No abstract

Binding of a cis,syn-cyclobutane pyrimidine dimer (CPD) to Escherichia coli DNA photolyase was examined as a function of temperature, enzyme oxidation state, salt, and substrate conformation using isothermal titration calorimetry. While the overall ΔG° of binding was relatively insensitive to most of the conditions examined, the enthalpic and entropic terms that make up the free energy of binding are sensitive to the conditions of the experiment. Substrate binding to DNA photolyase is generally driven by a negative change in enthalpy. Electrostatic interactions and protonation are affected by the oxidation state of the required FAD cofactor and substrate conformation. The fully reduced enzyme appears to bind approximately two additional water molecules as part of substrate binding. More significantly, the experimental change in heat capacity strongly suggests that the CPD lesion must be flipped out of the intrahelical base stacking prior to binding to the protein; the DNA repair enzyme appears to recognize a solvent-exposed CPD as part of its damage recognition mechanism.

Device closure of atrial septal defect (ASD) is commonly performed in older children and adults. Infants and toddlers (age <4 years) are seldom referred for ASD closure due to size constraints. However, in many cases device ASD closure can be performed in this population. Between 2002 and 2012, 61 infants and toddlers were taken to the catheterization laboratory at our institution for ASD closure. Precatheterization transthoracic echocardiograms, intracatheterization transesophageal echocardiograms, and catheterization reports were reviewed. Fifty-three infants and toddlers presented for percutaneous ASD occlusion. Forty-eight (79 %) underwent successful closure, and 13 were referred for surgery without device attempt (n = 8) or after unsuccessful device occlusion (n = 4). Median age and weight at time of ASD closure were 2.99 years (range 0.3-3.8) and 11.7 kg (range 3.7-16.5). The device-to-septal length ratio was 0.81 (range 0.44-1.03). The 12 unsuccessful cases occurred in patients with larger defects (ASD diameter 17.5 ± 6.1 vs. 12.1 ± 4.2, p < 0.01). Deficient rims (absent or ≤ 4 mm) were seen in 9 of 12 (75 %) unsuccessful cases and in 19 of 41 (46 %) successful cases (p = 0.12). Multivariate analysis showed that patient size and ASD size were not independently associated with procedural success but that ASD size-to-patient weight ratio <1.2 (hazard ratio 9.5 [range1.7-17]) was associated with successful ASD closure. ASD device occlusion can be safely achieved in small children. An ASD size-to-patient weight ratio >1.2, not absolute patient weight or age, is associated with failure of the percutaneous approach. The midterm outcomes in these young patients are excellent.

Transthoracic echocardiographic analysis should remain the modality of choice for diagnosis of the inferior sinus venosus defect. We report excellent surgical results with a patch or baffle, correctly redirecting the anomalous venoatrial connections.

There are few data on the epidemiology of pulmonary hypertension (PH)-related hospitalizations in children in the United States. Our aim was to determine hospital mortality, length of hospitalization, and hospital charges pertaining to PH-related hospitalizations and also the effects of codiagnoses and comorbidities. A retrospective review of the Kids' Inpatient Database during the years 2000, 2003, 2006, and 2009 was analyzed for patients ≤ 20 years of age with a diagnosis of PH by ICD-9 (International Classification of Diseases, Ninth Revision) codes, along with associated diagnoses and comorbidities. Descriptive statistics, including Rao-Scott χ 2 , ANOVA, and logistic regression models, were utilized on weighted values with survey analysis procedures. The number of PH-related hospital admissions is rising, from an estimated 7,331 (95% confidence interval [CI]: 5,556-9,106) in 2000 to 10,792 (95% CI: 8,568-13,016) in 2009. While infant age and congenital heart disease were most commonly associated with PH-related hospitalizations, they were not associated with mortality. Overall mortality for PH-related hospitalizations was greater than that for hospitalizations not associated with PH, 5.7% versus 0.4% (odds ratio: 16.22 [95% CI: 14.78%-17.8%], P < 0.001), but mortality is decreasing over time. Sepsis, respiratory failure, acute renal failure, hepatic insufficiency, arrhythmias, and the use of extracorporeal membrane oxygenation are associated with mortality. The number of PH-related hospitalizations is increasing in the United States. The demographics of PH in this study are evolving. Despite the increasing prevalence, mortality is improving.Keywords: pulmonary hypertension, pediatrics, epidemiology, survival. Pulmonary hypertension (PH) is a result of developmental lung abnormalities or aberrant remodeling, leading to both reversible and irreversible lesions of the pulmonary vasculature that result in elevated pulmonary artery pressures. 1 Over time, the disease can propagate to right heart failure and death. PH is defined by the World Health Organization (WHO) as a persistently elevated mean pulmonary arterial pressure of ≥25 mmHg and includes an additional requirement of a pulmonary capillary wedge pressure of ≤15 mmHg for precapillary PH. [1][2][3][4][5][6][7] Although excluded in the newer definition of PH, a pulmonary vascular resistance of ≥3 indexed Wood units is still considered in the diagnosis of children with PH. 8,9 Currently, PH in adults and children is classified into 5 groups: pulmonary arterial hypertension (PAH); PH associated with left-sided heart disease; PH associated with lung disease and/or hypoxia; chronic thromboembolic disease; and PH of unclear etiology or related to multiple factors. 7,10 PH is an uncommon but serious disease in children, with few data on its prevalence, morbidity, and mortality. Recent PH registries have revealed some information on the epidemiology of PH. 2,[4][5][6][7] Previous results estimated the incidence of PAH in adults and children at 1-2 ne...