A ventricular septal defect (VSD) is an integral part of most congenital heart defects (CHD). To determine the prevalence of VSD in various types of CHD and the distribution of their anatomic types.
...We reviewed 1178 heart specimens with CHD from the anatomic collection of the French Reference Centre for Complex Congenital Heart Defects. During the morphologic study a special attention was paid to the localisation of the VSD viewed from the right ventricular side. The VSDs were classified as muscular, central perimembranous, outlet located between the two limbs of the septal band, and inlet. The specimens were classified according to the 9 categories and 23 subcategories of the anatomic and clinical classification of CHD1 (ACC-CHD).
Ventricular septum was almost always intact in anomalies of pulmonary veins (4/73, 5%), Ebstein anomaly (3/21, 14%), and double-inlet right ventricle (DIRV, 1/10, 10%). There was always a VSD in tetralogy of Fallot and variants (TOF, 123 cases) and common arterial trunk (CAT, 55 cases), always of the outlet type. There was almost always a VSD in double inlet left ventricle (33/34, 97%, always muscular), congenitally corrected transposition of great arteries (ccTGA, 23/24, 96%), interrupted aortic arch (IAA, 25/27, 93%), and double outlet right ventricle (DORV, 92/106, 87%). A VSD was found in 68% of aortic coarctation (CoA, 43/63), 62% of heterotaxy syndromes (21/34), 54% of transposition of the great arteries (TGA, 104/194). The VSD was located between the two limbs of the septal band in 100% of TOF and CAT, 80% of IAA, 77% of DORV, 82% of DD. The VSD was of the inlet type in 17% of cc TGA and in 71% of heterotaxy syndromes. In TGA, the VSD was outlet in 40%, central perimembranous in 25%, muscular in 25%, inlet in 10%. In CoA, the VSD was outlet in 44%, central perimembranous in 35%, muscular in 21%. In the 10% hearts with isolated VSD, the distribution was outlet in 44%, central perimembranous in 36%, muscular in 18%, and inlet in 2%.
The anatomic distribution of VSD is similar in isolated VSD, CoA and TGA, while the VSD is predominantly outlet in outflow tract defects except TGA. This reinforces the allegedly different mechanisms in TGA and cardiac neural crest defects. This anatomic approach could provide new insights in the grouping and aetiology of CHD.
•We report a multicenter study on neurocognition and acyanotic CHD.•Patients treated surgically for acyanotic CHD display shortcomings in neuropsychological domains.•Parents of ASD-II patients report ...more school problems.•Socioeconomic status and medical factors were associated with outcomes.•Ongoing follow-up and cognitive screening is warranted in this group.
Inconsistent results on neuropsychological outcome in patients treated for acyanotic congenital heart disease (aCHD) questioned the clinical relevance of possible neurobehavioral sequelae in this group. This study was designed to objectify the neuropsychological profile and evaluate associations with medical data.
Patients with a corrected atrial or ventricular septal defect, ASD-II or VSD, (n=46; mean age 9 years, 2 months) and a matched control group were submitted to an intelligence test (Wechsler Intelligence Scale for Children, third edition, Dutch version) and evaluated with a neuropsychological test battery (Developmental Neuropsychological Assessment, second edition, Dutch version). Hospitalization variables were retrieved to evaluate associations with cognitive outcome. Parents completed a behavioral checklist (Achenbach Child Behavior Checklist for Children aged 6–18).
ASD-II patients showed lower scores in domains of visuospatial processing, language, attention, and social perception. VSD patients displayed subtle problems in attention and visuospatial information processing. Only few perioperative medical factors, but also socioeconomic variables were associated with cognitive outcomes. Parents of ASD-II patients reported more school problems when compared to controls.
After treatment for aCHD, subtle cognitive difficulties can present in domains of visuospatial information processing, language, attention, and social perception. These shortcomings might hamper school performances, as is suggested by lower school competence ratings. Ongoing follow-up and cognitive screening is warranted to promote developmental progress, in which both parents and clinicians share responsibility.
The 22q11.2 deletion syndrome has an estimated prevalence of 1 in 4–6,000 livebirths. The phenotype varies widely; the most common features include: facial dysmorphia, hypocalcemia, palate and speech ...disorders, feeding and gastrointestinal disorders, immunodeficiency, recurrent infections, neurodevelopmental and psychiatric disorders, and congenital heart disease. Approximately 60–80% of patients have a cardiac malformation most commonly including a subset of conotruncal defects (tetralogy of Fallot, truncus arteriosus, interrupted aortic arch type B), conoventricular and/or atrial septal defects, and aortic arch anomalies. Cardiac patients with a 22q11.2 deletion do not generally experience higher mortality upon surgical intervention but suffer more peri‐operative complications than their non‐syndromic counterparts. New guidelines suggest screening for a 22q11.2 deletion in the patient with tetralogy of Fallot, truncus arteriosus, interrupted aortic arch type B, conoventricular septal defects as well as those with an isolated aortic arch anomaly. Early identification of a 22q11.2 deletion in the neonate or infant when other syndromic features may not be apparent allows for timely parental screening for reproductive counseling and anticipatory evaluation of cardiac and noncardiac features. Screening the at‐risk child or adult allows for important age‐specific clinical, neurodevelopmental, psychiatric, and reproductive issues to be addressed.
Obstructive heart defects (OHDs) share common structural lesions in arteries and cardiac valves, accounting for ~25% of all congenital heart defects. OHDs are highly heritable, resulting from ...interplay among maternal exposures, genetic susceptibilities, and epigenetic phenomena. A genome‐wide association study was conducted in National Birth Defects Prevention Study participants (Ndiscovery = 3978; Nreplication = 2507), investigating the genetic architecture of OHDs using transmission/disequilibrium tests (TDT) in complete case‐parental trios (Ndiscovery_TDT = 440; Nreplication_TDT = 275) and case–control analyses separately in infants (Ndiscovery_CCI = 1635; Nreplication_CCI = 990) and mothers (case status defined by infant; Ndiscovery_CCM = 1703; Nreplication_CCM = 1078). In the TDT analysis, the SLC44A2 single nucleotide polymorphism (SNP) rs2360743 was significantly associated with OHD (pdiscovery = 4.08 × 10−9; preplication = 2.44 × 10−4). A CAPN11 SNP (rs55877192) was suggestively associated with OHD (pdiscovery = 1.61 × 10−7; preplication = 0.0016). Two other SNPs were suggestively associated (p < 1 × 10−6) with OHD in only the discovery sample. In the case–control analyses, no SNPs were genome‐wide significant, and, even with relaxed thresholds ( × discovery < 1 × 10−5 and preplication < 0.05), only one SNP (rs188255766) in the infant analysis was associated with OHDs (pdiscovery = 1.42 × 10−6; preplication = 0.04). Additional SNPs with pdiscovery < 1 × 10−5 were in loci supporting previous findings but did not replicate. Overall, there was modest evidence of an association between rs2360743 and rs55877192 and OHD and some evidence validating previously published findings.
Abstract
We have performed the first‐principles calculations on the structural, electronic, and magnetic properties of zigzag GaN nanoribbon (ZGaNNR) with period vacancy located at different sites ...across the ribbon width. The results show that, the formation of the N‐vacancy is easier than that of the Ga‐vacancy at each equivalent geometrical site and both of them are endothermic. An inward relaxation of the three nearest Ga atoms around a N‐vacancy occurs, while for the three nearest‐neighbor N atoms around the Ga‐vacancy, an outward relaxation occurs. Except for a typical nonedge N‐vacancy, the N‐, or Ga‐vacancies at other sites induce magnetic moment and spin polarization implying such vacancy‐defective ZGaNNRs can be useful in spintronics and nanomagnets. The magnetic moment of the N‐vacancy is dependent on defect sites, while for the Ga‐vacancy, it is less dependent on the defect sites. The net magnetic moment of the vacancy defective 8‐ZGaNNR is mainly contributed by the atoms around a vacancy.
Despite remarkable progress in hybrid perovskite solar cells (PSCs), the concern of toxic lead ions remains a major hurdle in the path towards PSC's commercialization; tin (Sn)‐based PSCs outperform ...the reported Pb‐free perovskites in terms of photovoltaic performance. However, it is of a particularly great challenge to develop effective passivation strategies to suppress Sn(II) induced defect densities and oxidation for attaining high‐performance all‐inorganic CsSnI3 PSCs. Herein, a facile yet effective thioamides passivation strategy to modulate defect state density at surfaces and grain boundaries in CsSnI3 perovskites is reported. The thiosemicarbazide (TSC) with SCN functional groups can make strong coordination interaction with charge defects, leading to enhanced electron cloud density around defects and increased vacancy formation energies. Importantly, the surface passivation can reduce the deep level trap state defect density originated from undercoordinated Sn2+ ion and Sn2+ oxidation, significantly restraining nonradiative recombination and elongating the carrier lifetime of TSC treated CsSnI3 PSCs. The surface passivated all‐inorganic CsSnI3 PSCs based on an inverted configuration delivers a champion power conversion efficiency (PCE) of 8.20%, with a prolonged lifetime over 90% of initial PCE, after 500 h of continuous illumination. The present strategy sheds light on surface defect passivation for achieving highly efficient all‐inorganic lead‐free Sn‐based PSCs.
A facile yet effective thioamides passivation strategy is proposed to suppress defects at the surface and grain boundary of CsSnI3 perovskite, which reduces the deep level trap density from undercoordinated Sn2+ and Sn2+ oxidation. The surface passivated CsSnI3 perovskite solar cell (PSC) delivers a efficiency of 8.20% which is the highest among all lead‐free all‐inorganic PSCs.
Aims
Human congenital heart disease linked to mutations in the homeobox transcription factor, NKX2-5, is characterized by cardiac anomalies, including atrial and ventricular septal defects as well as ...conduction and occasional defects in contractility. In the mouse, homozygous germline deletion of Nkx2-5 gene results in death around E10.5. It is, however, not established whether Nkx2-5 is necessary for cardiac development beyond this embryonic stage. Because human NKX2-5 mutations are related to septum secundum type atrial septal defects (ASD), we hypothesized that Nkx2-5 deficiency during the processes of septum secundum formation may cause cardiac anomalies; thus, we analysed mice with tamoxifen-inducible Nkx2-5 ablation beginning at E12.5 when the septum secundum starts to develop.
Methods and results
Using tamoxifen-inducible Nkx2-5 gene-targeted mice, this study demonstrates that Nkx2-5 ablation beginning at E12.5 results in embryonic death by E17.5. Analysis of mutant embryos at E16.5 shows arrhythmias, contraction defects, and cardiac malformations, including ASD. Quantitative measurements using serial section histology and three-dimensional reconstruction demonstrate growth retardation of the septum secundum and enlarged foramen ovale in Nkx2-5-ablated embryos. Functional cardiac defects may be attributed to abnormal expression of transcripts critical for conduction and contraction, including cardiac voltage-gated Na+ channel pore-forming α-subunit (Nav1.5-α), gap junction protein connexin40, cardiac myosin light chain kinase, and sarcolipin within 4 days after tamoxifen injection.
Conclusion
Nkx2-5 is necessary for survival after the mid-embryonic stage for cardiac function and formation by regulating the expression of its downstream target genes.
Neural Tube Defects (NTDs) are congenital malformations of the central nervous system resulting from the incomplete closure of the neural tube during early embryonic development. Neuroinflammation ...refers to the inflammatory response in the nervous system, typically resulting from damage to neural tissue. Immune-related processes have been identified in NTDs, however, the detailed relationship and underlying mechanisms between neuroinflammation and NTDs remain largely unclear. In this study, we utilized integrated multi-omics analysis to explore the role of neuroinflammation in NTDs and identify potential prenatal diagnostic markers using a murine model.
Nine public datasets from Gene Expression Omnibus (GEO) and ArrayExpress were mined using integrated multi-omics analysis to characterize the molecular landscape associated with neuroinflammation in NTDs. Special attention was given to the involvement of macrophages in neuroinflammation within amniotic fluid, as well as the dynamics of macrophage polarization and their interactions with neural cells at single-cell resolution. We also used qPCR assay to validate the key TFs and candidate prenatal diagnostic genes identified through the integrated analysis in a retinoic acid-induced NTDs mouse model.
Our analysis indicated that neuroinflammation is a critical pathological feature of NTDs, regulated both transcriptionally and epigenetically within central nervous system tissues. Key alterations in gene expression and pathways highlighted the crucial role of STATs molecules in the JAK-STAT signaling pathway in regulating NTDs-associated neuroinflammation. Furthermore, single-cell resolution analysis revealed significant polarization of macrophages and their interaction with neural cells in amniotic fluid, underscoring their central role in mediating neuroinflammation associated with NTDs. Finally, we identified a set of six potential prenatal diagnostic genes, including FABP7, CRMP1, SCG3, SLC16A10, RNASE6 and RNASE1, which were subsequently validated in a murine NTDs model, indicating their promise as prospective markers for prenatal diagnosis of NTDs.
Our study emphasizes the pivotal role of neuroinflammation in the progression of NTDs and underlines the potential of specific inflammatory and neural markers as novel prenatal diagnostic tools. These findings provide important clues for further understanding the underlying mechanisms between neuroinflammation and NTDs, and offer valuable insights for the future development of prenatal diagnostics.
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