Morbidity and mortality in Down syndrome (DS) are mainly related to congenital heart defects (CHDs). While CHDs with high prevalence in DS (typical CHDs), such as endocardial cushion defects, have ...been extensively described, little is known about the impact of less common CHDs (atypical CHDs), such as aortic coarctation and univentricular hearts. In our single‐center study, we analyzed, in observational, retrospective manner, data regarding cardiac features, surgical management, and outcomes of a cohort of DS patients. Literature review was performed to investigate previously reported studies on atypical CHDs in DS. Patients with CHDs were subclassified as having typical or atypical CHDs. Statistical analysis was performed for comparison between the groups. The study population encompassed 859 DS patients, 72.2% with CHDs, of which 4.7% were atypical. Statistical analysis showed a significant excess in multiple surgeries, all‐cause mortality and cardiac mortality in patients with atypical CHDs (p = .0067, p = .0038, p = .0001, respectively). According to the Kaplan–Meier method, survival at 10 and 40 years was significantly higher in typical CHDs (99 and 98% vs. 91 and 84%, log rank <0.05). Among atypical CHDs, it seems that particularly multiple complex defects in univentricular physiology associate with a worse outcome. This may be due to the surgical difficulty in managing univentricular hearts with multiple defects concurring to the clinical picture or to the severity of associated defects themselves. Further studies need to address this specific issue, also considering the higher pulmonary pressures, infective complications, and potential comorbidities in DS patients.
To evaluate perinatal outcomes and congenital heart defect (CHD) prognosis in a non-selected population.
The population-based surveillance data used in this assessment of CHDs were based on birth ...defect surveillance data collected from 2010-2012 in Liuyang City, China. Infants living with CHDs were followed up for 5 years to determine their prognosis. Prevalence, prenatal diagnosis, perinatal outcomes, and total and type-specific prognosis data were assessed using SPSS 18.0.
In total, 190 CHD cases were identified among the 53313 included perinatal infants (PIs), indicating a CHD prevalence of 35.64 per 10000 PIs in this non-selected population. The five most frequently identified types of CHDs were ventricular septal defects (VSDs, 38.95%), atrial septal defects (ASDs, 15.79%), cardiomegaly (7.89%), tetralogy of Fallot (TOF, 5.79%), and atrioventricular septal defects (AVSDs, 5.26%). Of the 190 CHD cases, 110 (57.89%) were diagnosed prenatally, 30 (15.79%) were diagnosed with associated malformations, and 69 (36.32%) resulted in termination of pregnancy (TOP). Moreover, 15 (7.89%) PIs died within 7 days after delivery, and 42 (22.10%) died within 1 year. In contrast, 79 (41.58%) were still alive after 5 years. When TOP cases were included, the 5-year survival rate of PIs with prenatally detected CHDs was lower than that of PIs with postnatally detected CHDs (25.45% vs. 63.75%). The CHD subtype associated with the highest rate of infant (less than 1 year old) mortality was transposition of the great arteries (100%). The subtypes associated with higher 5-year survival rates were patent ductus arteriosus (80%), ASD (63.33%), VSD (52.70%) and AVSD (50%).
The rates of prenatal CHD detection and TOP were high in this study population, and the 5-year survival rate of PIs with CHDs was low. The government should strengthen efforts to educate pediatricians regarding this issue and provide financial assistance to improve the prognosis of infants living with CHDs, especially during the first year of life.
The prevalence of congenital heart defects (CHD) in Kabuki syndrome ranges from 28% to 80%. Between January 2012 and December 2015, 28 patients had a molecularly proven diagnosis of Kabuki syndrome. ...Pathogenic variants in KMT2D (MLL2) were detected in 27 patients, and in KDM6A gene in one. CHD was diagnosed in 19/27 (70%) patients with KMT2D (MLL2) variant, while the single patient with KDM6A change had a normal heart. The anatomic types among patients with CHD included aortic coarctation (4/19 = 21%) alone or associated with an additional CHD, bicuspid aortic valve (4/19 = 21%) alone or associated with an additional CHD, perimembranous subaortic ventricular septal defect (3/19 = 16%), atrial septal defect ostium secundum type (3/19 = 16%), conotruncal heart defects (3/19 = 16%). Additional CHDs diagnosed in single patients included aortic dilatation with mitral anomaly and hypoplastic left heart syndrome. We also reviewed CHDs in patients with a molecular diagnosis of Kabuki syndrome reported in the literature. In conclusion, a CHD is detected in 70% of patients with KMT2D (MLL2) pathogenic variants, most commonly left‐sided obstructive lesions, including multiple left‐sided obstructions similar to those observed in the spectrum of the Shone complex, and septal defects. Clinical management of Kabuki syndrome should include echocardiogram at the time of diagnosis, with particular attention to left‐sided obstructive lesions and mitral anomalies, and annual monitoring for aortic arch dilatation.
Congenital heart defects constitute the most common human birth defect, however understanding of how these disorders originate is limited by our ability to model the human heart accurately in vitro. ...Here we report a method to generate developmentally relevant human heart organoids by self-assembly using human pluripotent stem cells. Our procedure is fully defined, efficient, reproducible, and compatible with high-content approaches. Organoids are generated through a three-step Wnt signaling modulation strategy using chemical inhibitors and growth factors. Heart organoids are comparable to age-matched human fetal cardiac tissues at the transcriptomic, structural, and cellular level. They develop sophisticated internal chambers with well-organized multi-lineage cardiac cell types, recapitulate heart field formation and atrioventricular specification, develop a complex vasculature, and exhibit robust functional activity. We also show that our organoid platform can recreate complex metabolic disorders associated with congenital heart defects, as demonstrated by an in vitro model of pregestational diabetes-induced congenital heart defects.
A complete defect detection task aims to achieve the specific class and precise location of each defect in an image, which makes it still challenging for applying this task in practice. The defect ...detection is a composite task of classification and location, leading to related methods is often hard to take into account the accuracy of both. The implementation of defect detection depends on a special detection data set that contains expensive manual annotations. In this paper, we proposed a novel defect detection system based on deep learning and focused on a practical industrial application: steel plate defect inspection. In order to achieve strong classification ability, this system employs a baseline convolution neural network (CNN) to generate feature maps at each stage, and then the proposed multilevel feature fusion network (MFN) combines multiple hierarchical features into one feature, which can include more location details of defects. Based on these multilevel features, a region proposal network (RPN) is adopted to generate regions of interest (ROIs). For each ROI, a detector, consisting of a classifier and a bounding box regressor, produces the final detection results. Finally, we set up a defect detection data set NEU-DET for training and evaluating our method. On the NEU-DET, our method achieves 74.8/82.3 mAP with baseline networks ResNet34/50 by using 300 proposals. In addition, by using only 50 proposals, our method can detect at 20 ft/s on a single GPU and reach 92% of the above performance, hence the potential for real-time detection.
The present work reports on a distinct and very reproducible bistable-like behavior of two defects at around EC − 0.5 eV in MOCVD-grown GaN. The kinetics of the thermally activated transformation ...between the two states are analyzed in an Arrhenius model, yielding an energy barrier of 0.4 ± 0.1 eV, and a frequency factor of 106±1 s−1. Depth profiles suggest that the charge state of the defects determines the observed amplitude variation. Relevant models for the observed behavior, and their shortcomings are discussed: (i) passivating properties of hydrogen, and (ii) bistable defect component(s). A proper explanation of the experimental observations represents, however, a further challenge.
Neural tube defects Greene, Nicholas D E; Copp, Andrew J
Annual review of neuroscience,
01/2014, Letnik:
37
Journal Article
Recenzirano
Odprti dostop
Neural tube defects (NTDs), including spina bifida and anencephaly, are severe birth defects of the central nervous system that originate during embryonic development when the neural tube fails to ...close completely. Human NTDs are multifactorial, with contributions from both genetic and environmental factors. The genetic basis is not yet well understood, but several nongenetic risk factors have been identified as have possibilities for prevention by maternal folic acid supplementation. Mechanisms underlying neural tube closure and NTDs may be informed by experimental models, which have revealed numerous genes whose abnormal function causes NTDs and have provided details of critical cellular and morphological events whose regulation is essential for closure. Such models also provide an opportunity to investigate potential risk factors and to develop novel preventive therapies.
Display omitted
•Optically active defects in 4H-SiC.•Mechanically introduced defects in SiC.•p-n junction electrical characteristics modification due to mechanical stress defects introduction.
We ...investigate defects in 4H-SiC p-n junction diodes introduced trough nanoindentation procedure. A nanoindentation load range between 3 mN and 15 mN was explored. Scanning Electron Microscopy and Transmission Electron Microscopy analysis are adopted for the morphological and crystallographic investigation of defects; electrical characterisations of junction diodes are performed to investigate the conduction mechanism, both at RT and versus measurement temperature. Electrical parameters such ideality factor, leakage current and series resistance, are extracted for the processed diodes and compared to virgin one. Activation energy of about 1.7 eV and 0.2 eV are extracted for defects in virgin and in mechanically processed devices, respectively. Electro-optical characterisation is performed adopting Emission Microscopy measurements evidencing a diffuse photons emission in the visible range from the full area in virgin device and an emission in the visible and in the near infrared ranges from nanoindentation sites in processed devices. Performed analysis evidenced both extended and point defects are mechanically introduced. Thanks to the performed experiment, a promising way is paved for the defects engineering, in a microscale spatially defined position, in end of processing devices.
Patients with simple shunt lesions, such as atrial septal defect (ASD), ventricular septal defect (VSD) and persistent arterial duct (PDA) remain at risk of developing pulmonary hypertension (PH) ...even after correction of their cardiac defect. We aimed to assess the contemporary prevalence of PH in a well characterized nationwide group of patients based on the German National Register for Congenital Heart Defects.
We included all patients >16 years of age with an isolated diagnosis of ASD, VSD or PDA. Only patients with previous surgical or interventional closure of the defect were included. Patients with genetic syndromes were excluded. Out of 49,597 CHD patients in the register we identified 825 patients with closed, isolated simple defects (52% ASD, 41% VSD, 7% PDA). Of these, 25 (3%) developed PH after a median follow-up of 16 years from defect closure. The risk of PH increased significantly with age at follow-up (p < 0.0001) and age at repair (p < 0.0001) on logistic regression analysis Patients with PH were significantly more likely to be symptomatic (59% vs. 9% in NYHA class ≥2, p < 0.0001) and had significantly higher mortality (hazard ratio 13.4, p < 0.0001) compared to the remaining patients.
Based on data from the German National Register CHD Register we report a PH prevalence of 3.0% in patients with corrected, simple lesions. Patients with PH were more symptomatic and had significantly increased mortality risk. Life-long surveillance and low threshold for workup is recommended to ascertain diagnosis of PH, which has important prognostic and clinical implications.
•Pulmonary hypertension (pH) is common in congenital heart disease.•Simple corrected lesions have increased life-long risk of developing PH.•The risk of developing PH ranges between 3 and 5% and increases with age.•Even minor shunt lesions warrant life-long follow-up and screening for PH.
Members of the GATA family of transcription factors are critical regulators of heart development and mutations in 2 of them,
GATA4 and
GATA6 are associated with outflow tract and septal defects in ...human. The heart expresses 3 GATA factors, GATA4, 5 and 6 in a partially overlapping pattern. Here, we report that compound
Gata4/
Gata5 and
Gata5/
Gata6 mutants die embryonically or perinatally due to severe congenital heart defects. Almost all
Gata4
+/−
Gata5
+/−
mutant embryos have double outlet right ventricles (DORV), large ventricular septal defects (VSD) as well as hypertrophied mitral and tricuspid valves. Only 25% of double compound
Gata4/
Gata5 heterozygotes survive to adulthood and these mice have aortic stenosis. Compound loss of a
Gata5 and a
Gata6 allele also leads to DORVs associated with subaortic VSDs. Expression of several transcription factors important for endocardial and myocardial cell differentiation, such as Tbx20, Mef2c, Hey1 and Hand2, was reduced in compound heterozygote embryos. These findings suggest the existence of important genetic interactions between Gata5 and the 2 other cardiac GATA factors in endocardial cushion formation and outflow tract morphogenesis. The data identify
GATA5 as a potential genetic modifier of congenital heart disease and provide insight for elucidating the genetic basis of an important class of human birth defects.
►We analyzed the genetic interactions between GATA5 and GATA4/6 in heart development. ►Double hets die embryonically and perinatally from severe congenital heart defects. ►Endocardial and myocardial differentiation markers are downregulated in double hets. ►This will help elucidate the molecular basis of an important class of CHDs. ►This identifies GATA5 as a potential genetic modifier of congenital heart defects.
PDF
