| 1. |
- 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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| 2. |
- Aprile, E., et al.
(författare)
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The XENON1T dark matter experiment
- 2017
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Ingår i: European Physical Journal C. - : Springer Science and Business Media LLC. - 1434-6044 .- 1434-6052. ; 77:12
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Tidskriftsartikel (refereegranskat)abstract
- The XENON1T experiment at the Laboratori Nazionali del Gran Sasso (LNGS) is the first WIMP dark matter detector operating with a liquid xenon target mass above the ton-scale. Out of its 3.2t liquid xenon inventory, 2.0t constitute the active target of the dual-phase time projection chamber. The scintillation and ionization signals from particle interactions are detected with low-background photomultipliers. This article describes the XENON1T instrument and its subsystems as well as strategies to achieve an unprecedented low background level. First results on the detector response and the performance of the subsystems are also presented.
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| 3. |
- Abila, R., et al.
(författare)
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Oil extraction imperils Africa’s Great Lakes
- 2016
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Ingår i: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 354:6312, s. 561-562
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- As the world's demands for hydrocarbons increase (1), remote areas previously made inaccessible by technological limitations are now being prospected for oil and gas deposits. Virtually unnoticed by the public, such activities are ongoing in the East African Great Lakes region, threatening these ecosystems famed for their hyper-diverse biota, including the unique adaptive radiations of cichlid fishes (2). Countries in the region see exploitation of hydrocarbon reserves as a vital economic opportunity. In the Lake Albert region of Uganda, for example, the government foresees a $3.6 billion oil profit per year starting in 2018—a sum almost as high as the country's current annual budget (3). However, oil extraction in the East African Great Lakes region poses grave risks to the environment and local communities.
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| 7. |
- Alves, Luis, et al.
(författare)
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New Insights on the Role of Urea on the Dissolution and Thermally-Induced Gelation of Cellulose in Aqueous Alkali
- 2018
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Ingår i: GELS. - : MDPI AG. - 2310-2861. ; 4:4
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Tidskriftsartikel (refereegranskat)abstract
- The gelation of cellulose in alkali solutions is quite relevant, but still a poorly understood process. Moreover, the role of certain additives, such as urea, is not consensual among the community. Therefore, in this work, an unusual set of characterization methods for cellulose solutions, such as cryo-transmission electronic microscopy (cryo-TEM), polarization transfer solid-state nuclear magnetic resonance (PTssNMR) and diffusion wave spectroscopy (DWS) were employed to study the role of urea on the dissolution and gelation processes of cellulose in aqueous alkali. Cryo-TEM reveals that the addition of urea generally reduces the presence of undissolved cellulose fibrils in solution. These results are consistent with PTssNMR data, which show the reduction and in some cases the absence of crystalline portions of cellulose in solution, suggesting a pronounced positive effect of the urea on the dissolution efficiency of cellulose. Both conventional mechanical macrorheology and microrheology (DWS) indicate a significant delay of gelation induced by urea, being absent until ca. 60 degrees C for a system containing 5wt % cellulose, while a system without urea gels at a lower temperature. For higher cellulose concentrations, the samples containing urea form gels even at room temperature. It is argued that since urea facilitates cellulose dissolution, the high entanglement of the cellulose chains in solution (above the critical concentration, C*) results in a strong three-dimensional network.
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| 8. |
- Alves, L., et al.
(författare)
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Unusual extraction and characterization of nanocrystalline cellulose from cellulose derivatives
- 2015
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Ingår i: Journal of Molecular Liquids. - : Elsevier BV. - 0167-7322 .- 1873-3166. ; 210, s. 106-112
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Tidskriftsartikel (refereegranskat)abstract
- Unlike many nanomaterials, nanocrystalline cellulose (CNC) is not synthesized from molecular or atomic components but rather extracted from naturally occurring cellulose. Undoubtedly, the exploitation of CNCs will become a bridge between nanoscience and natural resource products, which could play a major role in reviving the forest industry. In this work, CNC was successfully extracted from unusual sources, hydroxypropyl methylcellulose (HPMC) and carboxymethylcellulose (CMC). The extracted crystallites were purified and further characterized by Fourier transform infrared (FTIR), scanning electron microscopy (SEM), X-ray powder diffraction (XRD) and dynamic light scattering (DLS). The average size of the CNCs extracted from HPMC and CMC was found to be less (and with lower zeta potential) than the ones extracted from microcrystalline cellulose (MCC). On the other hand, FTIR and XRD revealed that native HPMC and CMC are unexpectedly highly crystalline and hence can be used as a source for CNCs. © 2014 Elsevier B.V.All rights reserved.
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| 9. |
- Antonelli, Alexandre, 1978, et al.
(författare)
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Amazonia is the primary source of Neotropical biodiversity
- 2018
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Ingår i: Proceedings of the National Academy of Sciences of the United States of America. - : Proceedings of the National Academy of Sciences. - 0027-8424. ; 115:23, s. 6034-6039
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Tidskriftsartikel (refereegranskat)abstract
- The American tropics (the Neotropics) are the most species-rich realm on Earth, and for centuries, scientists have attempted to understand the origins and evolution of their biodiversity. It is now clear that different regions and taxonomic groups have responded differently to geological and climatic changes. However, we still lack a basic understanding of how Neotropical biodiversity was assembled over evolutionary timescales. Here we infer the timing and origin of the living biota in all major Neotropical regions by performing a cross-taxonomic biogeographic analysis based on 4,450 species from six major clades across the tree of life (angiosperms, birds, ferns, frogs, mammals, and squamates), and integrate > 1.3 million species occurrences with large-scale phylogenies. We report an unprecedented level of biotic interchange among all Neotropical regions, totaling 4,525 dispersal events. About half of these events involved transitions between major environmental types, with a predominant directionality from forested to open biomes. For all taxonomic groups surveyed here, Amazonia is the primary source of Neotropical diversity, providing > 2,800 lineages to other regions. Most of these dispersal events were to Mesoamerica (similar to 1,500 lineages), followed by dispersals into open regions of northern South America and the Cerrado and Chaco biomes. Biotic interchange has taken place for > 60 million years and generally increased toward the present. The total amount of time lineages spend in a region appears to be the strongest predictor of migration events. These results demonstrate the complex origin of tropical ecosystems and the key role of biotic interchange for the assembly of regional biotas.
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| 12. |
- Grossi-Oliveira, G.A., et al.
(författare)
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Early Osseointegration Events on Neoss® ProActive and Bimodal Implants: A Comparison of Different Surfaces in an Animal Model
- 2015
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Ingår i: Clinical Implant Dentistry and Related Research. - : Wiley. - 1523-0899 .- 1708-8208. ; 17:6, s. 1060-1072
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Tidskriftsartikel (refereegranskat)abstract
- © 2015 Wiley Periodicals, Inc. Background: Cell interactions, adherence, and osseointegration at the bone-implant interface can be directly influenced by the surface properties of the titanium implant. Purpose: To characterize osseointegration of Neoss® implants with conventional (control group) and hydrophilic (test group) surface treatments. Materials and Methods: Six Labrador dogs received Neoss implants with conventional and hydrophilic surfaces. The bone-implant interfaces were evaluated 1 and 4 weeks after implantation, and osseointegration was evaluated using histological, histomorphometric, fluorescence, and resonance frequency analyses. The surfaces were also subjected to topographic and hydrophilicity analyses. Results: The topographic analyses revealed increased surface roughness in the test group compared with the control group (surface area roughness 0.42 and 0.78μm, respectively, for control and test group surfaces; p≤.05). The wettability values were higher in the test group (contact angles 67.2° and 27.2° for the control and test group surfaces, respectively; p≤.05). Implants in the test group also exhibited better stability, more bone-implant contact, and increased bone area compared with implants in the control group. Conclusion: Neoss implants in the test group improved bone formation in the early stages of osseointegration compared with implants in the control group.
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| 15. |
- Rosenblad, Carl, et al.
(författare)
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Vector-mediated l-3,4-dihydroxyphenylalanine delivery reverses motor impairments in a primate model of Parkinson's disease
- 2019
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Ingår i: Brain : a journal of neurology. - : Oxford University Press (OUP). - 1460-2156. ; , s. 2402-2416
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Tidskriftsartikel (refereegranskat)abstract
- Ever since its introduction 40 years ago l-3,4-dihydroxyphenylalanine (l-DOPA) therapy has retained its role as the leading standard medication for patients with Parkinson's disease. With time, however, the shortcomings of oral l-DOPA treatment have become apparent, particularly the motor fluctuations and troublesome dyskinetic side effects. These side effects, which are caused by the excessive swings in striatal dopamine caused by intermittent oral delivery, can be avoided by delivering l-DOPA in a more continuous manner. Local gene delivery of the l-DOPA synthesizing enzymes, tyrosine hydroxylase and guanosine-tri-phosphate-cyclohydrolase-1, offers a new approach to a more refined dopaminergic therapy where l-DOPA is delivered continuously at the site where it is needed i.e. the striatum. In this study we have explored the therapeutic efficacy of adeno-associated viral vector-mediated l-DOPA delivery to the putamen in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-treated rhesus monkeys, the standard non-human primate model of Parkinson's disease. Viral vector delivery of the two enzymes, tyrosine hydroxylase and guanosine-5'-tri-phosphate-cyclohydrolase-1, bilaterally into the dopamine-depleted putamen, induced a significant, dose-dependent improvement of motor behaviour up to a level identical to that obtained with the optimal dose of peripheral l-DOPA. Importantly, this improvement in motor function was obtained without any adverse dyskinetic effects. These results provide proof-of-principle for continuous vector-mediated l-DOPA synthesis as a novel therapeutic strategy for Parkinson's disease. The constant, local supply of l-DOPA obtained with this approach holds promise as an efficient one-time treatment that can provide long-lasting clinical improvement and at the same time prevent the appearance of motor fluctuations and dyskinetic side effects associated with standard oral dopaminergic medication.
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| 16. |
- Tordo, Julie, et al.
(författare)
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A novel adeno-associated virus capsid with enhanced neurotropism corrects a lysosomal transmembrane enzyme deficiency
- 2018
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Ingår i: Brain. - : Oxford University Press (OUP). - 0006-8950 .- 1460-2156. ; 141:7, s. 2014-2031
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Tidskriftsartikel (refereegranskat)abstract
- Recombinant adeno-associated viruses (AAVs) are popular in vivo gene transfer vehicles. However, vector doses needed to achieve therapeutic effect are high and some target tissues in the central nervous system remain difficult to transduce. Gene therapy trials using AAV for the treatment of neurological disorders have seldom led to demonstrated clinical efficacy. Important contributing factors are low transduction rates and inefficient distribution of the vector. To overcome these hurdles, a variety of capsid engineering methods have been utilized to generate capsids with improved transduction properties. Here we describe an alternative approach to capsid engineering, which draws on the natural evolution of the virus and aims to yield capsids that are better suited to infect human tissues. We generated an AAV capsid to include amino acids that are conserved among natural AAV2 isolates and tested its biodistribution properties in mice and rats. Intriguingly, this novel variant, AAV-TT, demonstrates strong neurotropism in rodents and displays significantly improved distribution throughout the central nervous system as compared to AAV2. Additionally, sub-retinal injections in mice revealed markedly enhanced transduction of photoreceptor cells when compared to AAV2. Importantly, AAV-TT exceeds the distribution abilities of benchmark neurotropic serotypes AAV9 and AAVrh10 in the central nervous system of mice, and is the only virus, when administered at low dose, that is able to correct the neurological phenotype in a mouse model of mucopolysaccharidosis IIIC, a transmembrane enzyme lysosomal storage disease, which requires delivery to every cell for biochemical correction. These data represent unprecedented correction of a lysosomal transmembrane enzyme deficiency in mice and suggest that AAV-TT-based gene therapies may be suitable for treatment of human neurological diseases such as mucopolysaccharidosis IIIC, which is characterized by global neuropathology.
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| 17. |
- Walter, Helene L, et al.
(författare)
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Treatment with AMD3100 attenuates the microglial response and improves outcome after experimental stroke.
- 2015
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Ingår i: Journal of Neuroinflammation. - : Springer Science and Business Media LLC. - 1742-2094. ; 12:24, s. 1-15
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Tidskriftsartikel (refereegranskat)abstract
- Recovery of lost neurological function after stroke is limited and dependent on multiple mechanisms including inflammatory processes. Selective pharmacological modulation of inflammation might be a promising approach to improve stroke outcome. Methods: We used 1,1'-[1,4-phenylenebis(methylene)] bis[1,4,8,11-tetraazacyclotetradecane] (AMD3100), an antagonist to the C-X-C chemokine receptor type 4 (CXCR4) and potential allosteric agonist to CXCR7, administered to mice twice daily from day 2 after induction of photothrombosis (PT). In addition to functional outcome, the dynamics of post-stroke microglia response were monitored in vivo by 2-photon-laser-microscopy in heterozygous transgenic CX(3)CR1-green fluorescent protein (GFP) mice (CX(3)CR1(GFP/+)) and complemented with analyses for fractalkine (FKN) and pro-inflammatory cytokines. Results: We found a significantly enhanced recovery and modified microglia activation without affecting infarct size in mice treated with AMD3100 after PT. AMD3100 treatment significantly reduced the number of microglia in the peri-infarct area accompanied by stabilization of soma size and ramified cell morphology. Within the ischemic infarct core of AMD3100 treated wild-type mice we obtained significantly reduced levels of the endogenous CX(3)CR1 ligand FKN and the pro-inflammatory cytokines interleukin (IL)-1 beta and IL-6. Interestingly, in CX(3)CR1-deficient mice (homozygous transgenic CX(3)CR1-GFP mice) subjected to PT, the levels of FKN were significantly lower compared to their wild-type littermates. Moreover, AMD3100 treatment did not induce any relevant changes of cytokine levels in CX(3)CR1 deficient mice. Conclusion: After AMD3100 treatment, attenuation of microglia activation contributes to enhanced recovery of lost neurological function in experimental stroke possibly due to a depression of FKN levels in the brain. We further hypothesize that this mechanism is dependent on a functional receptor CX(3)CR1.
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