Parent/Guardian Experiences With the Healthcare System and Community Supports for Pediatric Asthma Management.

Determinants of pediatric asthma management include child, family, healthcare, and community factors. The purpose of this study is to investigate how parents/guardians are impacted by and act on these factors to aid in their child's asthma self-management. Interviews were conducted in Fall 2020 with 12 female parents/guardians of Black/African American children who participated in a community paramedic pilot study with their child in South Carolina. Children in the initial study had an asthma diagnosis of moderate persistent asthma, had Medicaid insurance, and were determined high-risk for emergency room presentation. Inductive and deductive qualitative analysis identified that child management self-efficacy and independence, parent/guardian health literacy, parent and child negative experiences related to asthma diagnosis and management, asthma management tools, and social support from multiple sources impact child self-management. Findings from this study highlight the importance of clear asthma education and management tool recommendations from healthcare and community providers, particularly for parents/guardians with low health literacy. Health literacy impacted parental responses and likely how families comprehend Medicaid and clinical asthma guidance.

Role of tumor necrosis factor-alpha in myocardial dysfunction and apoptosis during hindlimb ischemia and reperfusion.

OBJECTIVE: Peripheral vascular surgery involving limb ischemia/reperfusion is associated with tumor necrosis factor-alpha production and an increased risk of cardiac complications. The objective of this study was to investigate the role of tumor necrosis factor-alpha in myocardial apoptosis and dysfunction following hindlimb ischemia/reperfusion. DESIGN: Randomized perspective animal study. SETTING: Research laboratory. SUBJECTS: Adults male tumor necrosis factor-alpha(-/-) and littermate wild-type mice. INTERVENTIONS: Bilateral hindlimb ischemia/reperfusion was induced in wild-type and tumor necrosis factor-alpha(-/-) mice using tourniquet occlusion. After 2 hrs of hindlimb ischemia, the tourniquets were released, allowing reperfusion for 0.5-24 hrs. MEASUREMENTS AND MAIN RESULTS: In wild-type mice, hindlimb ischemia/reperfusion resulted in myocardial depression early during the reperfusion period (p < .05). These effects were temporally correlated with enhanced levels of myocardial and plasma tumor necrosis factor-alpha. All variables were restored to baseline levels by 24 hrs of reperfusion. Myocardial apoptosis, assessed by cell death enzyme-linked immunosorbent assay, terminal deoxynucleotidyl transferase-mediated biotin-dUTP nick-end labeling staining, and caspase-3 activity, was also significantly higher at 6 hrs of reperfusion (p < .05) but returned to baseline levels by 24 hrs. Interestingly, cardiac dysfunction and myocardial apoptosis were abolished in tumor necrosis factor-alpha mice subjected to the same degree of hindlimb ischemia/reperfusion as the wild-type mice. Treatment of etanercept restored cardiac function in wild-type mice. CONCLUSIONS: Tumor necrosis factor-alpha contributes significantly to myocardial dysfunction and apoptosis in hindlimb ischemia/reperfusion. Although a causal link between myocardial apoptosis and cardiac dysfunction is not established, our study does suggest that tumor necrosis factor-alpha may be a potential therapeutic target for cardiac injury in clinical situations involving prolonged remote ischemia/reperfusion.

Modulation of apoptosis by nitric oxide: implications in myocardial ischemia and heart failure.

The purpose of this review is to summarize the regulation of apoptosis by nitric oxide (NO) and to discuss the potential role that NO plays in cardiomyocyte apoptosis during myocardial ischemia/reperfusion and development of heart failure. NO is an important regulator of apoptosis within the mammalian system, capable of both inducing and preventing apoptosis, depending upon the level of NO production and environmental milieu. This bifunctional capacity is well illustrated in the heart. It appears that high levels of NO produced by inducible nitric oxide synthase (iNOS) promote apoptosis while basal levels of NO production from endothelial nitric oxide synthase (eNOS) protect cardiomyocytes from apoptosis. Since permanent loss of cardiomyocytes due to apoptosis contributes to the development of heart failure, inhibition of cardiomyocyte apoptosis may have therapeutic implications. Given its pro- and anti-apoptotic capacity within the heart, NO may serve as a valuable therapeutic target in myocardial ischemia and heart failure.

Development of heart failure and congenital septal defects in mice lacking endothelial nitric oxide synthase.

BACKGROUND: Nitric oxide (NO) produced by endothelial NO synthase (eNOS) plays an important role in the regulation of cell growth, apoptosis, and tissue perfusion. Recent studies showed that mice deficient in eNOS developed abnormal aortic bicuspid valves. The aim of the present study was to additionally investigate the role of eNOS in heart development. METHODS AND RESULTS: We examined postnatal mortality, cardiac function, and septum defects in eNOS(-/-), eNOS(+/-), and wild-type mice. Postnatal mortality was significantly increased in eNOS(-/-) (85.1%) and eNOS(+/-) (38.3%) compared with wild-type mice (13.3%, P<0.001). Postmortem examination found severe pulmonary congestion with focal alveolar edema in mice deficient in eNOS. Heart shortening determined by ultrasound crystals was significantly decreased in eNOS(-/-) compared with wild-type mice (P<0.05). Congenital atrial and ventricular septal defects were found in neonatal hearts. The incidence of atrial or ventricular septal defects was significantly increased in eNOS(-/-) (75%) and eNOS(+/-) (32.4%) neonates compared with those of the wild-type mice (4.9%). At embryonic days 12.5 and 15.5, cardiomyocyte apoptosis and myocardial caspase-3 activity were increased in the myocardium of eNOS(-/-) compared with wild-type embryos (P<0.01), and increases in apoptosis persisted to neonatal stage in eNOS(-/-) mice. CONCLUSIONS: Deficiency in eNOS results in heart failure and congenital septal defects during cardiac development, which is associated with increases in cardiomyocyte apoptosis. Our data demonstrate that eNOS plays an important role in normal heart development.