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Water distribution and transmission lines are indispensable to urban infrastructure. The water pipelines are subject to both structural and functional deterioration due to various reasons including aging, negligence, and high demand for water supply. Hence, to ensure a safe and reliable water supply, the water utilities need to perform routine pipe condition assessments. The condition assessment is usually carried out by visual inspection with the machine vision system carried by a robotic platform. The inspection platforms will capture the internal condition of the water pipelines in a video stream. However, the robotic platform frequently experiences difficulties while traversing through the valves installed along the pipeline. This inhibits and disrupts the inspection process of the water pipelines. Therefore, this paper proposes a deep learning-based automatic valve detection framework to facilitate the robot's navigation and ensure continuous inspection without any interruptions. The valve detection model is developed by combining MobileNet-160 and Feature Pyramid Network (FPN) and is named as MFPN. The developed framework also employs a generative adversarial network to solve the sparse data set issues and improve the generality of the framework. The comparative study and ablation analyses demonstrate that the proposed framework can achieve a higher mAP value of 89.11% in comparison with the state-of-the-art. Hence, this light-weight and efficient solution can be deployed to the robotic platform for real-time valve detection and enable autonomous navigation of the robotic platform for condition assessment of water pipelines.

Condition assessment is an essential process to comprehend the condition of the water pipelines and facilitate the maintenance as well as the renewal plans. Nowadays, varied in-pipe inspection platforms equipped with closed-circuit cameras are employed to capture the internal condition of the water pipelines. However, the automated platform often faces the challenge to negotiate with the installed valves during the inspection. To ensure continuous inspection, the platform needs identify the valve automatically and activate the control mechanism to pass through it. Thus, the valves need to be detected to facilitate the negotiation and ensure that the control mechanism can take an action in time. This paper focuses on real-time valve detection using Jetson TX2™ and a lightweight algorithm, namely YOLOv3-tiny. The performance of the implementation is compared with state-of-the-art real-time detection models. The experimental results demonstrate that YOLOv3-tiny has a high detection speed in frame per second for valve detection and outperforms the state-of-the-art real-time algorithms. Hence, the deployment YOLOv3-tiny into the embedded system will aid the automated platform to accomplish the uninterrupted inspection and enhance the capability for the condition assessment of the water pipelines.

While heart rate variability (HRV) is an established marker of cardiovascular health, the extent to which continuously measured HRV changes over time and the relationship between these changes and clinical outcomes are less clear. We performed a health system analysis of 225 patients implanted with a cardiac defibrillator or cardiac resynchronization device (CRT) with continuous HRV recording capabilities. We found that continuously measured HRV changed modestly over 2 years. Low baseline HRV, which is associated with low parasympathetic tone and/or increases in sympathetic tone, pertains a worse clinical prognosis as reflected by a significant association with all-cause hospitalization. Observed changes in HRV over 6-months of follow-up were not associated with subsequent outcomes.

Patients with acute coronary syndrome (ACS) are at risk for recurrent adverse events, and multiple reports suggest that this risk is increased in patients with concomitant diabetes mellitus (DM) and peripheral artery disease (PAD). The aim of this article was to investigate cardiovascular outcomes in patients with DM presenting with ACS, stratified by PAD status. Data were derived from 4 randomized post-ACS trials (PLATO [Platelet Inhibition and Patient Outcomes], APPRAISE-2 p Apixaban for Prevention of Acute Ischemic Events 2], TRILOGY [Targeted Platelet Inhibition to Clarify the Optimal Strategy to Medically Manage], and TRACER [Thrombin Receptor Agonist for Clinical Event Reduction in Acute Coronary Syndrome]). Using Cox regression analysis, we investigated major adverse cardiovascular events (MACEs), a composite of cardiovascular mortality, myocardial infarction (MI), or stroke and the individual components of MACE and all-cause mortality in patients with DM, presenting with ACS, stratified by PAD status as the risk modifier. This study included 15,387 patients with a diagnosis of DM and ACS, of whom 1,751 had an additional diagnosis of PAD. PAD was associated with more than doubled rates of MACE (hazard ratio [HR] 2.03, 95% confidence interval [CI] 1.81 to 2.27), all-cause mortality (HR 2.48, 95% CI 2.14 to 2.87), cardiovascular mortality (HR 2.42, 95% CI 2.04 to 2.86), and MI (HR 2.07, 95% CI 1.79 to 2.38). Patients with both PAD and DM were also more optimally treated with antihypertensive, antidiabetic, and statin medication at baseline. In conclusion, this analysis of 4 major post-ACS trials showed that patients with DM and PAD had a substantially higher risk of MACE, cardiovascular mortality, all-cause mortality, and MI despite being optimally treated with guideline-based therapies.

Among patients with severe aortic stenosis (AS), there are limited data on aortic valve replacement (AVR), reasons for nonreceipt and mortality by race.Utilizing the Duke Echocardiography Laboratory Database, we analyzed data from 110,711 patients who underwent echocardiography at Duke University Medical Center between 1999 and 2013. We identified 1,111 patients with severe AS who met ≥1 of 3 criteria for AVR: ejection fraction ≤50%, diagnosis of heart failure, or need for coronary artery bypass surgery. Logistic regression models were used to assess the association between race, AVR and 1-year mortality. χ2 testing was used to assess potential racial differences in reasons for AVR nonreceipt.Among the 1,111 patients (143 AA and 968 CA) eligible for AVR, AA were more often women, had more diabetes, renal insufficiency, aortic regurgitation and left ventricular hypertrophy. CA were more often smokers, had more ischemic heart disease, hyperlipidemia and higher median income levels. There were no racial differences in surgical risk utilizing logistic euroSCORES. Relative to CA, AA had lower rates of AVR (adjusted odds ratio 0.46, 95% CI 0.3-0.71, P.001) yet similar 1-year mortality (aHR 0.81, 95% CI 0.57-1.17, P = .262). There were no significant differences in reasons for AVR nonreceipt.We identified 143 African Americans (AA) and 968 Caucasian Americans(CA) with severe AS who met prespecified criteria for AVR.. AA relative to CA were more often women, had more diabetes, renal insufficiency, and left ventricular hypertrophy, however had less tobacco use, ischemic heart disease, hyperlipidemia and lower median income levels. Among patients with severe AS, AA relative to CA had lower rates of AVR (adjusted odds ratio 0.46, 95% CI 0.3-0.71, P.001) without significant differences in reasons for AVR nonreceipt and similar 1-year mortality.

The water distribution network is one of the critical buried infrastructures of a nation. Failure of any water pipes or water mains can disrupt the everyday life of the inhabitants and can lead to significant economic loss. Hence, routine inspections are essential to sustain the water supply among the communities. Nowadays, inspection platforms with cameras, which can record the internal condition of the pipelines emerge to be one of the most attractive solutions. However, these inspection platforms often encounter some problems regarding autonomous navigation. As a result, an interruption occurs in the videotaping process which hampers the condition assessment process for the pipelines. Therefore, this paper presents a deep learning-based environment prediction model, which can predict the next instance of the environment inside the pipelines and enhance the autonomous navigation of the pipelines. The main objective of this paper is to make the inspection platforms intelligent enough to activate the control mechanisms and to pass through branches, curvature, elbows, etc. The results from the study show that integration of the environment prediction model with an embedded device can enhance the autonomous navigation inside the pipelines. This will also aid in the uninterrupted videotaping process and ensure better condition assessment of the water pipelines.

The water distribution network is one of the fundamental and expensive infrastructures to sustain the urban life. The aging of these infrastructures and pipe deterioration are becoming major issues to tackle as it leads to massive water loss and environmental adversities. To combat the aforementioned issues, the water municipalities have included condition assessment programs to assess the internal condition of the pipelines. The assessment is usually carried out through the in-pipe inspection device with closed-circuit television (CCTV) system to videotape inside the pipelines. However, the in-pipe inspection device faces challenges to navigate through the butterfly valves inside the pipelines. This impedes the videotaping process and disrupts the condition assessment process as well. Hence, this paper proposes a smart valve detection system to detect valves in real-time by adopting NASNet architecture combined with a Faster R-CNN object detector. The experimental results from the proposed system show that the integration of valve detection into the in-pipe inspection tool can help the device to enable the control mechanism and navigate through the butterfly valves and also, aid in the efficient management of the water infrastructure.

BACKGROUND: Asthma remains a leading cause of hospitalization in US children. Well-child care (WCC) visits are routinely recommended, but how WCC adherence relates to asthma outcomes is poorly described. METHODS: We conducted a retrospective longitudinal cohort study using electronic health records among 5 to 17 year old children residing in Durham County with confirmed asthma and receiving primary care within a single health system, to compare the association between asthma exacerbations and previous WCC exposure. Exacerbations included any International Classification of Diseases, Ninth Revision, or International Classification of Diseases, 10th Revision, coded asthma exacerbation encounter with an accompanying systemic glucocorticoid prescription. Exacerbations were grouped by severity: ambulatory encounter only, urgent care, emergency department, hospital encounters RESULTS: A total of 5656 children met eligibility criteria and were included in the primary analysis. Patients with the highest WCC visit attendance tended to be younger, had a higher prevalence of private insurance, had greater asthma medication usage, and were less likely to be obese. The presence of a WCC visit in the previous 12 months was associated with a reduced risk of all-cause exacerbations (hazard ratio: 0.90; 95% confidence interval: 0.83–0.98) and severe exacerbations requiring hospital admission (hazard ratio: 0.53; 95% confidence interval: 0.39–0.71). CONCLUSIONS: WCC visits were associated with a lower risk of subsequent severe exacerbations, including asthma-related emergency department visits and hospitalizations. Poor WCC visit adherence predicts pediatric asthma morbidity, especially exacerbations requiring hospitalization.

The goal of this study was to evaluate differences in clinical and patient-reported outcomes between women and men hospitalized for acute HF.Among patients hospitalized for heart failure (HF), it is unclear if symptom burden, response to therapy, and patient-reported quality of life (QOL) are different in women as compared with men.The ASCEND-HF (Acute Study of Clinical Effectiveness of Nesiritide in Decompensated Heart Failure) trial randomized 7,141 patients hospitalized for HF with reduced or preserved ejection fraction (EF) to receive nesiritide or placebo in addition to standard care. Clinical endpoints included 30-day mortality and rehospitalization and 180-day mortality. Patient-reported QOL was assessed at baseline, discharge, and 30 days using the EuroQOL 5 dimensions (EQ-5D) survey.Among 7,141 total patients, 4,697 (65.8%) were men and 2,444 (34.2%) were women. Among patients with EF ≤40%, women were less likely to receive angiotensin-converting enzyme inhibitor/angiotensin II receptor blocker and beta-blocker therapy, and less likely to have an implantable cardioverter-defibrillator (all p 0.03). Signs and symptoms of HF were similar between men and women (all p0.05), but women experienced less in-hospital weight loss and urine output (all p 0.01). In unadjusted and adjusted analyses, men and women had similar risk of all mortality and rehospitalization endpoints (all p ≥ 0.41). Women reported lower EQ-5D utility and visual analogue scores at admission, discharge, and 30 days. Women continued to have significantly lower EQ-5D scores at all in-hospital and post-discharge time points after adjustment for clinical characteristics (all p 0.01).In this acute HF population, women had similar risk of mortality and rehospitalization as compared with men, but experienced worse patient-reported QOL during and after hospitalization that persisted after adjustment for demographic and clinical factors. Current acute HF management may work similarly in either sex for purposes of preventing clinical events, but may be less equipped to improve patient-reported outcomes in women as compared with men.

Smoking is associated with incident heart failure (HF), yet limited data are available exploring the association between smoking status and long-term outcomes in HF with reduced vs. preserved ejection fraction (i.e., HFrEF vs. HFpEF).We performed a retrospective analysis of HF patients undergoing coronary angiography from 1990-2010. Patients with coronary artery disease (CAD) and HF were stratified by EF (50% vs. ≥50%), smoking status (prior/current vs. never smoker), and level of smoking (light/moderate vs. heavy). Time-from-catheterization-to-event was examined using Cox proportional hazard modeling for all-cause mortality (ACM), ACM/myocardial infarction/stroke (MACE), and ACM/HF hospitalization with testing for interaction by HF-type (HFrEF vs. HFpEF).Of 14,406 patients with CAD and HF, 85% (n = 12,326) had HFrEF and 15% (n = 2080) had HFpEF. At catheterization, 61% of HFrEF and 57% of HFpEF patients had a smoking history. After adjustment, there was a significant interaction between HF-type and the association between smoking status and MACE (interaction P = .009). Smoking history was associated with increased risk for MACE in patients with HFrEF (adjusted hazard ratio [HR] 1.18 [1.12-1.24]), but not HFpEF (HR 1.01 [0.90-1.12]). Active smokers had increased mortality following adjustment compared to former smokers regardless of HF-type (HFrEF HR 1.19 [1.06-1.32], HFpEF HR 1.30 [1.02-1.64], interaction P = .50). Heavy smokers trended towards increased risk of adverse outcomes versus light/moderate smokers; these findings were consistent across HF-type (interaction P .12).Smoking history was independently associated with worse outcomes in HFrEF but not HFpEF. Regardless of HF-type, current smokers had higher risk than former smokers.

Objectives Perioperative myocardial infarction (MI) after coronary artery bypass graft surgery (CABG) has been associated with adverse outcome. Whether perioperative MI should be treated with dual antiplatelet therapy (DAPT) is unknown. We compared the effect of DAPT versus aspirin alone on short-term outcomes among patients with perioperative MI following CABG. Methods We used data from 3 clinical trials that enrolled patients undergoing isolated CABG: PREVENT IV (2002–2003), MEND-CABG II (2004–2005), and RED-CABG (2009–2010) (n = 9117). Perioperative MI was defined as CK-MB >5 times the upper limit of normal within 24 h of surgery (n = 2052). DAPT was defined as DAPT given after surgery and prior to discharge. A Cox regression model was used to assess the association between DAPT and 30-day nonfatal MI, stroke, or mortality after adjustment for baseline covariates. Results DAPT (n = 527) and aspirin alone (n = 1525) cohorts were similar in baseline comorbidities. Off pump bypass was used in 5.2% (n = 106) of patients. There was no difference in the 30-day composite of death, MI or stroke between patients receiving DAPT versus aspirin alone, nor in any of the individual components. There were fewer all-cause re-hospitalizations at 30 days following surgery among patients in the DAPT group (adjusted HR 0.71, CI 0.52–0.97, P = .033). Conclusion One-quarter of CABG patients who had perioperative MI were treated with DAPT. DAPT was not associated with a difference in MI, stroke, or mortality at 30 days, but was associated with fewer re-hospitalizations. Further studies are needed to determine the optimal antiplatelet regimen following perioperative MI. What is already known about this subject? Perioperative myocardial infarction portends poor outcome but optimal management is currently unclear. While dual antiplatelet therapy is standard of care for acute coronary syndrome, its role in perioperative myocardial infarction is unknown. What does this study add? Dual antiplatelet therapy use during perioperative myocardial infarction was not associated with a difference in myocardial infarction, stroke or mortality at 30 days. It was, however, associated with fewer re-hospitalizations at 30 days. How might this impact on clinical practice? Dual antiplatelet therapy may be a potential treatment option for perioperative myocardial infarction after CABG surgery. Further studies are needed to better understand treatment for this disease process.

Objectives As the largest acute heart failure (AHF) trial conducted to date, the global ASCEND-HF (Acute Study of Clinical Effectiveness of Nesiritide in Decompensated Heart Failure) trial database presented an opportunity to systematically describe the relationship among time of hospital presentation, clinical profile, inpatient management, and outcomes among patients admitted with AHF. Background Time of hospital presentation has been shown to impact outcomes among patients hospitalized with many conditions. However, the association among time of presentation and patient characteristics, management, and clinical outcomes among patients hospitalized with AHF has not been well characterized. Methods A post hoc analysis of the ASCEND-HF trial was performed, which enrolled 7,141 patients hospitalized for AHF. Patients were divided based on when they presented to the hospital; regular hours were defined as 9 am to 5 pm, Monday through Friday, and off hours were defined as 5 pm to 9 am, Monday through Friday and weekends. Clinical characteristics and outcomes were compared by time of presentation. Results Overall, 3,298 patients (46%) presented during off hours. Off-hour patients were more likely to have orthopnea (80% vs. 74%, respectively) and rales (56% vs. 49%, respectively) than regular-hour patients. Off-hour patients were more likely to receive intravenous (IV) nitroglycerin (18% vs. 11%, respectively) and IV loop diuretics (92% vs. 86%, respectively) as initial therapy and reported greater relief from dyspnea at 24 h (odds ratio [OR]: 1.14; 95% confidence interval [CI]: 1.04 to 1.24; p = 0.01) than regular-hour patients. After adjustment, off-hour presentation was associated with significantly lower 30-day mortality (OR: 0.74; 95% CI: 0.57 to 0.96; p = 0.03) and 180-day mortality (hazard ratio [HR]: 0.82; 95% CI: 0.72 to 0.94; p = 0.01) but similar 30-day rehospitalization rates (p = 0.40). Conclusions In this AHF trial, patients admitted during off hours exhibited a distinct clinical profile, experienced greater dyspnea relief, and had lower post-discharge mortality than regular-hour patients. These findings have implications for future AHF trials.

Background Although aerobic exercise improves quality of life as assessed by a disease-specific instrument in ambulatory HF patients with a reduced ejection fraction (EF), the impact of an exercise intervention on general health status has not been previously reported. Methods A secondary analysis was performed of the HF-ACTION trial (ClinicalTrials.gov Number: NCT00047437), which enrolled 2331 medically stable outpatients with HF and an EF ≤35% and randomized them to aerobic exercise training, consisting of 36 supervised sessions followed by home-based training versus usual care for a median follow-up of 30 months. The EuroQOL 5-dimension questionnaire (EQ-5D) was administered to study participants at baseline, 3 months, and 12 months. EQ-5D includes functional dimensions (ie, mobility, self-care, usual activities, pain/discomfort, and anxiety/depression), which were mapped to corresponding utility scores (ie, 0=death and 1=perfect health), and a visual analogue scale (VAS) ranging from 0 (ie, "worst imaginable health state") to 100 (ie, "best imaginable health state"). Results Study participants had a median (25th, 75th) age of 59 (51, 68) years and 71% were male. A history of ischemic heart disease was reported in 51% of participants and the EF was 25% (20%, 30%). Baseline VAS and mapped utility scores were 65±19 and 0.81±0.14. Exercise training led to an improvement in VAS score compared with usual care from baseline to 3 months (exercise training: 6±17 vs usual care: 3±20; P P P Conclusion Ambulatory HF patients with a reduced EF had impaired health status at baseline which was associated with increased morbidity and mortality, in part mitigated by a structured aerobic exercise regimen.

BACKGROUND/OBJECTIVES: The extent to which individual knowledge, preferences, and priorities explain lower use of invasive cardiac care among older vs. younger adults presenting with acute coronary syndrome (ACS) is unknown. We directly surveyed a group of patients to ascertain their preferences and priorities for invasive cardiovascular care. DESIGN: We performed a prospective cohort study of adults hospitalized with ACS. We surveyed participants regarding their knowledge, preferences, goals, and concerns for cardiac care, as well as their risk tolerance for coronary artery bypass grafting (CABG). SETTING: Single academic medical center. PARTICIPANTS: 628 participants (373

Background Spinal cord infarction (SCI) is rare, accounting for approximately 1% of strokes. Case Report We present the case of a 63-year-old male who presented to the emergency department (ED) with chest pain and acute-onset generalized weakness and was ultimately diagnosed with SCI secondary to suspected occlusion of the artery of Adamkiewicz. Why Should an Emergency Physician Be Aware of This? SCI may present diagnostic challenges, with its predilection for mimicking other major emergency conditions, such as acute aortic dissection, aortic aneurysm rupture, spinal cord compressive myelopathy, or transverse myelitis. Its consequences are often significantly disabling initially, though patients may experience subsequent clinical improvement. It is important to include SCI in the differential for patients with chest or back pain coupled with neurologic symptoms.

Closed-circuit television (CCTV) is being widely adopted in water pipeline inspection. The inspector needs to spend a long time to watch the recorded video during the office-based survey and can get fatigue easily. An automated process can release the inspector’s work load and ensure the consistent quality of the survey. However, a fully automated survey of varied structural discontinuities still remains as a challenge. This study aims to first identify the anomaly frames of the CCTV video, which contain the major anomalies captured from the internal surface of the pipe. Thus, the inspector can focus more on these anomaly frames. In this paper, an anomaly frame detection framework based on steerable pyramid autoencoder (SPAE) is proposed. The SPAE can generate discriminative representations to be used in the prediction. Both the parameter optimization and comparative studies for the proposed SPAE were carried out in this research. The experimental results demonstrate that this novel SPAE algorithm can achieve 0.984 accuracy and 0.984 F1-score, which outperforms other state-of-the-art methods selected for comparison. Thus, the proposed framework can significantly improve the accuracy and efficiency for anomaly frame detection, which will highly facilitate the pipeline condition assessment through the CCTV inspection.

As the largest acute heart failure (AHF) trial conducted to date, the global ASCEND-HF (Acute Study of Clinical Effectiveness of Nesiritide in Decompensated Heart Failure) trial database presented an opportunity to systematically describe the relationship among time of hospital presentation, clinical profile, inpatient management, and outcomes among patients admitted with AHF.Time of hospital presentation has been shown to impact outcomes among patients hospitalized with many conditions. However, the association among time of presentation and patient characteristics, management, and clinical outcomes among patients hospitalized with AHF has not been well characterized.A post hoc analysis of the ASCEND-HF trial was performed, which enrolled 7,141 patients hospitalized for AHF. Patients were divided based on when they presented to the hospital; regular hours were defined as 9 am to 5 pm, Monday through Friday, and off hours were defined as 5 pm to 9 am, Monday through Friday and weekends. Clinical characteristics and outcomes were compared by time of presentation.Overall, 3,298 patients (46%) presented during off hours. Off-hour patients were more likely to have orthopnea (80% vs. 74%, respectively) and rales (56% vs. 49%, respectively) than regular-hour patients. Off-hour patients were more likely to receive intravenous (IV) nitroglycerin (18% vs. 11%, respectively) and IV loop diuretics (92% vs. 86%, respectively) as initial therapy and reported greater relief from dyspnea at 24 h (odds ratio [OR]: 1.14; 95% confidence interval [CI]: 1.04 to 1.24; p = 0.01) than regular-hour patients. After adjustment, off-hour presentation was associated with significantly lower 30-day mortality (OR: 0.74; 95% CI: 0.57 to 0.96; p = 0.03) and 180-day mortality (hazard ratio [HR]: 0.82; 95% CI: 0.72 to 0.94; p = 0.01) but similar 30-day rehospitalization rates (p = 0.40).In this AHF trial, patients admitted during off hours exhibited a distinct clinical profile, experienced greater dyspnea relief, and had lower post-discharge mortality than regular-hour patients. These findings have implications for future AHF trials.

Background Propofol is an anesthetic with pluripotent cytoprotective properties against various extrinsic insults. This study was designed to examine whether this agent could also ameliorate the infamous toxicity of doxorubicin, a widely-used chemotherapeutic agent against a variety of cancer diseases, on myocardial cells. Methods Cultured neonatal rat cardiomyocytes were administrated with vehicle, doxorubicin (1 μM), propofol (1 μM), or propofol plus doxorubicin (given 1 h post propofol). After 24 h, cells were harvested and specific analyses regarding oxidative/nitrative stress and cellular apoptosis were conducted. Results Trypan blue exclusion and MTT assays disclosed that viability of cardiomyocytes was significantly reduced by doxorubicin. Contents of reactive oxygen and nitrogen species were increased and antioxidant enzymes SOD1, SOD2, and GPx were decreased in these doxorubicin-treated cells. Mitochondrial dehydrogenase activity and membrane potential were also depressed, along with activation of key effectors downstream of mitochondrion-dependent apoptotic signaling. Besides, abundance of p53 was elevated and cleavage of PKC-δ was induced in these myocardial cells. In contrast, all of the above oxidative, nitrative and pro-apoptotic events could be suppressed by propofol pretreatment. Conclusions Propofol could extensively counteract oxidative/nitrative and multiple apoptotic effects of doxorubicin in the heart; hence, this anesthetic may serve as an adjuvant agent to assuage the untoward cardiac effects of doxorubicin in clinical application.

Background Whether Ginkgo biloba extract (EGb) 761, an herbal chemical with cytoprotective properties, could counteract hypoxia-induced apoptosis of cardiomyocytes remains unclear. Methods Cultured neonatal rat cardiomyocytes pretreated with vehicle or EGb 761 were exposed to anoxia for up to 24 h. Viability and apoptotic indexes of myocardial cells were assessed and relevant mediators in both the mitochondrion-dependent and the endoplasmic reticulum (ER) stress-activated apoptotic signaling pathways were examined. Results and conclusion Trypan blue exclusion, lactate dehydrogenase release and flow cytometric studies demonstrated hypoxia impaired viability and induced apoptosis of cardiomyocytes from 2 h of exposure throughout the whole 24 h. Immunofluorescence, protein and RNA analyses further illustrated hypoxia depolarized mitochondrial membrane potential, triggered cytochrome c release into cytosol and activated ER stress pathway mediators XBP-1, ATF4, eIF-2α, ATF6 and GRP 78 leading to up-regulation of downstream pro-apoptotic transcriptional factor C/EBP homologous protein. In contrast, EGb 761 pretreatment suppressed nearly all of the aformentioned apoptosis-evoking actions of hypoxia on myocardial cells except the expression of ATF4 and eIF-2α. Thus, EGb 761 effectively prevents hypoxia-induced cardiomyocyte apoptosis through inhibiting both mitochondrion-dependent and ER stress-activated signaling, and may thereby serve as an antagonist against this cytotoxic insult in clinical practice.

Data suggests differences in the incidence and prevalence of severe aortic stenosis (AS) among Caucasian-Americans (CA) and African Americans (AA). Among patients with severe AS there is limited data on the rates of aortic valve replacement (AVR) and mortality as a function of race. Our analysis

Although aerobic exercise improves quality of life as assessed by a disease-specific instrument in ambulatory HF patients with a reduced EF, the impact of an exercise intervention on general health status has not been reported. HF-ACTION enrolled 2331 outpatients with HF and an EF

Cardiac toxicity remains a serious yet unsolved complication of doxorubicin. This study was designed to examine whether doxycycline, a tetracycline-derived synthetic antibiotic with potential cytoprotective properties, could ameliorate this complication of doxorubicin. Male mice at 4-week of age were administrated with vehicle, doxorubicin (3 mg/kg intraperitoneally every other day at 3 doses), doxycycline (2.5 mg/kg intraperitoneally every other day for 3 doses), or doxycycline plus doxorubicin (each dose given 1 day post doxycycline). After 28 days, left ventricular geometric and systolic parameters were measured by transthoracic echocardiography, and hearts were harvested for extensive analyses regarding oxidative stress and cellular apoptosis. At 28 days, hearts of doxorubicin-treated mice were characterized by less weight compared with controls, also with remodeling and depressed systolic function of the left ventricle. Biochemical analyses disclosed that content of malondialdehyde was increased and activity of antioxidant enzymes, including superoxide dismutase and glutathione peroxidase, was decreased in these hearts. Both mitochondrion-dependent and endoplasmic reticulum stress-induced apoptotic pathways were also activated in the hearts of doxorubicin-treated mice as reflected by decreased Bcl-2/Bcl- XL and elevated Bax/Bad, p53/Apaf-1, endoplasmic reticulum glucose-related protein 78, C/EBP homologous protein, cytochrome c release from mitochondria, caspases-9/-3 cleavage, and cardiomyocyte apoptosis. In contrast, all the above left ventricular remodeling, systolic depressing, oxidative and pro-apoptotic actions of doxorubicin could be significantly alleviated by doxycycline pretreatment. Thus, doxycycline extensively counteracts multiple oxidative and apoptotic actions of doxorubicin in heart, hence may serve as an adjuvant agent to assuage the untoward cardiac effects of doxorubicin in clinical application.