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- Ilegems, E, et al.
(författare)
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HIF-1α inhibitor PX-478 preserves pancreatic β cell function in diabetes
- 2022
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Ingår i: Science translational medicine. - : American Association for the Advancement of Science (AAAS). - 1946-6242 .- 1946-6234. ; 14:638, s. eaba9112-
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Tidskriftsartikel (refereegranskat)abstract
- During progression of type 2 diabetes, pancreatic β cells are subjected to sustained metabolic overload. We postulated that this state mediates a hypoxic phenotype driven by hypoxia-inducible factor–1α (HIF-1α) and that treatment with the HIF-1α inhibitor PX-478 would improve β cell function. Our studies showed that the HIF-1α protein was present in pancreatic β cells of diabetic mouse models. In mouse islets with high glucose metabolism, the emergence of intracellular Ca2+oscillations at low glucose concentration and the abnormally high basal release of insulin were suppressed by treatment with the HIF-1α inhibitor PX-478, indicating improvement of β cell function. Treatment of db/db mice with PX-478 prevented the rise of glycemia and diabetes progression by maintenance of elevated plasma insulin concentration. In streptozotocin-induced diabetic mice, PX-478 improved the recovery of glucose homeostasis. Islets isolated from these mice showed hallmarks of improved β cell function including elevation of insulin content, increased expression of genes involved in β cell function and maturity, inhibition of dedifferentiation markers, and formation of mature insulin granules. In response to PX-478 treatment, human islet organoids chronically exposed to high glucose presented improved stimulation index of glucose-induced insulin secretion. These results suggest that the HIF-1α inhibitor PX-478 has the potential to act as an antidiabetic therapeutic agent that preserves β cell function under metabolic overload.
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- Iorizzo, L., et al.
(författare)
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Proposed cutoff for fetal scalp blood lactate in intrapartum fetal surveillance based on neonatal outcomes: a large prospective observational study
- 2022
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Ingår i: BJOG: An International Journal of Obstetrics and Gynaecology. - : Wiley. - 1470-0328 .- 1471-0528. ; 129:4, s. 636-646
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Tidskriftsartikel (refereegranskat)abstract
- Objective: Determination of lactate in fetal scalp blood (FBS) during labour has been recognised since the 1970s. The internationally accepted cutoff of >4.8mmol/l indicating fetal acidosis is exclusive for the point-of-care device (POC) LactatePro™, which is no longer in production. The aim of this study was to establish a new cutoff for scalp lactate based on neonatal outcomes with the use of the StatstripLactate®/StatstripXpress® Lactate system, the only POC designed for hospital use. Design: Observational study. Setting: January 2016 to March 2020 labouring women with indication for FBS were prospectively included from seven Swedish and one Australian delivery unit. Population: Inclusion criteria: singleton pregnancy, vertex presentation, ≥35+0weeks of gestation. Method: Based on the optimal correlation between FBS lactate and cord pH/lactate, only cases with ≤25minutes from FBS to delivery were included in the final calculations. Main outcome measures: Metabolic acidosis in cord blood defined as pH <7.05 plus BDecf >10mmol/l and/or lactate >10mmol/l. Results: A total of 3334 women were enrolled of whom 799 were delivered within 25minutes. The areas under the receiver operating characteristics curves (AUC) and corresponding optimal cutoff values were as follows; metabolic acidosis AUC 0.87 (95% CI 0.77–0.97), cutoff 5.7mmol/l; pH <7.0 AUC 0.83 (95% CI 0.68–0.97), cutoff 4.6mmol/l; pH <7.05 plus BDecf ≥12mmol/l AUC 0.97 (95% CI 0.92–1), cutoff 5.8mmol/l; Apgar score <7 at 5minutes AUC 0.74 (95% CI 0.63–0.86), cutoff 5.2mmol/l; and pH <7.10 plus composite neonatal outcome AUC 0.76 (95% CI 0.67–0.85), cutoff 4.8mmol/l. Conclusion: A scalp lactate level <5.2mmol/l using the StatstripLactate®/StatstripXpress® system will safely rule out fetal metabolic acidosis. Tweetable abstract: Scalp blood lactate <5.2mmol/l using the StatstripLactate®/StatstripXpress system has an excellent ability to rule out fetal acidosis.
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- Lundeborg Hammarström, Inger, 1956-, et al.
(författare)
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Scandcleft Project Trial 2—Comparison of Speech Outcome in 1- and 2-Stage Palatal Closure in 5-Year-Olds With UCLP
- 2020
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Ingår i: Cleft Palate-Craniofacial Journal. - : SAGE Publications. - 1055-6656 .- 1545-1569. ; 57:4, s. 458-469
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Tidskriftsartikel (refereegranskat)abstract
- Objective: To investigate in-depth speech results in the Scandcleft Trial 2 with comparisons between surgical protocols and centers and with benchmarks from peers without cleft palate. Design: A prospective randomized clinical trial. Setting: Two Swedish and one Finnish Cleft Palate center. Participants: One hundred twelve participants were 5-years-old born with unilateral cleft lip and palate randomized to either lip repair and soft palate closure at 4 months and hard palate closure at 12 months or lip repair at 3 to 4 months (Arm A), or a closure of both the soft and hard palate at 12 months (Arm C). Main Outcome Measures: A composite measure dichotomized into velopharyngeal competency (VPC) or velopharyngeal incompetency (VPI), overall assessment of velopharyngeal function (VPC-Rate), percentage of consonants correct (PCC score), and consonant errors. In addition, number of speech therapy visits, average hearing thresholds, and secondary surgeries were documented to assess burden of treatment. Results: Across the trial, 53.5% demonstrated VPC and 46.5% VPI with no significant differences between arms or centers. In total, 27% reached age-appropriate PCC scores with no statistically significant difference between the arms. The Finnish center had significantly higher PCC scores, the Swedish centers had higher percentages of oral consonant errors. Number of speech therapy visits was significantly higher in the Finnish center. Conclusion: At age 5, poor speech outcomes with some differences between participating centers were seen but could not be attributed to surgical protocol. As one center had very few participants, the results from that center should be interpreted with caution. © 2019, American Cleft Palate-Craniofacial Association.
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