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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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- Scutelnic, Adrian, et al.
(författare)
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Characteristics and outcomes of cerebral venous thrombosis associated with COVID-19
- 2024
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Ingår i: EUROPEAN STROKE JOURNAL. - 2396-9873 .- 2396-9881.
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Tidskriftsartikel (refereegranskat)abstract
- Introduction: Previous reports and meta-analyses derived from small case series reported a mortality rate of up to 40% in patients with coronavirus disease 2019 associated cerebral venous thrombosis (COVID-CVT). We assessed the clinical characteristics and outcomes in an international cohort of patients with COVID-CVT. Patients and methods: This was a registry study of consecutive COVID-CVT patients diagnosed between March 2020 and March 2023. Data collected by the International Cerebral Venous Thrombosis Consortium from patients with CVT diagnosed between 2017 and 2018 served as a comparison. Outcome analyses were adjusted for age and sex. Results: We included 70 patients with COVID-CVT from 23 hospitals in 15 countries and 206 controls from 14 hospitals in 13 countries. The proportion of women was smaller in the COVID-CVT group (50% vs 68%, p < 0.01). A higher proportion of COVID-CVT patients presented with altered mental state (44% vs 25%, p < 0.01), the median thrombus load was higher in COVID-CVT patients (3 [IQR 2-4] vs 2 [1-3], p < 0.01) and the length of hospital stay was longer compared to controls (11 days [IQR 7-20] vs 8 [4-15], p = 0.02). In-hospital mortality did not differ (5/67 [7%, 95% CI 3-16] vs 7/206 [3%, 2-7], aOR 2.6 [95% CI 0.7-9]), nor did the frequency of functional independence after 6 months (modified Rankin Scale 0-2; 45/58 [78%, 95% CI 65-86] vs 161/185 [87%, 81-91], aOR 0.5 [95% CI 0.2-1.02]). Conclusion: In contrast to previous studies, the in-hospital mortality rate and functional outcomes during follow-up did not differ between COVID-CVT patients and the pre-COVID-19 controls.
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- Gavali, S, et al.
(författare)
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Ubiquitination in T-Cell Activation and Checkpoint Inhibition: New Avenues for Targeted Cancer Immunotherapy
- 2021
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Ingår i: International journal of molecular sciences. - : MDPI AG. - 1422-0067. ; 22:19
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Tidskriftsartikel (refereegranskat)abstract
- The advent of T-cell-based immunotherapy has remarkably transformed cancer patient treatment. Despite their success, the currently approved immunotherapeutic protocols still encounter limitations, cause toxicity, and give disparate patient outcomes. Thus, a deeper understanding of the molecular mechanisms of T-cell activation and inhibition is much needed to rationally expand targets and possibilities to improve immunotherapies. Protein ubiquitination downstream of immune signaling pathways is essential to fine-tune virtually all immune responses, in particular, the positive and negative regulation of T-cell activation. Numerous studies have demonstrated that deregulation of ubiquitin-dependent pathways can significantly alter T-cell activation and enhance antitumor responses. Consequently, researchers in academia and industry are actively developing technologies to selectively exploit ubiquitin-related enzymes for cancer therapeutics. In this review, we discuss the molecular and functional roles of ubiquitination in key T-cell activation and checkpoint inhibitory pathways to highlight the vast possibilities that targeting ubiquitination offers for advancing T-cell-based immunotherapies.
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- Paolino, M, et al.
(författare)
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Cbl-b in T-cell activation
- 2010
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Ingår i: Seminars in immunopathology. - 1863-2300. ; 32:2, s. 137-148
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Tidskriftsartikel (refereegranskat)
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- Schapiro, Igor, et al.
(författare)
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Synthesis, spectroscopy and QM/MM simulations of a biomimetic ultrafast light-driven molecular motor
- 2019
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Ingår i: Photochemical and Photobiological Sciences. - : Springer Science and Business Media LLC. - 1474-9092 .- 1474-905X. ; 18:9, s. 2259-2269
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Tidskriftsartikel (refereegranskat)abstract
- A molecular motor potentially performing a continuous unidirectional rotation is studied by a multidisciplinary approach including organic synthesis, transient spectroscopy and excited state trajectory calculations. A stereogenic center was introduced in the N-alkylated indanylidene-pyrroline Schiff base framework of a previously investigated light-driven molecular switch in order to achieve the unidirectional C[double bond, length as m-dash]C rotary motion typical of Feringa's motor. Here we report that the specific substitution pattern of the designed chiral molecule must critically determine the unidirectional efficiency of the light-induced rotary motion. More specifically, we find that a stereogenic center containing a methyl group and a hydrogen atom as substituents does not create a differential steric effect large enough to fully direct the motion in either the clockwise or counterclockwise direction especially along the E→Z coordinate. However, due to the documented ultrafast character and electronic circular dichroism activity of the investigated system, we find that it provides the basis for development of a novel generation of rotary motors with a biomimetic framework and operating on a picosecond time scale.
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| 19. |
- Smith, Vanessa, et al.
(författare)
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Standardisation of nailfold capillaroscopy for the assessment of patients with Raynaud's phenomenon and systemic sclerosis
- 2020
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Ingår i: Autoimmunity Reviews. - : Elsevier BV. - 1568-9972. ; 19:3
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Forskningsöversikt (refereegranskat)abstract
- Capillaroscopy is a non-invasive and safe tool which allows the evaluation of the morphology of the microcirculation. Since its recent incorporation in the 2013 American College of Rheumatology (ACR)/European League Against Rheumatism (EULAR) classification criteria for systemic sclerosis together with its assessed role to monitor disease progression, capillaroscopy became a ‘mainstream’ investigation for rheumatologists. Given its increasing use by a variety of physicians internationally both in daily practice to differentiate primary from secondary Raynaud's phenomenon, as well as in research context to predict disease progression and monitor treatment effects, standardisation in capillaroscopic image acquisition and analysis seems paramount. To step forward to this need, experts in the field of capillaroscopy/microcirculation provide in this very consensus paper their view on image acquisition and analysis, different capillaroscopic techniques, normal and abnormal capillaroscopic characteristics and their meaning, scoring systems and reliability of image acquisition and interpretation.
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| 20. |
- Vigliotta, Giovanni, et al.
(författare)
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Nitrite metabolism in Debaryomyces hansenii TOB-Y7, a yeast strain involved in tobacco fermentation
- 2007
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Ingår i: Applied Microbiology and Biotechnology. - : Springer. - 0175-7598 .- 1432-0614. ; 75:3, s. 633-645
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Tidskriftsartikel (refereegranskat)abstract
- The Italian cigar manufacturing process includes a fermentation step that leads to accumulation of nitrite and tobacco-specific nitrosamines (TSNA), undesirable by-products due to their negative impact on health. In this study, growth and biochemical properties of Debaryomyces hansenii TOB-Y7, a yeast strain that predominates during the early phase of fermentation, have been investigated. With respect to other D. hansenii collection strains (Y7426, J26, and CBS 1796), TOB-Y7 was characterized by the ability to tolerate very high nitrite levels and to utilize nitrite, but not nitrate, as a sole nitrogen source in a chemically defined medium, a property that was enhanced in microaerophilic environment. The ability to assimilate nitrite was associated to the presence of YNI1, the gene encoding the assimilatory NAD(P)H:nitrite reductase (NiR), absent in Y7426, J26, and CBS 1796 by Southern blot data. YNI1 from TOB-Y7 was entirely sequenced, and its expression was analyzed in different media by Northern blot and reverse transcriptase polymerase chain reaction. The evidence that, in D. hansenii TOB-Y7, YNI1 was transcriptional active also in the presence of high ammonia concentration typical of tobacco fermentation, stimulated the development of an improved process that, on a laboratory scale, was proved to be effective in minimizing nitrite and TSNA accumulation.
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