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- Adam, M., et al.
(författare)
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Hydroxysteroid (17 beta) dehydrogenase 13 deficiency triggers hepatic steatosis and inflammation in mice
- 2018
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Ingår i: Faseb Journal. - 0892-6638. ; 32:6, s. 3434-3447
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Tidskriftsartikel (refereegranskat)abstract
- Hydroxysteroid (17(3) dehydrogenases (HSD17Bs) form an enzyme family characterized by their ability to catalyze reactions in steroid and lipid metabolism. In the present study, we characterized the phenotype of HSD17B13-knockout (HSD17B13KO) mice deficient in Hsd1 7b13. In these studies, hepatic steatosis was detected in HSD17B13KO male mice, indicated by histologic analysis and by the increased triglyceride concentration in the liver, whereas reproductive performance and serum steroid concentrations were normal in HSD17B13KO mice. In line with these changes, the expression of key proteins in fatty acid synthesis, such as FAS, acetyl-CoA carboxylase 1, and SCD1, was increased in the HSD17B13KO liver. Furthermore, the knockout liver showed an increase in 2 acylcamitines, suggesting impaired mitochondrial beta-oxidation in the presence of unaltered malonyl CoA and AMPK expression. The glucose tolerance did not differ between wild-type and HSD17B13KO mice in the presence of lower levels of glucose 6-phosphatase in HSD17B13KO liver compared with wild-type liver. Furthermore, microgranulomas and increased portal inflammation together with up-regulation of immune response genes were observed in HSD17B13KO mice. Our data indicate that disruption of Hsdl7b13 impairs hepatic-lipid metabolism in mice, resulting in liver steatosis and inflammation, but the enzyme does not play a major role in the regulation of reproductive functions.
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- Escudero-Martinez, I, et al.
(författare)
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Cerebral Edema in Patients with severe Hemispheric Syndrome: Incidence, Risk Factors, and Outcomes-Data from SITS-ISTR
- 2023
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Ingår i: Journal of stroke. - : Korean Stroke Society. - 2287-6391 .- 2287-6405. ; 25:1, s. 101-
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Tidskriftsartikel (refereegranskat)abstract
- Background and Purpose Cerebral edema (CED) in ischemic stroke can worsen prognosis and about 70% of patients who develop severe CED die if treated conservatively. We aimed to describe incidence, risk factors and outcomes of CED in patients with extensive ischemia.Methods Oservational study based on Safe Implementation of Treatments in Stroke-International Stroke Treatment Registry (2003–2019). Severe hemispheric syndrome (SHS) at baseline and persistent SHS (pSHS) at 24 hours were defined as National Institutes of Health Stroke Score (NIHSS) >15. Outcomes were moderate/severe CED detected by neuroimaging, functional independence (modified Rankin Scale 0–2) and death at 90 days.Results Patients (n=8,560) presented with SHS and developed pSHS at 24 hours; 82.2% received intravenous thrombolysis (IVT), 10.5% IVT+thrombectomy, and 7.3% thrombectomy alone. Median age was 77 and NIHSS 21. Of 7,949 patients with CED data, 3,780 (47.6%) had any CED and 2,297 (28.9%) moderate/severe CED. In the multivariable analysis, age <50 years (relative risk [RR], 1.56), signs of acute infarct (RR, 1.29), hyperdense artery sign (RR, 1.39), blood glucose >128.5 mg/dL (RR, 1.21), and decreased level of consciousness (RR, 1.14) were associated with moderate/severe CED (for all P<0.05). Patients with moderate/severe CED had lower odds to achieve functional Independence (adjusted odds ratio [aOR], 0.35; 95% confidence interval [CI], 0.23 to 0.55) and higher odds of death at 90 days (aOR, 2.54; 95% CI, 2.14 to 3.02).Conclusions In patients with extensive ischemia, the most important predictors for moderate/ severe CED were age <50, high blood glucose, signs of acute infarct, hyperdense artery on baseline scans, and decreased level of consciousness. CED was associated with worse functional outcome and a higher risk of death at 3 months.
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- Nguyen, Thanh N, et al.
(författare)
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Global Impact of the COVID-19 Pandemic on Stroke Volumes and Cerebrovascular Events: A 1-Year Follow-up.
- 2023
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Ingår i: Neurology. - 1526-632X. ; 100:4, s. e408-e421
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Tidskriftsartikel (refereegranskat)abstract
- Declines in stroke admission, IV thrombolysis (IVT), and mechanical thrombectomy volumes were reported during the first wave of the COVID-19 pandemic. There is a paucity of data on the longer-term effect of the pandemic on stroke volumes over the course of a year and through the second wave of the pandemic. We sought to measure the effect of the COVID-19 pandemic on the volumes of stroke admissions, intracranial hemorrhage (ICH), IVT, and mechanical thrombectomy over a 1-year period at the onset of the pandemic (March 1, 2020, to February 28, 2021) compared with the immediately preceding year (March 1, 2019, to February 29, 2020).We conducted a longitudinal retrospective study across 6 continents, 56 countries, and 275 stroke centers. We collected volume data for COVID-19 admissions and 4 stroke metrics: ischemic stroke admissions, ICH admissions, IVT treatments, and mechanical thrombectomy procedures. Diagnoses were identified by their ICD-10 codes or classifications in stroke databases.There were 148,895 stroke admissions in the 1 year immediately before compared with 138,453 admissions during the 1-year pandemic, representing a 7% decline (95% CI [95% CI 7.1-6.9]; p < 0.0001). ICH volumes declined from 29,585 to 28,156 (4.8% [5.1-4.6]; p < 0.0001) and IVT volume from 24,584 to 23,077 (6.1% [6.4-5.8]; p < 0.0001). Larger declines were observed at high-volume compared with low-volume centers (all p < 0.0001). There was no significant change in mechanical thrombectomy volumes (0.7% [0.6-0.9]; p = 0.49). Stroke was diagnosed in 1.3% [1.31-1.38] of 406,792 COVID-19 hospitalizations. SARS-CoV-2 infection was present in 2.9% ([2.82-2.97], 5,656/195,539) of all stroke hospitalizations.There was a global decline and shift to lower-volume centers of stroke admission volumes, ICH volumes, and IVT volumes during the 1st year of the COVID-19 pandemic compared with the prior year. Mechanical thrombectomy volumes were preserved. These results suggest preservation in the stroke care of higher severity of disease through the first pandemic year.This study is registered under NCT04934020.
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- Arpaia, Riccardo, 1985, et al.
(författare)
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High-temperature superconducting nanowires for photon detection
- 2015
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Ingår i: Physica C: Superconductivity and its Applications. - : Elsevier BV. - 0921-4534. ; 509, s. 16-21
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Tidskriftsartikel (refereegranskat)abstract
- The possible use of high-temperature superconductors (HTS) for realizing superconducting nanowire single-photon detectors is a challenging, but also promising, aim because of their ultrafast electron relaxation times and high operating temperatures. The state-of-the-art HTS nanowires with a 50-nm thickness and widths down to 130 nm have been fabricated and tested under a 1550-nm wavelength laser irradiation. Experimental results presenting both the amplitude and rise times of the photoresponse signals as a function of the normalized detector bias current, measured in a wide temperature range, are discussed. The presence of two distinct regimes in the photoresponse temperature dependence is clearly evidenced, indicating that there are two different response mechanisms responsible for the HTS photoresponse mechanisms.
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- Escudero-Martinez, I, et al.
(författare)
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Dabigatran initiation in patients with non-valvular AF and first acute ischaemic stroke: a retrospective observational study from the SITS registry
- 2020
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Ingår i: BMJ open. - : BMJ. - 2044-6055. ; 10:5, s. e037234-
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Tidskriftsartikel (refereegranskat)abstract
- The optimal timing for initiation of dabigatran after acute ischaemic stroke (AIS) is not established. We aimed to evaluate initiation timing and clinical outcomes of dabigatran in AIS patients with non-valvular atrial fibrillation (NVAF).DesignRetrospective study based on prospectively collected data in SITS (Safe Implementation of Treatment in Stroke) Thrombolysis and Thrombectomy Registry from July 2014 to July 2018.ParticipantsEuropean NVAF patients (≥18 years) hospitalised after first-ever ischaemic stroke.SettingA multinational, observational monitoring register.InterventionDabigatran initiation within 3 months after the ischaemic stroke.Primary and secondary outcomesThe primary outcome was time from first-ever ischaemic stroke (index event) to dabigatran initiation. Additional outcomes included physicians’ reasons for delaying dabigatran initiation beyond acute hospital discharge and outcomes within 3 months of index event.MethodsWe identified patients with NVAF who received dabigatran within 3 months of the index event. We performed descriptive statistics for baseline and demographic data and clinical outcomes after dabigatran initiation.ResultsIn total, 1489 patients with NVAF received dabigatran after AIS treated with thrombolysis and/or thrombectomy. Of these, 1240 had available initiation time. At baseline, median age was 75 years; 53% of patients were women, 15% were receiving an oral anticoagulant, 29% acetylsalicylic acid and 4% clopidogrel. Most patients (82%) initiated dabigatran within 14 days after the index event. Patients initiating earlier had lower stroke severity from median NIHSS 8 (IQR 6–13) if initiated within 7 days to NIHSS 15 (9–19) if initiated between 28 days and 3 months. Most common reasons for delaying initiation were haemorrhagic transformation or intracranial haemorrhage, stroke severity and infarct size. Few thrombotic/haemorrhagic events occurred within 3 months after the index event (20 of 926 patients, 2.2% with the available data).ConclusionsOur findings, together with previous observational studies, indicate that dabigatran initiated within the first days after an AIS is safe in patients treated with intravenous thrombolysis, endovascular thrombectomy or both.Trial registration numberSITS Thrombolysis and Thrombectomy Registry (NCT03258645).
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- Farahi, N, et al.
(författare)
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Effects of the cyclin-dependent kinase inhibitor R-roscovitine on eosinophil survival and clearance.
- 2011
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Ingår i: Clinical and Experimental Allergy. - : Wiley. - 1365-2222 .- 0954-7894. ; 41:5, s. 673-687
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Tidskriftsartikel (refereegranskat)abstract
- Background Eosinophils are pro-inflammatory cells implicated in the pathogenesis of asthma and atopy. Apoptosis has been proposed as a potential mechanism underlying the resolution of eosinophilic inflammation and studies have indicated the ability of interventions that induce human eosinophil apoptosis to promote the resolution of eosinophilic inflammation. Recently, the cyclin-dependent kinase (CDK) inhibitor R-roscovitine was shown to enhance neutrophil apoptosis and promote the resolution of neutrophilic inflammation. Objective The purpose of this study was to examine the expression of CDKs in human blood eosinophils, the effects of R-roscovitine on eosinophil survival in vitro and whether R-roscovitine could influence eosinophilic lung inflammation in vivo. Methods Eosinophils were isolated from human peripheral blood and the effects of R-roscovitine on apoptosis, degranulation and phagocytic uptake examined in vitro. The effects of R-roscovitine on eosinophilic lung inflammation in vivo were also assessed using an ovalbumin mouse model. Results Our data demonstrate that human eosinophils express five known targets for R-roscovitine: CDK1, -2, -5, -7 and -9. R-roscovitine induced eosinophil apoptosis in a time- and concentration-dependent manner but also accelerated transition to secondary necrosis as assessed by microscopy, flow cytometry and caspase activation. In addition, we show that R-roscovitine can override the anti-apoptotic signals of GM-CSF and IL-5. We report that the pro-apoptotic effect of R-roscovitine is associated with suppression of Mcl-1L expression and that this compound enhanced phagocytic clearance of eosinophils by macrophages. Finally, we show that R-roscovitine induces apoptosis in murine peripheral blood and spleen-derived eosinophils; despite this, R-roscovitine did not modulate the tissue and lumen eosinophilia characteristic of the ovalbumin mouse model of airway eosinophilia. Conclusion and Clinical Relevance These data demonstrate that R-roscovitine is capable of inducing rapid apoptosis and secondary necrosis in eosinophils but does not affect the onset or improve the resolution of eosinophilic airway inflammation in vivo.
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| 9. |
- Parlato, L., et al.
(författare)
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Investigation of dark counts in innovative materials for superconducting nanowire single-photon detector applications
- 2017
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Ingår i: Proceedings of SPIE - The International Society for Optical Engineering. - : SPIE. - 0277-786X .- 1996-756X. - 9781510609594 ; 10229, s. Article no 102290I-
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Konferensbidrag (refereegranskat)abstract
- The phenomenon of dark counts in nanostripes of different superconductor systems such as high-temperature superconducting YBa 2 Cu 3 O 7-x and superconductor/ferromagnet hybrids consisting of either NbN/NiCu or YBa 2 Cu 3 O 7-x /L 0.7 Sr 0.3 MnO 3 bilayers have been investigated. For NbN/NiCu the rate of dark-count transients have been reduced with respect to pure NbN nanostripes and the events were dominated by a single vortex entry from the edge of the stripe. In the case of nanostripes based on YBa 2 Cu 3 O 7-x , we have found that thermal activation of vortices was also, apparently, responsible for triggering dark-count signals.
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- Pepe, G. P., et al.
(författare)
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Y-Ba-Cu-O Nanostripes for Optical Photon Detection
- 2015
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Ingår i: Proceedings of SPIE - The International Society for Optical Engineering. - : SPIE. - 0277-786X .- 1996-756X. - 9781628416251 ; 9504
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Konferensbidrag (refereegranskat)abstract
- Nanowires of Y-Ba-Cu-O, with the thickness of 50 nm and the width ranging from 90 nm to 500 nm have been successfully grown on lanthanum aluminate substrates for photon detection experiments. The nanowires were up to 10-mu m long and formed a meander structure, covering the area of up to 30x10 mu m(2) with a fill factor of 50%. The samples were excited using optical laser pulses at a 1550 nm wavelength and resulting photoresponse signals were measured as a function of both temperature and normalized bias current. Presence of two, distinct regimes in the photoresponse temperature dependence has been clearly evidenced, suggesting different physical mechanisms of the signal formation. Presented experimental results shed new light on prospects of implementation of high-temperature superconducting oxides in photon detection and counting.
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