| 1. |
- Mazzurana, Luca, et al.
(författare)
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Tissue-specific transcriptional imprinting and heterogeneity in human innate lymphoid cells revealed by full-length single-cell RNA-sequencing
- 2021
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Ingår i: Cell Research. - : Springer Science and Business Media LLC. - 1748-7838 .- 1001-0602. ; 31:5, s. 554-568
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Tidskriftsartikel (refereegranskat)abstract
- The impact of the microenvironment on innate lymphoid cell (ILC)-mediated immunity in humans remains largely unknown. Here we used full-length Smart-seq2 single-cell RNA-sequencing to unravel tissue-specific transcriptional profiles and heterogeneity of CD127+ ILCs across four human tissues. Correlation analysis identified gene modules characterizing the migratory properties of tonsil and blood ILCs, and signatures of tissue-residency, activation and modified metabolism in colon and lung ILCs. Trajectory analysis revealed potential differentiation pathways from circulating and tissue-resident naïve ILCs to a spectrum of mature ILC subsets. In the lung we identified both CRTH2+ and CRTH2− ILC2 with lung-specific signatures, which could be recapitulated by alarmin-exposure of circulating ILC2. Finally, we describe unique TCR-V(D)J-rearrangement patterns of blood ILC1-like cells, revealing a subset of potentially immature ILCs with TCR-δ rearrangement. Our study provides a useful resource for in-depth understanding of ILC-mediated immunity in humans, with implications for disease.
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| 2. |
- Thålin, Charlotte, et al.
(författare)
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Elevated Troponin Levels in Acute Stroke Patients Predict Long-term Mortality
- 2015
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Ingår i: Journal of Stroke & Cerebrovascular Diseases. - : Elsevier BV. - 1052-3057 .- 1532-8511. ; 10, s. 285-286
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Forskningsöversikt (refereegranskat)abstract
- Background: Elevated plasma levels of troponin in acute stroke patients are common and have in several studies been shown to predict in-hospital and short-term mortality. Little is, however, known about the long-term prognosis of these patients. The aim of this study was to determine patient characteristics and 5-year mortality in patients with acute stroke and troponin elevation on admission. Methods: A retrospective cohort study of all consecutive patients with acute stroke and a plasma troponin I (TnI) analyzed on admission to Danderyd Hospital between January 1, 2005, and January 1, 2006 (n = 247). Patient characteristics were obtained from the Swedish National Stroke Register, Riksstroke, as well as hospital records. Mortality data were obtained from the Swedish Cause of Death Register. Results: There were 133 patients (54%) with TnI less than .03 mu g/L (normal), 74 patients (30%) with TnI .03-.11 mu g/L (low elevation), and 40 patients (16%) with TnI greater than .11 mu g/L (high elevation). TnI elevations were associated with a higher age, prior ischemic stroke, chronic heart failure, renal insufficiency, stroke severity, and ST segment elevation or depression on admission. The rate of hyperlipidemia decreased with increasing TnI. Adjusted for age and comorbidity, elevated TnI values on admission had a significantly and sustained increased mortality over the 5-year follow-up, with a hazard ratio of 1.90 (95% confidence interval, 1.33-2.70). Conclusions: Troponin elevation in patients with acute stroke, even when adjusted for several possible confounders, is associated with an almost 2-fold increased risk of 5-year mortality.
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| 3. |
- Aaro Jonsson, Catherine C., et al.
(författare)
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Variability in quality of life 13 years after traumatic brain injury in childhood
- 2014
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Ingår i: International Journal of Rehabilitation Research. - : Wolters Kluwer. - 0342-5282 .- 1473-5660. ; 37:4, s. 317-322
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Tidskriftsartikel (refereegranskat)abstract
- With the aim of describing variability in the long-term outcome of quality of life after neurosurgically treated pediatric traumatic brain injury, mostly self-reports of 21 individuals with mild or moderate/severe injury were gathered using Mayo-Portland Adaptability Inventory in telephone interviews 13 years aftyer injury. A majority of the participants reported brain injury-related problems. The median outcome on Mayo-Portland Adaptability Inventory was mild to moderate limitations. The variation within the moderate/severe group varied between relatively good outcome and moderate/severe limitations. Concentration, irritability, fatigue, and transportation were reported as the most problematic areas, whereas self-care was reported as well functioning. Societal participation appeared to be the best functional domain in this Swedish study. Examples of individual reports of the life-situation at various outcome levels were provided. Variability in outcome is large within severity groups, and research may gain by addressing both outcomes of the individuals and groups. Objective questions of outcome should be accompanied by questions of actual functioning in everyday life. To ensure long-term support for quality of life for those with remaining dysfunction after pediatric traumatic brain injury, healthcare systems should implement systematic routines for referral to rehabilitation and support.
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| 4. |
- Aaro Jonsson, Catherine, et al.
(författare)
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Cognitive Recovery and Development after Traumatic Brain Injury in Childhood : A Person-Oriented, Longitudinal Study
- 2013
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Ingår i: Journal of Neurotrauma. - : Mary Ann Liebert Inc. - 0897-7151 .- 1557-9042. ; 30:2, s. 76-83
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Tidskriftsartikel (refereegranskat)abstract
- Influence of childhood traumatic brain injury (TBI) on cognitive recovery and subsequent development is poorly understood. In this longitudinal study we used cluster analysis to explore acute stage individual profiles of injury age and cognition in 118 children with traumatic brain injury. Repeated measures of cognitive function were conducted at 30 months, indicating recovery, and 10 years post-injury, indicating development. Nine clusters were identified. Recovery was evident in three clusters, two of them with low functioning profiles. Developmental gains occurred for three clusters and an acute profile of higher freedom from distractibility (FFD) and lower processing speed (PS) was related to positive differences. One cluster, average low functioning and especially low verbal comprehension, demonstrated a slower development than peers. This suggests that developmental change after TBI in childhood takes place on a continuum, with both chance of long-term catching up, and risk of poor development. An acute profile of higher FFD and lower PS seemed to reflect injury consequences and were followed by developmental gains. These results challenge previous findings, and warrant further investigation.
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| 5. |
- Aaro Jonsson, Catherine, 1963-, et al.
(författare)
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Long-term cognitive outcome after neurosurgically treated childhood traumatic brain injury
- 2009
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Ingår i: Brain Injury. - : Taylor & Francis. - 0269-9052 .- 1362-301X. ; 23:13-14, s. 1008-1016
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Tidskriftsartikel (refereegranskat)abstract
- Objective: To explore the cognitive long term outcome of two cohorts of patients neurosurgically treated for childhood traumatic brain injury (CTBI), either in 1987-1991 according to an older concept, or 1997-2001 with a stronger emphasis on volume targeted interventions. Research design and methods: Participants in the two cohorts were subject to an extensive neuropsychological assessment, 13.2 and 6.1 years post injury, respectively. In a between group design, assessment results of the two cohorts, n 18 and n 23, were compared to each other and to controls. Data were analyzed with multivariate analyses of variance. Results: Long-term cognitive deficits for both groups of similar magnitude and character were observed in both groups. Abilities were especially low regarding executive and memory function and verbal IQ. The cognitive results are discussed in terms of vulnerability of verbal functions and decreased executive control over memory-functions. Conclusions: There is a definite need for long term follow up of cognitive deficits after neurosurgically treated CTBI, also with the newer neurosurgical concept. Verbal learning and the executive control over memory functions should be addressed with interventions aimed at restoration, coping and compensation.
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| 6. |
- Aaro Jonsson, Catherine
(författare)
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Long-term cognitive outcome of childhood traumatic brain injury
- 2010
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- There is limited knowledge of cognitive outcome extending beyond 5 years after childhood traumatic brain injury, CTBI. The main objectives of this thesis were to investigate cognitive outcome at 6-14 years after CTBI, and to evaluate if advancements in the neurosurgical care, starting 1992, did influence long-term outcome and early epidemiology. An additional aim was to study the relationship between early brain injury parameters and early functional outcome. Study 1 evaluated cognitive progress during 14 years after CTBI, over three neuropsychological assessments in 8 patients with serious CTBI. Study 2 used patient records to investigate early epidemiology, received rehabilitation and medical follow up in two clinical cohorts, n=82 and n=46, treated neurosurgically for CTBI before and after 1992. An exploratory cluster analysis was applied to analyse the relation between early brain injury severity parameters and early functional outcome. In Study 3, participants in the two cohorts, n=18 and n=23, treated neurosurgically for CTBI before and after 1992, were subject to an extensive neuropsychological assessment, 13 and 6 years after injury, respectively. Assessment results of the two cohorts were compared with each other and with controls. Data were analysed with multivariate analyses of variance. Results and discussion. There were significant long-term cognitive deficits of similar magnitude and character in the two cohorts with CTBI, treated before and after the advancements in neurosurgical care. At 6-14 years after injury, long-term deficits in verbal intellectual and executive functions were found, and were discussed in terms of their late maturation and a decreased executive control over verbal memory-functions after CTBI. Visuospatial functions had a slightly better long-term recovery. The amount of rehabilitation received was equally low in both cohorts. The length of time spent in intensive care and the duration of care in the respirator may have a stronger relationship to early outcome than does a single measure of level of consciousness at admission. Main conclusions are that cognitive deficits are apparent at long-term follow up, 6-13 years after neurosurgically treated CTBI, even after advancements in the neurosurgical care in Sweden. Measures of verbal IQ, verbal memory and executive functions were especially low while visuospatial intellectual functions appear to have a better long-term recovery.
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| 7. |
- Andresen Bergström, Moa, 1978, et al.
(författare)
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A skin-like cytochrome P450 cocktail activates prohaptens to contact allergenic metabolites.
- 2007
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Ingår i: The Journal of investigative dermatology. - : Elsevier BV. - 1523-1747 .- 0022-202X. ; 127:5, s. 1145-53
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Tidskriftsartikel (refereegranskat)abstract
- Allergic contact dermatitis is a complex syndrome representing immunological responses to cutaneous exposure to protein-reactive chemicals. Although many contact sensitizers directly can elicit this disorder, others (prohaptens) require activation. Knowledge regarding the activating mechanisms remains limited, but one possibility is metabolic activation by cytochrome P450 (CYP) enzymes in the skin. We have, after quantitative reverse transcriptase-PCR studies of the CYP content in 18 human skin samples, developed an enriched skin-like recombinant human (rh) CYP cocktail using CYP1A1, 1B1, 2B6, 2E1, and 3A5. To validate the rhCYP cocktail, a prohaptenic conjugated diene ((5R)-5-isopropenyl-2-methyl-1-methylene-2-cyclohexene) was investigated using: the skin-like rhCYP cocktail, a liver-like rhCYP cocktail, single rhCYP enzymes, liver microsomes, keratinocytes, and a dendritic cell (DC) assay. The diene was activated to sensitizing epoxides in all non-cell-based incubations including the skin-like rhCYP cocktail. An exocyclic epoxide metabolite ((7R)-7-isopropenyl-4-methyl-1-oxaspiro[2.5]oct-4-ene) was found to be mainly responsible for the allergenic activity of the diene. This epoxide also induced pronounced DC activation indicated by upregulation of IL-8. The skin-like rhCYP cocktail provides a simplified alternative to using skin tissue preparations in mechanistic studies of CYP-mediated skin metabolism of prohaptens and offers the future possibility of designing in vitro predictive assays for assessment of allergenic activity of prohaptens.
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| 8. |
- Bjerkeli, Pernilla J., et al.
(författare)
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Refill Adherence in Relation to Substitution and the Use of Multiple Medications: A Nationwide Population Based Study on New ACE-Inhibitor Users
- 2016
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Ingår i: Plos One. - : Public Library of Science (PLoS). - 1932-6203. ; 11:5
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Tidskriftsartikel (refereegranskat)abstract
- Objective Generic substitution has contributed to economic savings but switching products may affect patient adherence, particularly among those using multiple medications. The aim was to analyse if use of multiple medications influenced the association between switching products and refill adherence to angiotensin-converting-enzyme (ACE) inhibitors in Sweden. New users of ACE-inhibitors, starting between 1 July 2006 and 30 June 2007, were identified in the Swedish Prescribed Drug Register. Refill adherence was assessed using the continuous measure of medication acquisition (CMA) and analysed with linear regression and analysis of covariance. The study population included 42735 individuals whereof 51.2% were exposed to switching ACE-inhibitor and 39.6% used multiple medications. Refill adherence was higher among those exposed to switching products than those not, but did not vary depending on the use of multiple medications or among those not. Refill adherence varied with age, educational level, household income, country of birth, previous hospitalisation and previous cardiovascular diagnosis. The results indicate a positive association between refill adherence and switching products, mainly due to generic substitution, among new users of ACE-inhibitors in Sweden. This association was independent of use of multiple medications.
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| 9. |
- Bråred Christensson, Johanna, 1965, et al.
(författare)
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Limonene hydroperoxide analogues differ in allergenic activity
- 2008
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Ingår i: Contact Dermatitis. - : Wiley. - 0105-1873 .- 1600-0536. ; 59:6, s. 344-352
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Tidskriftsartikel (refereegranskat)abstract
- Background: The fragrance terpene R-limonene is a very weak sensitizer but forms allergenic oxidation products upon contact with air. Oxidized (ox.) limonene is a frequent cause of contact allergy in clinical testing. Objectives: This study investigates the sensitizing potencies of ox. and non-ox. limonene and of structurally closely related limonene hydroperoxides. The clinical importance of the difference in sensitizing potency of two hydroperoxides in autoxidized limonene was studied. Patients/Methods: Ox. and non-ox. limonene were investigated in the murine local lymph node assay (LLNA). Limonene hydroperoxides were investigated using a modified LLNA involving non-pooled lymph nodes and statistical calculations; patch testing of patients with known contact allergy to ox. limonene was performed. Results: A marked increase in the sensitizing potency of ox. limonene compared with that of pure limonene was observed in the LLNA. One analogue, limonene-1-hydroperoxide, was a significantly more potent sensitizer than the other hydroperoxides and gave more positive test reactions in the allergic patients. Conclusions: The results support that hydroperoxides have a specific reactivity indicating that oxygen-centred radicals are important in hapten–protein complex formation of hydroperoxides. The primary oxidation products of ox. limonene, the hydroperoxides, have an important impact on the sensitizing capacity of the oxidation mixture.
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| 10. |
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