Zobrazení zdroje stránky Gravesenmcnulty2004

Articulation rate increased in both treatment groups, although not differentially across treatments. Conclusions Findings from this first treatment study on intelligibility in francophone children with dysarthria suggest that SIT shows promise for increasing narrative intelligibility in this population. Acoustic contributors to the increased intelligibility remain to be explored further. Supplemental Material https//doi.org/10.23641/asha.14161943.Background The risk of cardiovascular disease is known to increase after menopause. Mitochondria, which undergo quality control via mitochondrial autophagy, play a crucial role in the regulation of cellular senescence. The aim of this study was to investigate whether the effect of estrogen-mediated protection from senescence on arteries is attributed to the induction of mitochondrial autophagy. Methods and Results We used human umbilical vein cells, vascular smooth muscle cells, and 12-week-old female C57BL/6 mice. The administration of 17β-estradiol (E2) to cells inhibited cellular senescence and mitochondrial dysfunction. Furthermore, E2 increased mitochondrial autophagy, maintaining mitochondrial function, and retarding cellular senescence. Of note, E2 did not modulate LC3 (light chain 3), and ATG7 (autophagy related 7) deficiency did not suppress mitochondrial autophagy in E2-treated cells. Conversely, E2 increased the colocalization of Rab9 with LAMP2 (lysosomal-associated membrane protein 2) signals. The E2-mediated effects on mitochondrial autophagy were abolished by the knockdown of either Ulk1 or Rab9. These results suggest that E2-mediated mitochondrial autophagy is associated with Rab9-dependent alternative autophagy. E2 upregulated SIRT1 (sirtuin 1) and activated LKB1 (liver kinase B1), AMPK (adenosine monophosphate-activated protein kinase), and Ulk1, indicating that the effect of E2 on the induction of Rab9-dependent alternative autophagy is mediated by the SIRT1/LKB1/AMPK/Ulk1 pathway. Compared with the sham-operated mice, ovariectomized mice showed reduced mitochondrial autophagy and accelerated mitochondrial dysfunction and arterial senescence; these detrimental alterations were successfully rescued by the administration of E2. Conclusions We showed that E2-induced mitochondrial autophagy plays a crucial role in the delay of vascular senescence. The Rab9-dependent alternative autophagy is behind E2-induced mitochondrial autophagy.Background Sex is a prominent risk factor for abdominal aortic aneurysms (AAAs), and angiotensin II (Ang II) induces AAA formation to a greater degree in male than in female mice. We previously reported that cytochrome P450 1B1 contributes to the development of hypertension, as well as AAAs, in male mice. We also found that a cytochrome P450 1B1-generated metabolite of testosterone, 6β-hydroxytestosterone (6β-OHT), contributes to Ang II-induced hypertension and associated cardiovascular and renal pathogenesis in male mice. The current study was conducted to determine the contribution of 6β-OHT to Ang II-induced AAA development in Apoe-/- male mice. Methods and Results Intact or castrated Apoe-/-/Cyp1b1+/+ and Apoe-/-/Cyp1b1-/- male mice were infused with Ang II or its vehicle for 28 days, and administered 6β-OHT every third day for the duration of the experiment. Abdominal aortas were then evaluated for development of AAAs. We observed a significant increase in the incidence and severity of AAAs in intact Ang II-infused Apoe-/-/Cyp1b1+/+ mice, compared with vehicle-treated mice, which were minimized in castrated Apoe-/-/Cyp1b1+/+ and intact Apoe-/-/Cyp1b1-/- mice infused with Ang II. Treatment with 6β-OHT significantly restored the incidence and severity of AAAs in Ang II-infused castrated Apoe-/-/Cyp1b1+/+ and intact Apoe-/-/Cyp1b1-/- mice. However, administration of testosterone failed to increase AAA incidence and severity in Ang II-infused intact Apoe-/-/Cyp1b1-/- mice. Conclusions Our results indicate that the testosterone-cytochrome P450 1B1-generated metabolite 6β-OHT contributes to Ang II-induced AAA development in Apoe-/- male mice.Background We determined if the sodium glucose co-transporter 2 inhibitor empagliflozin attenuates pressure overload-induced heart failure in non-diabetic mellitus mice by direct cardiac effects and the mechanisms involved. Methods and Results Male C57BL/6J mice (4-6 months of age) were subjected to sham surgeries or transverse aortic constriction to produce cardiac pressure overload. Two weeks after transverse aortic constriction, empagliflozin (10 mg/kg per day) or vehicle was administered daily for 4 weeks. Empagliflozin increased survival rate and significantly attenuated adverse left ventricle remodeling and cardiac fibrosis after transverse aortic constriction. Empagliflozin also attenuated left ventricular systolic and diastolic dysfunction, evaluated by echocardiography, and increased exercise endurance by 36% in mice with transverse aortic constriction-induced heart failure. Empagliflozin significantly increased glucose and fatty acid oxidation in failing hearts, while reducing glycolysis. These beneon-diabetic mellitus mice.Background Mounting evidence suggests that circulating microRNAs (miRNAs) are critical indicators of cardiovascular disease. However, prospective studies linking circulating miRNAs to incident acute coronary syndrome (ACS) are limited, and the underlying effect of associated miRNA on incident ACS remains unknown. Methods and Results Based on a 2-stage prospective nested case-control design within the Dongfeng-Tongji cohort, we profiled plasma miRNAs from 23 pairs of incident ACS cases and controls by microarray and validated the candidate miRNAs in 572 incident ACS case-control pairs using quantitative real-time polymerase chain reaction. We observed that plasma miR-4286 was associated with higher risk of ACS (adjusted odds ratio according to an interquartile range increase, 1.26 [95% CI, 1.07-1.48]). Further association analysis revealed that triglyceride was positively associated with plasma miR-4286, and an interquartile range increase in triglyceride was associated with an 11.04% (95% CI, 3.77%-18.83%) increase in plasma miR-4286. In addition, the Mendelian randomization analysis suggested a potential causal effect of triglyceride on plasma miR-4286 (β coefficients 0.27 [95% CI, 0.01-0.53] and 0.27 [95% CI, 0.07-0.47] separately by inverse variance-weighted and Mendelian randomization-pleiotropy residual sum and outlier tests). Moreover, the causal mediation analysis indicated that plasma miR-4286 explained 5.5% (95% CI, 0.7%-17.0%) of the association of triglyceride with incident ACS. Conclusions Higher level of plasma miR-4286 was associated with an increased risk of ACS. The upregulated miR-4286 in plasma can be attributed to higher triglyceride level and may mediate the effect of triglyceride on incident ACS.Background Influenza infection causes considerable morbidity and mortality in patients with cardiovascular disease. We assessed the effects of the influenza vaccine on mortality and cardiovascular outcomes in patients with cardiovascular disease. Methods and Results We searched PubMed, Embase, and the Cochrane Library through January 2020 for randomized controlled trials and observational studies assessing the effects of influenza vaccine on mortality and cardiovascular outcomes in patients with cardiovascular disease. Estimates were reported as random effects risk ratios (RRs) with 95% CIs. Analyses were stratified by study design into randomized controlled trials and observational studies. A total of 16 studies (n=237 058), including 4 randomized controlled trials (n=1667) and 12 observational studies (n=235 391), were identified. [https://www.selleckchem.com/products/tepp-46.html TEPP46] Participants' mean age was 69.2±7.01 years, 36.6% were women, 65.1% had hypertension, 31.1% had diabetes mellitus, and 23.4% were smokers. At a median follow-up duration of 19.5 months, influenza vaccine was associated with a lower risk of all-cause mortality (RR, 0.75; 95% CI, 0.60-0.93 [P=0.01]), cardiovascular mortality (RR, 0.82; 95% CI, 0.80-0.84 [P less then 0.001]), and major adverse cardiovascular events (RR, 0.87; 95% CI, 0.80-0.94 [P less then 0.001]) compared with control. The use of the influenza vaccine was not associated with a statistically significant reduction of myocardial infarction (RR, 0.73; 95% CI, 0.49-1.09 [P=0.12]) compared with control. Conclusions Data from both randomized controlled trials and observational studies support the use of the influenza vaccine in adults with cardiovascular disease to reduce mortality and cardiovascular events, as currently supported by clinical guidelines. Clinicians and health systems should continue to promote the influenza vaccine as part of comprehensive secondary prevention.Background Cardiac resynchronization therapy (CRT) is rarely used in patients with congenital heart disease, and reported follow-up is short. We sought to evaluate long-term impact of CRT in a single-center cohort of patients with congenital heart disease. Methods and Results Thirty-two consecutive patients with structural congenital heart disease (N=30) or congenital atrioventricular block (N=2), aged median of 12.9 years at CRT with pacing capability device implantation, were followed up for a median of 8.7 years. CRT response was defined as an increase in systemic ventricular ejection fraction or fractional area of change by &gt;10 units and improved or unchanged New York Heart Association class. Freedom from cardiovascular death, heart failure hospitalization, or new transplant listing was 92.6% and 83.2% at 5 and 10 years, respectively. Freedom from CRT complications, leading to surgical system revision (elective generator replacement excluded) or therapy termination, was 82.7% and 72.2% at 5 and 10 years, respectively. The overall probability of an uneventful therapy continuation was 76.3% and 58.8% at 5 and 10 years, respectively. There was a significant increase in ejection fraction/fractional area of change (P less then 0.001) mainly attributable to patients with systemic left ventricle (P=0.002) and decrease in systemic ventricular end-diastolic dimensions (P less then 0.05) after CRT. New York Heart Association functional class improved from a median 2.0 to 1.25 (P less then 0.001). Long-term CRT response was present in 54.8% of patients at last follow-up and was more frequent in systemic left ventricle (P less then 0.001). Conclusions CRT in patients with congenital heart disease was associated with acceptable survival and long-term response in ≈50% of patients. Probability of an uneventful CRT continuation was modest.Background Patients with aortic disease (AD) might have a higher prevalence of intracranial aneurysm (IA). The present study evaluated the prevalence of IA in patients with AD and identified potential risk factors of IA using nationwide representative cohort sample data. Methods and Results We defined AD as both aortic dissections and aortic aneurysms. This study used a nationwide representative cohort sample from the Korea National Health Insurance Service-National Sample Cohort database from 1.1million patients. Using χ2 or Fisher's exact tests, the prevalence of the IA in patients with AD and potential risk factors for their concurrence were analyzed. The prevalence of IA in patients with AD was 6.8% (155/2285). The adjusted odds ratios (OR) for having concurrent IA in patients with AD was 3.809 (95% CI, 3.191-4.546; P4, 3, and 2 times more likely to be affected by IA, respectively (adjusted OR, 4.291, 3.469, and 1.983, respectively; 95% CI, 3.914-4.704, 3.152-3.878, and 1.779-2.112, respectively). Subgroup analysis with socioeconomic status or disability revealed that the prevalence of IA was significantly higher in all groups.