| 1. |
- Antonsson, Malin, 1986, et al.
(författare)
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High-level language ability in healthy individuals and its relationship with verbal working memory
- 2016
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Ingår i: Clinical Linguistics & Phonetics. - : Informa UK Limited. - 0269-9206 .- 1464-5076. ; 30:12, s. 944-958
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Tidskriftsartikel (refereegranskat)abstract
- The aims of the study were to investigate healthy subjects' performance on a clinical test of high-level language (HLL) and how it is related to demographic characteristics and verbal working memory (VWM). One hundred healthy subjects (20-79 years old) were assessed with the Swedish BeSS test (Laakso, Brunnegard, Hartelius, & Ahlsen, 2000) and two digit span tasks. Relationships between the demographic variables, VWM and BeSS were investigated both with bivariate correlations and multiple regression analysis. The results present the norms for BeSS. The correlations and multiple regression analysis show that demographic variables had limited influence on test performance. Measures of VWM were moderately related to total BeSS score and weakly to moderately correlated with five of the seven subtests. To conclude, education has an influence on the test as a whole but measures of VWM stood out as the most robust predictor of HLL.
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| 2. |
- Askelöf, U., et al.
(författare)
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Wait a minute? : An observational cohort study comparing iron stores in healthy Swedish infants at 4 months of age after 10-, 60- and 180-second umbilical cord clamping
- 2017
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Ingår i: BMJ Open. - : BMJ Publishing Group. - 2044-6055. ; 7:12
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Tidskriftsartikel (refereegranskat)abstract
- Background and objective: Umbilical cord blood (UCB) is a valuable stem cell source used for transplantation. Immediate umbilical cord (UC) clamping is widely practised, but delayed UC clamping is increasingly advocated to reduce possible infant anaemia. The aim of this study was to investigate an intermediate UC clamping time point and to evaluate iron status at the age of 4 months in infants who had the UC clamped after 60 s and compare the results with immediate and late UC clamping. Design: Prospective observational study with two historical controls. Setting: A university hospital in Stockholm, Sweden, and a county hospital in Halland, Sweden. Methods: Iron status was assessed at 4 months in 200 prospectively recruited term infants whose UC was clamped 60 s after birth. The newborn baby was held below the uterine level for the first 30 s before placing the infant on the mother's abdomen for additional 30 s. The results were compared with data from a previously conducted randomised controlled trial including infants subjected to UC clamping at ≤10 s (n=200) or ≥180 s (n=200) after delivery. Results: After adjustment for age differences at the time of follow-up, serum ferritin concentrations were 77, 103 and 114 μg/L in the 10, 60 and 180 s groups, respectively. The adjusted ferritin concentration was significantly higher in the 60 s group compared with the 10 s group (P=0.002), while the difference between the 60 and 180 s groups was not significant (P=0.29). Conclusion: In this study of healthy term infants, 60 s UC clamping with 30 s lowering of the baby below the uterine level resulted in higher serum ferritin concentrations at 4 months compared with 10 s UC clamping. The results suggest that delaying the UC clamping for 60 s reduces the risk for iron deficiency. © 2017 Article author(s).
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| 3. |
- Bergqvist, Cecilia, et al.
(författare)
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Monitoring of chromatin organization in live cells by FRIC. Effects of the inner nuclear membrane protein Samp1
- 2019
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Ingår i: Nucleic Acids Research. - : Oxford University Press (OUP). - 0305-1048 .- 1362-4962. ; 47:9
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Tidskriftsartikel (refereegranskat)abstract
- In most cells, transcriptionally inactive heterochromatin is preferentially localized in the nuclear periphery and transcriptionally active euchromatin is localized in the nuclear interior. Different cell types display characteristic chromatin distribution patterns, which change dramatically during cell differentiation, proliferation, senescence and different pathological conditions. Chromatin organization has been extensively studied on a cell population level, but there is a need to understand dynamic reorganization of chromatin at the single cell level, especially in live cells. We have developed a novel image analysis tool that we term Fluorescence Ratiometric Imaging of Chromatin (FRIC) to quantitatively monitor dynamic spatiotemporal distribution of euchromatin and total chromatin in live cells. A vector (pTandemH) assures stoichiometrically constant expression of the histone variants Histone 3.3 and Histone 2B, fused to EGFP and mCherry, respectively. Quantitative ratiometric (H3.3/H2B) imaging displayed a concentrated distribution of heterochromatin in the periphery of U2OS cell nuclei. As proof of concept, peripheral heterochromatin responded to experimental manipulation of histone acetylation. We also found that peripheral heterochromatin depended on the levels of the inner nuclear membrane protein Samp1, suggesting an important role in promoting peripheral heterochromatin. Taken together, FRIC is a powerful and robust new tool to study dynamic chromatin redistribution in live cells.
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| 4. |
- Guan, Jikui, et al.
(författare)
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Clinical response of the novel activating ALK-I1171T mutation in neuroblastoma to the ALK inhibitor ceritinib.
- 2018
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Ingår i: Cold Spring Harbor molecular case studies. - : Cold Spring Harbor Laboratory. - 2373-2873. ; 4:4
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Tidskriftsartikel (refereegranskat)abstract
- Tumors with Anaplastic Lymphoma Kinase (ALK) fusion rearrangements, including non-small cell lung cancer and anaplastic large cell lymphoma, are highly sensitive to ALK tyrosine kinase inhibitors (TKIs), underscoring the notion that such cancers are addicted to ALK activity. While mutations in ALK are heavily implicated in childhood neuroblastoma, response to the ALK TKI crizotinib has been disappointing. Embryonal tumors in patients with DNA repair defects such as Fanconi anemia (FA) often have a poor prognosis, due to lack of therapeutic options. Here we report a child with underlying FA and ALK mutant high-risk neuroblastoma responding strongly to precision therapy with the ALK TKI ceritinib. Conventional chemotherapy treatment caused severe, life-threatening toxicity. Genomic analysis of the initial biopsy identified germ-line FANCA mutations as well as a novel ALK-I1171T variant. ALK-I1171T generates a potent gain-of-function mutant, as measured in PC12 cell neurite outgrowth and NIH3T3 transformation. Pharmacological inhibition profiling of ALK-I1171T in response to various ALK TKIs identified an 11-fold improved inhibition of ALK-I1171T with ceritinib when compared with crizotinib. Immunoaffinity-coupled LC-MS/MS phosphoproteomics analysis indicated a decrease in ALK signaling in response to ceritinib. Ceritinib was therefore selected for treatment in this child. Mono-therapy with ceritinib was well tolerated and resulted in normalized catecholamine markers and tumor shrinkage. After 7.5 months treatment, residual primary tumor was surgically removed and exhibited hallmarks of differentiation together with reduced Ki67 levels. Clinical follow-up after 21 months treatment revealed complete clinical remission including all metastatic sites. Therefore, ceritinib presents a viable therapeutic option for ALK-positive neuroblastoma.
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| 5. |
- Hellström, Ann, 1959, et al.
(författare)
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IGF-1 as a Drug for Preterm Infants : A Step-Wise Clinical Development
- 2017
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Ingår i: Current Pharmaceutical Design. - : Bentham Science Publishers Ltd.. - 1381-6128 .- 1873-4286. ; 23:38, s. 5964-5970
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Forskningsöversikt (refereegranskat)abstract
- BACKGROUND: Insulin-like growth factor 1 (IGF-1) is a mitogenic hormone involved in many processes such as growth, metabolism, angiogenesis and differentiation. After very preterm birth, energy demands increase while maternal supplies of nutrients and other factors are lost and the infant may become dependent on parenteral nutrition for weeks. Low postnatal IGF-1 concentrations in preterm infants are associated with poor weight gain, retinopathy of prematurity (ROP) and other morbidities. We will describe the process by which we aim to develop supplementation with recombinant human (rh) IGF-1 and its binding protein rhIGFBP-3 as a possible therapy to promote growth and maturation and reduce morbidities in extremely preterm infants.METHODS: In order to calculate a dose of IGF-1 tolerated by neonates, a pharmacokinetic study of transfusion with fresh frozen plasma was performed, which provided a relatively low dose of IGF-1, (on average 1.4 µg/kg), that increased serum IGF-1 to levels close to those observed in fetuses and preterm infants of similar GAs. Thereafter, a Phase I 3 hours IV infusion of rhIGF-1/rhIGFBP-3 was conducted in 5 infants, followed by a Phase II study with four sections (A-D). In the Phase II, sections A-D studies, time on infusion increased and younger gestational ages were included.RESULTS: IV infusion increased IGF-1 but with short half-life (0.5h) implying a need for continuous infusion. In order to obtain in utero levels of IGF-I, the dose was increased from 100 to 250 µg/kg/24 h and the infusion was prolonged from 3 weeks postnatal age until a postmenstrual age of 29 weeks and 6 days.CONCLUSION: The purpose has been to ensure high-quality research into the development of a new drug for preterm infants. We hope that our work will help to establish a new standard for the testing of medications for preterm infants.
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| 6. |
- Hellström, Ann, 1959, et al.
(författare)
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Insulin-like growth factor 1 has multisystem effects on foetal and preterm infant development.
- 2016
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Ingår i: Acta paediatrica (Oslo, Norway : 1992). - : Wiley. - 1651-2227 .- 0803-5253. ; 105:6, s. 576-86
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Tidskriftsartikel (refereegranskat)abstract
- Poor postnatal growth after preterm birth does not match the normal rapid growth in utero and is associated with preterm morbidities. Insulin-like growth factor 1 (IGF-1) axis is the major hormonal mediator of growth in utero, and levels of IGF-1 are often very low after preterm birth. We reviewed the role of IGF-1 in foetal development and the corresponding preterm perinatal period to highlight the potential clinical importance of IGF-1 deficiency in preterm morbidities.
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| 7. |
- Hellström, Ann, 1959, et al.
(författare)
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Role of Insulinlike Growth Factor 1 in Fetal Development and in the Early Postnatal Life of Premature Infants
- 2016
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Ingår i: American Journal of Perinatology. - : Georg Thieme Verlag KG. - 0735-1631 .- 1098-8785. ; 33:11, s. 1067-1071
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Tidskriftsartikel (refereegranskat)abstract
- The neonatal period of very preterm infants is often characterized by a difficult adjustment to extrauterine life, with an inadequate nutrient supply and insufficient levels of growth factors, resulting in poor growth and a high morbidity rate. Long-term multisystem complications include cognitive, behavioral, and motor dysfunction as a result of brain damage as well as visual and hearing deficits and metabolic disorders that persist into adulthood. Insulinlike growth factor 1 (IGF-1) is a major regulator of fetal growth and, development of most organs especially the central nervous system including the retina. Glucose metabolism in the developing brain is controlled by IGF-1 which also stimulates differentiation and prevents apoptosis. Serum concentrations of IGF-1 decrease to very low levels after very preterm birth and remain low for most of the perinatal development. Strong correlations have been found between low neonatal serum concentrations of IGF-1 and poor brain and retinal growth as well as poor general growth with multiorgan morbidities, such as intraventricular hemorrhage, retinopathy of prematurity, bronchopulmonary dysplasia, and necrotizing enterocolitis. Experimental and clinical studies indicate that early supplementation with IGF-1 can improve growth in catabolic states and reduce brain injury after hypoxic/ischemic events. A multicenter phase II study is currently underway to determine whether intravenous replacement of human recombinant IGF-1 up to normal intrauterine serum concentrations can improve growth and development and reduce prematurity-associated morbidities.
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| 8. |
- Lundgren, Pia, 1967, et al.
(författare)
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Aggressive Posterior Retinopathy of Prematurity Is Associated with Multiple Infectious Episodes and Thrombocytopenia
- 2017
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Ingår i: Neonatology. - : S. Karger AG. - 1661-7800 .- 1661-7819. ; 111:1, s. 79-85
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Tidskriftsartikel (refereegranskat)abstract
- © 2016 S. Karger AG, BaselBackground: The most severe form of rapidly progressing retinopathy of prematurity (ROP) is termed aggressive posterior ROP (APROP). APROP frequently causes severe visual impairment in affected preterm infants despite timely and appropriate laser treatment. Objectives: We investigated the postnatal characteristics associated with APROP development in a national Swedish cohort. Methods: This retrospective, 1:1 matched case-control study included all infants that developed APROP in zone 1 (n = 9) between 2008 and 2012. Control infants, matched for gestational age and birth weight, developed ROP no worse than stage 2 (n = 9). We retrieved data from medical records on infant birth characteristics, postnatal morbidities, and blood analyses from birth to the first ROP treatment. Infectious episodes included sepsis, C-reactive protein ≥10 mg/l, and other clinical signs of infection that required antibiotic treatment. A platelet count <100 × 109/l was considered to be thrombocytopenia. Results: All APROP cases postnatally developed at least two infectious episodes, one in the first month and one around the time of ROP diagnosis. All APROP cases exhibited thrombocytopenia in the first month, and 6/9 exhibited thrombocytopenia around the time of ROP diagnosis. Compared to the controls, APROP cases more frequently developed necrotizing enterocolitis (8/9 vs. 1/9; p < 0.01) and sepsis (9/9 vs. 3/9; p < 0.01), and they had significantly lower median platelet counts (90 × 109/l, range 4-459, vs. 158 × 109/l, range 20-500; p < 0.001). Conclusion: Multiple infectious episodes and thrombocytopenia, particularly around the time of ROP diagnosis, were associated with APROP development.
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| 9. |
- Norman, M., et al.
(författare)
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Association Between Year of Birth and 1-Year Survival Among Extremely Preterm Infants in Sweden During 2004-2007 and 2014-2016
- 2019
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Ingår i: Jama-Journal of the American Medical Association. - Chicago : American Medical Association (AMA). - 0098-7484 .- 1538-3598. ; 321:12, s. 1188-1199
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Tidskriftsartikel (refereegranskat)abstract
- IMPORTANCE Since 2004-2007, national guidelines and recommendations have been developed for the management of extremely preterm births in Sweden. If and how more uniform management has affected infant survival is unknown. OBJECTIVE To compare survival of extremely preterm infants born during 2004-2007 with survival of infants born during 2014-2016. DESIGN, SETTING AND PARTICIPANTS All births at 22-26weeks' gestational age (n = 2205) between April 1, 2004, and March 31, 2007, and between January 1, 2014, and December 31, 2016, in Sweden were studied. Prospective data collection was used during 2004-2007. Data were obtained from the Swedish pregnancy, medical birth, and neonatal quality registries during 2014-2016. EXPOSURES Delivery at 22-26 weeks' gestational age. MAIN OUTCOMES AND MEASURES The primary outcomewas infant survival to the age of 1 year. The secondary outcome was 1-year survival among live-born infants who did not have any major neonatal morbidity (specifically, without intraventricular hemorrhage grade 3-4, cystic periventricular leukomalacia, necrotizing enterocolitis, retinopathy of prematurity stage 3-5, or severe bronchopulmonary dysplasia). RESULTS During 2004-2007, 1009 births (3.3/1000 of all births) occurred at 22-26 weeks' gestational age compared with 1196 births (3.4/1000 of all births) during 2014-2016 (P =.61). One-year survival among live-born infants at 22-26 weeks' gestational age was significantly lower during 2004-2007 (497 of 705 infants [70%]) than during 2014-2016 (711 of 923 infants [77%]) (difference, -7%[95% CI, -11% to -2.2%], P =.003). One-year survival among live-born infants at 22-26 weeks' gestational age and without any major neonatal morbidity was significantly lower during 2004-2007 (226 of 705 infants [32%]) than during 2014-2016 (355 of 923 infants [38%]) (difference, -6%[95% CI, -11% to -1.7%], P =.008). CONCLUSIONS AND RELEVANCE Among live births at 22-26 weeks' gestational age in Sweden, 1-year survival improved between 2004-2007 and 2014-2016.
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