| 1. |
- Hörnell, Agneta, et al.
(author)
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Perspective: An extension of the STROBE statement for observational studies in nutritional epidemiology (STROBE-nut): Explanation and elaboration
- 2017
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In: Advances in Nutrition. - : Elsevier BV. - 2161-8313 .- 2156-5376. ; 8, s. 652-678
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Journal article (peer-reviewed)abstract
- © 2017 American Society for Nutrition. Nutritional epidemiology is an inherently complex and multifaceted research area. Dietary intake is a complex exposure and is challenging to describe and assess, and links between diet, health, and disease are difficult to ascertain. Consequently, adequate reporting is necessary to facilitate comprehension, interpretation, and generalizability of results and conclusions. The STrengthening the Reporting of OBservational studies in Epidemiology (STROBE) statement is an international and collaborative initiative aiming to enhance the quality of reporting of observational studies. We previously presented a checklist of 24 reporting recommendations for the field of nutritional epidemiology, called "the STROBE-nut." The STROBE-nut is an extension of the general STROBE statement, intended to complement the STROBE recommendations to improve and standardize the reporting in nutritional epidemiology. The aim of the present article is to explain the rationale for, and elaborate on, the STROBE-nut recommendations to enhance the clarity and to facilitate the understanding of the guidelines. Examples from the published literature are used as illustrations, and references are provided for further reading.
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| 2. |
- Asp, Michaela, et al.
(author)
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A Spatiotemporal Organ-Wide Gene Expression and Cell Atlas of the Developing Human Heart
- 2019
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In: Cell. - : CELL PRESS. - 0092-8674 .- 1097-4172. ; 179:7, s. 1647-
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Journal article (peer-reviewed)abstract
- The process of cardiac morphogenesis in humans is incompletely understood. Its full characterization requires a deep exploration of the organ-wide orchestration of gene expression with a single-cell spatial resolution. Here, we present a molecular approach that reveals the comprehensive transcriptional landscape of cell types populating the embryonic heart at three developmental stages and that maps cell-type-specific gene expression to specific anatomical domains. Spatial transcriptomics identified unique gene profiles that correspond to distinct anatomical regions in each developmental stage. Human embryonic cardiac cell types identified by single-cell RNA sequencing confirmed and enriched the spatial annotation of embryonic cardiac gene expression. In situ sequencing was then used to refine these results and create a spatial subcellular map for the three developmental phases. Finally, we generated a publicly available web resource of the human developing heart to facilitate future studies on human cardiogenesis.
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| 3. |
- Asp, Michaela, et al.
(author)
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An organ‐wide gene expression atlas of the developing human heart
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Other publication (other academic/artistic)abstract
- The human developing heart holds a greater proportion of stem-cell-like cells than the adult heart. However, it is not completely understood how these stem cells differentiate into various cardiac cell types. We have performed an organ-wide transcriptional landscape analysis of the developing heart to advance our understanding of cardiac morphogenesis in humans. Comprehensive spatial gene expression analyses identified distinct profiles that correspond not only to individual chamber compartments, but also distinctive regions within the outflow tract. Furthermore, the generated spatial expression reference maps facilitated the assignment of 3,787 human embryonic cardiac cells obtained from single-cell RNA-sequencing to an in situlocation. Through this approach we reveal that the outflow tract contains a wider range of cell types than the chambers, and that the epicardium expression profile can be traced to several cell types that are activated at different stages of development. We also provide a 3D spatial model of human embryonic cardiac cells to enable further studies of the developing human heart.
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| 4. |
- Grauers, Anna, et al.
(author)
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Candidate gene analysis and exome sequencing confirm LBX1 as a susceptibility gene for idiopathic scoliosis
- 2015
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In: The Spine Journal. - Stockholm : Karolinska Institutet, Dept of Clinical Science, Intervention and Technology. - 1529-9430 .- 1878-1632.
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Journal article (peer-reviewed)abstract
- Background: Idiopathic scoliosis is a spinal deformity affecting approximately 3% of otherwise healthy children or adolescents. The etiology is still largely unknown but has an important genetic component. Genome-wide association studies have identified a number of common genetic variants that are significantly associated with idiopathic scoliosis in Asian and Caucasian populations, rs11190870 close to the LBX1 gene being the most replicated finding. Purpose: The aim of the present study was to investigate the genetics of idiopathic scoliosis in a Scandinavian cohort by performing a candidate gene study of four variants previously shown to be associated with idiopathic scoliosis and exome sequencing of idiopathic scoliosis patients with a severe phenotype to identify possible novel scoliosis risk variants. Study design: This was a case control study. Patient sample: A total of 1,739 patients with idiopathic scoliosis and 1,812 controls were included. Outcome measure: The outcome measure was idiopathic scoliosis. Methods: The variants rs10510181, rs11190870, rs12946942, and rs6570507 were genotyped in 1,739 patients with idiopathic scoliosis and 1,812 controls. Exome sequencing was performed on pooled samples from 100 surgically treated idiopathic scoliosis patients. Novel or rare missense, nonsense, or splice site variants were selected for individual genotyping in the 1,739 cases and 1,812 controls. In addition, the 5′UTR, noncoding exon and promoter regions of LBX1, not covered by exome sequencing, were Sanger sequenced in the 100 pooled samples. Results: Of the four candidate genes, an intergenic variant, rs11190870, downstream of the LBX1 gene, showed a highly significant association to idiopathic scoliosis in 1,739 cases and 1,812 controls (p=7.0×10−18). We identified 20 novel variants by exome sequencing after filtration and an initial genotyping validation. However, we could not verify any association to idiopathic scoliosis in the large cohort of 1,739 cases and 1,812 controls. We did not find any variants in the 5′UTR, noncoding exon and promoter regions of LBX1. Conclusions: Here, we confirm LBX1 as a susceptibility gene for idiopathic scoliosis in a Scandinavian population and report that we are unable to find evidence of other genes of similar or stronger effect.
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| 5. |
- Gyllensvaerd, Johan, et al.
(author)
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Antibiotic Use in Late Preterm and Full-Term Newborns
- 2024
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In: JAMA Network Open. - : AMER MEDICAL ASSOC. - 2574-3805. ; 7:3
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Journal article (peer-reviewed)abstract
- Importance Antibiotic treatment saves lives in newborns with early-onset sepsis (EOS), but unwarranted antibiotic use is associated with resistant bacteria and adverse outcomes later in life. Surveillance is needed to optimize treatment strategies. Objective To describe antibiotic use in association with the incidence and mortality from EOS among late-preterm and full-term newborns. Design, Setting, and Participants The Sweden Neonatal Antibiotic Use study was a nationwide observational study that included all late-preterm and full-term neonates born from January 1, 2012, to December 31, 2020, in neonatal units of all levels. All hospital live births from 34 weeks' gestation during the study period were included in the study. Data were collected from the Swedish Neonatal Quality Register and the Swedish Medical Birth Register. Data were analyzed from August 2022 to May 2023. Exposure Admission for neonatal intensive care during the first week of life. Main Outcomes and Measures The main outcomes were the usage of intravenous antibiotics during the first week of life, the duration of antibiotic therapy, the rate of culture-proven EOS, and mortality associated with EOS. Results A total of 1 025 515 newborns were included in the study; 19 286 neonates (1.88%; 7686 girls [39.9%]; median [IQR] gestational age, 40 [38-41] weeks; median [IQR] birth weight, 3610 [3140-4030] g) received antibiotics during the first week of life, of whom 647 (3.4%) had EOS. The median (IQR) duration of antibiotic treatment in newborns without EOS was 5 (3-7) days, and there were 113 antibiotic-days per 1000 live births. During the study period there was no significant change in the exposure to neonatal antibiotics or antibiotic-days per 1000 live births. The incidence of EOS was 0.63 per 1000 live births, with a significant decrease from 0.74 in 2012 to 0.34 in 2020. Mortality associated with EOS was 1.39% (9 of 647 newborns) and did not change significantly over time. For each newborn with EOS, antibiotic treatment was initiated in 29 newborns and 173 antibiotic-days were dispensed. Conclusions and Relevance This large nationwide study found that a relatively low exposure to antibiotics is not associated with an increased risk of EOS or associated mortality. Still, future efforts to reduce unwarranted neonatal antibiotic use are needed.
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| 6. |
- Hashemian, Sanazalsadat, 1983-
(author)
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Interaction between nerve fiber formation and astrocytes
- 2014
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Doctoral thesis (other academic/artistic)abstract
- Parkinson’s disease, the second most common neurodegenerative disorder,is characterized by loss of nigrostriatal dopaminergic neurons. To date,there is no defined cause and cure for the disease. An ideal treatmentstrategy is to replace the lost neurons by transplanting fetal dopaminergicneurons to the brain of parkinsonian patients. Clinical trials have beenperformed and the outcome was variable where one significant obstaclewas the limited graft reinnervation of the host brain. To study this issue,organotypic tissue culture can be utilized to monitor dopaminergic nervefiber outgrowth in vitro and their association with astrocytes. Using thisculture technique, dopaminergic nerve fibers appear in twomorphologically and temporally different types. The early appearing nervefibers are formed in the absence of astrocytes, reach long distances, andare called non-glial-associated tyrosine hydroxylase (TH) -positive nervefibers. After a few days, the second sequence of nerve fibers, the glialassociatedTH-positive nerve fibers, are formed, and their growth arelimited to the presence of astrocytes, that migrate and form a monolayersurrounding the plated tissue. The aim of this thesis was to study theinteraction between nerve fiber formation and astrocytes with a specialfocus on the long-distance growing nerve fibers. Ventral mesencephalic(VM) organotypic slice cultures from embryonic day (E) 12, E14, and E18were incubated for 14, 21, 28, and 35 days in vitro (DIV). The resultsrevealed that the two morphologically different processes were found incultures from the younger stages, while no non-glial-associated growthwas found in cultures of tissue from E18. Instead neurons had migratedonto the migrating astrocytes. Astrocytes migrated longer distances intissue from older stages, and the migration reached a plateau at 21 DIV.Co-cultures of E14 VM tissue pieces and cell suspension of matureastrocytes promoted migration of neurons, as seen in E18 cultures. Thus,9the maturity of the astrocytes was an important factor for nerve fiberoutgrowth. Hence, targeting molecules secreted by astrocytes might bebeneficial for regeneration. Chondroitin sulfate proteoglycan (CSPG), amember of proteoglycan family, is produced by the astrocytes and has adual role of being permissive during development and inhibitory afterbrain injury in adult brain. Cultures were treated with chondroitinase ABC(ChABC) or methyl-umbelliferyl-β-D-xyloside (β-xyloside) in twodifferent protocols, early and late treatments. The results from the earlytreated cultures showed that both compounds inhibited the outgrowth ofnerve fibers and astrocytic migration in cultures from E14 tissue, while β-xyloside but not ChABC promoted the non-glial-associated growth incultures derived from E18 fetuses. In addition, β-xyloside but not ChABCinhibited neuronal migration in E18 cultures. Taken together, β-xylosideappeared more effective than ChABC in promoting nerve fiber growth.Another potential candidate, integrin-associated protein CD47, was studiedbecause of its role in synaptogenesis, which is important for nerve fibergrowth. Cultures from E14 CD47 knockout (CD47-/-) mice were plated andcompared to their wildtypes. CD47-/- cultures displayed a massive and longnon-glial-associated TH-positive nerve fiber outgrowth despite theirnormal astrocytic migration. Blocking either signal regulatory protein-α(SIRPα) or thrombospondin-1 (TSP-1), which bind to CD47, had nogrowth promoting effect. In conclusion, to promote nerve growth, youngertissue can grow for longer distances than older tissue, and inhibiting CSPGproduction promotes nerve growth in older tissue, while gene deletion ofCD47 makes the astrocytes permissive for a robust nerve fiber growth.
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| 7. |
- Hoeber, Jan, 1986-, et al.
(author)
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A Combinatorial Approach to Induce Sensory Axon Regeneration into the Dorsal Root Avulsed Spinal Cord
- 2017
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In: Stem Cells and Development. - : Mary Ann Liebert Inc. - 1547-3287 .- 1557-8534. ; 26:14, s. 1065-1077
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Journal article (peer-reviewed)abstract
- Spinal root injuries result in newly formed glial scar formation, which prevents regeneration of sensory axons causing permanent sensory loss. Previous studies showed that delivery of trophic factors or implantation of human neural progenitor cells supports sensory axon regeneration and partly restores sensory functions. In this study, we elucidate mechanisms underlying stem cell-mediated ingrowth of sensory axons after dorsal root avulsion (DRA). We show that human spinal cord neural stem/progenitor cells (hscNSPC), and also, mesoporous silica particles loaded with growth factor mimetics (MesoMIM), supported sensory axon regeneration. However, when hscNSPC and MesoMIM were combined, sensory axon regeneration failed. Morphological and tracing analysis showed that sensory axons grow through the newly established glial scar along "bridges" formed by migrating stem cells. Coimplantation of MesoMIM prevented stem cell migration, "bridges" were not formed, and sensory axons failed to enter the spinal cord. MesoMIM applied alone supported sensory axons ingrowth, but without affecting glial scar formation. In vitro, the presence of MesoMIM significantly impaired migration of hscNSPC without affecting their level of differentiation. Our data show that (1) the ability of stem cells to migrate into the spinal cord and organize cellular "bridges" in the newly formed interface is crucial for successful sensory axon regeneration, (2) trophic factor mimetics delivered by mesoporous silica may be a convenient alternative way to induce sensory axon regeneration, and (3) a combinatorial approach of individually beneficial components is not necessarily additive, but can be counterproductive for axonal growth.
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| 8. |
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| 9. |
- Kolar, Mallappa K., 1981-
(author)
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Transplantation of mesenchymal stem cells and injections of microRNA as therapeutics for nervous system repair
- 2016
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Doctoral thesis (other academic/artistic)abstract
- Traumatic injuries to the spinal cord (SCI) and peripheral nerve (PNI) affect several thousand people worldwide every year. At present, there is no effective treatment for SCI and despite continuous improvements in microsurgical reconstructive techniques for PNI, many patients are still left with permanent, devastating neurological dysfunction. This thesis investigates the effects of mesenchymal stem cells (MSC) derived from adipose (ASC) and dental (DSC) tissue and chitosan/microRNA-124 polyplex particles on regeneration after spinal cord and peripheral nerve injury in adult rats. Dental stem cells were obtained from apical papilla, dental pulp, and periodontal ligament. ASC and DSC expressed MSC surface markers (CD73, CD90, CD105 and CD146) and various neurotrophic molecules including BDNF, GDNF, NGF, VEGF-A and angiopoietin-1. Growth factor stimulation of the stem cells resulted in increased secretion of these proteins. Both ASC and DSC supported in vitro neurite outgrowth and in contrast to Schwann cells, ASC did not induce activation of astrocytes. Stimulated ASC also showed an enhanced ability to induce capillary-like tube formation in an in vitro angiogenesis assay. In a peripheral nerve injury model, ASC and DSC were seeded into a fibrin conduit, which was used to bridge a 10 mm rat sciatic nerve gap. After 2 weeks, both ASC and DSC promoted axonal regeneration in the conduit and reduced caspase-3 expression in the dorsal root ganglion (DRG). ASC also enhanced GAP-43 and ATF-3 expression in the spinal cord, reduced c-jun expression in the DRG and increased the vascularity of the implant. After transplantation into injured C3-C4 cervical spinal cord, ASC continued to express neurotrophic factors and laminin and stimulated extensive ingrowth of 5HT-positive raphaespinal axons into the trauma zone. In addition, ASC induced sprouting of raphaespinal terminals in C2 contralateral ventral horn and C6 ventral horn on both sides. Transplanted cells also changed the structure and the density of the astroglial scar. Although the transplanted cells had no effect on the density of capillaries around the lesion site, the reactivity of OX42-positive microglial cells was markedly reduced. However, ASC did not enhance recovery of forelimb function. In order to reduce activation of microglia/macrophages and the secondary tissue damage after SCI, the role of microRNA-124 was investigated. In vitro transfection of chitosan/microRNA-124 polyplex particles into rat microglia resulted in the reduction of reactive oxygen species and TNF-α levels and lowered expression of MHC-II. Upon microinjection into uninjured rat spinal cords, particles formed with Cy3-labeled control sequence RNA, were specifically internalized by OX42 positive macrophages and microglia. Alternatively, particles injected in the peritoneum were transported by macrophages to the site of spinal cord injury. Microinjections of chitosan/microRNA-124 particles significantly reduced the number of ED-1 positive macrophages after SCI. In summary, these results show that human MSC produce functional neurotrophic and angiogenic factors, creating a more desirable microenvironment for neural regeneration after spinal cord and peripheral nerve injury. The data also suggests that chitosan/microRNA-124 particles could be potential treatment technique to reduce neuroinflammation.
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| 10. |
- Kurek, Magdalena, et al.
(author)
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Spermatogonia Loss Correlates with LAMA 1 Expression in Human Prepubertal Testes Stored for Fertility Preservation
- 2021
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In: Cells. - : MDPI AG. - 2073-4409. ; 10:2
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Journal article (peer-reviewed)abstract
- Fertility preservation for male childhood cancer survivors not yet capable of producing mature spermatozoa, relies on experimental approaches such as testicular explant culture. Although the first steps in somatic maturation can be observed in human testicular explant cultures, germ cell depletion is a common obstacle. Hence, understanding the spermatogonial stem cell (SSC) niche environment and in particular, specific components such as the seminiferous basement membrane (BM) will allow progression of testicular explant cultures. Here, we revealed that the seminiferous BM is established from 6 weeks post conception with the expression of laminin alpha 1 (LAMA 1) and type IV collagen, which persist as key components throughout development. With prepubertal testicular explant culture we found that seminiferous LAMA 1 expression is disrupted and depleted with culture time correlating with germ cell loss. These findings highlight the importance of LAMA 1 for the human SSC niche and its sensitivity to culture conditions.
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| 11. |
- König, Niclas, et al.
(author)
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Forced Runx1 expression in human neural stem/progenitor cells transplanted to the rat dorsal root ganglion cavity results in extensive axonal growth specifically from spinal cord-derived neurospheres
- 2011
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In: Stem Cells and Development. - : Mary Ann Liebert Inc. - 1547-3287 .- 1557-8534. ; 20:11, s. 1847-1857
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Journal article (peer-reviewed)abstract
- Cell replacement therapy holds great promise for treating a wide range of human disorders. However, ensuring the predictable differentiation of transplanted stem cells, eliminating their risk of tumor formation, and generating fully functional cells after transplantation remain major challenges in regenerative medicine. Here, we explore the potential of human neural stem/progenitor cells isolated from the embryonic forebrain (hfNSPCs) or the spinal cord (hscNSPCs) to differentiate to projection neurons when transplanted into the dorsal root ganglion cavity of adult recipient rats. To stimulate axonal growth, we transfected hfNSPC- and hscNSPC-derived neurospheres, prior to their transplantation, with a Tet-Off Runx1-overexpressing plasmid to maintain Runx1 expression in vivo after transplantation. Although pronounced cell differentiation was found in the Runx1-expressing transplants from both cell sources, we observed extensive, long-distance growth of axons exclusively from hscNSPC-derived transplants. These axons ultimately reached the dorsal root transitional zone, the boundary separating peripheral and central nervous systems. Our data show that hscNSPCs have the potential to differentiate to projection neurons with long-distance axonal outgrowth and that Runx1 overexpression is a useful approach to induce such outgrowth in specific sources of NSPCs.
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| 12. |
- König, Niclas, 1986-, et al.
(author)
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Human spinal cord neural progenitors alone but not in combination with growth factor mimetic loaded mesoporous silica assist regeneration of sensory fibers into the spinal cord after dorsal root avulsion
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Other publication (other academic/artistic)abstract
- Spinal root avulsion injuries result in permanent loss of sensory function and often cause neuropathic pain. We recently showed that human embryonic stem cells derived neural progenitors (hNP) transplanted to the site of avulsed dorsal roots assist regeneration of sensory fibers into the adult mouse spinal cord. Here, we explored the potential of human spinal cord neural stem/progenitor cells (hscNSPCs) and of growth factor mimetics loaded nanoparticles to repair spinal root avulsion injury. We found that hscNSPCs and to some extent mimetic loaded nanoparticles support regeneration of sensory axons into the spinal cord when they are applied separately, whereas hscNSPCs implanted together with mimetic-loaded nanoparticles failed to support sensory regeneration. These findings suggest that the positive effect of hscNSPCs may be eliminated by nanoparticle mediated release of neurotrophic factors due to changes in stem cell properties or surrounding cells at the place of avulsion, preventing growth of injured sensory axons into the spinal cord. Thus, hscNSPCs are able to assist restoration of sensory connections between the PNS and spinal cord, although not in combination with nanoparticle-delivered neurotrophic factor mimetics.
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| 13. |
- Larsson, C. L., et al.
(author)
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Strengthening the Reporting of Observational Studies in Epidemiology - nutritional epidemiology (STROBE-nut) : An extension of the STROBE statement
- 2016
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In: Nutrition Bulletin. - : Wiley. - 1471-9827 .- 1467-3010. ; 13:6
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Journal article (peer-reviewed)abstract
- Concerns have been raised about the quality of reporting in nutritional epidemiology. Research reporting guidelines such as the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) statement can improve quality of reporting in observational studies. Herein, we propose recommendations for reporting nutritional epidemiology and dietary assessment research by extending the STROBE statement into Strengthening the Reporting of Observational Studies in Epidemiology - Nutritional Epidemiology (STROBE-nut). Recommendations for the reporting of nutritional epidemiology and dietary assessment research were developed following a systematic and consultative process, co-ordinated by a multidisciplinary group of 21 experts. Consensus on reporting guidelines was reached through a three-round Delphi consultation process with 53 external experts. In total, 24 recommendations for nutritional epidemiology were added to the STROBE checklist. When used appropriately, reporting guidelines for nutritional epidemiology can contribute to improve reporting of observational studies with a focus on diet and health.
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| 14. |
- Mak, Jonathan K. L., et al.
(author)
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Development of an Electronic Frailty Index for Hospitalized Older Adults in Sweden
- 2022
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In: The journals of gerontology. Series A, Biological sciences and medical sciences. - : Oxford University Press. - 1079-5006 .- 1758-535X. ; 77:11, s. 2311-2319
-
Journal article (peer-reviewed)abstract
- Background Frailty assessment in the Swedish health system relies on the Clinical Frailty Scale (CFS), but it requires training, in-person evaluation, and is often missing in medical records. We aimed to develop an electronic frailty index (eFI) from routinely collected electronic health records (EHRs) and assess its association with adverse outcomes in hospitalized older adults. Methods EHRs were extracted for 18 225 patients with unplanned admissions between 1 March 2020 and 17 June 2021 from 9 geriatric clinics in Stockholm, Sweden. A 48-item eFI was constructed using diagnostic codes, functioning and other health indicators, and laboratory data. The CFS, Hospital Frailty Risk Score, and Charlson Comorbidity Index were used for comparative assessment of the eFI. We modeled in-hospital mortality and 30-day readmission using logistic regression; 30-day and 6-month mortality using Cox regression; and length of stay using linear regression. Results Thirteen thousand one hundred and eighty-eight patients were included in analyses (mean age 83.1 years). A 0.03 increment in the eFI was associated with higher risks of in-hospital (odds ratio: 1.65; 95% confidence interval: 1.54-1.78), 30-day (hazard ratio [HR]: 1.43; 1.38-1.48), and 6-month mortality (HR: 1.34; 1.31-1.37) adjusted for age and sex. Of the frailty and comorbidity measures, the eFI had the highest area under receiver operating characteristic curve for in-hospital mortality of 0.813. Higher eFI was associated with longer length of stay, but had a rather poor discrimination for 30-day readmission. Conclusions An EHR-based eFI has robust associations with adverse outcomes, suggesting that it can be used in risk stratification in hospitalized older adults.
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| 15. |
- Mak, Jonathan K. L., et al.
(author)
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Two Years with COVID-19 : The Electronic Frailty Index Identifies High-Risk Patients in the Stockholm GeroCovid Study
- 2023
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In: Gerontology. - : S. Karger. - 0304-324X .- 1423-0003. ; 69:4, s. 396-405
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Journal article (peer-reviewed)abstract
- Introduction: Frailty, a measure of biological aging, has been linked to worse COVID-19 outcomes. However, as the mortality differs across the COVID-19 waves, it is less clear whether a medical record-based electronic frailty index (eFI) that we have previously developed for older adults could be used for risk stratification in hospitalized COVID-19 patients. Objectives: The aim of the study was to examine the association of frailty with mortality, readmission, and length of stay in older COVID-19 patients and to compare the predictive accuracy of the eFI to other frailty and comorbidity measures. Methods: This was a retrospective cohort study using electronic health records (EHRs) from nine geriatric clinics in Stockholm, Sweden, comprising 3,980 COVID-19 patients (mean age 81.6 years) admitted between March 2020 and March 2022. Frailty was assessed using a 48-item eFI developed for Swedish geriatric patients, the Clinical Frailty Scale, and the Hospital Frailty Risk Score. Comorbidity was measured using the Charlson Comorbidity Index. We analyzed in-hospital mortality and 30-day readmission using logistic regression, 30-day and 6-month mortality using Cox regression, and the length of stay using linear regression. Predictive accuracy of the logistic regression and Cox models was evaluated by area under the receiver operating characteristic curve (AUC) and Harrell's C-statistic, respectively. Results: Across the study period, the in-hospital mortality rate decreased from 13.9% in the first wave to 3.6% in the latest (Omicron) wave. Controlling for age and sex, a 10% increment in the eFI was significantly associated with higher risks of in-hospital mortality (odds ratio = 2.95; 95% confidence interval = 2.42-3.62), 30-day mortality (hazard ratio [HR] = 2.39; 2.08-2.74), 6-month mortality (HR = 2.29; 2.04-2.56), and a longer length of stay (beta-coefficient = 2.00; 1.65-2.34) but not with 30-day readmission. The association between the eFI and in-hospital mortality remained robust across the waves, even after the vaccination rollout. Among all measures, the eFI had the best discrimination for in-hospital (AUC = 0.780), 30-day (Harrell's C = 0.733), and 6-month mortality (Harrell's C = 0.719). Conclusion: An eFI based on routinely collected EHRs can be applied in identifying high-risk older COVID-19 patients during the continuing pandemic.
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| 16. |
- Mälstam, Emelie, et al.
(author)
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The Feasibility of Make My Day—A Randomized Controlled Pilot Trial of a Stroke Prevention Program in Primary Healthcare
- 2023
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In: International Journal of Environmental Research and Public Health. - : MDPI. - 1661-7827 .- 1660-4601. ; 20:19
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Journal article (peer-reviewed)abstract
- Incorporating and sustaining engaging everyday activities (EEAs) in everyday life holds potential for improving health and wellbeing; thus, there is reason to explore EEAs as a behavioral change technique in stroke prevention. The aim of this study was to evaluate the feasibility of the stroke prevention program Make My Day (MMD) for people with moderate-to-high risk for stroke in a primary healthcare setting, where EEAs are utilized to promote healthy activity patterns. A randomized controlled pilot trial was designed to evaluate the feasibility of MMD. Twenty-nine persons at risk for stroke were recruited and randomized into either an intervention group (n = 14) receiving MMD or a control group (n = 15) receiving brief health advice and support with goal setting. The results suggest that MMD is feasible, with timely recruitment, overall high response rates and study completion, and sensitivity to change in key outcome measures. Moreover, the results demonstrate that the application of EEAs can be useful for promoting behavioral change in stroke prevention. Recommendations for improvements for a full-scale trial include recruiting a relevant sample, using reliability- and validity-tested outcome measures, and implementing strategies to limit missing data.
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| 17. |
- Mälstam, Emelie, et al.
(author)
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'Weaving lifestyle habits' : Complex pathways to health for persons at risk for stroke.
- 2022
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In: Scandinavian Journal of Occupational Therapy. - : Taylor & Francis. - 1103-8128 .- 1651-2014. ; 29:2, s. 152-164
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Journal article (peer-reviewed)abstract
- BACKGROUND: It is important to understand how healthy lifestyle habits can be developed as they are essential in cardiovascular disease (CVD) prevention. There is limited knowledge regarding whether, and how, engaging occupations (things that people do and occupy themselves with) can promote and help sustain healthy lifestyle habits for persons at risk for CVDs, including stroke.AIM: The aim was to develop knowledge of how engaging in occupations can contribute to changes in lifestyle habits among persons at risk for stroke.METHODS: Six adults presenting with stroke risk factors were interviewed on several occasions after participating in an occupation-focused stroke prevention programme. Grounded theory was utilised, and constant comparative methods guided the analysis.FINDINGS: Changing lifestyle habits was perceived as a complex process, much like weaving a fabric with many parallel and interlacing threads. Literacy of both health and occupations and participation in engaging occupations were important facilitators for promoting healthy lifestyle habits, yet engagement in health-promoting occupations was described as conditioned behaviour.CONCLUSIONS: CVD prevention programmes can benefit from incorporating engaging occupations to promote healthy lifestyle habits and literacy of health and occupations. However, contextual factors conditioning health and occupations should be considered when developing and implementing sustainable interventions.
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| 18. |
- Patomella, Ann-Helen, et al.
(author)
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Primary prevention of stroke : randomised controlled pilot trial protocol on engaging everyday activities promoting health
- 2019
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In: BMJ Open. - : BMJ Publishing Group Ltd. - 2044-6055. ; 9:11
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Journal article (peer-reviewed)abstract
- IntroductionStroke is a globally common disease that has detrimental effects on the individual and, more broadly, on society. Lifestyle change can contribute to reducing risk factors for stroke. Although a healthy lifestyle has direct benefits, sustaining and incorporating healthy activities into everyday life is a challenge. Engaging everyday activities have the potential to support lifestyle change and to promote sustainable activity patterns. Current healthcare is failing to reduce modifiable risk factors in people at risk, and in addition to current practice, there is a need for systematic and efficient non-pharmacological and non-surgical stroke-prevention strategies. The aim of the pilot study was to increase knowledge about the effects of a prevention programme and its feasibility to promote sustainable and healthy activity patterns among persons at risk of stroke.Methods and analysisThe proposed pilot study will be a two-armed randomised, assessor-blinded, parallel pilot trial. The study will include feasibility data, investigating acceptability and delivery of the intervention. Persons at risk of stroke (n=60) will be included in a mobile phone-supported prevention programme. The 10-week programme will be conducted at primary healthcare clinics, combining group meetings and online resources to support self-management of lifestyle change. Main outcomes are stroke risk, lifestyle habits and healthy activity patterns. Assessments will be performed at baseline and at follow-up (immediately following the end of the programme and at 6 and 12 months). Effects of the programme will be analysed using inferential statistics. Feasibility will be analysed using both qualitative and quantitative methods.Ethics and disseminationThe study has been approved by the Regional Ethical Review Board in Stockholm, Sweden, being granted reference numbers 2015/834-31, 2016/2203-32 and 2019/01444. Study results will be disseminated through peer-review journals and presentations to mixed audiences at regional and international conferences. Trial registration number NCT03730701.
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| 19. |
- Rytter, Elisabet, 1960-, et al.
(author)
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Biomarkers of oxidative stress in overweight men are not influenced by a combination of antioxidants
- 2010
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In: Free radical research. - : Informa UK Limited. - 1071-5762 .- 1029-2470. ; 44:5, s. 522-528
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Journal article (peer-reviewed)abstract
- The effect of antioxidant supplementation on biomarkers of oxidative stress was investigated in a 6-week intervention study in 60 overweight men. The supplement contained a combination of antioxidants aiming to correspond to the antioxidant content found in a diet rich in fruit and vegetables. Placebo, single or double dose of antioxidants was provided to the subjects. Metabolic variables, plasma antioxidants and biomarkers of oxidative stress (lipid peroxidation and DNA damage) were measured. No effect of supplementation on biomarkers of oxidative stress was observed. Both intervention groups showed substantial increases of plasma antioxidants. This study demonstrated that supplementation with a combination of antioxidants did not affect lipid peroxidation and DNA damage in overweight men, despite increased concentrations of plasma antioxidants. The absence of antioxidant supplement effect might possibly be explained by the chosen study group having a normal level of oxidative stress, duration of the intervention and/or doses of antioxidants.
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| 20. |
- Seiger Cronfalk, Berit, et al.
(author)
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A qualitative study-Patient experience of tactile massage after stroke.
- 2020
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In: Nursing Open. - : John Wiley & Sons. - 2054-1058. ; 7:5, s. 1446-1452
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Journal article (peer-reviewed)abstract
- Aim: The aim was to evaluate emotional experiences of gentle skin massage, combined with regular rehabilitation in patients shortly after being diagnosed with stroke.Design: A randomized study with two groups: standard individualized rehabilitation and tactile massage for 20 min three times per week (max nine times) or individual standardized rehabilitations.Methods: This study applied a qualitative approach using semi-structured questions to evaluate experiences of receiving tactile massage among patients with first-time-ever stroke. The interviews lasted between 6-25 min and analysed using manifest content analysis. Data was collected between 2015-2017. This study applies to the COREQ checklist.Results: Eight patients >18 years of age participated. The participants experienced emotional worries especially during the night hours affecting their sleep negatively. Receiving tactile massage was reported to relax and to ease worries and anxiety momentarily, during the session and for a longer period. The results also show that physical touch generates feelings of closeness. The findings will be presented in two categories: Human touch and The future.
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| 21. |
- von Euler, Mia, 1967-, et al.
(author)
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Motor Performance Score : A New Algorithm for Accurate Behavioral Testing of Spinal Cord Injury in Rats
- 1996
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In: Experimental Neurology. - New York, USA : Academic Press. - 0014-4886 .- 1090-2430. ; 137:2, s. 242-254
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Journal article (peer-reviewed)abstract
- To evaluate the usefulness of standard neurological tests in predicting the neurological outcome after photochemically induced spinal cord lesions in rats, we inflicted injuries of different severity to adult female rats. The behavior of the rats was followed for 6 weeks and the results of the behavioral tests were correlated with morphological indicators of tissue destruction at the end of this period. We found many behavioral tests to be highly correlated with the loss of tissue, whereas some tests were inaccurate in correlating with degree of tissue destruction. Motor score, beam walk, and righting reflex were all highly correlated with the volume of the lesion as well as with the depth of the lesion cavity at its epicenter. We propose a protocol for neurological evaluation of this type of spinal cord injury consisting of six individual tests, hierarchally organized such that injured rats can be divided into 11 groups of neurological deficit, scored from 10 to 0. This so-called motor performance score is fast and easy to perform and shows high correlation with the lesion volume, and is thus suitable for neurological evaluation of photochemically induced spinal cord injury.
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| 22. |
- Wahman, Kerstin, et al.
(author)
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Translation and validation of two International Spinal Cord Injury (SCI) Data Sets : a modified process
- 2019
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In: Spinal Cord Series and Cases. - : Springer Nature. - 2058-6124. ; 5:1
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Journal article (peer-reviewed)abstract
- Study design: A descriptive design was used of a reflective process of problem solving among individuals working together to improve the process of translating.Setting: Sweden.Objectives: The aim of this study was to describe a modified process for translation and validation of the International Spinal Cord Injury (SCI) Quality of Life (QoL) and Activity and Participation (A&P) Basic Data Sets from English into Swedish.Methods: The process of translation followed the Executive Committee for the International SCI Standards and Data Sets (ECSCI) recommendations. The initial translation was performed by translators. Experts in SCI were then assembled to scrutinize the translations and to reach a consensus for defining a final version.Results: The whole process was time consuming. To save time in future translations, the start-up planning is of great importance. To identify appropriate participants with knowledge and interest to be part of the project is crucial. In addition, the consensus meetings, when scrutinizing the translated International SCI Data Sets, should be well prepared and structured. We identified a few steps that could make the process more efficient.Conclusions: By adding a few steps as well as defining the role of a project coordinator, we believe that future translations of the International SCI Data Sets for non-English-speaking countries could be facilitated.
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| 23. |
- Xu, Hong, et al.
(author)
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Decreased Mortality Over Time During the First Wave in Patients With COVID-19 in Geriatric Care : Data From the Stockholm GeroCovid Study.
- 2021
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In: Journal of the American Medical Directors Association. - : Elsevier. - 1525-8610 .- 1538-9375. ; 22:8, s. 1565-1573
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Journal article (peer-reviewed)abstract
- OBJECTIVE: To describe temporal changes in treatment, care, and short-term mortality outcomes of geriatric patients during the first wave of the COVID-19 pandemic.DESIGN: Observational study.SETTING AND PARTICIPANTS: Altogether 1785 patients diagnosed with COVID-19 and 6744 hospitalized for non-COVID-19 causes at 7 geriatric clinics in Stockholm from March 6 to July 31, 2020, were included.METHODS: Across admission month, patient vital signs and pharmacological treatment in relationship to risk for in-hospital death were analyzed using the Poisson regression model. Incidence rates (IRs) and incidence rate ratios (IRRs) of death are presented.RESULTS: In patients with COVID-19, the IR of mortality were 27%, 17%, 10%, 8%, and 2% from March to July, respectively, after standardization for demographics and vital signs. Compared with patients admitted in March, the risk of in-hospital death decreased by 29% [IRR 0.71, 95% confidence interval (CI) 0.51-0.99] in April, 61% (0.39, 0.26-0.58) in May, 68% (0.32, 0.19-0.55) in June, and 86% (0.14, 0.03-0.58) in July. The proportion of patients admitted for geriatric care with oxygen saturation <90% decreased from 13% to 1%, which partly explains the improvement of COVID-19 patient survival. In non-COVID-19 patients during the pandemic, mortality rates remained relatively stable (IR 1.3%-2.3%). Compared with non-COVID-19 geriatric patients, the IRR of death declined from 11 times higher (IRR 11.7, 95% CI 6.11-22.3) to 1.6 times (2.61, 0.50-13.7) between March and July in patients with COVID-19.CONCLUSIONS AND IMPLICATIONS: Mortality risk in geriatric patients from the Stockholm region declined over time throughout the first pandemic wave of COVID-19. The improved survival rate over time was only partly related to improvement in saturation status at the admission of the patients hospitalized later throughout the pandemic. Lower incidence during the later months could have led to less severe hospitalized cases driving down mortality.
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| 24. |
- Åkesson, Elisabet
(author)
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Human spinal cord transplantation : experimental and clinical application
- 2000
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Doctoral thesis (other academic/artistic)abstract
- The main objectives of this Thesis was to further characterize the in situ human first trimester spinal cord tissue and to evaluate the survival, integration and possible neurological effects of solid human embryonic spinal cord grafts transplanted to cavities in the spinal cord of rat and man. Human-specific neurofilament and Thy-1 positive fibers were observed already at 5 weeks of gestation in the in situ human spinal cord, the earliest stage at which donor tissue was used for intraspinal transplantation. Radiating glial fibrillary acidic protein (GFAP) immunoreactivity (IR) suggestive of radial glia was first observed at 7.5 weeks of gestation. Binding sites for [3H]AMPA, [3H]kainate and [3H]MK-801 as well as immunoreactive bands corresponding to the NMDA receptor subunits NR1, NR2A, NR2B, NR2C and NR2D were demonstrated by receptor autoradiography and immunoblotting, respectively, already at 4-7 weeks of gestation and increased continuously during the first trimester. This indicated ionotropic glutamate receptor expression in the human spinal cord already during embryogenesis. Human leukocyte antigen (HLA) class I expression was observed in 5-17% and class II in 0-9% of first trimester human spinal cord cells. After 8 days in culture with [gamma]-interferon, >87% of the spinal cord cells expressed HLA class II. However, mixed cultures of human adult peripheral lymphocytes and immature human spinal cord cells, showed no induction of lymphocyte proliferation prior to or after [gamma]-interferon exposure in culture. In conclusion, non-immunogenic expression of HLA antigens was observed in the human first trimester spinal cord. Solid grafts of human embryonic spinal cord showed >94% survival rate after implantation to chronic and acute unilateral spinal cord cavities in the immune-incompetent rodent. However, 6 months after transplantation the graft volume was significantly larger in the chronic compared to the acute cavity group. The noduli-shaped grafts grew to fill the volume of the unilateral cavity in a restrictive manner and continued its human-specific neural differentiation expressing human specific neurofilament and Thy-1 IR fibers. The graft-host fiber integration was similarly substantial in the grafted chronic and acute cavity group. At 6 months, the grafted groups showed significantly lower degree of GFAP IR at the graft-host border, compared to that of the unilateral cavity alone group. Furthermore, grafted groups presented less deformations of the central canal compared to that of the non- grafted group. The open-field locomotor function as evaluated with the BBB scale showed no significant difference between the grafted and non-grafted groups, suggesting neither negative nor beneficial effects by the human spinal cord grafts in this lesion model. Solid human spinal cord grafts were implanted, in conjunction with conventional neurosurgical intervention, in three patients with progressive post-traumatic cystic myelopathy. The aim was to fuse the cyst walls and substitute for tissue loss with the grafts in order to reduce the risk of reexpansion of the cysts. For the first time, MRI-verified survival of transplanted solid human spinal cord tissue was observed after transplantation to man. The solid human spinal cord grafts obliterated the cysts at the site of implantation, as detected with MRI. Halted progression of the pre-operative neurological symtoms and modest neurological improvement showed that the surgical intervention was successful.
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| 25. |
- Åkesson, Elisabet, et al.
(author)
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Long-term survival, robust neuronal differentiation, and extensive migration of human forebrain stem/progenitor cells transplanted to the adult rat dorsal root ganglion cavity
- 2008
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In: Cell Transplantation. - : SAGE Publications. - 0963-6897 .- 1555-3892. ; 17:10-11, s. 1115-1123
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Journal article (peer-reviewed)abstract
- Neurons in dorsal root ganglia (DRGs) transmit sensory information from peripheral tissues to the spinal cord. This pathway can be interrupted, for example, as the result of physical violence, traffic accidents, or complications during child delivery. As a consequence, the patient permanently loses sensation and often develops intractable neuropathic pain in the denervated area. Here we investigate whether human neural stem/progenitor cells (hNSPCs) transplanted to the DRG cavity can serve as a source for repairing lost peripheral sensory connections. We found that hNSPCs robustly differentiate to neurons, which survive long-term transplantation. The neuronal population in the transplants was tightly surrounded by astrocytes, suggesting their active role in neuron survival. Furthermore, 3 months after grafting hNSPCs were found in the dorsal root transitional zone (DRTZ) and within the spinal cord. The level of differentiation of transplanted cells was high in the core of the transplants whereas cells that migrated to the DRTZ and spinal cord were undifferentiated, nestin-expressing precursors. These data indicate that peripherally transplanted hNPSCs can be used for repair of dorsal root avulsion or spinal cord injuries; however, additional factors are required to guide their differentiation to the desired type of neurons. Furthermore, hNPSCs that migrate from the DRG cavity graft site to the DRTZ and spinal cord may provide trophic support for regenerating dorsal root axons, thereby allowing them to reenter the host spinal cord.
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| 26. |
- Åkesson, Karolina, et al.
(author)
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Kynurenine pathway is altered in patients with SLE and associated with severe fatigue
- 2018
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In: Lupus Science and Medicine. - : BMJ Publishing Group Ltd. - 2053-8790. ; 5:1
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Journal article (peer-reviewed)abstract
- Objective: Fatigue has been reported as the most disturbing symptom in a majority of patients with SLE. Depression is common and often severe. Together these symptoms cause significant morbidity and affect patients with otherwise relatively mild disease. Tryptophan and its metabolites in the kynurenine pathway are known to be important in several psychiatric conditions, for example, depression, which are often also associated with fatigue. We therefore investigated the kynurenine pathway in patients with SLE and controls.Methods: In a cross-sectional design plasma samples from 132 well-characterised patients with SLE and 30 age-matched and gender-matched population-based controls were analysed by liquid chromatography tandem mass spectrometry to measure the levels of tryptophan and its metabolites kynurenine and quinolinic acid. Fatigue was measured with Fatigue Severity Scale and depression with Hospital Anxiety and Depression Scale. SLE disease activity was assessed with Systemic Lupus Erythematosus Disease Activity Index (SLEDAI).Results: The kynurenine/tryptophan ratio, as a measure of indoleamine 2,3-dioxygenase (IDO) activity, was increased in patients with SLE. Patients with active disease (SLEDAI >= 6) showed lower tryptophan levels compared with controls (54 mu M, SD=19 vs 62 mu M, SD=14, p=0.03), although patients with SLE overall did not differ compared with controls. Patients with SLE had higher levels of tryptophan metabolites kynurenine (966 nM, SD=530) and quinolinic acid (546 nM, SD=480) compared with controls (kynurenine: 712 nM, SD=230, p=0.0001; quinolinic acid: 380 nM, SD=150, p=0.001). Kynurenine, quinolinic acid and the kynurenine/tryptophan ratio correlated weakly with severe fatigue (r(s)=0.34, r(s)=0.28 and r(s)=0.24, respectively) but not with depression.Conclusions: Metabolites in the kynurenine pathway are altered in patients with SLE compared with controls. Interestingly, fatigue correlated weakly with measures of enhanced tryptophan metabolism, while depression did not. Drugs targeting enzymes in the kynurenine pathway, for example, IDO inhibitors or niacin (B12) supplementation, which suppresses IDO activity, merit further investigation as treatments in SLE.
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