| 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. |
- Namkoong, H, et al.
(författare)
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DOCK2 is involved in the host genetics and biology of severe COVID-19
- 2022
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 1476-4687 .- 0028-0836. ; 609:7928, s. 754-
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Tidskriftsartikel (refereegranskat)abstract
- Identifying the host genetic factors underlying severe COVID-19 is an emerging challenge1–5. Here we conducted a genome-wide association study (GWAS) involving 2,393 cases of COVID-19 in a cohort of Japanese individuals collected during the initial waves of the pandemic, with 3,289 unaffected controls. We identified a variant on chromosome 5 at 5q35 (rs60200309-A), close to the dedicator of cytokinesis 2 gene (DOCK2), which was associated with severe COVID-19 in patients less than 65 years of age. This risk allele was prevalent in East Asian individuals but rare in Europeans, highlighting the value of genome-wide association studies in non-European populations. RNA-sequencing analysis of 473 bulk peripheral blood samples identified decreased expression of DOCK2 associated with the risk allele in these younger patients. DOCK2 expression was suppressed in patients with severe cases of COVID-19. Single-cell RNA-sequencing analysis (n = 61 individuals) identified cell-type-specific downregulation of DOCK2 and a COVID-19-specific decreasing effect of the risk allele on DOCK2 expression in non-classical monocytes. Immunohistochemistry of lung specimens from patients with severe COVID-19 pneumonia showed suppressed DOCK2 expression. Moreover, inhibition of DOCK2 function with CPYPP increased the severity of pneumonia in a Syrian hamster model of SARS-CoV-2 infection, characterized by weight loss, lung oedema, enhanced viral loads, impaired macrophage recruitment and dysregulated type I interferon responses. We conclude that DOCK2 has an important role in the host immune response to SARS-CoV-2 infection and the development of severe COVID-19, and could be further explored as a potential biomarker and/or therapeutic target.
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| 3. |
- Valiente-Dobon, J. J., et al.
(författare)
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Lifetime Measurements of the Neutron-Rich N=30 Isotones Ca-50 and Sc-51: Orbital Dependence of Effective Charges in the fp Shell
- 2009
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Ingår i: Physical Review Letters. - 1079-7114. ; 102:24
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Tidskriftsartikel (refereegranskat)abstract
- The lifetimes of the first excited states of the N=30 isotones Ca-50 and Sc-51 have been determined using the Recoil Distance Doppler Shift method in combination with the CLARA-PRISMA spectrometers. This is the first time such a method is applied to measure lifetimes of neutron-rich nuclei populated via a multinucleon transfer reaction. This extends the lifetime knowledge beyond the f(7/2) shell closure and allows us to derive the effective proton and neutron charges in the fp shell near the doubly magic nucleus Ca-48, using large-scale, shell-model calculations. These results indicate an orbital dependence of the core polarization along the fp shell.
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| 4. |
- Hartley, D. J., et al.
(författare)
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Wobbling mode in Ta-167
- 2009
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Ingår i: Physical Review C (Nuclear Physics). - 0556-2813. ; 80:4
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Tidskriftsartikel (refereegranskat)abstract
- The collective wobbling mode, the strongest signature for the rotation of a triaxial nucleus, has previously been seen only in a few Lu isotopes in spite of extensive searches in nearby isotopes. A sequence of transitions in the N = 94 Ta-167 nucleus exhibiting features similar to those attributed to the wobbling bands in the Lu nuclei has now been found. This band feeds into the pi i(13/2) band at a relative energy similar to that seen in the established wobbling bands and its dynamic moment of inertia and alignment properties are nearly identical to the i(13/2) structure over a significant frequency range. Given these characteristics, it is likely that the wobbling mode has been observed for the first time in a nucleus other than Lu, making this collective motion a more general phenomenon.
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| 5. |
- Riazifar, M., et al.
(författare)
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Stem Cell-Derived Exosomes as Nanotherapeutics for Autoimmune and Neurodegenerative Disorders
- 2019
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Ingår i: ACS Nano. - : American Chemical Society (ACS). - 1936-0851 .- 1936-086X. ; 13:6, s. 6670-6688
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Tidskriftsartikel (refereegranskat)abstract
- To dissect therapeutic mechanisms of transplanted stem cells and develop exosome-based nanotherapeutics in treating autoimmune and neurodegenerative diseases, we assessed the effect of exosomes secreted from human mesenchymal stem cells (MSCs) in treating multiple sclerosis using an experimental autoimmune encephalomyelitis (EAE) mouse model. We found that intravenous administration of exosomes produced by MSCs stimulated by IFN (IFN-Exo) (i) reduced the mean clinical score of EAE mice compared to PBS control, (ii) reduced demyelination, (iii) decreased neuroinflammation, and (iv) upregulated the number of CD4+CD25+FOXP3+ regulatory T cells (Tregs) within the spinal cords of EAE mice. Co-culture of IFN-Exo with activated peripheral blood mononuclear cells (PBMCs) cells in vitro reduced PBMC proliferation and levels of pro-inflammatory Th1 and Th17 cytokines including IL-6, IL-12p70, IL-17AF, and IL-22 yet increased levels of immunosuppressive cytokine indoleamine 2,3-dioxygenase. IFN-Exo could also induce Tregs in vitro in a murine splenocyte culture, likely mediated by a third-party accessory cell type. Further, IFN-Exo characterization by deep RNA sequencing suggested that IFN-Exo contains anti-inflammatory RNAs, where their inactivation partially hindered the exosomes potential to induce Tregs. Furthermore, we found that IFN-Exo harbors multiple anti-inflammatory and neuroprotective proteins. These results not only shed light on stem cell therapeutic mechanisms but also provide evidence that MSC-derived exosomes can potentially serve as cell-free therapies in creating a tolerogenic immune response to treat autoimmune and central nervous system disorders. © 2019 American Chemical Society.
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| 6. |
- Fujita, Y, et al.
(författare)
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Evidence for the existence of the [202]3/2 deformed band in mirror nuclei Mg-25 and Al-25
- 2004
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Ingår i: Physical Review Letters. - 1079-7114. ; 92:6
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Tidskriftsartikel (refereegranskat)abstract
- After 50 years of its prediction, the highest-lying [2 0 2]3/2 orbit among the six Nilsson single-particle orbits originating from the sd shells in prolately deformed nuclei and the rotational band on this orbit were identified. The band members were observed in Al-25 at excitation energies of 6-7.5 MeV in a high-resolution Mg-25(He-3,t) charge-exchange reaction at 0degrees having a strong selectivity for Gamow-Teller transitions. In the comparison with the analogous M1 transitions in Mg-25, the J(pi)=3/2(+) bandhead state and the excited 5/2(+) and 7/2(+) members were clearly assigned.
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| 7. |
- Fujita, Y., et al.
(författare)
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Identification of the [202]3/2 deformed band in mirror nuclei Mg-25 and Al-25 and implications for unstable nuclei
- 2006
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Ingår i: Physica Scripta. - 0031-8949. ; T125, s. 194-195
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Tidskriftsartikel (refereegranskat)abstract
- Fifty years after its prediction, the highest-lying [ 2 0 2] 3) 2 orbit among the six Nilsson single-particle orbits originating from the sd shell in prolately deformed nuclei and the rotational band on this orbit were identified. The band members were observed in Al-25 at excitation energies of 6-7.5MeV in a high-resolution Mg-25(He-3,t) charge-exchange reaction at 0 degrees having a strong selectivity for Gamow-Teller transitions. In comparison with the analogous M1 transitions in Mg-25, the J(pi) = 3/+ band-head state and the excited 5/+ and 7/2+ members were clearly assigned.
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| 8. |
- Shein, A. M. S., et al.
(författare)
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Novel intranasal phage-CaEDTA-ceftazidime/avibactam triple combination therapy demonstrates remarkable efficacy in treating Pseudomonas aeruginosa lung infection
- 2023
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Ingår i: Biomedicine & Pharmacotherapy. - 0753-3322. ; 168
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Tidskriftsartikel (refereegranskat)abstract
- Given the rise of multidrug-resistant (MDR) Pseudomonas aeruginosa infections, alternative treatments are needed. Anti-pseudomonal phage therapy shows promise, but its clinical application is limited due to the development of resistance and a lack of biofilm penetration. Recently, adjuvants like CaEDTA have shown the ability to enhance the effectiveness of combined antimicrobial agents. Here, we tested a phage-adjuvant com-bination and demonstrated the effectiveness of intranasally inhaled phage (KKP10) + CaEDTA in addition to ceftazidime/avibactam (CZA) for chronic P. aeruginosa lung infections. The results emphasize that intranasal inhalation of phage along with CaEDTA can successfully re-sensitize MDR P. aeruginosa to CZA in a triple combination treatment. This promising approach shows potential as a therapy for chronic respiratory tract infections.
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| 9. |
- Shimbara, Y, et al.
(författare)
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Suppression of Gamow-Teller and M1 transitions in deformed mirror nuclei Mg-25 and Al-25 - Direct observation of K selection rules
- 2004
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Ingår i: European Physical Journal A. Hadrons and Nuclei. - : Springer Science and Business Media LLC. - 1434-6001. ; 19:1, s. 25-31
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Tidskriftsartikel (refereegranskat)abstract
- The mirror nuclei Mg-25 and Al-25 are expected to have very similar structures. The Gamow-Teller (GT) transitions from the J(pi) = 5/2(+) ground state of Mg-25 to the excited states in Al-25 were studied by high-resolution measurements of the Mg-25(He-3,t) charge-exchange reaction at 0degrees and at 140 MeV/nucleon. Assuming the usual DeltaJ(pi) = 1(+) selection rule for the spin-isospin-type GT transitions, the states with J(pi) = 3/2(+), 5/2(+), and 7/2 (+) should be excited. However, of the more than ten states with these J(pi) values below 6 MeV excitation energy, only the 5/2 (+) ground state and the 7/2 (+) , 1.613 MeV state in Al-25 were strongly populated, while all other states were strongly suppressed. The analysis of M1 transitions in Mg-25 also suggested a very similar feature for the analogous M1 transitions. Both Mg-25 and Al-25 are known to be largely deformed, and most low-lying states can be interpreted in terms of one-particle quantum numbers in the deformed potential and the associated rotational spectra. The observed suppression can be explained in terms of the K quantum number selection rules that are inherent to axially deformed nuclei.
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