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- Mercuri, E., et al.
(författare)
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Safety and effectiveness of ataluren: comparison of results from the STRIDE Registry and CINRG DMD Natural History Study
- 2020
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Ingår i: Journal of Comparative Effectiveness Research. - : Becaris Publishing Limited. - 2042-6305 .- 2042-6313. ; 9:5, s. 341-360
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Tidskriftsartikel (refereegranskat)abstract
- Aim: Strategic Targeting of Registries and International Database of Excellence (STRIDE) is an ongoing, multicenter registry providing real-world evidence regarding ataluren use in patients with nonsense mutation Duchenne muscular dystrophy (nmDMD). We examined the effectiveness of ataluren + standard of care (SoC) in the registry versus SoC alone in the Cooperative International Neuromuscular Research Group (CINRG) Duchenne Natural History Study (DNHS), DMD genotype-phenotype/-ataluren benefit correlations and ataluren safety. Patients & methods: Propensity score matching was performed to identify STRIDE and CINRG DNHS patients who were comparable in established disease progression predictors (registry cut-off date, 9 July 2018). Results & conclusion: Kaplan-Meier analyses demonstrated that ataluren + SoC significantly delayed age at loss of ambulation and age at worsening performance in timed function tests versus SoC alone (p <= 0.05). There were no DMD genotype-phenotype/ataluren benefit correlations. Ataluren was well tolerated. These results indicate that ataluren + SoC delays functional milestones of DMD progression in patients with nmDMD in routine clinical practice. ClinicalTrials.gov identifier: NCT02369731. ClinicalTrials.gov identifier: NCT02369731.
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| 2. |
- Mercuri, E., et al.
(författare)
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Safety and effectiveness of ataluren in patients with nonsense mutation DMD in the STRIDE Registry compared with the CINRG Duchenne Natural History Study (2015-2022): 2022 interim analysis
- 2023
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Ingår i: Journal of Neurology. - 0340-5354. ; 270, s. 3896-3913
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Tidskriftsartikel (refereegranskat)abstract
- ObjectiveStrategic Targeting of Registries and International Database of Excellence (STRIDE) is an ongoing, international, multicenter registry of real-world ataluren use in individuals with nonsense mutation Duchenne muscular dystrophy (nmDMD) in clinical practice. This updated interim report (data cut-off: January 31, 2022), describes STRIDE patient characteristics and ataluren safety data, as well as the effectiveness of ataluren plus standard of care (SoC) in STRIDE versus SoC alone in the Cooperative International Neuromuscular Research Group (CINRG) Duchenne Natural History Study (DNHS).MethodsPatients are followed up from enrollment for at least 5 years or until study withdrawal. Propensity score matching was performed to identify STRIDE and CINRG DNHS patients who were comparable in established predictors of disease progression.ResultsAs of January 31, 2022, 307 patients were enrolled from 14 countries. Mean (standard deviation [SD]) ages at first symptoms and at genetic diagnosis were 2.9 (1.7) years and 4.5 (3.7) years, respectively. Mean (SD) duration of ataluren exposure was 1671 (56.8) days. Ataluren had a favorable safety profile; most treatment-emergent adverse events were mild or moderate and unrelated to ataluren. Kaplan-Meier analyses demonstrated that ataluren plus SoC significantly delayed age at loss of ambulation by 4 years (p < 0.0001) and age at decline to %-predicted forced vital capacity of < 60% and < 50% by 1.8 years (p = 0.0021) and 2.3 years (p = 0.0207), respectively, compared with SoC alone.ConclusionLong-term, real-world treatment with ataluren plus SoC delays several disease progression milestones in individuals with nmDMD. NCT02369731; registration date: February 24, 2015.
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| 4. |
- Bianchi, Marta, et al.
(författare)
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Evaluating foods and diets from a multi-dimensional perspective : nutrition, health and environment
- 2020
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Ingår i: Proceedings of the Nutrition Society. - : Cambridge University Press. - 0029-6651 .- 1475-2719. ; 79:OCE2, s. E336-E336
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Introduction: The study of the environmental impact of dietary patterns in relation to their nutrition quality and health impact is of recent development and great interest for both nutrition and environmental scientists. Preliminary research has been conducted on the potential application of nutrition and health indexes as reference units (i.e. functional units) in the life cycle assessment of foods. Although proposed methods to include nutrition and health aspects exist, more research is needed to increase the scientific quality and societal usefulness of such assessments.Materials and Methods: SLF Healthy Diets is a 20-month project where 64 food items from the FFQ used in the population study “Västerbotten Intervention Programme” (VIP) will be characterized for their nutrition density and matched to the carbon footprint from life cycle assessment studies. Several nutrition density scores will be analyzed, among which the NRF9.3 score, a dietary-dependent NQI score, and a new nutrient index tailored for the Swedish population. Hazard ratios for total mortality will be estimated for 100.000 participants to the VIP study, and associations with reported intake of food products, nutrient density and environmental performance described.Results and Discussion: Multiple results are expected from the project, among which a synthesis of the combined nutritional and environmental performance of the analyzed foods according to different methods, and hence the identification of the best nutritional index to apply in environmental studies. Additionally, the assessment in the VIP cohort of the associations between reported intake of food products and observed health outcomes will evaluate the ability of the suggested nutrition scores to predict the total mortality in the studied population.The present project will allow for more robust quantification and communication of food products’ sustainability performance. Specifically, the project will: develop clear advice on which nutrition scores can best be used in LCA food studies; evaluate pros and cons of combined environmental, nutritional, and health metrics; validate nutrition and health metrics ability to predict health outcomes within a Swedish population-based cohort; investigate and propose how combined environmental, nutritional and health metrics can be implemented and used by food chain stakeholders.
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| 8. |
- Rauch, Alexander, et al.
(författare)
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Glucocorticoids suppress bone formation by attenuating osteoblast differentiation via the monomeric glucocorticoid receptor.
- 2010
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Ingår i: Cell metabolism. - : Elsevier BV. - 1932-7420 .- 1550-4131. ; 11:6, s. 517-31
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Tidskriftsartikel (refereegranskat)abstract
- Development of osteoporosis severely complicates long-term glucocorticoid (GC) therapy. Using a Cre-transgenic mouse line, we now demonstrate that GCs are unable to repress bone formation in the absence of glucocorticoid receptor (GR) expression in osteoblasts as they become refractory to hormone-induced apoptosis, inhibition of proliferation, and differentiation. In contrast, GC treatment still reduces bone formation in mice carrying a mutation that only disrupts GR dimerization, resulting in bone loss in vivo, enhanced apoptosis, and suppressed differentiation in vitro. The inhibitory GC effects on osteoblasts can be explained by a mechanism involving suppression of cytokines, such as interleukin 11, via interaction of the monomeric GR with AP-1, but not NF-kappaB. Thus, GCs inhibit cytokines independent of GR dimerization and thereby attenuate osteoblast differentiation, which accounts, in part, for bone loss during GC therapy.
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| 9. |
- Sezgin, E, et al.
(författare)
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Creating Supported Plasma Membrane Bilayers Using Acoustic Pressure
- 2020
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Ingår i: Membranes. - : MDPI AG. - 2077-0375. ; 10:2
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Tidskriftsartikel (refereegranskat)abstract
- Model membrane systems are essential tools for the study of biological processes in a simplified setting to reveal the underlying physicochemical principles. As cell-derived membrane systems, giant plasma membrane vesicles (GPMVs) constitute an intermediate model between live cells and fully artificial structures. Certain applications, however, require planar membrane surfaces. Here, we report a new approach for creating supported plasma membrane bilayers (SPMBs) by bursting cell-derived GPMVs using ultrasound within a microfluidic device. We show that the mobility of outer leaflet molecules is preserved in SPMBs, suggesting that they are accessible on the surface of the bilayers. Such model membrane systems are potentially useful in many applications requiring detailed characterization of plasma membrane dynamics.
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| 10. |
- Stride, A, et al.
(författare)
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The genetic abnormality in the beta cell determines the response to an oral glucose load
- 2002
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Ingår i: Diabetologia. - : Springer Science and Business Media LLC. - 1432-0428 .- 0012-186X. ; 45:3, s. 427-435
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Tidskriftsartikel (refereegranskat)abstract
- Aims/hypothesis. We assessed how the role of genes genetic causation in causing maturity-onset diabetes of the young (MODY) alters the response to an oral glucose tolerance test (OGTT). Methods. We studied OGTT in 362 MODY subjects, from seven European centres; 245 had glucokinase gene mutations and 117 had Hepatocyte Nuclear Factor-1 alpha (HNF-1alpha) gene mutations. Results. BMI and age were similar in the genetically defined groups. Fasting plasma glucose (FPG) was less than 5.5 mmol/l in 2% glucokinase subjects and 46% HNF-1alpha subjects (p < 0.0001). Glucokinase subjects had a higher FPG than HNF-1a subjects ([means +/- SD] 6.8 +/- 0.8 vs 6.0 +/- 1.9 mmol/l, p < 0.0001), a lower 2-h value (8.9 +/- 2.3 vs 11.2 +/- 5.2 mmol/l, p < 0.0001) and a lower OGTT increment (2-h - fasting) (2.1 +/- 2.3 vs 5.2 +/- 3.9 mmol/l, p < 0.0001). The relative proportions classified as diabetic depended on whether fasting (38% vs 22%, glucokinase vs HNF-1alpha) or 2-h values (19% vs 44%) were used. Fasting and 2-h glucose values were not correlated in the glucokinase subjects (r = -0.047, p = 0.65) but were strongly correlated in HNF-1alpha subjects (r = 0.8, p < 0.001). Insulin concentrations were higher in the glucokinase subjects throughout the OGTT. Conclusion/interpretation. The genetic cause of the beta-cell defect results in clear differences in both the fasting glucose and the response to an oral glucose load and this can help diagnostic genetic testing in MODY. OGTT results reflect not only the degree of hyperglycaemia but also the underlying cause.
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