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| 2. |
- 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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- Mogensen, Ida, et al.
(författare)
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Lung function before and after COVID-19 in young adults : A population-based study.
- 2022
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Ingår i: The journal of allergy and clinical immunology. Global. - : University of Wisconsin Press. - 2772-8293. ; 1:2, s. 37-42
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: There is limited evidence on the long-term impact of mild-to-moderate coronavirus disease 2019 (COVID-19) on lung function among young adults.OBJECTIVES: We aimed to assess whether COVID-19 has a negative impact on lung function in young adults and whether asthma, allergic sensitization, or use of inhaled corticosteroids (ICSs) modifies a potential association.METHODS: Participants from the population-based BAMSE (Barn, Allergi, Miljö, Stockholm, Epidemiologi) cohort with spirometry assessed before (2016-2019) and after onset of the COVID-19 pandemic (2020-2021) were included. Serum levels of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) receptor-binding domain-specific IgG, IgM, and/or IgA (determined with ELISA) defined seropositivity. Mean change in lung function (ie, change in FEV1, forced vital capacity [FVC], and FEV1/FVC ratio expressed as percent of predicted [pp]) from before to after onset of the pandemic were compared between the seronegative and seropositive participants. In seropositive participants, change in lung function was assessed in relation to allergic sensitization and self-reported ICS use.RESULTS: Of the 853 included participants, 29% (n = 243) were seropositive. There were no differences in change in lung function between the seronegative and seropositive participants (for mean change in FEV1 pp [SD], seropositivity = 0.87% [4.79%] and seronegativity = 1.03% (4.76%) [P = .66] for difference using a t test; FVC pp (SD), seropositivity = 1.34% (4.44%) and seronegativity = 1.29% (4.27%) [P = .87]; and for FEV1/FVC pp (SD), seropositivity = -0.25% (3.13%) and seronegativity = -0.13% (3.15%) [P = .61]). Similar results were observed among participants with asthma (n = 147 [17%]). Among seropositive participants, allergic sensitization or ICS use did not influence lung function.CONCLUSION: We found no evidence of mild-to-moderate COVID-19 affecting lung function long term in a population-based cohort of young adults. Moreover, neither asthma nor allergic sensitization nor ICS use affected the results.
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- Niss, Frida, 1991-
(författare)
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Imaging the molecular pathways of neurodegeneration : New pathologies of SCA7
- 2022
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Spinocerebellar Ataxia type 7 (SCA7) is a genetic neurodegenerative disease with lethal outcome that affects the cerebellum and retina of patients. This thesis focuses on characterising molecular pathological pathways that cause toxicity and cell death in SCA7. Using primarily an inducible cell model and patient fibroblasts I found that the three RNA binding proteins FUS, TDP-43 and TIA1 are co-sequestered into aggregates formed by the SCA7 causing protein, ATXN7. Consequently I investigated the cellular functions in which these proteins have important roles. I found that FUS’ ability to regulate mRNAs is altered due to mislocalisation, DNA damage is increased, and that stress granules (SGs) are induced in a SCA7 cell model and in patient fibroblasts. Surprisingly, I also found that ATXN7 was present within SGs, and that SGs exhibited an altered shape upon induction of mutant ATXN7. I also participated in developing a microscopy-based method for monitoring chromatin organisation in live cells called FRIC. FRIC is able to detect even subtle changes to peripheral chromatin organisation, and since ATXN7 is a subunit of the transcription regulational complex SAGA, we used FRIC to investigate the effect of mutant ATXN7 on peripheral chromatin organisation. While we found no evidence that mutant ATXN7 affected peripheral chromatin organisation, the inner nuclear membrane protein Samp1 was found to be important for normal chromatin organisation in the nuclear periphery. Finally, I characterised the effect of mutant ATXN7 expression on the nuclear lamina, nuclear pore complexes, and nucleocytoplasmic transport. I found that although key transport factors such as Ran and Importin ß intermittently co-localised with ATXN7 aggregates, there were no apparent defects in nucleocytoplasmic protein import or nuclear envelope integrity. In summation, my investigations resulted in new findings that may be built upon to find key targets for treating SCA7 patients.
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| 5. |
- Niss, Frida, et al.
(författare)
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Key Modulators of the Stress Granule Response TIA1, TDP-43, and G3BP1 are Altered by Polyglutamine Expanded ATXN7
- 2022
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Ingår i: Molecular Neurobiology. - : Springer Science and Business Media LLC. - 0893-7648 .- 1559-1182. ; 59:8, s. 5236-5251
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Tidskriftsartikel (refereegranskat)abstract
- Spinocerebellar ataxia type 7 (SCA7) and other polyglutamine (polyQ) diseases are caused by expansions of polyQ repeats in disease-specific proteins. Aggregation of the polyQ proteins resulting in various forms of cellular stress, that could induce the stress granule (SG) response, is believed to be a common pathological mechanism in these disorders. SGs can contribute to cell survival but have also been suggested to exacerbate disease pathology by seeding protein aggregation. In this study, we show that two SG-related proteins, TDP-43 and TIA1, are sequestered into the aggregates formed by polyQ-expanded ATXN7 in SCA7 cells. Interestingly, mutant ATXN7 also localises to induced SGs, and this association altered the shape of the SGs. In spite of this, neither the ability to induce nor to disassemble SGs, in response to arsenite stress induction or relief, was affected in SCA7 cells. Moreover, we could not observe any change in the number of ATXN7 aggregates per cell following SG induction, although a small, non-significant, increase in total aggregated ATXN7 material could be detected using filter trap. However, mutant ATXN7 expression in itself increased the speckling of the SG-nucleating protein G3BP1 and the SG response. Taken together, our results indicate that the SG response is induced, and although some key modulators of SGs show altered behaviour, the dynamics of SGs appear normal in the presence of mutant ATXN7.
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| 6. |
- Niss, Frida, et al.
(författare)
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Monitoring of Chromatin Organization at the Nuclear Pore Complex, Inner Nuclear Membrane, and Nuclear Interior in Live Cells by Fluorescence Ratiometric Imaging of Chromatin (FRIC)
- 2022
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Ingår i: The Nuclear Pore Complex. - New York : Humana Press Inc.. - 9781071623367 - 9781071623374 ; , s. 151-160
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Bokkapitel (refereegranskat)abstract
- The image analysis tool FRIC (Fluorescence Ratiometric Imaging of Chromatin) quantitatively monitors 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 a proof of concept, peripheral heterochromatin responded to experimental manipulation of histone acetylation as well as expression of the mutant lamin A protein “progerin,” which causes Hutchinson-Gilford Progeria Syndrome. In summary FRIC is versatile, unbiased, robust, requires a minimum of experimental steps and is suitable for screening purposes.
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| 7. |
- Niss, Frida, et al.
(författare)
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Polyglutamine expanded Ataxin-7 induces DNA damage and alters FUS localization and function
- 2021
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Ingår i: Molecular and Cellular Neuroscience. - : Elsevier BV. - 1044-7431 .- 1095-9327. ; 110
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Tidskriftsartikel (refereegranskat)abstract
- Polyglutamine (polyQ) diseases, such as Spinocerebellar ataxia type 7 (SCA7), are caused by expansions of polyQ repeats in disease specific proteins. The sequestration of vital proteins into aggregates formed by polyQ proteins is believed to be a common pathological mechanism in these disorders. The RNA-binding protein FUS has been observed in polyQ aggregates, though if disruption of this protein plays a role in the neuronal dysfunction in SCA7 or other polyQ diseases remains unclear. We therefore analysed FUS localisation and function in a stable inducible PC12 cell model expressing the SCA7 polyQ protein ATXN7. We found that there was a high degree of FUS sequestration, which was associated with a more cytoplasmic FUS localisation, as well as a decreased expression of FUS regulated mRNAs. In contrast, the role of FUS in the formation of gamma H2AX positive DNA damage foci was unaffected. In fact, a statistical increase in the number of gamma H2AX foci, as well as an increased trend of single and double strand DNA breaks, detected by comet assay, could be observed in mutant ATXN7 cells. These results were further corroborated by a clear trend towards increased DNA damage in SCA7 patient fibroblasts. Our findings suggest that both alterations in the RNA regulatory functions of FUS, and increased DNA damage, may contribute to the pathology of SCA7.
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