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- Ruilope, LM, et al.
(författare)
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Design and Baseline Characteristics of the Finerenone in Reducing Cardiovascular Mortality and Morbidity in Diabetic Kidney Disease Trial
- 2019
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Ingår i: American journal of nephrology. - : S. Karger AG. - 1421-9670 .- 0250-8095. ; 50:5, s. 345-356
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Tidskriftsartikel (refereegranskat)abstract
- <b><i>Background:</i></b> Among people with diabetes, those with kidney disease have exceptionally high rates of cardiovascular (CV) morbidity and mortality and progression of their underlying kidney disease. Finerenone is a novel, nonsteroidal, selective mineralocorticoid receptor antagonist that has shown to reduce albuminuria in type 2 diabetes (T2D) patients with chronic kidney disease (CKD) while revealing only a low risk of hyperkalemia. However, the effect of finerenone on CV and renal outcomes has not yet been investigated in long-term trials. <b><i>Patients and</i></b> <b><i>Methods:</i></b> The Finerenone in Reducing CV Mortality and Morbidity in Diabetic Kidney Disease (FIGARO-DKD) trial aims to assess the efficacy and safety of finerenone compared to placebo at reducing clinically important CV and renal outcomes in T2D patients with CKD. FIGARO-DKD is a randomized, double-blind, placebo-controlled, parallel-group, event-driven trial running in 47 countries with an expected duration of approximately 6 years. FIGARO-DKD randomized 7,437 patients with an estimated glomerular filtration rate ≥25 mL/min/1.73 m<sup>2</sup> and albuminuria (urinary albumin-to-creatinine ratio ≥30 to ≤5,000 mg/g). The study has at least 90% power to detect a 20% reduction in the risk of the primary outcome (overall two-sided significance level α = 0.05), the composite of time to first occurrence of CV death, nonfatal myocardial infarction, nonfatal stroke, or hospitalization for heart failure. <b><i>Conclusions:</i></b> FIGARO-DKD will determine whether an optimally treated cohort of T2D patients with CKD at high risk of CV and renal events will experience cardiorenal benefits with the addition of finerenone to their treatment regimen. Trial Registration: EudraCT number: 2015-000950-39; ClinicalTrials.gov identifier: NCT02545049.
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- Sugita, S., et al.
(författare)
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The geomorphology, color, and thermal properties of Ryugu: Implications for parent-body processes
- 2019
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Ingår i: Science. - : AAAS. - 0036-8075 .- 1095-9203. ; 364:6437
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Tidskriftsartikel (refereegranskat)abstract
- Asteroids fall to Earth in the form of meteorites, but these provide little information about their origins. The Japanese mission Hayabusa2 is designed to collect samples directly from the surface of an asteroid and return them to Earth for laboratory analysis. Three papers in this issue describe the Hayabusa2 team's study of the near-Earth carbonaceous asteroid 162173 Ryugu, at which the spacecraft arrived in June 2018 (see the Perspective by Wurm). Watanabeet al.measured the asteroid's mass, shape, and density, showing that it is a “rubble pile” of loose rocks, formed into a spinning-top shape during a prior period of rapid spin. They also identified suitable landing sites for sample collection. Kitazatoet al.used near-infrared spectroscopy to find ubiquitous hydrated minerals on the surface and compared Ryugu with known types of carbonaceous meteorite. Sugitaet al.describe Ryugu's geological features and surface colors and combined results from all three papers to constrain the asteroid's formation process. Ryugu probably formed by reaccumulation of rubble ejected by impact from a larger asteroid. These results provide necessary context to understand the samples collected by Hayabusa2, which are expected to arrive on Earth in December 2020.Science, this issue p.268, p.272, p.eaaw0422; see also p.230
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- Iwata, S., et al.
(författare)
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Therapeutic hypothermia can be induced and maintained using either commercial water bottles or a "phase changing material'' mattress in a newborn piglet model
- 2009
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Ingår i: Archives of Disease in Childhood. - : BMJ. - 0003-9888 .- 1468-2044. ; 94:5, s. 387-391
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Tidskriftsartikel (refereegranskat)abstract
- Background: Therapeutic hypothermia, a safe and effective treatment for neonatal encephalopathy in an intensive care setting, is not available in low-resource settings. Aims/Methods: To assess two low-tech, low-cost cooling devices for use in low-resource settings: (i) commercially available water bottles filled with tepid water (25 degrees C); (ii) a mattress made of phase changing material (PCM) with a melting point of 32 degrees C (PCM works as a heat buffer at this temperature). Eleven anaesthetised newborn piglets were studied following transient hypoxia-ischaemia. The cooling device was applied 2-26 h after hypoxia-ischaemia with a target rectal temperature (T-rectal) of 33-34 degrees C. T-rectal undershoot was adjusted using cotton blankets; the cooling device was renewed when T-rectal rose above 35 degrees C. T-rectal data during cooling were dichotomised (within or without target) to assess: (a) the total period within the target T-rectal range; (b) the stability and fluctuation of T-rectal during cooling. Results: Therapeutic hypothermia was achieved with both water bottles (n=5) and the PCM mattress (n=6). The mean (SD) time to reach target T-rectal was 1.8 (0.5) h with water bottles and 1.9 (0.3) h with PCM. PCM cooling led to a longer period within the target T-rectal range (p<0.01) and more stable cooling (p<0.05). Water bottle cooling required device renewal (in four out of five piglets). Conclusion: Simple, low-tech cooling devices can induce and maintain therapeutic hypothermia effectively in a porcine model of neonatal encephalopathy, although frequent fine tuning by adjusting the number of blankets insulating the piglet was required to maintain a stable temperature. PCM may induce more stable cooling compared with water bottles.
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- Mathieu, C., et al.
(författare)
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Efficacy and Safety of Dapagliflozin in Patients With Inadequately Controlled Type 1 Diabetes (the DEPICT-2 Study): 24-Week Results From a Randomized Controlled Trial
- 2018
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Ingår i: Diabetes Care. - : American Diabetes Association. - 0149-5992 .- 1935-5548. ; 41:9, s. 1938-1946
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVEThis 24-week, double-blinded, phase 3 clinical trial (DEPICT-2; ClinicalTrials.gov, NCT02460978) evaluated efficacy and safety of dapagliflozin as adjunct therapy to adjustable insulin in patients with inadequately controlled type 1 diabetes (HbA(1c) 7.5-10.5%).RESEARCH DESIGN AND METHODSPatients were randomized 1:1:1 to dapagliflozin 5 mg (n = 271), dapagliflozin 10 mg (n = 270), or placebo (n = 272) plus insulin. Insulin dose was adjusted by investigators according to self-monitored glucose readings, local guidance, and individual circumstances.RESULTSBaseline characteristics were balanced between treatment groups. At week 24, dapagliflozin significantly decreased HbA(1c) (primary outcome; difference vs. placebo: dapagliflozin 5 mg -0.37% [95% CI -0.49, -0.26], dapagliflozin 10 mg -0.42% [-0.53, -0.30]), total daily insulin dose (-10.78% [-13.73, -7.72] and -11.08% [-14.04, -8.02], respectively), and body weight (-3.21% [-3.96, -2.45] and -3.74% [-4.49, -2.99], respectively) (P < 0.0001 for all). Mean interstitial glucose, amplitude of glucose excursion, and percent of readings within target glycemic range (>70 to 180 mg/dL) versus placebo were significantly improved. More patients receiving dapagliflozin achieved a reduction in HbA(1c) 0.5% without severe hypoglycemia compared with placebo. Adverse events were reported for 72.7%, 67.0%, and 63.2% of patients receiving dapagliflozin 5 mg, dapagliflozin 10 mg, and placebo, respectively. Hypoglycemia, including severe hypoglycemia, was balanced between groups. There were more adjudicated definite diabetic ketoacidosis (DKA) events with dapagliflozin: 2.6%, 2.2%, and 0% for dapagliflozin 5 mg, dapagliflozin 10 mg, and placebo, respectively.CONCLUSIONSDapagliflozin as adjunct therapy to adjustable insulin in patients with type 1 diabetes was well tolerated and improved glycemic control with no increase in hypoglycemia versus placebo but with more DKA events.
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- Ahltorp, Magnus, et al.
(författare)
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Medical vocabulary mining using distributional semantics on Japanese patient blogs
- 2014
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Ingår i: SMBM 2014 - Proceedings of the 6th International Symposium on Semantic Mining in Biomedicine. - : University of Aveiro. ; , s. 57-62
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Konferensbidrag (refereegranskat)abstract
- Random indexing has previously been successfully used for medical vocabulary expansion for Germanic languages. In this study, we used this approach to extract medical terms from a Japanese patient blog corpus. The corpus was segmented into semantic units by a semantic role labeller, and different pre-processing and parameter settings were then evaluated. The evaluation showed that similar settings are suitable for Japanese as for previously explored Germanic languages, and that distributional semantics is equally useful for semi-automatic expansion of Japanese medical vocabularies as for medical vocabularies in Germanic languages.
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| 15. |
- Lozano, Manuel, et al.
(författare)
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DNA methylation changes associated with prenatal mercury exposure : A meta-analysis of prospective cohort studies from PACE consortium
- 2022
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Ingår i: Environmental Research. - : Elsevier BV. - 0013-9351 .- 1096-0953. ; 204
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Tidskriftsartikel (refereegranskat)abstract
- Mercury (Hg) is a ubiquitous heavy metal that originates from both natural and anthropogenic sources and is transformed in the environment to its most toxicant form, methylmercury (MeHg). Recent studies suggest that MeHg exposure can alter epigenetic modifications during embryogenesis. In this study, we examined associations between prenatal MeHg exposure and levels of cord blood DNA methylation (DNAm) by meta-analysis in up to seven independent studies (n = 1462) as well as persistence of those relationships in blood from 7 to 8 year-old children (n = 794). In cord blood, we found limited evidence of differential DNAm at cg24184221 in MED31 (β = 2.28 × 10−4, p-value = 5.87 × 10−5) in relation to prenatal MeHg exposure. In child blood, we identified differential DNAm at cg15288800 (β = 0.004, p-value = 4.97 × 10−5), also located in MED31. This repeated link to MED31, a gene involved in lipid metabolism and RNA Polymerase II transcription function, may suggest a DNAm perturbation related to MeHg exposure that persists into early childhood. Further, we found evidence for association between prenatal MeHg exposure and child blood DNAm levels at two additional CpGs: cg12204245 (β = 0.002, p-value = 4.81 × 10−7) in GRK1 and cg02212000 (β = −0.001, p-value = 8.13 × 10−7) in GGH. Prenatal MeHg exposure was associated with DNAm modifications that may influence health outcomes, such as cognitive or anthropometric development, in different populations.
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| 16. |
- Phillip, M., et al.
(författare)
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Long-term efficacy and safety of dapagliflozin in patients with inadequately controlled type 1 diabetes: pooled 52-week outcomes from the DEPICT-1 and-2 studies
- 2021
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Ingår i: Diabetes Obesity & Metabolism. - : Wiley. - 1462-8902 .- 1463-1326. ; 23:2, s. 549-560
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Tidskriftsartikel (refereegranskat)abstract
- Aim To evaluate the efficacy and safety of adjunct dapagliflozin therapy in patients with type 1 diabetes (T1D). Materials and Methods DEPICT-1 and -2 were randomized, double-blind, parallel-group, 24-week studies, with 28-week extension periods. Adults with T1D and HbA1c 7.5%-10.5% were randomized (1:1:1) to receive dapagliflozin 5 mg, 10 mg or placebo. The short- and long-term efficacy and safety of dapagliflozin were examined in an exploratory pooled analysis of both studies. Results Efficacy analyses included 530, 529 and 532 and safety analysis included 548, 566 and 532 patients in the dapagliflozin 5 mg, 10 mg and placebo groups, respectively. Baseline characteristics were similar between treatment groups. At week 24, reductions were seen with dapagliflozin 5 and 10 mg compared with placebo in HbA1c (-0.40%, -0.43% vs. 0.00%) and body weight (-2.45, -2.91 vs. 0.11 kg). HbA1c and body weight reductions versus placebo were also seen after 52 weeks of treatment. There was no imbalance in occurrence of severe hypoglycaemic events between groups. The proportion of patients experiencing definite diabetic ketoacidosis (DKA) was higher with dapagliflozin 5 mg (4.0%) and 10 mg (3.5%) compared with placebo (1.1%) over 52 weeks; most events were of mild or moderate severity, and all resolved with treatment. Conclusions Over 52 weeks, dapagliflozin provided glycaemic and weight benefits, with no increased frequency of severe hypoglycaemia compared with placebo. More DKA events were reported with dapagliflozin than placebo, highlighting the importance of appropriate patient selection, education and risk-mitigation strategies.
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- Sakaguchi, M., et al.
(författare)
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FoxK1 and FoxK2 in insulin regulation of cellular and mitochondrial metabolism
- 2019
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Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 10
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Tidskriftsartikel (refereegranskat)abstract
- A major target of insulin signaling is the FoxO family of Forkhead transcription factors, which translocate from the nucleus to the cytoplasm following insulin-stimulated phosphorylation. Here we show that the Forkhead transcription factors FoxK1 and FoxK2 are also downstream targets of insulin action, but that following insulin stimulation, they translocate from the cytoplasm to nucleus, reciprocal to the translocation of FoxO1. FoxK1/FoxK2 translocation to the nucleus is dependent on the Akt-mTOR pathway, while its localization to the cytoplasm in the basal state is dependent on GSK3. Knockdown of FoxK1 and FoxK2 in liver cells results in upregulation of genes related to apoptosis and down-regulation of genes involved in cell cycle and lipid metabolism. This is associated with decreased cell proliferation and altered mitochondrial fatty acid metabolism. Thus, FoxK1/K2 are reciprocally regulated to FoxO1 following insulin stimulation and play a critical role in the control of apoptosis, metabolism and mitochondrial function.
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| 18. |
- Schoehe, S., et al.
(författare)
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Free-charge carrier parameters of n-type, p-type and compensated InN:Mg determined by infrared spectroscopic ellipsometry
- 2014
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Ingår i: Thin Solid Films. - : Elsevier. - 0040-6090 .- 1879-2731. ; 571, s. 384-388
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Tidskriftsartikel (refereegranskat)abstract
- Infrared spectroscopic ellipsometry is applied to investigate the free-charge carrier properties of Mg-doped InN films. Two representative sets of In-polar InN grown by molecular beam epitaxy with Mg concentrations ranging from 1.2 x 10(17) cm(-3) to 8 x 10(20) cm(-3) are compared. P-type conductivity is indicated for the Mg concentration range of 1 x 10(18) cm(-3) to 9 x 10(19) cm(-3) from a systematic investigation of the longitudinal optical phonon plasmon broadening and the mobility parameter in dependence of the Mg concentration. A parameterized model that accounts for the phonon-plasmon coupling is applied to determine the free-charge carrier concentration and mobility parameters in the doped bulk InN layer as well as the GaN template and undoped InN buffer layer for each sample. The free-charge carrier properties in the second sample set are consistent with the results determined in a comprehensive analysis of the first sample set reported earlier [Schoche et al., J. Appl. Phys. 113, 013502 (2013)]. In the second set, two samples with Mg concentration of 2.3 x 10(20) cm(-3) are identified as compensated n-type InN with very low electron concentrations which are suitable for further investigation of intrinsic material properties that are typically governed by high electron concentrations even in undoped InN. The compensated n-type InN samples can be clearly distinguished from the p-type conductive material of similar plasma frequencies by strongly reduced phonon plasmon broadening.
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| 22. |
- Xie, Mengyao, et al.
(författare)
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Effect of Mg doping on the structural and free-charge carrier properties of InN
- 2014
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Ingår i: Journal of Applied Physics. - : AIP Publishing. - 0021-8979 .- 1089-7550. ; 115:16, s. 163504-
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Tidskriftsartikel (refereegranskat)abstract
- We study the structural and free-charge carrier properties of two sets of InN films grown by molecular beam epitaxy doped with different Mg concentrations from 1x1018 cm-3 to 3.9x1021 cm-3. We determine the effect of Mg doping on surface morphology, lattice parameters, structural characteristics and carrier properties. We show that infrared spectroscopic ellipsometry can be used to evidence successful p-type doping in InN, which is an important issue in InN. High resolution X-ray diffraction, combined with atomic force microscopy measurements reveals a drastic decrease in structural quality of the film for Mg concentrations above 1020 cm-3, accompanied with a significant increase in surface roughness. In addition, a decrease of the c-lattice parameter and an increase of the a-lattice parameter are found with increasing Mg concentration. Different contributions to the strain are discussed and it is suggested that the incorporation of Mg leads to a change of growth mode and generation of tensile growth strain. At high Mg concentrations zinc-blende InN inclusions appear which are suggested to originate from higher densities of stacking faults. Infrared spectroscopic ellipsometry analysis shows a reduced LPP-coupling, manifested as a characteristic dip in the IRSE data, and qualitatively different broadening behavior for Mg concentrations between 1.1x1018 cm−3 and 2.9x1019 cm−3 indicate the existence of a p-type conducting bulk InN layer for these Mg concentrations.
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