| 1. |
- Nelson, D. W., et al.
(författare)
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The Karolinska NeuroCOVID study protocol: Neurocognitive impairment, biomarkers and advanced imaging in critical care survivors
- 2022
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Ingår i: Acta Anaesthesiologica Scandinavica. - : Wiley. - 0001-5172 .- 1399-6576. ; 66:6, s. 759-766
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Tidskriftsartikel (refereegranskat)abstract
- Background: This is the study plan of the Karolinska NeuroCOVID study, a study of neurocognitive impairment after severe COVID-19, relating post-intensive care unit (ICU) cognitive and neurological deficits to biofluid markers and MRI. The COVID-19 pandemic has posed enormous health challenges to individuals and health- systems worldwide. An emerging feature of severe COVID-19 is that of temporary and extended neurocognitive impairment, exhibiting a myriad of symptoms and signs. The causes of this symptomatology have not yet been fully elucidated. Methods: In this study, we aim to investigate patients treated for severe COVID-19 in the ICU, as to describe and relate serum-, plasma- and cerebrospinal fluid-borne molecular and cellular biomarkers of immune activity, coagulopathy, cerebral damage, neuronal inflammation, and degeneration, to the temporal development of structural and functional changes within the brain as evident by serial MRI and extensive cognitive assessments at 3-12 months after ICU discharge. Results: To date, we have performed 51 3-month follow-up MRIs in the ICU survivors. Of these, two patients (similar to 4%) have had incidental findings on brain MRI findings requiring activation of the Incidental Findings Management Plan. Furthermore, the neuropsychological and neurological examinations have so far revealed varying and mixed patterns. Several patients expressed cognitive and/or mental concerns and fatigue, complaints closely related to brain fog. Conclusion: The study goal is to gain a better understanding of the pathological mechanisms and neurological consequences of this new disease, with a special emphasis on neurodegenerative and neuroinflammatory processes, in order to identify targets of intervention and rehabilitation.
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| 2. |
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| 3. |
- Kleinhans, C., et al.
(författare)
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A perfusion bioreactor system efficiently generates cell-loaded bone substitute materials for addressing critical size bone defects
- 2015
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Ingår i: Biotechnology Journal. - : Wiley-VCH Verlagsgesellschaft. - 1860-6768 .- 1860-7314. ; 10:11, s. 1727-1738
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Tidskriftsartikel (refereegranskat)abstract
- Critical size bone defects and non-union fractions are still challenging to treat. Cell-loaded bone substitutes have shown improved bone ingrowth and bone formation. However, a lack of methods for homogenously colonizing scaffolds limits the maximum volume of bone grafts. Additionally, therapy robustness is impaired by heterogeneous cell populations after graft generation. Our aim was to establish a technology for generating grafts with a size of 10.5 mm in diameter and 25 mm of height, and thus for grafts suited for treatment of critical size bone defects. Therefore, a novel tailor-made bioreactor system was developed, allowing standardized flow conditions in a porous poly(L-lactide-co-caprolactone) material. Scaffolds were seeded with primary human mesenchymal stem cells derived from four different donors. In contrast to static experimental conditions, homogenous cell distributions were accomplished under dynamic culture. Additionally, culture in the bioreactor system allowed the induction of osteogenic lineage commitment after one week of culture without addition of soluble factors. This was demonstrated by quantitative analysis of calcification and gene expression markers related to osteogenic lineage. In conclusion, the novel bioreactor technology allows efficient and standardized conditions for generating bone substitutes that are suitable for the treatment of critical size defects in humans.
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| 4. |
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| 5. |
- Ramani-Mohan, R. -K, et al.
(författare)
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Deformation strain is the main physical driver for skeletal precursors to undergo osteogenesis in earlier stages of osteogenic cell maturation
- 2018
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Ingår i: Journal of Tissue Engineering and Regenerative Medicine. - : John Wiley and Sons Ltd. - 1932-6254 .- 1932-7005. ; 12:3, s. e1474-e1479
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Tidskriftsartikel (refereegranskat)abstract
- Mesenchymal stem cells play a major role during bone remodelling and are thus of high interest for tissue engineering and regenerative medicine applications. Mechanical stimuli, that is, deformation strain and interstitial fluid-flow-induced shear stress, promote osteogenic lineage commitment. However, the predominant physical stimulus that drives early osteogenic cell maturation is not clearly identified. The evaluation of each stimulus is challenging, as deformation and fluid-flow-induced shear stress interdepend. In this study, we developed a bioreactor that was used to culture mesenchymal stem cells harbouring a strain-responsive AP-1 luciferase reporter construct, on porous scaffolds. In addition to the reporter, mineralization and vitality of the cells was investigated by alizarin red staining and 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide. Quantification of the expression of genes associated to bone regeneration and bone remodelling was used to confirm alizarin red measurements. Controlled perfusion and deformation of the 3-dimensional scaffold facilitated the alteration of the expression of osteogenic markers, luciferase activity, and calcification. To isolate the specific impact of scaffold deformation, a computational model was developed to derive a perfusion flow profile that results in dynamic shear stress conditions present in periodically loaded scaffolds. In comparison to actually deformed scaffolds, a lower expression of all measured readout parameters indicated that deformation strain is the predominant stimulus for skeletal precursors to undergo osteogenesis in earlier stages of osteogenic cell maturation.
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| 6. |
- Rydhstrom, H, et al.
(författare)
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Myometrial norepinephrine in human pregnancy. Elevated levels in various disorders leading to cesarean section
- 1989
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Ingår i: Journal of Reproductive Medicine. - 0024-7758. ; 34:11, s. 901-904
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Tidskriftsartikel (refereegranskat)abstract
- Myometrial norepinephrine was measured consecutively with high-performance liquid chromatography in women who delivered by cesarean section. The previously recorded marked reduction in tissue norepinephrine at the end of normal pregnancy was confirmed. When cesarean section was performed because of abruptio placentae/hemorrhage, impending asphyxia, dystocia or preeclampsia, the norepinephrine concentrations were six to ten times higher than in normal pregnancy. When an emergency cesarean section was carried out for premature breech presentation, transverse position of the fetus or prolapse of the umbilical cord (following an otherwise-normal pregnancy), the reduced norepinephrine values were not significantly different from those measured in a control group of women who underwent elective cesarean section. It is possible that the abnormally elevated levels of myometrial norepinephrine are part of the primary pathophysiologic condition associated with sympathetic overactivity, resulting in disturbed myometrial circulation and/or motor activity.
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