| 1. |
- Masoumi, Zahra, et al.
(författare)
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Assessing erythroferrone and iron homeostasis in preeclamptic and normotensive pregnancies : A retrospective study
- 2023
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Ingår i: Placenta. - : Elsevier BV. - 0143-4004. ; 133, s. 10-18
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Tidskriftsartikel (refereegranskat)abstract
- Introduction: Preeclampsia (PE) is a pregnancy-related disorder associated with maternal hypertension and placental dysfunction. A significant micronutrient during pregnancy is iron, which is important in cellular functions. While iron absorption increases in pregnancy, little is known about the exact mechanisms regulating maternal iron levels and transfer through the placenta in normal and complicated pregnancies. Methods: In this retrospective study, we investigated the regulation of maternal and placental iron availability and storage, in normotensive and pregnancies complicated by early- or late-onset PE. Methods used were analysis of clinical records, ELISA analysis on plasma samples, immunofluorescent and Prussian Blue analysis on placenta biopsies. Results: Focusing on erythroferrone (ERFE) as a new marker and hormonal regulator of iron, our results demonstrated altered maternal ERFE levels in PE. We are the first to report the expression of ERFE in trophoblasts and indicate its lower levels in early-onset PE placentas. These changes were associated with lower placental transferrin receptor 1 (TfR1) in syncytiotrophoblasts in both early- and late-onset PE. In addition, maternal plasma ERFE levels were elevated in both early- and late-onset PE and hepcidin levels reduced in early-onset PE. Unaltered maternal plasma IL-6 levels suggest mechanism other than inflammation being involved in altered iron regulation in PE pregnancy. Discussion: Our data supports a deregulation in maternal iron bioavailability in early- and late-onset PE vs normotensive pregnancies. The exact role of placental ERFE in regulating maternal-placental-fetal iron transport axis requires further investigation.
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| 2. |
- Masoumi, Zahra, et al.
(författare)
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Hypoxia-induced alpha-globin expression in syncytiotrophoblasts mimics the pattern observed in preeclamptic placentas
- 2021
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Ingår i: International Journal of Molecular Sciences. - : MDPI AG. - 1661-6596 .- 1422-0067. ; 22:7
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Tidskriftsartikel (refereegranskat)abstract
- Preeclampsia (PE) is a pregnancy disorder associated with placental dysfunction and elevated fetal hemoglobin (HbF). Early in pregnancy the placenta harbors hematopoietic stem and progenitor cells (HSPCs) and is an extramedullary source of erythropoiesis. However, globin expression is not unique to erythroid cells and can be triggered by hypoxia. To investigate the role of the placenta in increasing globin levels previously reported in PE, flow cytometry, histological and immunostaining and in situ analyses were used on placenta samples and ex vivo explant cultures. Our results indicated that in PE pregnancies, placental HSPC homing and erythropoiesis were not affected. Non-erythroid alpha-globin mRNA and protein, but not gamma-globin, were detected in syncytiotrophoblasts and stroma of PE placenta samples. Similarly, alpha-globin protein and mRNA were upregulated in normal placenta explants cultured in hypoxia. The upregulation was inde-pendent of HIF1 and NRF2, the two main candidates of globin transcription in non-erythroid cells. Our study is the first to demonstrate alpha-globin mRNA expression in syncytiotrophoblasts in PE, induced by hypoxia. However, gamma-globin was only expressed in erythrocytes. We conclude that alpha-globin, but not HbF, is expressed in placental syncytiotrophoblasts in PE and may contribute to the pathology of the disease.
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| 3. |
- Masoumi, Zahra, et al.
(författare)
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Preeclampsia is Associated with Sex-Specific Transcriptional and Proteomic Changes in Fetal Erythroid Cells
- 2019
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Ingår i: International Journal of Molecular Sciences. - : MDPI AG. - 1422-0067. ; 20:8
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Tidskriftsartikel (refereegranskat)abstract
- Preeclampsia (PE) has been associated with placental dysfunction, resulting in fetal hypoxia, accelerated erythropoiesis, and increased erythroblast count in the umbilical cord blood (UCB). Although the detailed effects remain unknown, placental dysfunction can also cause inflammation, nutritional, and oxidative stress in the fetus that can affect erythropoiesis. Here, we compared the expression of surface adhesion molecules and the erythroid differentiation capacity of UCB hematopoietic stem/progenitor cells (HSPCs), UCB erythroid profiles along with the transcriptome and proteome of these cells between male and female fetuses from PE and normotensive pregnancies. While no significant differences were observed in UCB HSPC migration/homing and in vitro erythroid colony differentiation, the UCB HSPC transcriptome and the proteomic profile of the in vitro differentiated erythroid cells differed between PE vs. normotensive samples. Accordingly, despite the absence of significant differences in the UCB erythroid populations in male or female fetuses from PE or normotensive pregnancies, transcriptional changes were observed during erythropoiesis, particularly affecting male fetuses. Pathway analysis suggested deregulation in the mammalian target of rapamycin complex 1/AMP-activated protein kinase (mTORC1/AMPK) signaling pathways controlling cell cycle, differentiation, and protein synthesis. These results associate PE with transcriptional and proteomic changes in fetal HSPCs and erythroid cells that may underlie the higher erythroblast count in the UCB in PE.
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| 4. |
- Aleksenko, Larysa, et al.
(författare)
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Pregnant alpha-1-microglobulin (A1M) knockout mice exhibit features of kidney and placental damage, hemodynamic changes and intrauterine growth restriction
- 2020
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Ingår i: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 10:1
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Tidskriftsartikel (refereegranskat)abstract
- Alpha-1-microglobulin (A1M) is an antioxidant previously shown to be elevated in maternal blood during pregnancies complicated by preeclampsia and suggested to be important in the endogenous defense against oxidative stress. A knockout mouse model of A1M (A1Mko) was used in the present study to assess the importance of A1M during pregnancy in relation to the kidney, heart and placenta function. Systolic blood pressure (SBP) and heart rate (HR) were determined before and throughout gestation. The morphology of the organs was assessed by both light and electron microscopy. Gene expression profiles relating to vascular tone and oxidative stress were analyzed using RT-qPCR with validation of selected gene expression relating to vascular tone and oxidative stress response. Pregnant age-matched wild type mice were used as controls. In the A1Mko mice there was a significantly higher SBP before pregnancy that during pregnancy was significantly reduced compared to the control. In addition, the HR was higher both before and during pregnancy compared to the controls. Renal morphological abnormalities were more frequent in the A1Mko mice, and the gene expression profiles in the kidney and the heart showed downregulation of transcripts associated with vasodilation. Simultaneously, an upregulation of vasoconstrictors, blood pressure regulators, and genes for osmotic stress response, ion transport and reactive oxygen species (ROS) metabolism occurred. Fetal weight was lower in the A1Mko mice at E17.5. The vessels in the labyrinth zone of the placentas and the endoplasmic reticulum in the spongiotrophoblasts were collapsed. The gene profiles in the placenta showed downregulation of antioxidants, ROS metabolism and oxidative stress response genes. In conclusion, intact A1M expression is necessary for the maintenance of normal kidney, heart as well as placental structure and function for a normal pregnancy adaptation.
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| 5. |
- Appelin, Katja, et al.
(författare)
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Changes in self-perceived performance and satisfaction with performance of daily activities following interdisciplinary rehabilitation in people with late effects of polio
- 2024
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Ingår i: NeuroRehabilitation. - Amsterdam : IOS Press. - 1053-8135 .- 1878-6448. ; 54:2, s. 331-342
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: People with late effects of polio (LEoP) may need rehabilitation to manage everyday life but knowledge of the benefits of interdisciplinary rehabilitation is limited. OBJECTIVE: To evaluate changes in performance and satisfaction with performance of activities among people with LEoP following interdisciplinary rehabilitation. METHODS: A pre-post retrospective study based on data on 102 participants with LEoP from a rehabilitation clinic. Changes in performance and satisfaction with performance of daily activities before and after interdisciplinary rehabilitation were assessed with the Canadian Occupational Performance Measure (COPM). RESULTS: There were statistically significant increases in the mean performance and mean satisfaction with performance COPM scores from admission to discharge. Twenty-three percent and 19% of the participants, respectively, had improved their performance and satisfaction with performance, 25% and 26% of the participants had no changes, and 19% and 22% of the participants, respectively, rated their performance and satisfaction lower at discharge compared to admission. CONCLUSION: Interdisciplinary rehabilitation can enhance self-rated performance and satisfaction with performance of daily activities among people with LEoP. Future studies of rehabilitation for people with LEoP should use a prospective design and capture the participants’ process of change related to their rehabilitation period. © 2024 – The authors. Published by IOS Press.
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| 6. |
- Ayala, Ana, et al.
(författare)
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Newborn infants who received skin-to-skin contact with fathers after Caesarean sections showed stable physiological patterns.
- 2021
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Ingår i: Acta Paediatrica. - : Wiley. - 0803-5253 .- 1651-2227. ; 110:5, s. 1461-1467
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Tidskriftsartikel (refereegranskat)abstract
- AIM: Separating infants and their parents after a Caesarean section is still the routine care worldwide. This study investigated three caregiving models on the wakefulness and physiological parameters of full-term infants after an elective Caesarean section.METHODS: Newborn infants born in a Chilean public hospital in 2009-12 were randomised to three groups: cot, fathers' arms or skin-to-skin contact with their father. They were assessed at 15-minute intervals, from 45 to 120 minutes after the Caesarean section. Their physiological parameters were measured, and their wakefulness was assessed using the Neonatal Behavioural Assessment Scale.RESULTS: We studied 95 infant (53% girls) born at a mean gestational age of 38.9 ± 0.9 weeks. Heart rates were significantly higher in the skin-to-skin than cot or fathers' arms groups and showed greater stability over time. Wakefulness was initially higher in the skin-to-skin group, but there were no significant differences by the end of the observation. There were no differences between the groups in peripheral oxygen saturation. Skin-to-skin contact had no negative impact on the infants.CONCLUSION: The skin-to-skin group showed some advantages over the cot and fathers' arms groups when it came to establishing stable physiological parameters and wakefulness. This approach should be supported during mother-infant separation.
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| 7. |
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| 8. |
- Brun, Eva, et al.
(författare)
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Early prediction of treatment outcome in head and neck cancer with 2-18FDG PET
- 1997
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Ingår i: Acta Oncologica. - : Informa UK Limited. - 1651-226X .- 0284-186X. ; 36:7, s. 741-747
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Tidskriftsartikel (refereegranskat)abstract
- The development of alternative treatment regimens in clinical oncology has increased the need for early prediction of cancer therapy outcome. The aim of this study was, early in the treatment phase, to identify patients with advanced head and neck cancer, responding or not responding to initiated therapy. The tumour metabolic rate of glucose (MRgl) examined by 2-18FDG-PET was determined in 17 patients before and after the first weeks of either radiotherapy (16-35 Gy) or one course of combination chemotherapy. Metabolic values uptake values normalized to plasma activity integrals--were correlated to loco-regional outcome, as evaluated 5-6 weeks after completion of treatment. Initial low tumour MRgl (<20 micromol/min/100 g tissue), in primary lesions or regional metastases, predicted a local complete response. When a high initial tumour MRgl was found, the magnitude of the reduction of MRgl in the second PET examination might be an adjunct in predicting local tumour response.
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| 9. |
- Dhapola, Parashar, et al.
(författare)
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Scarf enables a highly memory-efficient analysis of large-scale single-cell genomics data
- 2022
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Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 13
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Tidskriftsartikel (refereegranskat)abstract
- As the scale of single-cell genomics experiments grows into the millions, the computational requirements to process this data are beyond the reach of many. Herein we present Scarf, a modularly designed Python package that seamlessly interoperates with other single-cell toolkits and allows for memory-efficient single-cell analysis of millions of cells on a laptop or low-cost devices like single-board computers. We demonstrate Scarf's memory and compute-time efficiency by applying it to the largest existing single-cell RNA-Seq and ATAC-Seq datasets. Scarf wraps memory-efficient implementations of a graph-based t-stochastic neighbour embedding and hierarchical clustering algorithm. Moreover, Scarf performs accurate reference-anchored mapping of datasets while maintaining memory efficiency. By implementing a subsampling algorithm, Scarf additionally has the capacity to generate representative sampling of cells from a given dataset wherein rare cell populations and lineage differentiation trajectories are conserved. Together, Scarf provides a framework wherein any researcher can perform advanced processing, subsampling, reanalysis, and integration of atlas-scale datasets on standard laptop computers. Scarf is available on Github: https://github.com/parashardhapola/scarf .
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| 10. |
- Edvinsson, Camilla, et al.
(författare)
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Intensive care patients with preeclampsia – Clinical risk factors and biomarkers for oxidative stress and angiogenic imbalance as discriminators for severe disease
- 2022
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Ingår i: Pregnancy Hypertension. - : Elsevier BV. - 2210-7789. ; 30, s. 88-94
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Tidskriftsartikel (refereegranskat)abstract
- Background: Approximately 180 mothers are treated in Swedish Intensive Care Units (ICU) due to preeclampsia each year. Although several clinical risk factors are known, prediction of critical disease is challenging. Two scavenger proteins, hemopexin (Hpx) and alpha-1-microglobulin (A1M) have been suggested to be associated with the oxidative stress seen in preeclampsia. The ratio of two other biomarkers, soluble fms-like tyrosine kinase (sFlt-1) to placental growth factor (PIGF), is predictive of adverse pregnancy outcomes. Methods: In total 121 women were included in this study where we compared risk factors for preeclampsia, plasma levels of Hpx and A1M in ICU-patients with preeclampsia (n = 41) compared to uncomplicated preeclampsia cases (n = 40) and normotensive pregnancies (n = 40), with the objective to identify clinical risk patterns for severe disease. The sFlt-1/PIGF ratio was investigated in early and late onset preeclampsia ICU-patients. Blood samples were collected at admission to ICU and within 27 h postpartum for all groups. Results: Hemopexin and A1M levels were significantly lower in the preeclampsia ICU-cohort compared to uncomplicated preeclampsia patients. The sFlt-1/PIGF-ratio was elevated in the ICU-patients but there was no difference between early and late onset preeclampsia. The ICU-patients had more clinical risk factors, refractory hypertension, and an increased rate of emergency Caesarean section. Conclusion: Intensive care patients have more clinical risk factors and a Hpx and A1M profile suggestive of depletion and thereby a reduced capacity to respond to oxidative stress. The ratios of sFlt-1/PIGF were high in the ICU-cohort and in accordance with pre-delivery levels predictive of adverse pregnancy outcomes.
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