686 research outputs found
'Parachute' accessory mitral leaflet and pulmonary valve stenosis in an asymptomatic 85-year-old man
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Sildenafil Prevents Endothelial Dysfunction Induced by Ischemia and Reperfusion via Opening of Adenosine Triphosphate–Sensitive Potassium Channels
Background—
Animal studies have demonstrated that administration of sildenafil can limit myocardial damage induced by prolonged ischemia, an effect that appears to be mediated by opening of adenosine triphosphate–sensitive potassium (K
ATP
) channels. No study has investigated whether sildenafil can also prevent the impairment in endothelium-dependent vasodilatation induced by ischemia-reperfusion (IR) in humans.
Methods and Results—
In a double-blind, placebo-controlled, crossover design, 10 healthy male volunteers (25 to 45 years old) were randomized to oral sildenafil (50 mg) or placebo. Two hours later, endothelium-dependent, flow-mediated dilatation (FMD) of the radial artery was measured before and after IR (15 minutes of ischemia at the level of the brachial artery followed by 15 minutes of reperfusion). Seven days later, subjects received the other treatment (ie, placebo or sildenafil) and underwent the same protocol. Pre-IR radial artery diameter and FMD, as well as baseline radial artery diameter after IR, were similar between visits (
P
=NS). After placebo administration, IR significantly blunted FMD (before IR: 7.9±1.1%; after IR: 1.2±0.7%,
P
<0.01). Importantly, sildenafil limited this impairment in endothelium-dependent vasodilatation (before IR: 7.0±0.9%; after IR: 6.2±1.1%,
P
=NS;
P
<0.01 compared with placebo). In a separate protocol, this protective effect was completely prevented by previous administration of the sulfonylurea glibenclamide (glyburide, 5 mg), a blocker of K
ATP
channels (n=7; FMD before IR: 10.3±1.5%; after IR: 1.3±1.4%,
P
<0.05).
Conclusions—
In humans, oral sildenafil induces potent protection against IR-induced endothelial dysfunction through opening of K
ATP
channels. Further studies are needed to test the potential clinical implications of this finding
Once Daily Therapy With Isosorbide-5-Mononitrate Causes Endothelial Dysfunction in Humans Evidence of a Free-Radical–Mediated Mechanism
ObjectivesThe aim of the study was to determine if isosorbide-5-mononitrate (IS-5-MN) 120 mg, taken once daily for 7 days, is associated with evidence of endothelial dysfunction and whether this effect is determined by increased free radical production.BackgroundTolerance to nitroglycerin is associated with increased free radical production and abnormal endothelial function. To date, no data is available concerning the effect of IS-5-MN, administered in clinically employed dosages, on endothelial function in humans.MethodsA total of 19 healthy volunteers were randomized in a double-blind fashion to therapy with IS-5-MN (120 mg once daily) or placebo. After 7 days of treatment, forearm blood flow responses to acetylcholine (Ach; 7.5, 15, and 30 μg/min) and N-monomethyl-L-arginine (L-NMMA; 1, 2, and 4 μmol/min) were measured. In a separate study, after 7 days of therapy with IS-5-MN 120 mg once daily, the responses to Ach were assessed during intra-arterial coinfusion of vitamin C (24 mg/min) or saline.ResultsAs compared with placebo, IS-5-MN caused significant blunting of the responses to both Ach (peak responses: placebo 127 ± 31%; IS-5-MN 52 ± 24%) and L-NMMA (peak responses: placebo 41 ± 5%; IS-5-MN 22 ± 8%). Vitamin C completely restored the forearm blood flow responses to Ach (peak responses: vitamin C 180 ± 33%; saline 107 ± 17%).ConclusionsWe document for the first time that IS-5-MN impairs endothelial function in humans in vivo. Suggesting a role of oxygen free radicals, nitrate-induced abnormalities in endothelium-dependent vasomotor responses were reversed by the antioxidant vitamin C
Italian Crossword Generator: Enhancing Education through Interactive Word Puzzles
Educational crosswords offer numerous benefits for students, including
increased engagement, improved understanding, critical thinking, and memory
retention. Creating high-quality educational crosswords can be challenging, but
recent advances in natural language processing and machine learning have made
it possible to use language models to generate nice wordplays. The exploitation
of cutting-edge language models like GPT3-DaVinci, GPT3-Curie, GPT3-Babbage,
GPT3-Ada, and BERT-uncased has led to the development of a comprehensive system
for generating and verifying crossword clues. A large dataset of clue-answer
pairs was compiled to fine-tune the models in a supervised manner to generate
original and challenging clues from a given keyword. On the other hand, for
generating crossword clues from a given text, Zero/Few-shot learning techniques
were used to extract clues from the input text, adding variety and creativity
to the puzzles. We employed the fine-tuned model to generate data and labeled
the acceptability of clue-answer parts with human supervision. To ensure
quality, we developed a classifier by fine-tuning existing language models on
the labeled dataset. Conversely, to assess the quality of clues generated from
the given text using zero/few-shot learning, we employed a zero-shot learning
approach to check the quality of generated clues. The results of the evaluation
have been very promising, demonstrating the effectiveness of the approach in
creating high-standard educational crosswords that offer students engaging and
rewarding learning experiences.Comment: Accepted Paper for CLiC-it 2023 - 9th Italian Conference on
Computational Linguistic
Coronary evaginations and peri-scaffold aneurysms following implantation of bioresorbable scaffolds: incidence, outcome, and optical coherence tomography analysis of possible mechanisms
Background Peri-stent coronary evaginations may disturb flow and have been proposed as possible risk factor for late stent thrombosis. We describe incidence, predictors, and possible mechanisms of coronary evaginations 12 months after implantation of bioresorbable vascular scaffolds (BVS).Methods and results One hundred and two BVS implanted in 90 patients (age 63 ± 13 years, 71 males, 14 diabetics) were analysed with angiography and optical coherence tomography (OCT) 12 months after implantation. Evaginations were identified as any hollow in the luminal vessel contour between well-apposed struts and were classified as major when extending ≥3 mm with a depth ≥10% of the BVS diameter. Fifty-five (54%) of the BVS (50(56%) of the patients) had at least one evagination (6.1 ± 6.2 evaginations per BVS), with a mean volume of 1.9 ± 1.9 mm³. Major evaginations were only found in one patient, and in-BVS aneurysms in three patients (4BVS). The presence of evaginations was strongly associated with that of malapposition (P = 0.003) and strut fractures (P = 0.01). No association could be shown between the presence and volume of the evaginations and any clinical variable or the presence of uncovered struts (P > 0.5). Peri-strut low- intensity areas (PSLIA) were present in 29 (53%) of the BVS with evaginations and 12 (26%) of those without (P = 0.0049); their presence was independently associated with the presence, the number (P P = 0.004) and with that of strut fracture. Conclusions Optical coherence tomography-detected evaginations are relatively common after BVS implantation, but, as for modern drug-eluting metallic stents, major evaginations are very rare. Optical coherence tomography evidence of immature neointima and strut fractures were associated with more severe development of evaginations
Predictors for target vessel failure after recanalization of chronic total occlusions in patients undergoing surveillance coronary angiography
(1) Background: Knowledge about predictors for the long-time patency of recanalized chronic total coronary occlusions (CTOs) is limited. Evidence from invasive follow-up in the absence of acute coronary syndrome (routine surveillance coronary angiography) is scarce. (2) Methods: In a monocentric-retrospective analysis, we obtained baseline as well as periprocedural data of patients undergoing routine invasive follow-up. We defined target vessel failure (TVF) as a combined primary endpoint, consisting of re-occlusion, restenosis, and target vessel revascularization (TVR). (3) Results: We included 93 consecutive patients (15.1% female) from October 2013 to May 2018. After a follow-up period of 206 ± 129 days (median 185 (IQR 127–237)), re-occlusion had occurred in 7.5%, restenosis in 11.8%, and TVR in 5.4%; the cumulative incidence of TVF was 15.1%. Reduced TIMI-flow immediately after recanalization (OR for TVR: 11.0 (95% CI: 2.7–45.5), p = 0.001) as well as female gender (OR for TVR: 11.0 (95% CI: 2.1–58.5), p = 0.005) were found to be predictive for pathological angiographic findings at follow-up. Furthermore, higher blood values of high-sensitive troponin after successful revascularization were associated with all endpoints. Interestingly, neither the J-CTO score nor the presence of symptoms at the follow-up visit could be correlated to adverse angiographic results. (4) Conclusions: In this medium-sized cohort of patients with surveillance coronary angiography, we were able to identify reduced TIMI flow and female gender as the strongest predictors for future TVF.
Keywords: chronic total occlusion; target vessel failure; re-occlusion; surveillance coronary angiograph
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