| 1. |
- Aad, G., et al.
(författare)
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- 2011
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swepub:Mat__t (refereegranskat)
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| 2. |
- Aad, G., et al.
(författare)
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- 2012
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swepub:Mat__t (refereegranskat)
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| 3. |
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| 4. |
- Campbell, PJ, et al.
(författare)
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Pan-cancer analysis of whole genomes
- 2020
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 1476-4687 .- 0028-0836. ; 578:7793, s. 82-
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Tidskriftsartikel (refereegranskat)abstract
- Cancer is driven by genetic change, and the advent of massively parallel sequencing has enabled systematic documentation of this variation at the whole-genome scale1–3. Here we report the integrative analysis of 2,658 whole-cancer genomes and their matching normal tissues across 38 tumour types from the Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium of the International Cancer Genome Consortium (ICGC) and The Cancer Genome Atlas (TCGA). We describe the generation of the PCAWG resource, facilitated by international data sharing using compute clouds. On average, cancer genomes contained 4–5 driver mutations when combining coding and non-coding genomic elements; however, in around 5% of cases no drivers were identified, suggesting that cancer driver discovery is not yet complete. Chromothripsis, in which many clustered structural variants arise in a single catastrophic event, is frequently an early event in tumour evolution; in acral melanoma, for example, these events precede most somatic point mutations and affect several cancer-associated genes simultaneously. Cancers with abnormal telomere maintenance often originate from tissues with low replicative activity and show several mechanisms of preventing telomere attrition to critical levels. Common and rare germline variants affect patterns of somatic mutation, including point mutations, structural variants and somatic retrotransposition. A collection of papers from the PCAWG Consortium describes non-coding mutations that drive cancer beyond those in the TERT promoter4; identifies new signatures of mutational processes that cause base substitutions, small insertions and deletions and structural variation5,6; analyses timings and patterns of tumour evolution7; describes the diverse transcriptional consequences of somatic mutation on splicing, expression levels, fusion genes and promoter activity8,9; and evaluates a range of more-specialized features of cancer genomes8,10–18.
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| 5. |
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- 2019
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Tidskriftsartikel (refereegranskat)
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| 6. |
- Weinstein, John N., et al.
(författare)
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The cancer genome atlas pan-cancer analysis project
- 2013
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 45:10, s. 1113-1120
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Forskningsöversikt (refereegranskat)abstract
- The Cancer Genome Atlas (TCGA) Research Network has profiled and analyzed large numbers of human tumors to discover molecular aberrations at the DNA, RNA, protein and epigenetic levels. The resulting rich data provide a major opportunity to develop an integrated picture of commonalities, differences and emergent themes across tumor lineages. The Pan-Cancer initiative compares the first 12 tumor types profiled by TCGA. Analysis of the molecular aberrations and their functional roles across tumor types will teach us how to extend therapies effective in one cancer type to others with a similar genomic profile. © 2013 Nature America, Inc. All rights reserved.
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| 7. |
- Hudson, Thomas J., et al.
(författare)
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International network of cancer genome projects
- 2010
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 464:7291, s. 993-998
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Tidskriftsartikel (refereegranskat)abstract
- The International Cancer Genome Consortium (ICGC) was launched to coordinate large-scale cancer genome studies in tumours from 50 different cancer types and/or subtypes that are of clinical and societal importance across the globe. Systematic studies of more than 25,000 cancer genomes at the genomic, epigenomic and transcriptomic levels will reveal the repertoire of oncogenic mutations, uncover traces of the mutagenic influences, define clinically relevant subtypes for prognosis and therapeutic management, and enable the development of new cancer therapies.
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| 8. |
- Costea, P. I., et al.
(författare)
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Enterotypes in the landscape of gut microbial community composition
- 2018
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Ingår i: Nature Microbiology. - : Springer Science and Business Media LLC. - 2058-5276. ; 3:1
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Tidskriftsartikel (refereegranskat)abstract
- Population stratification is a useful approach for a better understanding of complex biological problems in human health and wellbeing. The proposal that such stratification applies to the human gut microbiome, in the form of distinct community composition types termed enterotypes, has been met with both excitement and controversy. In view of accumulated data and re-analyses since the original work, we revisit the concept of enterotypes, discuss different methods of dividing up the landscape of possible microbiome configurations, and put these concepts into functional, ecological and medical contexts. As enterotypes are of use in describing the gut microbial community landscape and may become relevant in clinical practice, we aim to reconcile differing views and encourage a balanced application of the concept.
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| 9. |
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| 10. |
- Kennedy, K. M., et al.
(författare)
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Questioning the fetal microbiome illustrates pitfalls of low-biomass microbial studies
- 2023
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 613:7945, s. 639-649
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Tidskriftsartikel (refereegranskat)abstract
- Whether the human fetus and the prenatal intrauterine environment (amniotic fluid and placenta) are stably colonized by microbial communities in a healthy pregnancy remains a subject of debate. Here we evaluate recent studies that characterized microbial populations in human fetuses from the perspectives of reproductive biology, microbial ecology, bioinformatics, immunology, clinical microbiology and gnotobiology, and assess possible mechanisms by which the fetus might interact with microorganisms. Our analysis indicates that the detected microbial signals are likely the result of contamination during the clinical procedures to obtain fetal samples or during DNA extraction and DNA sequencing. Furthermore, the existence of live and replicating microbial populations in healthy fetal tissues is not compatible with fundamental concepts of immunology, clinical microbiology and the derivation of germ-free mammals. These conclusions are important to our understanding of human immune development and illustrate common pitfalls in the microbial analyses of many other low-biomass environments. The pursuit of a fetal microbiome serves as a cautionary example of the challenges of sequence-based microbiome studies when biomass is low or absent, and emphasizes the need for a trans-disciplinary approach that goes beyond contamination controls by also incorporating biological, ecological and mechanistic concepts.
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| 11. |
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| 12. |
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| 13. |
- Bischof, P., et al.
(författare)
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Implantation of the human embryo: Research lines and models
- 2006
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Ingår i: Gynecologic and Obstetric Investigation. - : S. Karger AG. - 1423-002X .- 0378-7346. ; 62:4, s. 206-216
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Forskningsöversikt (refereegranskat)abstract
- Infertility is an increasing problem all over the world, and it has been estimated that 10 - 15% of couples in fertile age have fertility problems. Likewise induced unsafe abortion is a serious threat to women's health. Despite advances made in assisted reproduction techniques, little progress has been made in increasing the success rate during fertility treatment. This document describes a wide range of projects carried out to increase the understanding in the field of embryo implantation research. The 'Fruitful' research network was created to encourage collaborations within the consortium and to describe our different research potentials to granting agencies or private sponsors. Copyright (c) 2006 S. Karger AG, Basel.
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| 14. |
- Bischof, P, et al.
(författare)
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Implantation of the human embryo: research lines and models. From the implantation research network 'Fruitful'.
- 2006
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Ingår i: Gynecologic and obstetric investigation. - : S. Karger AG. - 0378-7346 .- 1423-002X. ; 62:4, s. 206-16
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Tidskriftsartikel (refereegranskat)abstract
- Infertility is an increasing problem all over the world, and it has been estimated that 10-15% of couples in fertile age have fertility problems. Likewise induced unsafe abortion is a serious threat to women's health. Despite advances made in assisted reproduction techniques, little progress has been made in increasing the success rate during fertility treatment. This document describes a wide range of projects carried out to increase the understanding in the field of embryo implantation research. The 'Fruitful' research network was created to encourage collaborations within the consortium and to describe our different research potentials to granting agencies or private sponsors.
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| 15. |
- Bukur, M., et al.
(författare)
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Efficacy of beta-blockade after isolated blunt head injury : Does race matter? (vol 72, pg 1013, 2012)
- 2012
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Ingår i: Journal of Trauma and Acute Care Surgery. - : Lippincott Williams & Wilkins. - 2163-0755 .- 2163-0763. ; 72:6, s. 1725-1725
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Several retrospective clinical studies and recent prospective animal models demonstrate improved outcomes with beta-blocker administration after isolated blunt head injury. However, no investigations to date have examined the influence of race on the potential therapeutic effectiveness of these medications. Our hypothesis was that mortality benefits associated with beta-blocker exposure after isolated blunt head injury varies based on ethnicity.METHODS: The trauma registry and the surgical intensive care unit (ICU) databases of an academic Level I trauma center were used to identify all patients sustaining blunt head injury requiring ICU admission from July 1998 to December 2009. Patients sustaining major associated extracranial injuries (Abbreviated Injury Scale [AIS] score ≥3 in any body region) were excluded. Patient demographics, injury profile, Injury Severity Score, and beta-blocker exposure were abstracted. The primary outcome evaluated was in-hospital mortality stratified by ethnicity.RESULTS: During the 11-year study period, 3,750 patients were admitted to the Los Angeles County + University of Southern California Medical Center trauma ICU because of blunt trauma. Of these, 65% (n = 2,446) had an “isolated” head injury. When stratified by race, most patients were Hispanics (60%), followed by Whites (21%), Asians (11%), and African Americans (8%). After adjusting for confounding variables with multivariate regression, only those of Asian and Hispanic descent demonstrated significantly improved outcomes associated with beta-blocker administration.CONCLUSIONS: Our results indicate that beta-blockade after traumatic brain injury may not benefit all races equally. Further prospective research is necessary to assess this discrepancy in treatment benefit and explore other possible therapeutic interventions.LEVEL OF EVIDENCE: III, therapeutic study; II, prognostic study.
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| 16. |
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| 17. |
- Gümüş, H. G., et al.
(författare)
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Behavioral testing and litter effects in the rabbit
- 2018
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Ingår i: Behavioural Brain Research. - : Elsevier BV. - 0166-4328. ; 353, s. 236-241
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Tidskriftsartikel (refereegranskat)abstract
- Background: Behavioral testing provides an essential approach in further developing our understanding of brain structure and function. The aim of our study was to outline a more expanded approach to cognition- and anxiety-related behavior in the rabbit. Methods: Twenty-one 70-day old rabbits (13 female, 8 male) were exposed to open field test, dark-light box test and object recognition testing with variations in inter-trial-interval, olfactory recognition and object location testing. Independent T-tests were used to compare data by individual baseline characteristics, i.e. birth weight, weight at testing, sex, litter #, litter size. Results: In the open field test, median time spent in the center was 3.64 s (0.84-41.36) for the 9 rabbits who entered the center; median distance moved in the arena was 874.42 cm (54.20-3444.83). In the dark light box test, 12 rabbits entered the light compartment. In the object recognition task, rabbits spent significantly less time exploring the familiar object compared to the novel (0.40 s [0-2.8] vs. 3.17 s [1.30-32.69]; P = 0.003) when using a 30-min inter-trial interval, as well with a 90-min inter-trial interval: 0.87 s [0-7.8] vs. 7.65 s [0-37.6] (P = 0.008). However, recognition was lost when using a 24-h inter-trial interval (time spent exploring the familiar object: 3.33 [0-10.90]; novel object:3.87 [1.15-48.53]; n.s). In the object location task and in olfactory object recognition task, median discrimination indexes were 0.69 (-1 to 1) and 0.37 (-0.38 to 0.78) respectively, higher than level expected by chance (P < 0.001). Litter size >3 during the neonatal period was associated with increased explorative behavior in the dark light box test (P = 0.046) and in the visual object recognition task (P = 0.005), whereas body weight and sex were not. Conclusions: Settings and outcome measures for multiple behavioral tests, providing reference values and considerations for future developmental studies are reported. Discrimination and memory in the rabbit appear to relate to litter characteristics, although a larger sample size is needed to confirm our findings.
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| 18. |
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| 19. |
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| 20. |
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| 21. |
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| 22. |
- Arai, M, et al.
(författare)
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Both mosquito-derived xanthurenic acid and a host blood-derived factor regulate gametogenesis of Plasmodium in the midgut of the mosquito
- 2001
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Ingår i: Molecular and biochemical parasitology (Print). - : Elsevier. - 0166-6851 .- 1872-9428. ; 116:1, s. 17-24
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Tidskriftsartikel (refereegranskat)abstract
- Gametogenesis of Plasmodium in vitro can be induced by the combined stimulus of a 5 degrees C fall in temperature and the presence of xanthurenic acid (XA). In-vitro experiments showed that P. gallinaceum (EC(50)=80 nM) is much more sensitive to XA than P. berghei (9 microM), P. yoelii (8 microM), and P. falciparum (2 microM). However, in the mosquito vector, we do not know whether the temperature shift and XA are the only gametocyte-activating factors (GAF), nor do we know with certainty the true source(s) of XA in the mosquito blood meal. Previous studies indicate that XA is the only source of GAF in the mosquito. By defining, and then contrasting, the ability of an XA-deficient mutant of Aedes aegypti, with the wild-type mosquito to support exflagellation and ookinete formation in vivo, we determined the roles of parasite-, mosquito- and host blood-derived GAF in the regulation of gametogenesis of P. gallinaceum. Removal of both host and vector sources of GAF totally inhibited both exflagellation and ookinete production, whilst the lack of either single source resulted in only a partial reduction of exflagellation and ookinete formation in the mosquito gut. Both sources can be effectively replaced/substituted by synthetic XA. This suggests (1) both mosquito- and vertebrate-derived factors act as GAF in the mosquito gut in vivo; (2) the parasite itself is unable to produce any significant GAF activity. Studies are underway to determine whether vertebrate-derived GAF is XA. These data may form the basis of further studies of the development of new methods of interrupting malarial transmission.
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| 23. |
- Bäckhed, Fredrik, 1973, et al.
(författare)
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Host-bacterial mutualism in the human intestine
- 2005
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Ingår i: Science. ; 307:5717, s. 1915-20
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Forskningsöversikt (refereegranskat)abstract
- The distal human intestine represents an anaerobic bioreactor programmed with an enormous population of bacteria, dominated by relatively few divisions that are highly diverse at the strain/subspecies level. This microbiota and its collective genomes (microbiome) provide us with genetic and metabolic attributes we have not been required to evolve on our own, including the ability to harvest otherwise inaccessible nutrients. New studies are revealing how the gut microbiota has coevolved with us and how it manipulates and complements our biology in ways that are mutually beneficial. We are also starting to understand how certain keystone members of the microbiota operate to maintain the stability and functional adaptability of this microbial organ.
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| 24. |
- Caretta, Martina Angela, et al.
(författare)
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Water
- 2022
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Ingår i: Climate Change 2022: Impacts, Adaptation and Vulnerability : Contribution of Working Group II to the Sixth Assessment Report of the Intergovernmental Panel on Climate Change - Contribution of Working Group II to the Sixth Assessment Report of the Intergovernmental Panel on Climate Change.
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Bokkapitel (övrigt vetenskapligt/konstnärligt)
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| 25. |
- Carvalho, F. A., et al.
(författare)
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Transient Inability to Manage Proteobacteria Promotes Chronic Gut Inflammation in TLR5-Deficient Mice
- 2012
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Ingår i: Cell Host & Microbe. - : Elsevier BV. - 1931-3128. ; 12:2, s. 139-152
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Tidskriftsartikel (refereegranskat)abstract
- Colitis results from breakdown of homeostasis between intestinal microbiota and the mucosal immune system, with both environmental and genetic influencing factors. Flagellin receptor TLR5-deficient mice (T5KO) display elevated intestinal proinflammatory gene expression and colitis with incomplete penetrance, providing a genetically sensitized system to study the contribution of microbiota to driving colitis. Both colitic and noncolitic T5KO exhibited transiently unstable microbiotas, with lasting differences in colitic T5KO, while their noncolitic siblings stabilized their microbiotas to resemble wild-type mice. Transient high levels of proteobacteria, especially enterobacteria species including E. coli, observed in close proximity to the gut epithelium were a striking feature of colitic microbiota. A Crohn's disease-associated E. coli strain induced chronic colitis in T5KO, which persisted well after the exogenously introduced bacterial species had been eliminated. Thus, an innate immune deficiency can result in unstable gut microbiota associated with low-grade inflammation, and harboring proteobacteria can drive and/or instigate chronic colitis.
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| 26. |
- Cizmeci, Mehmet N, et al.
(författare)
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Assessment of Brain Injury and Brain Volumes after Posthemorrhagic Ventricular Dilatation : A Nested Substudy of the Randomized Controlled ELVIS Trial
- 2019
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Ingår i: Journal of Pediatrics. - : Elsevier BV. - 1097-6833 .- 0022-3476. ; 208, s. 2-197
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: To compare the effect of early and late intervention for posthemorrhagic ventricular dilatation on additional brain injury and ventricular volume using term-equivalent age-MRI.STUDY DESIGN: In the Early vs Late Ventricular Intervention Study (ELVIS) trial, 126 preterm infants ≤34 weeks of gestation with posthemorrhagic ventricular dilatation were randomized to low-threshold (ventricular index >p97 and anterior horn width >6 mm) or high-threshold (ventricular index >p97 + 4 mm and anterior horn width >10 mm) groups. In 88 of those (80%) with a term-equivalent age-MRI, the Kidokoro Global Brain Abnormality Score and the frontal and occipital horn ratio were measured. Automatic segmentation was used for volumetric analysis.RESULTS: The total Kidokoro score of the infants in the low-threshold group (n = 44) was lower than in the high-threshold group (n = 44; median, 8 [IQR, 5-12] vs median 12 [IQR, 9-17], respectively; P < .001). More infants in the low-threshold group had a normal or mildly increased score vs more infants in the high-threshold group with a moderately or severely increased score (46% vs 11% and 89% vs 54%, respectively; P = .002). The frontal and occipital horn ratio was lower in the low-threshold group (median, 0.42 [IQR, 0.34-0.63]) than the high-threshold group (median 0.48 [IQR, 0.37-0.68], respectively; P = .001). Ventricular cerebrospinal fluid volumes could be calculated in 47 infants and were smaller in the low-threshold group (P = .03).CONCLUSIONS: More brain injury and larger ventricular volumes were demonstrated in the high vs the low-threshold group. These results support the positive effects of early intervention for posthemorrhagic ventricular dilatation.TRIAL REGISTRATION: ISRCTN43171322.
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| 27. |
- Cizmeci, Mehmet N, et al.
(författare)
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Randomized Controlled Early versus Late Ventricular Intervention Study in Posthemorrhagic Ventricular Dilatation : Outcome at 2 Years
- 2020
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Ingår i: Journal of Pediatrics. - : Elsevier BV. - 1097-6833 .- 0022-3476. ; 226, s. 3-35
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: To compare the effect of intervention at low vs high threshold of ventriculomegaly in preterm infants with posthemorrhagic ventricular dilatation on death or severe neurodevelopmental disability.STUDY DESIGN: This multicenter randomized controlled trial reviewed lumbar punctures initiated after either a low threshold (ventricular index of >p97 and anterior horn width of >6 mm) or high threshold (ventricular index of >p97 + 4 mm and anterior horn width of >10 mm). The composite adverse outcome was defined as death or cerebral palsy or Bayley composite cognitive/motor scores <-2 SDs at 24 months corrected age.RESULTS: Outcomes were assessed in 113 of 126 infants. The composite adverse outcome was seen in 20 of 58 infants (35%) in the low threshold group and 28 of 55 (51%) in the high threshold (P = .07). The low threshold intervention was associated with a decreased risk of an adverse outcome after correcting for gestational age, severity of intraventricular hemorrhage, and cerebellar hemorrhage (aOR, 0.24; 95% CI, 0.07-0.87; P = .03). Infants with a favorable outcome had a smaller fronto-occipital horn ratio (crude mean difference, -0.06; 95% CI, -0.09 to -0.03; P < .001) at term-equivalent age. Infants in the low threshold group with a ventriculoperitoneal shunt, had cognitive and motor scores similar to those without (P = .3 for both), whereas in the high threshold group those with a ventriculoperitoneal shunt had significantly lower scores than those without a ventriculoperitoneal shunt (P = .01 and P = .004, respectively).CONCLUSIONS: In a post hoc analysis, earlier intervention was associated with a lower odds of death or severe neurodevelopmental disability in preterm infants with progressive posthemorrhagic ventricular dilatation.TRIAL REGISTRATION: ISRCTN43171322.
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| 28. |
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| 29. |
- Fu, Zhongjie, et al.
(författare)
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Photoreceptor glucose metabolism determines normal retinal vascular growth
- 2018
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Ingår i: EMBO Molecular Medicine. - : EMBO. - 1757-4676 .- 1757-4684. ; 10:1, s. 76-90
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Tidskriftsartikel (refereegranskat)abstract
- The neural cells and factors determining normal vascular growth are not well defined even though vision-threatening neovessel growth, a major cause of blindness in retinopathy of prematurity (ROP) (and diabetic retinopathy), is driven by delayed normal vascular growth. We here examined whether hyperglycemia and low adiponectin (APN) levels delayed normal retinal vascularization, driven primarily by dysregulated photoreceptor metabolism. In premature infants, low APN levels correlated with hyperglycemia and delayed retinal vascular formation. Experimentally in a neonatal mouse model of postnatal hyperglycemia modeling early ROP, hyperglycemia caused photoreceptor dysfunction and delayed neurovascular maturation associated with changes in the APN pathway; recombinant mouse APN or APN receptor agonist AdipoRon treatment normalized vascular growth. APN deficiency decreased retinal mitochondrial metabolic enzyme levels particularly in photoreceptors, suppressed retinal vascular development, and decreased photoreceptor platelet-derived growth factor (Pdgfb). APN pathway activation reversed these effects. Blockade of mitochondrial respiration abolished AdipoRon-induced Pdgfb increase in photoreceptors. Photoreceptor knockdown of Pdgfb delayed retinal vascular formation. Stimulation of the APN pathway might prevent hyperglycemia-associated retinal abnormalities and suppress phase I ROP in premature infants.
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| 30. |
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| 31. |
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| 32. |
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| 33. |
- Hellström, Ann, 1959, et al.
(författare)
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Effect of Enteral Lipid Supplement on Severe Retinopathy of Prematurity A Randomized Clinical Trial
- 2021
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Ingår i: JAMA Pediatrics. - : American Medical Association (AMA). - 2168-6203 .- 2168-6211. ; 175:4, s. 359-367
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Tidskriftsartikel (refereegranskat)abstract
- IMPORTANCE Lack of arachidonic acid (AA) and docosahexaenoic acid (DHA) after extremely preterm birth may contribute to preterm morbidity, including retinopathy of prematurity (ROP). OBJECTIVE To determine whether enteral supplementation with fatty acids from birth to 40 weeks' postmenstrual age reduces ROP in extremely preterm infants. DESIGN, SETTING, AND PARTICIPANTS The Mega Donna Mega trial, a randomized clinical trial, was a multicenter study performed at 3 university hospitals in Sweden from December 15, 2016, to December 15, 2019. The screening pediatric ophthalmologists were masked to patient groupings. A total of 209 infants born at less than 27 weeks' gestation were tested for eligibility, and 206 infants were included. Efficacy analyses were performed on as-randomized groups on the intention-to-treat population and on the per-protocol population using as-treated groups. Statistical analyses were performed from February to April 2020. INTERVENTIONS Infants received either supplementation with an enteral oil providing AA (100mg/kg/d) and DHA (50mg/kg/d) (AA:DHA group) or no supplementation within 3 days after birth until 40 weeks' postmenstrual age. MAIN OUTCOMES AND MEASURES The primary outcomewas severe ROP (stage 3 and/or type 1). The secondary outcomes were AA and DHA serum levels and rates of other complications of preterm birth. RESULTS A total of 101 infants (58 boys [57.4%]; mean [SD] gestational age, 25.5 [1.5] weeks) were included in the AA:DHA group, and 105 infants (59 boys [56.2%]; mean [SD] gestational age, 25.5 [1.4] weeks) were included in the control group. Treatment with AA and DHA reduced severe ROP compared with the standard of care (16 of 101 [15.8%] in the AA:DHA group vs 35 of 105 [33.3%] in the control group; adjusted relative risk, 0.50 [95% CI, 0.28-0.91]; P =.02). The AA:DHA group had significantly higher fractions of AA and DHA in serum phospholipids compared with controls (overall mean difference in AA:DHA group, 0.82 mol% [95% CI, 0.46-1.18 mol%]; P <.001; overall mean difference in control group, 0.13 mol% [95% CI, 0.01-0.24 mol%]; P =.03). There were no significant differences between the AA:DHA group and the control group in the rates of bronchopulmonary dysplasia (48 of 101 [47.5%] vs 48 of 105 [45.7%]) and of any grade of intraventricular hemorrhage (43 of 101 [42.6%] vs 42 of 105 [40.0%]). In the AA:DHA group and control group, respectively, sepsis occurred in 42 of 101 infants (41.6%) and 53 of 105 infants (50.5%), serious adverse events occurred in 26 of 101 infants (25.7%) and 26 of 105 infants (24.8%), and 16 of 101 infants (15.8%) and 13 of 106 infants (12.3%) died. CONCLUSIONS AND RELEVANCE This study found that, compared with standard of care, enteral AA:DHA supplementation lowered the risk of severe ROP by 50% and showed overall higher serum levels of both AA and DHA. Enteral lipid supplementation with AA:DHA is a novel preventive strategy to decrease severe ROP in extremely preterm infants.
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| 34. |
- Hellström, William, et al.
(författare)
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Postnatal serum IGF-1 levels associate with brain volumes at term in extremely preterm infants
- 2023
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Ingår i: Pediatric Research. - : Springer Science and Business Media LLC. - 0031-3998 .- 1530-0447. ; 93:3, s. 666-674
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Tidskriftsartikel (refereegranskat)abstract
- Background Growth factors important for normal brain development are low in preterm infants. This study investigated the link between growth factors and preterm brain volumes at term. Material/methods Infants born <28 weeks gestational age (GA) were included. Endogenous levels of insulin-like growth factor (IGF)-1, brain-derived growth factor, vascular endothelial growth factor, and platelet-derived growth factor (expressed as area under the curve [AUC] for serum samples from postnatal days 1, 7, 14, and 28) were utilized in a multivariable linear regression model. Brain volumes were determined by magnetic resonance imaging (MRI) at term equivalent age. Results In total, 49 infants (median [range] GA 25.4 [22.9-27.9] weeks) were included following MRI segmentation quality assessment and AUC calculation. IGF-1 levels were independently positively associated with the total brain (p < 0.001, beta = 0.90), white matter (p = 0.007, beta = 0.33), cortical gray matter (p = 0.002, beta = 0.43), deep gray matter (p = 0.008, beta = 0.05), and cerebellar (p = 0.006, beta = 0.08) volume adjusted for GA at birth and postmenstrual age at MRI. No associations were seen for other growth factors. Conclusions Endogenous exposure to IGF-1 during the first 4 weeks of life was associated with total and regional brain volumes at term. Optimizing levels of IGF-1 might improve brain growth in extremely preterm infants. Impact High serum levels of insulin-like growth factor (IGF)-1 during the first month of life were independently associated with increased total brain volume, white matter, gray matter, and cerebellar volume at term equivalent age in extremely preterm infants. IGF-1 is a critical regulator of neurodevelopment and postnatal levels are low in preterm infants. The effects of IGF-1 levels on brain development in extremely preterm infants are not fully understood. Optimizing levels of IGF-1 may benefit early brain growth in extremely preterm infants. The effects of systemically administered IGF-1/IGFBP3 in extremely preterm infants are now being investigated in a randomized controlled trial (Clinicaltrials.gov: NCT03253263).
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| 35. |
- Horsch, S., et al.
(författare)
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Randomized Control Trial of Postnatal rhIGF-1/rhIGFBP-3 Replacement in Preterm Infants: Post-hoc Analysis of Its Effect on Brain Injury
- 2020
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Ingår i: Frontiers in Pediatrics. - : Frontiers Media SA. - 2296-2360. ; 8
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Tidskriftsartikel (refereegranskat)abstract
- Background: Postnatal insulin-like growth factor-1 (IGF-1) replacement with recombinant human (rh)IGF-1 and IGF binding protein-3 (rhIGF-1/rhIGFBP-3) is being studied as a potential treatment to reduce comorbidities of prematurity. We have recently reported on a phase II, multicenter, randomized, controlled trial comparing postnatal rhIGF-1/rhIGFBP-3 replacement with standard of care (SOC) in extremely preterm infants (NCT01096784). Maximum severity of retinopathy of prematurity was the primary endpoint of the trial and presence of GMH-IVH/PHI one of the pre-specified secondary endpoints. Infants therefore received serial cranial ultrasound scans (CUS) between birth and term age. In this post-hoc analysis we present a detailed analysis of the CUS data of this trial and evaluate the effect of postnatal rhIGF-1/rhIGFBP-3 replacement on the incidence of different kinds of brain injury in extremely preterm infants. Methods: This report is an exploratory post-hoc analysis of a phase II trial in which infants <28 weeks gestational age were randomly allocated to rhIGF-1/rhIGFBP-3 or SOC. Serial cranial ultrasounds were performed between birth and term-equivalent age. Presence of germinal matrix hemorrhage and intraventricular hemorrhage (GMH-IVH), periventricular hemorrhagic infarction (PHI), post-hemorrhagic ventricular dilatation, and white matter injury (WMI) were scored by two independent masked readers. Results: The analysis included 117 infants; 58 received rhIGF-1/rhIGFBP-3 and 59 received SOC. A trend toward less grade II-III GMH-IVH and PHI was observed in treated infants vs. SOC. A subanalysis of infants without evidence of GMH-IVH at study entry (n = 104) showed reduced progression to GMH-IVH in treated infants (25.0% [13/52] vs. 40.4% [21/52]; not significant). No effects of rhIGF-1/rhIGFBP-3 on WMI were observed. Conclusion: The potential protective effect of rhIGF-1/rhIGFBP-3 on the occurrence of GMH-IVH/PHI appeared most pronounced in infants with no evidence of GMH-IVH at treatment start.
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| 36. |
- Klevebro, S., et al.
(författare)
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Elevated levels of IL-6 and IGFBP-1 predict low serum IGF-1 levels during continuous infusion of rhIGF-1/rhIGFBP-3 in extremely preterm infants
- 2020
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Ingår i: Growth Hormone and IGF Research. - : Elsevier BV. - 1096-6374. ; 50, s. 1-8
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Tidskriftsartikel (refereegranskat)abstract
- Objective: Steady state insulin-like growth factor-1 (IGF-1) levels vary significantly during continuous intravenous infusion of recombinant human insulin-like growth factor-1/recombinant human insulin-like growth factor binding protein-3 (rhIGF-1/rhIGFBP-3) in the first weeks of life in extremely preterm infants. We evaluated interleukin-6 (IL-6) and insulin-like growth factor binding protein-1 (IGFBP-1) levels as predictors of low IGF-1 levels. Methods: Nineteen extremely preterm infants were enrolled in a trial, 9 received rhIGF-1/rhIGFBP-3 and 10 received standard neonatal care. Blood samples were analyzed daily for IGF-1, IL-6 and IGFBP-1 during intervention with rhIGF-1/rhIGFBP-3. Results: Thirty seven percent of IGF-1 values during active treatment were <20 μg/L. Among treated infants, higher levels of IL-6, one and two days before sampled IGF-1, were associated with IGF-1 < 20 μg/L, gestational age adjusted OR 1.30 (95% CI 1.03–1.63), p = .026, and 1.57 (95% CI 1.26–1.97), p < .001 respectively. Higher levels of IGFBP-1 one day before sampled IGF-1 was also associated with IGF-1 < 20 μg/L, gestational age adjusted OR 1.74 (95% CI 1.19–2.53), p = .004. Conclusion: In preterm infants receiving continuous infusion of rhIGF-1/rhIGFBP-3, higher levels of IL-6 and IGFBP-1 preceded lower levels of circulating IGF-1. These findings demonstrate a need to further evaluate if inflammation and/or infection suppress serum IGF-1 levels. The trial is registered at ClinicalTrials.gov (NCT01096784). © 2019
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| 37. |
- Ley, D, et al.
(författare)
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Abnormal fetal aortic velocity waveform and intellectual function at 7 years of age
- 1996
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Ingår i: Ultrasound in obstetrics & gynecology : the official journal of the International Society of Ultrasound in Obstetrics and Gynecology. - : Wiley. - 0960-7692. ; 8:3, s. 5-160
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Tidskriftsartikel (refereegranskat)abstract
- Measurements of fetal aortic blood flow velocity and fetal growth were performed in 178 pregnancies. In 87 cases, the estimated fetal weight was > 2 SD below the gestational age-related mean of the population. Three fetuses died in utero. In 148 children (84%) an assessment of overall intellectual ability was performed at 6.5 years of age. Verbal and global IQ was lower in the group with an abnormal fetal aortic blood flow velocity waveform (mean +/- SD 96.0 +/- 17.7 and 95.9 +/- 15.7, respectively; n = 41) compared to the group with a normal waveform (102.1 +/- 12.2 and 102.9 +/- 13.2, respectively; n = 105; p < 0.05). Logistic regression analysis revealed that abnormal fetal aortic velocity waveform, both independently and in combination with other factors, was a significant predictor of impaired intellectual outcome. The association found between abnormal fetal aortic velocity waveform and impaired intellectual outcome suggests that hemodynamic evaluation of the fetus has a predictive value regarding postnatal intellectual development.
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| 38. |
- Ley, D, et al.
(författare)
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Abnormal fetal aortic velocity waveform and minor neurological dysfunction at 7 years of age
- 1996
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Ingår i: Ultrasound in obstetrics & gynecology : the official journal of the International Society of Ultrasound in Obstetrics and Gynecology. - : Wiley. - 0960-7692. ; 8:3, s. 9-152
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Tidskriftsartikel (refereegranskat)abstract
- Measurements of fetal aortic blood flow velocity and fetal growth were performed in 178 pregnancies. In 87 cases, the estimated fetal weight was > or = 2 SD below the gestational age-related mean of the population. Three fetuses died in utero. In 149 children (85%), a neurological examination was performed at 7 years of age with special emphasis on minor neurological dysfunction. The frequency of the more severe form of minor neurological dysfunction, MND-2, was higher in the group with blood flow class (BFC) III (absent or reversed end-diastolic flow velocity (8/21) than in the group with BFC 0 (normal velocity waveform) (14/105). Logistic regression analysis revealed that abnormal blood flow class, both independently and in combination with other factors, was the most significant predictor of MND-2. The association found between abnormal fetal aortic velocity waveforms and adverse outcome in terms of minor neurological dysfunction suggests that hemodynamic evaluation of the fetus has a predictive value regarding postnatal neurological development.
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| 39. |
- Ley, D, et al.
(författare)
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Abnormal fetal aortic velocity waveform and postnatal growth
- 2000
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Ingår i: Acta Pædiatrica. - 0803-5253. ; 89:11, s. 5-1330
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Tidskriftsartikel (refereegranskat)abstract
- Postnatal growth from birth up to 7 y of age was evaluated in 151 children with varying degrees of intrauterine growth retardation who were previously examined in their intrauterine life with Doppler velocimetry of the thoracic descending aorta. The children with abnormal fetal aortic blood flow class (BFC), of which 39/46 (85%) had a birthweight > or = 2 SD below the mean of the population, were lean at birth and had a high rate of catch-up growth in weight and length during the first 3 and 6 mo, respectively. After the initial phases of rapid catch-up in weight and length, mean values of SD scores for weight and height remained relatively unchanged up until 2 y of age, thereafter increasing gradually up to 7 y of age, leaving 4/46 (8%) and 4/46 (8%) below -2 SD for weight and height, respectively. The pattern of changes in length/height and weight over time did not differ between those infants with abnormal BFC and those with normal BFC. The abnormal fetal aortic waveform was not related to rate of early catch-up growth or to height or weight at 7 y of age after adjustment for deviation in growth at birth. The magnitude of deficit in weight and length at birth was more predictive of subsequent growth.
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| 40. |
- Ley, D, et al.
(författare)
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Aortic vessel wall characteristics and blood pressure in children with intrauterine growth retardation and abnormal foetal aortic blood flow
- 1997
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Ingår i: Acta Pædiatrica. - : Wiley. - 0803-5253 .- 1651-2227. ; 86:3, s. 299-305
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Tidskriftsartikel (refereegranskat)abstract
- Blood pressure and pulsatile diameter changes of the abdominal aorta were measured in 68 children (mean age 9 years), with varying degrees of intrauterine growth retardation who were previously examined in their intrauterine life with Doppler velocimetry of the thoracic descending aorta. Diastolic blood pressure was lower (p < 0.05) and pulse pressure was increased (p < 0.01) in children with a birthweight small for gestational age as compared to those with a birthweight appropriate for gestational age. Systolic blood pressure was positively associated with relative increase in weight from birth up to the time of examination (p < 0.01), but not to early catch-up growth. Aortic vessel wall diameters were smaller in children born small for gestational age, both before and after correction for current body surface area (p < 0.01). Blood pressure and aortic vessel wall characteristics exhibited no relationship to the foetal aortic Doppler wave-form. Changes in foetal haemodynamics associated with intrauterine growth retardation do not appear to contribute to a later increase in blood pressure. Within a group of foetuses with suspected growth retardation, increasing foetal weight deviation and a birthweight small for gestational age is associated with lower diastolic blood pressure at 9 years of age.
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| 41. |
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| 42. |
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| 43. |
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| 44. |
- Ley, R. E., et al.
(författare)
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Obesity alters gut microbial ecology
- 2005
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Ingår i: Proc Natl Acad Sci U S A. ; 102:31, s. 11070-11075
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Tidskriftsartikel (refereegranskat)abstract
- We have analyzed 5,088 bacterial 16S rRNA gene sequences from the distal intestinal (cecal) microbiota of genetically obese ob/ob mice, lean ob/+ and wild-type siblings, and their ob/+ mothers, all fed the same polysaccharide-rich diet. Although the majority of mouse gut species are unique, the mouse and human microbiota(s) are similar at the division (superkingdom) level, with Firmicutes and Bacteroidetes dominating. Microbial-community composition is inherited from mothers. However, compared with lean mice and regardless of kinship, ob/ob animals have a 50% reduction in the abundance of Bacteroidetes and a proportional increase in Firmicutes. These changes, which are division-wide, indicate that, in this model, obesity affects the diversity of the gut microbiota and suggest that intentional manipulation of community structure may be useful for regulating energy balance in obese individuals. The sequences reported in this paper have been deposited in the GenBank database [accession nos. DQ 014552--DQ 015671 (mothers) and AY 989911--AY 993908 (offspring)].
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| 45. |
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| 46. |
- Marsál, K, et al.
(författare)
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Intrauterine blood flow and postnatal neurological development in growth-retarded fetuses
- 1992
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Ingår i: Biology of the Neonate. - : S. Karger AG. - 0006-3126. ; 62:4, s. 64-258
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Tidskriftsartikel (refereegranskat)abstract
- Intrauterine growth retardation (IUGR) is associated with abnormal neuro-developmental outcome. Aortic blood flow velocity waveforms have been shown to predict fetal distress in IUGR. Fetal aortic blood flow velocity waveforms were correlated to neuro-developmental performance at 7 years of age. Results suggest that abnormal fetal aortic blood flow velocity waveforms are associated with neuro-developmental impairment.
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| 47. |
- Mechler, R., et al.
(författare)
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Loss and Damage and limits to adaptation : recent IPCC insights and implications for climate science and policy
- 2020
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Ingår i: Sustainability Science. - : Springer Science and Business Media LLC. - 1862-4065 .- 1862-4057. ; 15:4, s. 1245-1251
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Tidskriftsartikel (refereegranskat)abstract
- Recent evidence shows that climate change is leading to irreversible and existential impacts on vulnerable communities and countries across the globe. Among other effects, this has given rise to public debate and engagement around notions of climate crisis and emergency. The Loss and Damage (L&D) policy debate has emphasized these aspects over the last three decades. Yet, despite institutionalization through an article on L&D by the United Nations Framework Convention on Climate Change (UNFCCC) in the Paris Agreement, the debate has remained vague, particularly with reference to its remit and relationship to adaptation policy and practice. Research has recently made important strides forward in terms of developing a science perspective on L&D. This article reviews insights derived from recent publications by the Intergovernmental Panel on Climate Change (IPCC) and others, and presents the implications for science and policy. Emerging evidence on hard and soft adaptation limits in certain systems, sectors and regions holds the potential to further build momentum for climate policy to live up to the Paris ambition of stringent emission reductions and to increase efforts to support the most vulnerable. L&D policy may want to consider actions to extend soft adaptation limits and spur transformational, that is, non-standard risk management and adaptation, so that limits are not breached. Financial, technical, and legal support would be appropriate for instances where hard limits are transgressed. Research is well positioned to further develop robust evidence on critical and relevant risks at scale in the most vulnerable countries and communities, as well as options to reduce barriers and limits to adaptation.
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| 48. |
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| 49. |
- Nilsson, Anders K., 1982, et al.
(författare)
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Preterm infant circulating sex steroid levels are not altered by transfusion with adult male plasma: a retrospective multicentre cohort study
- 2022
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Ingår i: Archives of Disease in Childhood-Fetal and Neonatal Edition. - : BMJ. - 1359-2998 .- 1468-2052. ; 107:6, s. 577-582
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Tidskriftsartikel (refereegranskat)abstract
- Sex hormones delivered via plasma transfusions from adult male donors to very preterm infants do not alter the circulating plasma concentrations in the infant, irrespective of gender. Objective To determine if plasma transfusions with male donor plasma to very preterm infants affect circulatory levels of sex steroids. Design and patients Retrospective multicentre cohort study in 19 infants born at gestational age Setting Three neonatal intensive care units in Sweden. Main outcome measures Concentrations of sex steroids and sex hormone-binding globulin (SHBG) in donor plasma and infant plasma measured before and after a plasma transfusion and at 6, 12, 24 and 72 hours. Results The concentrations of progesterone, dehydroepiandrosterone and androstenedione were significantly lower in donor plasma than in infant plasma before the transfusion (median (Q1-Q3) 37.0 (37.0-37.0), 1918 (1325-2408) and 424 (303-534) vs 901 (599-1774), 4119 (2801-14 645) and 842 (443-1684) pg/mL), while oestrone and oestradiol were higher in donor plasma (17.4 (10.4-20.1) and 16.0 (11.7-17.2) vs 3.1 (1.1-10.2) and 0.25 (0.25-0.25) pg/mL). Median testosterone and dihydrotestosterone (DHT) levels were 116-fold and 21-fold higher in donor plasma than pre-transfusion levels in female infants, whereas the corresponding difference was not present in male infants. Plasma sex steroid levels were unchanged after completed transfusion compared with pre-transfusion levels, irrespective of the gender of the receiving infant. The SHBG concentration was significantly higher in donor than in recipient plasma (22.8 (17.1-33.5) vs 10.2 (9.1-12.3) nmol/L) before transfusion but did not change in the infants after the transfusion. Conclusions A single transfusion of adult male plasma to preterm infants had no impact on circulating sex steroid levels.
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| 50. |
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