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Prenatal diagnosis of congenital heart disease (CHD) often leads affected families to experience psychological stress. Pediatric cardiology consultation is important in providing parents with sufficient information and reducing their anxiety to make an informed pregnancy decision. Involving a fetal nurse coordinator may optimize fetal anomaly care. Our study aimed to identify factors associated with parental decision-making for choosing to use pediatric cardiology consultations and pregnancy termination.From September 2017 to December 2018, all fetal CHD cases diagnosed in the second trimester from a primary screening clinic in Taiwan were included (n = 145). Univariate and multivariate logistic regression were performed to analyze maternal, fetal, and medical factors for predictors of parental decisions for consultation use and pregnancy termination.Acceptance for fetal nurse coordinator care and pediatric cardiology consultation were 84.8% (n = 123) and 83.4% (n = 121), respectively. Predictors for termination of pregnancy included the following: multiple anomalies (OR: 10.6; 95% CI: 3.6-35.7), chromosomal/genetic abnormalities (OR: 20.2; 95% CI: 3.1-395.8), severe CHDs (OR: 9.8; 95% CI: 4.3-23.4), CHDs that required surgery (OR: 32.4; 95% CI: 11.4-117.8), and physiological single-ventricle (OR: 47.3; 95% CI: 12.4-312.5). Parents who had pediatric cardiology counseling were less likely to terminate the pregnancy (OR: 0.1; 95% CI: 0.0-0.7). Parents with fetal diagnosis having multiple anomalies (OR: 0.2; 95% CI: 0.1-0.7) or chromosomal/genetic abnormalities (OR: 0.1; 95% CI: 0.03-0.9) were less likely to make use of cardiology consultation. Parents who accepted fetal nurse coordinator care were more likely to have pediatric cardiology consultation before pregnancy decision (OR: 149.5, 95% CI: 37.8-821.5).Anomaly complexity appeared to be a strong predictor for termination of pregnancy beyond non-acceptability of prenatal cardiology consultation. Prenatal cardiology counseling may help support the parental decision to continue with the pregnancy. Incorporation of a fetal nurse coordinator care into the multidisciplinary fetal medicine team improved the acceptability of prenatal consultation.

Bacterial cells are encased in peptidoglycan (PG), a polymer of disaccharide N-acetyl-glucosamine (GlcNAc) and N-acetyl-muramic acid (MurNAc) cross-linked by peptide stems. PG is synthesized in the cytoplasm as UDP-MurNAc-peptide precursors, of which the amino-acid composition of the peptide is unique, with L-Ala added at the first position in most bacteria but L-Ser or Gly in some bacteria. YfiH is a PG-editing factor whose absence causes misincorporation of L-Ser instead of L-Ala into peptide stems; but its mechanistic function is unknown. Here we report the crystal structures of substrate-bound and product-bound YfiH, showing that YfiH is a cytoplasmic amidase that controls the incorporation of the correct amino acid to the nucleotide precursors by preferentially cleaving the nucleotide precursor byproduct UDP-MurNAc-L-Ser. This work reveals an editing mechanism in the cytoplasmic steps of peptidoglycan biosynthesis.

Description, One-way translocation and processive cleavage of substrate polypeptide occur in each of the Lon proteolytic active sites., The Lon protease is the prototype of a family of proteolytic machines with adenosine triphosphatase modules built into a substrate degradation chamber. Lon is known to degrade protein substrates in a processive fashion, cutting a protein chain processively into small peptides before commencing cleavages of another protein chain. Here, we present structural and biochemical evidence demonstrating that processive substrate degradation occurs at each of the six proteolytic active sites of Lon, which forms a deep groove that partially encloses the substrate polypeptide chain by accommodating only the unprimed residues and permits processive cleavage in the C-to-N direction. We identify a universally conserved acidic residue at the exit side of the binding groove indispensable for the proteolytic activity. This noncatalytic residue likely promotes processive proteolysis by carboxyl-carboxylate interactions with cleaved intermediates. Together, these results uncover a previously unrecognized mechanism for processive substrate degradation by the Lon protease.

Description, Full-length structures of the Lon protease complex reveal a tensegrity helix triangle for substrate selection and unfolding., Lon is an evolutionarily conserved proteolytic machine carrying out a wide spectrum of biological activities by degrading misfolded damaged proteins and specific cellular substrates. Lon contains a large N-terminal domain and forms a hexameric core of fused adenosine triphosphatase and protease domains. Here, we report two complete structures of Lon engaging a substrate, determined by cryo–electron microscopy to 2.4-angstrom resolution. These structures show a multilayered architecture featuring a tensegrity triangle complex, uniquely constructed by six long N-terminal helices. The interlocked helix triangle is assembled on the top of the hexameric core to spread a web of six globular substrate-binding domains. It serves as a multipurpose platform that controls the access of substrates to the AAA+ ring, provides a ruler-based mechanism for substrate selection, and acts as a pulley device to facilitate unfolding of the translocated substrate. This work provides a complete framework for understanding the structural mechanisms of Lon.

The Lon AAA+ (adenosine triphosphatases associated with diverse cellular activities) protease (LonA) converts ATP-fuelled conformational changes into sufficient mechanical force to drive translocation of a substrate into a hexameric proteolytic chamber. To understand the structural basis for the substrate translocation process, we determined the cryo-electron microscopy (cryo-EM) structure of Meiothermus taiwanensis LonA (MtaLonA) in a substrate-engaged state at 3.6 A resolution. Our data indicate that substrate interactions are mediated by the dual pore loops of the ATPase domains, organized in spiral staircase arrangement from four consecutive protomers in different ATP-binding and hydrolysis states. However, a closed AAA+ ring is maintained by two disengaged ADP-bound protomers transiting between the lowest and highest position. This structure reveals a processive rotary translocation mechanism mediated by LonA-specific nucleotide-dependent allosteric coordination among the ATPase domains, which is induced by substrate binding.

Objective: To present an accurate prenatal diagnosis of coarctation of the aorta with ventricular septal defect and to illustrate how early diagnosis in prenatal period with proper referral and counseling can optimize management. Case report: A case with coarctation of the aorta with ventricle septal defect was found to have an abnormal three vessel view at 12 weeks, and with close follow-ups, coarctation of the aorta with ventricle septal defect was diagnosed at 24 weeks. Following the support from a multidisciplinary team that provided counseling, diagnosis, and follow-ups, the pregnant woman decided to continue with the pregnancy and had a vaginal delivery at a medical center. The newborn made an uneventful recovery after undergoing cardiac surgery on day 9. Conclusion: The case demonstrates the role a fetal medicine team plays in diagnosing, supporting, and seamlessly transferring the congenital heart disease case from the first line obstetrician to the cardiac surgeon. A multi-disciplinary team approach was able to lead to improved perinatal outcome of the congenital heart disease case. Keywords: Aorta, Fetal, Prenatal, Ultrasound, VSD

The Lon AAA+ protease (LonA) is a ubiquitous ATP-dependent proteolytic machine, which selectively degrades damaged proteins or native proteins carrying exposed motifs (degrons). Here we characterize the structural basis for substrate recognition and discrimination by the N-terminal domain (NTD) of LonA. The results reveal that the six NTDs are attached to the hexameric LonA chamber by flexible linkers such that the formers tumble independently of the latter. Further spectral analyses show that the NTD selectively interacts with unfolded proteins, protein aggregates, and degron-tagged proteins by two hydrophobic patches of its N-lobe, but not intrinsically disordered substrate, α-casein. Moreover, the NTD selectively binds to protein substrates when they are thermally induced to adopt unfolded conformations. Collectively, our findings demonstrate that NTDs enable LonA to perform protein quality control to selectively degrade proteins in damaged states and suggest that substrate discrimination and selective degradation by LonA are mediated by multiple NTD interactions., eLife digest There are many different types of protein which each have different roles in biology. Most proteins are surrounded by water and are folded so that their water-attracting regions are on the outside and more fat-like regions, which repel water, are on the inside. When a protein becomes damaged or is assembled incorrectly, some of the fat-like regions end up on the outside of the protein and become exposed to water. This can prevent the protein from performing its role and harm the cell instead. LonA proteases are responsible for dismantling and recycling these harmful proteins, as well as proteins that have been labelled for destruction. They do this by unfolding the unwanted protein and transporting it into an enclosed chamber made of six LonA molecules. Once inside the chamber, the target protein is broken down into smaller fragments that can be used to build other structures. LonA proteases contain a region called the N-terminal domain, or NTD for short, which is thought to be responsible for identifying which proteins need degrading. Yet it remained unclear how the NTD recognizes and binds to these target proteins. To answer this question, Tzeng et al. studied the detailed structure of a LonA protease that had been purified from bacteria cells. This revealed that the NTD of LonA contains two water-repelling regions which bind to fat-like segments on the surface of proteins that have become unfolded or tagged for destruction. Further experiments showed that the NTD is bound to the main body of LonA via a ‘flexible linker’. This led Tzeng et al. to propose that the NTD sways around loosely at the end of LonA searching for proteins with exposed water-repelling regions. Once an NTD identifies and attaches to a target, the NTDs of the other LonA molecules then bind to the protein and help insert it into the chamber. Proteases are a vital component of all biological systems. Controlling protein destruction and recycling is a key factor in how cells divide and respond to a changing environment. This study provides new insights into how LonA operates in bacteria, which may apply to proteases more widely. This contributes to our knowledge of fundamental biology and may also be relevant in a range of diseases where protein recycling is defective or inefficient.

OBJECTIVES Many surgeons develop unique techniques for unmet needs for right ventricular outflow reconstruction to resolve pulmonary regurgitation after corrective surgery for congenital heart diseases. Expanded polytetrafluoroethylene (ePTFE) stands out as a reliable synthetic material, and clinical results with handmade ePTFE valves have been promising. This review focuses on the historical evolution of the use of ePTFE in pulmonary valve replacement and in the techniques for pioneering the translation of the handmade ePTFE trileaflet design for the transcatheter approach. METHODS We searched for and reviewed publications from 1990 to 2020 in the Pubmed database. Nineteen clinical studies from 2005 to 2019 that focused on ePTFE-based valves were summarized. The evolution of the ePTFE-based valve over 3 decades and recent relevant in vitro studies were investigated. RESULTS The average freedom from reintervention or surgery in the recorded ePTFE-based valve population was 90.2% at 5 years, and the survival rate was 96.7% at 3 years. CONCLUSIONS Non-inferior clinical results of this ePTFE handmade valve were revealed compared to allograft or xenograft options for pulmonary valve replacement. Future investigations on transferring ePTFE trileaflet design to transcatheter devices should be considered.

The Lon AAA+ (adenosine triphosphatases associated with diverse cellular activities) protease (LonA) converts ATP-fuelled conformational changes into sufficient mechanical force to drive translocation of the substrate into a hexameric proteolytic chamber. To understand the structural basis for the substrate translocation process, we have determined the cryo-electron microscopy (cryo-EM) structure of Meiothermus taiwanensis LonA (MtaLonA) at 3.6 Å resolution in a substrate-engaged state. Substrate interactions are mediated by the dual pore-loops of the ATPase domains, organized in spiral staircase arrangement from four consecutive protomers in different ATP-binding and hydrolysis states; a closed AAA+ ring is nevertheless maintained by two disengaged ADP-bound protomers transiting between the lowest and highest position. The structure reveals a processive rotary translocation mechanism mediated by LonA-specific nucleotide-dependent allosteric coordination among the ATPase domains, which is induced by substrate binding.

Objectives A wide variety of right ventricular outflow tract (RVOT) and pulmonary artery (PA) geometries has been reported in patients with repaired tetralogy of Fallot (rTOF). We aimed to investigate the associations between RVOT/PA geometries and outcome indicators in a large rTOF cohort receiving non-conduit repair. Methods Three-dimensional magnetic resonance angiographic images of 206 patients with rTOF who had a pulmonary regurgitation (PR) fraction ≥20% were reviewed. Patients' RVOT geometry was quantitatively classified into 4 distinct shapes (tubular, hourglass, pyramid, and inverted trapezoid). Bilateral PA size discrepancy was defined as the diameter of the smaller side being less than 70% of that of the bigger side. Results Based on lateral projection of the 3-dimensional images, patients with an inverted trapezoid-shaped RVOT had the smallest RV end-diastolic volume index (EDVi) (108.7 ± 24.3 mL/m2) and pulmonary valve annulus diameter, and shortest QRS duration, whereas those with a pyramid-shaped RVOT had the largest RV EDVi (161.0 ± 44.6 mL/m2) and pulmonary valve annulus diameter. Similar trends of differences were also observed if such classifications were based on the frontal projections. Multivariable analysis revealed that RVOT shapes, subvalvular diameter, PR fraction, QRS duration, and the presence of bilateral PA size discrepancy were independent determinants of RV EDVi. Furthermore, having bilateral PA size discrepancy (25.2%) was independently associated with lower peak oxygen consumption (P = .041). Conclusions Distinct RVOT morphologies and branch PA size discrepancy are associated with variations in RV remodeling and exercise capacity in patients with rTOF. These findings may aid decision-making regarding reintervention for PR and branch PA size discrepancy.

Prc, also known previously as Tsp, is the founding member of the carboxyl-terminal processing protease (CTP) family of PDZ domain-containing proteases that include CtpA and CtpB. The substrate-binding PDZ domain is responsible for regulating the protease activity of CTP proteases; however, the regulatory role of PDZ domain is stimulatory in Prc but inhibitory in CtpA/B. By determining a series of crystal structures of Prc in the unliganded resting state, this study presents the structural basis for PDZ-dependent activation of Prc, the results of which explain the contrasting roles of the PDZ domain in the regulation of the protease activity of CTPs., Carboxyl (C)-terminal processing proteases (CTPs) participate in protective and regulatory proteolysis in bacteria. The PDZ domain is central to the activity of CTPs but plays inherently different regulatory roles. For example, the PDZ domain inhibits the activity of the signaling protease CtpB by blocking the active site but is required for the activation of Prc (or Tsp), a tail-specific protease that degrades SsrA-tagged proteins. Here, by structural and functional analyses, we show that in the unliganded resting state of Prc, the PDZ domain is docked inside the bowl-shaped scaffold without contacting the active site, which is kept in a default misaligned conformation. In Prc, a hydrophobic substrate sensor distinct from CtpB engages substrate binding to the PDZ domain and triggers a structural remodeling to align the active-site residues. Therefore, this work reveals the structural basis for understanding the contrasting roles of the PDZ domain in the regulation of CTPs.

OBJECTIVES Handmade trileaflet expanded polytetrafluoroethylene valved conduit developed using the flip-over method has been tailored for pulmonary valve reconstruction with satisfactory outcomes. We investigated the in vitro performance of the valve design in a mock circulatory system with various conduit sizes. In our study, the design was transformed into a transcatheter stent graft system which could fit in original valved conduits in a valve-in-valve fashion. METHODS Five different sizes of valved polytetrafluoroethylene vascular grafts (16, 18, 20, 22 and 24 mm) were mounted onto a mock circulatory system with a prism window for direct leaflets motion observation. Transvalvular pressure gradients were recorded using pressure transducers. Mean and instant flows were determined via a rotameter and a flowmeter. Similar flip-over trileaflet valve design was then carried out in 3 available stent graft sizes (23, 26 and 28.5 mm, Gore aortic extender), which were deployed inside the valved conduits. RESULTS Peak pressure gradient across 5 different sized graft valves, in their appropriate flow setting (2.0, 2.5 and 5.0 l/min), ranged from 4.7 to 13.2 mmHg. No significant valve regurgitation was noted (regurgitant fraction: 1.6–4.9%) in all valve sizes and combinations. Three sizes of the trileaflet-valved stent grafts were implanted in the 4 sizes of valved conduits except for the 16-mm conduit. Peak pressure gradient increase after valved-stent graft-in-valved-conduit setting was CONCLUSIONS The study showed excellent in vitro performance of trileaflet polytetrafluoroethylene valved conduits. Its valved stent graft transformation provided data which may serve as a reference for transcatheter valve-in-valve research in the future.

The Lon AAA+ protease (LonA) plays important roles in protein homeostasis and regulation of diverse biological processes. LonA behaves as a homomeric hexamer in the presence of magnesium (Mg(2+)) and performs ATP-dependent proteolysis. However, it is also found that LonA can carry out Mg(2+)-dependent degradation of unfolded protein substrate in an ATP-independent manner. Here we show that in the presence of Mg(2+) LonA forms a non-secluded hexameric barrel with prominent openings, which explains why Mg(2+)-activated LonA can operate as a diffusion-based chambered protease to degrade unstructured protein and peptide substrates efficiently in the absence of ATP. A 1.85 Å crystal structure of Mg(2+)-activated protease domain reveals Mg(2+)-dependent remodeling of a substrate-binding loop and a potential metal-binding site near the Ser-Lys catalytic dyad, supported by biophysical binding assays and molecular dynamics simulations. Together, these findings reveal the specific roles of Mg(2+) in the molecular assembly and activation of LonA.

Peptidoglycan (PG) is a highly cross-linked, protective mesh-like sacculus that surrounds the bacterial cytoplasmic membrane. Expansion of PG is tightly coupled to growth of a bacterial cell and requires hydrolases to cleave the cross-links for insertion of nascent PG material. In Escherichia coli, a proteolytic system comprising the periplasmic PDZ-protease Prc and the lipoprotein adaptor NlpI contributes to PG enlargement by regulating cellular levels of MepS, a cross-link-specific hydrolase. Here, we demonstrate how NlpI binds Prc to facilitate the degradation of its substrate MepS by structural and mutational analyses. An NlpI homodimer binds two molecules of Prc and forms three-sided MepS-docking cradles using its tetratricopeptide repeats. Prc forms a monomeric bowl-shaped structure with a lid-like PDZ domain connected by a substrate-sensing hinge that recognizes the bound C terminus of the substrate. In summary, our study reveals mechanistic details of protein degradation by the PDZ-protease Prc bound to its cognate adaptor protein., MepS is a peptidoglycan (PG) cross-link specific hydrolase needed for cell wall expansion and its cellular levels must be tightly regulated. Here the authors present the structure of the MepS degrading protease Prc bound to its adaptor NlpI and propose a model how the NlpI-Prc complex mediates MepS degradation.

OBJECTIVES We report our surgical experience in congenitally corrected transposition of great arteries (CCTGAs) and the long-term follow-up result. METHODS From January 1995 to February 2012, 56 patients with CCTGA received definite surgical repair; 15 patients received conventional repair (Group I), 18 patients received anatomical repair (Group II) and 23 patients received single ventricular palliation (Group III). They were followed for early and late mortality, long-term survival, postoperative morbidity and reintervention or reoperation. RESULTS The overall survival rate was 80% at 16 years in Group I, 53% at 13 years in Group II and 100% at 13 years in Group III. After excluding the early surgical mortality, the long-term survival rate was 92% at 16 years in Group I, 64% at 13 years in Group II and 100% at 13 years in Group III. Patients with significant tricuspid valve regurgitation showed the worst outcome after surgery. CONCLUSIONS Our series showed good results with single ventricular palliation (SVP) in CCTGA with complex anatomy, but the long-term result should be followed. Anatomical repair is the choice of operation only for those with favourable anatomy. The more complicated intracardiac repair may result in late left ventricular outflow tract obstruction, various degrees of atrioventricular block, systemic or pulmonary venous return obstruction and the lack of an ideal conduit (e.g. homograft) for Rastelli reconstruction. Therefore, we preferred SVP in patients with complex and unfavourable anatomy.

Background Neonates with severe forms of Ebstein anomaly present a surgical challenge, and the Starnes operation as single ventricle palliation is highly advocated. Cone reconstruction for tricuspid valvuloplasty (TVP) has become a widely accepted technique, although very few cases of TVP have been reported in neonates. This report describes a surgical strategy for neonatal Ebstein anomaly, with an aim toward biventricular repair. Methods Since 2007, 7 neonates or young infants with severe Ebstein anomalies have received TVP at the National Taiwan University Hospital, Taipei, Taiwan. The principle of cone reconstruction was applied with mobilization of all three leaflets and reattachment to the normal tricuspid annulus. The atrialized right ventricle was not plicated. In patients with pulmonary stenosis, the interatrial communication was not totally closed (n = 5), and a systemic-pulmonary shunt was added if needed (n = 3). Results All patients presented with intractable heart failure or severe cyanosis requiring mechanical ventilation, or both. All patients had marked adherence of the anterior leaflet to the right ventricular free wall. Intracardiac anomalies including ventricular septal defect (n = 2) and tetralogy of Fallot (n = 1) were also repaired simultaneously. Six of the 7 patients (86%) survived. There were no late deaths or repeat TVPs for a median follow-up of 4.3 years (range, 0.8 to 9.9 years). Conclusions Reconstruction of the tricuspid valve is an acceptable surgical strategy in patients with severe neonatal Ebstein anomaly. Fenestrated atrial septal defect and systemic-pulmonary shunt can help overcome anatomic pulmonary stenosis and high pulmonary resistance in the neonatal period. This surgical strategy has a good survival outcome and preserves the possibility of complete biventricular repair.

The aim of this study was to establish reference curves and formulas for aortic cross-sectional area in patients from infancy to young adulthood.Patients (aged 2 days to 18.1 years) who underwent electrocardiographically gated cardiac computed tomography between May 2004 and December 2011 were retrospectively examined. These patients were further divided into a group of normal controls (without aortic disease) and a group with coarctation of aorta. In the group of normal controls, the cross-sectional area of the aorta was measured at six locations: the sinotubular junction, distal ascending aorta, proximal arch, distal arch, aortic isthmus, and descending aorta (DAO). Interobserver and intraobserver variability, gender differences, the relationship between aortic cross-sectional areas and age, and the ratio to the DAO were also examined. The area ratio to the DAO was also examined in the group with coarctation of the aorta.A total of 65 patients and 365 measurable aortic segments were included in the analysis (55 normal controls and 10 patients with coarctation of aorta). Interobserver and intraobserver variability was limited (aside from measurements of the sinotubular junction). There were no gender differences in age and the cross-sectional areas of the different aortic segments. In the group of normal controls, the cross-sectional area of each aortic segment was highly correlated with age (all0.90, P.001). The reference curves and formulas for aortic cross-sectional area by age were also determined for further clinical use. In the normal controls, the95% confidence intervals of the ratios of aortic isthmus to DAO, distal arch to DAO, and proximal arch to DAO were approximately 0.6, 0.8, and 1.0, respectively. In addition, in the group with coarctation, all area ratios of aortic isthmus to DAO were0.6, which was significantly different from the group of normal controls (P.001). The area ratios of distal arch to DAO and proximal arch to DAO were also significantly different between two groups (P.001 for both).Measurement of aortic area was reproducible. The established reference curves and formulas and minimal area ratios were convenient for further clinical use.

Genetic syndromes, especially 22q11 deletion (del22q11) syndrome, are common in patients with pulmonary atresia and ventricular septal defect (PA-VSD), but their association with long-term outcomes varies. The purpose of this study was to evaluate the long-term outcome after complete repair of PA-VSD and to determine the impact of genetic syndromes.We reviewed our experience of 125 patients with PA-VSD who received primary or staged repair between 1978 and 2010. Evaluations for genetic syndromes included clinical features, cytogenetic analysis, and fluorescence in situ hybridization or multiplex ligation-dependent probe amplification.Genetic syndromes were documented in 26 patients (20.8%), including del22q11 in 16 patients, trisomy 21 in 2 patients, and other syndromes in 8 patients. The prevalence of hypoplastic pulmonary arteries was not significantly different between the syndromic and nonsyndromic groups. After 1,069 patient-years of follow-up, 20-year survival was 90% ± 6% in patients without syndromes and 14% ± 23% in patients with syndromes (p0.01). Multivariate analysis identified the presence of a genetic syndrome as an important risk factor for hospital and late mortality. Subgroup analysis showed that genetic syndromes other than del22q11 were associated with worse outcome. The rate of 10-year freedom from cardiac reintervention after repair was 53% ± 11%, with hypoplastic pulmonary arteries before repair as a major risk factor (p = 0.02).Genetic syndromes significantly affect survival after repair of PA-VSD, whereas genetic syndromes do not represent additional risk for reintervention. Repair is feasible in patients with syndromes, but suboptimal long-term outcome should be addressed when counseling parents.

Balloon angioplasty of native coarctation of the aorta, though effective, is frequently associated with early restenosis, repeated interventions and aneurysm formation, especially in very young patients. However, available long-term data are limited.From Jan. 1986 to Dec. 2007, eighty-eight patients with simple aortic coarctation, isolated or associated with patent ductus arteriosus or ventricular septal defect, and survived angioplasty (n = 17) or surgery (n = 71) within 3 months of age in National Taiwan University Hospital were enrolled.The average length of follow-up was 10.1 ± 5.1 years. The long-term outcomes between these two groups were comparable in hypertension, left ventricular outflow tract obstruction, and aortic aneurysm. Patients in the angioplasty group had a greater likelihood of reintervention (64.7% vs. 42.3%, p = 0.096) and repeated reintervention (29.4% vs. 7.0%, p = 0.027) as compared with surgery group. The 10-year freedom from reintervention was 35.3% and 59.2% in the angioplasty and surgery group, respectively (p = 0.046); there were no deaths reported in that 10-year span. Patients with angioplasty and those with patent ductus arteriosus were more likely to require surgical aortoplasty at reintervention.The long-term outcomes of aortic coarctation in newborns and young infants after balloon angioplasty were effective and beneficial. However, those outcomes were accompanied by concomitant higher risks of reintervention and surgical reintervention, particularly in those with patent ductus arteriosus.Aortic operation; Coarctation; Infant; Outcomes.

The clinical usage of extracorporeal membranous oxygenation began more than 40 years ago. Although the indications for its use have expanded over the years, it has been challenging to conduct randomized controlled trials to prove that extracorporeal membranous oxygenation is more effective than traditional approaches. Through a review of retrospective reports and data from registries, we attempted to evaluate the appropriateness of its application for acute respiratory distress syndrome, cardiopulmonary resuscitation, postcardiotomy cardiogenic shock, and sepsis. Our investigation revealed that using extracorporeal membranous oxygenation when readily available is appropriate for all patients with cardiopulmonary resuscitation or postcardiotomy cardiogenic shock, and for selected patients with acute respiratory distress syndrome or sepsis.Acute respiratory distress syndrome; Cardiopulmonary resuscitation; Extracorporeal membranous oxygenation; Postcardiotomy cardiogenic shock; Sepsis.

Access to experimental X-ray diffraction image data is fundamental for validation and reproduction of macromolecular models and indispensable for development of structural biology processing methods. Here, we established a diffraction data publication and dissemination system, Structural Biology Data Grid (SBDG; data.sbgrid.org), to preserve primary experimental data sets that support scientific publications. Data sets are accessible to researchers through a community driven data grid, which facilitates global data access. Our analysis of a pilot collection of crystallographic data sets demonstrates that the information archived by SBDG is sufficient to reprocess data to statistics that meet or exceed the quality of the original published structures. SBDG has extended its services to the entire community and is used to develop support for other types of biomedical data sets. It is anticipated that access to the experimental data sets will enhance the paradigm shift in the community towards a much more dynamic body of continuously improving data analysis., The validation and analysis of X-ray crystallographic data is essential for reproducibility and the development of crystallographic methods. Here, the authors describe a repository for crystallographic datasets and demonstrate some of the ways it could serve the crystallographic community.

Background Total anomalous pulmonary venous connection (TAPVC) is a rare congenital heart disease in which the connection between the pulmonary vein (PV) and left atrium needs to be surgically created. This study investigated the spectrum and outcome of a Taiwanese cohort. Methods Isolated TAPVC cases were identified from our institutional database between 1995 and 2009. We reviewed the medical chart and conducted telephone interviews with those lost to follow-up. Results There were 78 patients (52% male). The anomalous drainage sites were mainly supracardiac type (42.3%) and cardiac type (39.8%). Before operation, PV stenosis was found in 100% of infracardiac type, and in 69.7% of supracardiac type. Among the 75 patients undergoing operation, the surgical mortality was 9% (7/75). Perioperative arrhythmias (mainly of atrial origin) occurred in 35% of the patients. Of the 68 patients who survived the first operation, 28 (41%) developed pulmonary vein restenosis. Half of them progressed to severe PV stenosis, which required reintervention or resulted in mortality. Preoperative PV stenosis was the most significant predictor for postoperative PV restenosis and PV re-intervention. For the cohort, the 1-year and 5-year survivals were 78.9% and 74.2%, respectively, and the predictor for survival was again preoperative PV stenosis. Conclusion The surgical mortality of isolated TAPVC is now low. Preoperative PV stenosis not only increased the risk of late PV restenosis and its reintervention, but also the overall mortality. The spectrum of PV drainage, per se, was not associated with worse outcome. PV restenosis remained the most important issue after correction of TAPVC.

Objectives Pulmonary artery sling is frequently associated with tracheal and/or bronchial stenosis. A number of patients receive only re-implantation or relocation of the left pulmonary artery (LPA) while other patients may require tracheoplasty for stenosis of the airway. This study used computer tomography (CT) scans for the evaluation of airways and to evaluate the trachea diameter and the clinical outcomes with or without tracheoplasty. Methods A total of 15 patients with PA sling who received CT scans were included in this study. We reviewed the clinical outcomes and the severity of trachea stenosis, and evaluated various surgical strategies. Results Among the 15 patients, one received only conservative treatment, 14 (93%) patients received LPA re-implantation, and eight (53%) received tracheoplasty. For the eight patients that received LPA reimplantation and tracheoplasty, five received slide tracheoplasty and all survived, two patients had pericardial patch augmentation and both died, and one patient received a resection and end-to-end anastomosis and survived. The diameter of the trachea in survivors without tracheoplasty was significantly larger than those who died or received tracheoplasty (3.2 ± 0.3 mm vs. 2.2 ± 0.4 mm, P = 0.003). Establishing 3.0 mm as the threshold, the positive predictive value for tracheoplasty or mortality was 89% and the negative predictive value was 83%. Conclusions In this study cohort, approximately 60% of the patients with PA sling received tracheoplasty. A diameter of the trachea

The Lon AAA+ protease (LonA) is an evolutionarily conserved protease that couples the ATPase cycle into motion to drive substrate translocation and degradation. A hallmark feature shared by AAA+ proteases is the stimulation of ATPase activity by substrates. Here we report the structure of LonA bound to three ADPs, revealing the first AAA+ protease assembly where the six protomers are arranged alternately in nucleotide-free and bound states. Nucleotide binding induces large coordinated movements of conserved pore loops from two pairs of three non-adjacent protomers and shuttling of the proteolytic groove between the ATPase site and a previously unknown Arg paddle. Structural and biochemical evidence supports the roles of the substrate-bound proteolytic groove in allosteric stimulation of ATPase activity and the conserved Arg paddle in driving substrate degradation. Altogether, this work provides a molecular framework for understanding how ATP-dependent chemomechanical movements drive allosteric processes for substrate degradation in a major protein-destruction machine.

Our aim was to evaluate the feasibility of using computed tomography (CT) to define the pulmonary artery anatomy in patients with tetralogy of Fallot and pulmonary atresia (TOF-PA). We retrospectively reviewed 110 patients with TOF-PA between 1995 and 2008. Those who received cardiac catheterization and surgery within 3 months of their CT examinations were enrolled. Based on Dr. Somerville’s classification, the pulmonary arterial pattern was determined, including identifiable pulmonary trunk (type I), the presence of both left and right pulmonary arteries without trunk (II), only left or right pulmonary artery present (III), and absent intrapericardial pulmonary arteries (IV). The accuracy of both imaging modalities was evaluated with operation findings as the golden standard. The effective radiation doses and adverse events were also recorded. In the 64 eligible patients (median age, 23 months), CT and catheterization demonstrated accurate pulmonary arterial morphology in 60 (60/64) and 53 (53/64) TOF-PA patients, respectively. Thirty-two of 35 type I patients were correctly identified by CT, whereas 26 were correctly identified by catheterization (p = 0.03). Of the 20 type II TOF-PA patients, 19 were diagnosed by CT, whereas 18 were diagnosed by catheterization. CT and catheterization both successfully defined six type III and three type IV patients. The median calculated radiation doses caused by CT and catheterization were 4.5 and 5.6 mSv, respectively (p > 0.05). Conclusions: For patients with TOF-PA, CT could accurately delineate pulmonary arterial morphology with the same level of accuracy as cardiac catheterization. Therefore, CT can be considered a reasonable diagnostic alternative for such patients.

Background Infected aneurysm of the suprarenal abdominal aorta is rare and can be fatal without surgery. There have been only sporadic case reports or small case series. We review our experience with 14 patients over 13 years. Methods Retrospective chart review. Results Between 1997 and 2010, 14 cases of infected aneurysms of the suprarenal abdominal aorta were treated at our hospital. There were 11 men with median age of 75.5 years (range, 35-88). Of the 13 pathogens isolated, the most common responsible microorganism was nontyphoid Salmonella in eight (62%) followed by Staphylococcus aureus in three (23%) and Streptococcus in two patients (15%). At the first admission, six patients had medical treatment alone, five patients underwent early open in situ graft repair, and three patients underwent hybrid endovascular stenting and visceral debranching. Of the six medically treated patients, two patients died in the hospital because of aneurysm rupture, and two patients underwent late open in situ graft repair because of aneurysm progression or rupture. Of the five open surgically treated patients, one patient died in the hospital because of nosocomial sepsis, and four patients were alive without major postoperative complication. Of the three endovascularly treated patients, one patient died in the hospital because of intestinal ischemia, one patient died 6 months later because of postoperative complication, and one patient was alive with complications of paraplegia, renal failure, and permanent dialysis. The aneurysm-related mortality rate was 33% (2/6) in medical treatment alone, 20% (1/5) in open in situ grafting, and 67% (2/3) in hybrid endovascular stenting. Conclusions Infected aneurysm of the suprarenal abdominal aorta was rare. Nontyphoid Salmonella was the most common responsible microorganism. Open in situ graft repair remained a preferred and durable treatment strategy.

OBJECTIVE Malignancy is the leading cause of death among heart-transplant recipients. There is a higher incidence of post-transplant malignancy in heart-transplant recipients than in kidney-transplant recipients. This study sought to assess the incidence of malignancy in heart-transplant recipients in Taiwan. METHODS This is a retrospective chart review. RESULTS From 1987 to 2008, 291 patients who underwent heart transplantation and survived for more than 1 month were enrolled. Seventeen patients (5.8%) developed de novo malignancies including skin cancers (three), post-transplant lymphoproliferative diseases (seven) and solid-organ malignancies (seven). Solid-organ malignancies affected prostate, liver, urinary bladder, kidney, lung, larynx, pancreas and brain in seven patients. Malignancy was responsible for 7% and 13% of all death for heart-transplant recipients who lived for more than 1 year and more than 5 years. The cumulative incidence of 1.03% at 1 year, 4.2% at 5 years and 8.1% at 10 years in our patients was much lower than the incidences reported in the multicentre registry of the International Society for the Heart and Lung Transplantation and in the Western series. The incidence was especially low for skin cancers. Compared with previous reports of kidney-transplant recipients in Taiwan, the incidence of post-transplant malignancy was not significantly increased. CONCLUSIONS The incidence of post-transplant malignancy was low in Chinese heart-transplant recipients compared with heart-transplant recipients in Western countries. It resulted from a relative rarity of skin cancers in the Chinese population.

Pulmonary regurgitation after repair of tetralogy of Fallot has always been an important issue for pediatric cardiac surgeons. Some of the patients may need pulmonary valve replacement in the future. Conventional prosthesis valves were seldom custom made for the pulmonary valve and were often inadequate to use because of variable age and size of these patients. Through evolution of techniques, we have developed a simple, efficient, and theoretically anatomic way of constructing trileaflet polytetrafluoroethylene valved conduit used for right ventricle outflow tract reconstruction. It was surprisingly straightforward, time efficient, and capable of being produced in various sizes.

Objectives: Initiation and maintenance of pro-inflammatory reactions elicited by bacterial lipopolysaccharide and/or cytokines in the macrophage lineage have been reported to play a crucial role in acute and chronic pathogenic effects. Whether pro-inflammatory responses triggered by lipopolysaccharide in growth arrested cells differ from those in proliferating cells remains unanswered. Materials and methods: Olomoucine and roscovitine are cyclin-dependent kinase (CDK) inhibitors that prevent progression through the cell cycle. After treatment with CDK inhibitors, expression of pro-inflammatory genes was analysed by reverse transcriptase–polymerase chain reaction. Protein levels of inducible nitric oxide synthase (iNOS) and nuclear factor kappaB (NF-κB) were determined by Western blotting. Promoter activity of iNOS was measured by the luciferase activity assay. Results: In this study we have demonstrated that both olomoucine and roscovitine inhibit cell proliferation and diminish nitric oxide production and cytokine gene expression, in lipopolysaccharide-stimulated murine RAW264.7 macrophages. In addition, olomoucine reduces iNOS promoter activity and alleviates NF-κB transcription activation. After co-transfection with E2F1 interference RNA, suppression of lipopolysaccharide-mediated iNOS promoter activity and NF-κB activation was observed. Furthermore, we demonstrated that olomoucine-induced growth arrested cells reduce expression of the p65 subunit of NF-κB. Conclusions: The findings of this study suggest that inhibition of cell-cycle progression is capable of reducing pro-inflammatory responses via down-regulation of NF-κB.

Congenital left main coronary artery (LMCA) atresia is a rare anomaly and surgical revascularization is recommended once the diagnosis is confirmed. In some cases, LMCA atresia will coexist with other cardiac anomalies, mostly in pediatric patients. A 32-year-old woman had congenital LMCA atresia associated with patent ductus arteriosus (PDA), aortic regurgitation (AR), and moderate pulmonary hypertension. The PDA and AR were repaired surgically and the patient's symptoms improved. Coronary revascularization was not performed because the LCA was supplied by 2 large conus arteries, as "naturally occurring" bypass arteries. The patient remained asymptomatic at the 2.5-year follow-up visit. Given the positive outcome in this patient, surgical repair of the associated cardiac defect without coronary revascularization may be a reasonable approach for patients with congenital LMCA atresia, in which the left coronary arterial tree is supplied by other "naturally occurring" bypass arteries.

Background Infected aneurysm of the aorta is almost always fatal without undergoing aortic resection. Medical treatment was attempted selectively in patients who were considered too high risk for surgery. We review our experience with 22 patients treated without undergoing aortic resection over 12 years. Methods Retrospective chart review. Results Between 1995 and 2007, 22 cases of infected aortic aneurysms treated without undergoing aortic resection during the first admission were included. There were 17 men with a median age of 76 years (range, 35 to 88 years). Of 18 pathogens isolated, the most common responsible microorganism was nontyphoid Salmonella in 11 followed by Staphylococcus aureus in five. The site of infection was thoracic in eight and abdominal in 14. The hospital mortality rate was 50%, and the aneurysm-related mortality rate after long-term follow-up was 59%. The event-free survival rate at one year was 32%. Of 11 patients with Salmonella infection, eight patients have lived beyond 30 days and six were event-free after one year. Of 11 patients with non-Salmonella, four patients have lived beyond 30 days and only one was event-free after one year. The overall aneurysm-related mortality rate was 36% in Salmonella infected patients and 82% in non-Salmonella infected patients. Conclusion Clinical results of medical treatment using current antibiotics in patients with infected aortic aneurysm were poor. Traditional surgical excision of infected aortic aneurysms with revascularization remains the gold standard and should be attempted except in high risk patients.