact configurations (leads 6180, SureStim1) were performed using homogeneous and patient-specific (heterogeneous) brain tissue models. Steering effects of 6180 and SureStim1 were compared with symmetric stimulation fields. To make relative comparisons between simulations, an EF isolevel of 0.2 V/mm was chosen based on neuron model simulations (n = 832) applied before EF visualization and comparisons. The simulations show that the EF distribution is largely influenced by the heterogeneity of the tissue, and the operating mode. Equivalent contact configurations result in similar EF distributions. In steering configurations, larger EF volumes were achieved in current mode using equivalent amplitudes. The methodology was demonstrated in a patient-specific simulation around the zona incerta and a “virtual” ventral intermediate nucleus target. In conclusion, lead design differences are enhanced when using patient-specific tissue models and current stimulation mode.
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| 2. |
- Göransson, Nathanael, et al.
(författare)
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Postoperative lead movement after deep brain stimulation surgery and changes of stimulation area
- 2017
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- IntroductionLead movement after deep brain stimulation (DBS) may occur and influence the area of stimulation. The cause of the displacement is not fully understood. The aim of the study was to investigate differences in lead position between the day after surgery and approximately one month postoperatively and also simulate the electric field (EF) around the active contacts.Methods23 patients with movement disorders underwent DBS surgery (37 leads). CT at the two time points were co-fused respectively with the stereotactic images in Surgiplan. The coordinates (x, y, z) of the lead tips were compared between the two dates (paired t-test). 8 of these patients were selected for the EF simulation in Comsol Multiphysics.ResultsThere was a significant discrepancy (mean ± s.d.) on the left lead: x (0.44 ± 0.72, p < 0.01), y (0.64 ± 0.54, p < 0.001), z (0.62 ± 0.71, p < 0.001). On the right lead, corresponding values were: x (-0.11 ± 0.61, n.s.), y (0.71 ± 0.54, p < 0.001), z (0.49 ± 0.81, p < 0.05). No correlation was found between bilateral (n =14) vs. unilateral DBS, gender (n = 17 male) and age < 60 years (n = 8). The lead movement affected the EF spread (Fig. 1).ConclusionThe left lead tip displayed a tendency to move lateral, anterior and inferior and the right a tendency to move anterior and inferior. Lead movement after DBS can be a factor to consider before starting the stimulation. The differences in the area of stimulation might affect clinical outcome.
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| 3. |
- Göransson, Nathanael, et al.
(författare)
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Postoperative Lead Movement after Deep Brain Stimulation Surgery and the Change of Stimulation Volume
- 2021
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Ingår i: Stereotactic and Functional Neurosurgery. - : S. Karger. - 1011-6125 .- 1423-0372. ; 99:3, s. 221-229
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Tidskriftsartikel (refereegranskat)abstract
- Introduction: Lead movement after deep brain stimulation may occur and influence the affected volume of stimulation. The aim of the study was to investigate differences in lead position between the day after surgery and approximately 1 month postoperatively and also simulate the electric field (EF) around the active contacts in order to investigate the impact of displacement on affected volume. Methods: Twenty-three patients with movement disorders underwent deep brain stimulation surgery (37 leads). Computed tomography at the 2 time points were co-fused respectively with the stereotactic images in Surgiplan. The coordinates (x, y, and z) of the lead tips were compared between the 2 dates. Eleven of these patients were selected for the EF simulation in Comsol Multiphysics. Postoperative changes of EF spread in the tissue due to conductivity changes in perielectrode space and due to displacement were evaluated by calculating the coverage coefficient and the Sorensen-Dice coefficient. Results: There was a significant displacement (mean +/- SD) on the left lead: x (0.44 +/- 0.72, p < 0.01), y (0.64 +/- 0.54, p < 0.001), and z (0.62 +/- 0.71, p < 0.001). On the right lead, corresponding values were: x (-0.11 +/- 0.61, ns), y (0.71 +/- 0.54, p < 0.001), and z (0.49 +/- 0.81, p < 0.05). The anchoring technique was a statistically significant variable associated with displacement. No correlation was found between bilateral (n = 14) versus unilateral deep brain stimulation, gender (n = 17 male), age <60 years (n = 8), and calculated air volume. The simulated stimulation volume was reduced after 1 month because of the perielectrode space. When considering perielectrode space and displacement, the volumes calculated the day after surgery and approximately 1 month later were partly overlapped. Conclusion: The left lead tip displayed a tendency to move lateral, anterior, and inferior and the right a tendency to move anterior and inferior. The anchoring technique was associated to displacement. New brain territory was affected due to the displacement despite considering the reduced stimulated volume after 1 month. Postoperative changes in perielectrode space and small lead movements are reasons for delaying programming to 4 weeks following surgery.
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| 4. |
- Köhnke, Rickard, et al.
(författare)
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Thylakoids suppress appetite by increasing cholecystokinin resulting in lower food intake and body weight in high-fat fed mice.
- 2009
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Ingår i: Phytotherapy Research. - : Wiley. - 1099-1573 .- 0951-418X. ; 23, s. 1778-1783
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Tidskriftsartikel (refereegranskat)abstract
- Thylakoids are membranes isolated from plant chloroplasts which have previously been shown to inhibit pancreatic lipase/colipase catalysed hydrolysis of fat in vitro and induce short-term satiety in vivo. The purpose of the present study was to examine if dietary supplementation of thylakoids could affect food intake and body weight during long-term feeding in mice. Female apolipoprotein E-deficient mice were fed a high-fat diet containing 41% of fat by energy with and without thylakoids for 100 days. Mice fed the thylakoid-enriched diet had suppressed food intake, body weight gain and body fat compared with the high-fat fed control mice. Reduced serum glucose, serum triglyceride and serum free fatty acid levels were found in the thylakoid-treated animals. The satiety hormone cholecystokinin was elevated, suggesting this hormone mediates satiety. Leptin levels were reduced, reflecting a decreased fat mass. There was no sign of desensitization in the animals treated with thylakoids. The results suggest that thylakoids are useful to suppress appetite and body weight gain when supplemented to a high-fat food during long-term feeding. Copyright (c) 2009 John Wiley & Sons, Ltd.
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| 5. |
- Patel, Kashyap, et al.
(författare)
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The LKB1-salt-inducible kinase pathway functions as a key gluconeogenic suppressor in the liver.
- 2014
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Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 5:Aug 4
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Tidskriftsartikel (refereegranskat)abstract
- LKB1 is a master kinase that regulates metabolism and growth through adenosine monophosphate-activated protein kinase (AMPK) and 12 other closely related kinases. Liver-specific ablation of LKB1 causes increased glucose production in hepatocytes in vitro and hyperglycaemia in fasting mice in vivo. Here we report that the salt-inducible kinases (SIK1, 2 and 3), members of the AMPK-related kinase family, play a key role as gluconeogenic suppressors downstream of LKB1 in the liver. The selective SIK inhibitor HG-9-91-01 promotes dephosphorylation of transcriptional co-activators CRTC2/3 resulting in enhanced gluconeogenic gene expression and glucose production in hepatocytes, an effect that is abolished when an HG-9-91-01-insensitive mutant SIK is introduced or LKB1 is ablated. Although SIK2 was proposed as a key regulator of insulin-mediated suppression of gluconeogenesis, we provide genetic evidence that liver-specific ablation of SIK2 alone has no effect on gluconeogenesis and insulin does not modulate SIK2 phosphorylation or activity. Collectively, we demonstrate that the LKB1-SIK pathway functions as a key gluconeogenic gatekeeper in the liver.
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| 6. |
- Tapper, Sofie, 1989-, et al.
(författare)
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A pilot study of essential tremor: cerebellar GABA+/Glx ratio is correlated with tremor severity
- 2020
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Ingår i: Cerebellum & ataxias. - : BioMed Central. - 2053-8871. ; 7
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Tidskriftsartikel (refereegranskat)abstract
- Essential tremor is a common movement disorder with an unclear origin. Emerging evidence suggests the role of the cerebellum and the thalamus in tremor pathophysiology. We examined the two main neurotransmitters acting inhibitory (GABA+) and excitatory (Glx) respectively, in the thalamus and cerebellum, in patients diagnosed with severe essential tremor. Furthermore, we also investigated the relationship between determined neurotransmitter concentrations and tremor severity in the essential tremor patients.
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| 7. |
- Van der Borght, Karin, et al.
(författare)
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Reduced neurogenesis in the rat hippocampus following high fructose consumption.
- 2011
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Ingår i: Regulatory Peptides. - : Elsevier BV. - 1873-1686 .- 0167-0115. ; 167, s. 26-30
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Tidskriftsartikel (refereegranskat)abstract
- In this study, we investigated how prolonged consumption of sugar solution affects hippocampal neurogenesis. We gave rats sucrose or fructose solution for four weeks and observed a 40% reduction in BrdU/NeuN-immunoreactive cells in the hippocampal dentate gyrus. This reduction in hippocampal neurogenesis was accompanied by increased apoptosis in the hippocampus and increased circulating levels of TNF-α. Therefore, we hypothesize that the reduction in hippocampal neurogenesis may be due to the increased apoptosis induced by TNF-α. Our results suggest that chronic ingestion of fructose is detrimental to the survival of newborn hippocampal neurones. The results presented in the present study add to the list of harmful effects associated with prolonged and excessive consumption of sugary beverages and soft drinks.
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| 8. |
- Wein, Marc N., et al.
(författare)
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SIKs control osteocyte responses to parathyroid hormone
- 2016
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Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 7
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Tidskriftsartikel (refereegranskat)abstract
- Parathyroid hormone (PTH) activates receptors on osteocytes to orchestrate bone formation and resorption. Here we show that PTH inhibition of SOST (sclerostin), a WNT antagonist, requires HDAC4 and HDAC5, whereas PTH stimulation of RANKL, a stimulator of bone resorption, requires CRTC2. Salt inducible kinases (SIKs) control subcellular localization of HDAC4/5 and CRTC2. PTH regulates both HDAC4/5 and CRTC2 localization via phosphorylation and inhibition of SIK2. Like PTH, new small molecule SIK inhibitors cause decreased phosphorylation and increased nuclear translocation of HDAC4/5 and CRTC2. SIK inhibition mimics many of the effects of PTH in osteocytes as assessed by RNA-seq in cultured osteocytes and following in vivo administration. Once daily treatment with the small molecule SIK inhibitor YKL-05-099 increases bone formation and bone mass. Therefore, a major arm of PTH signalling in osteocytes involves SIK inhibition, and small molecule SIK inhibitors may be applied therapeutically to mimic skeletal effects of PTH.
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