Congenital heart defects comprise the most common form of major birth defects, affecting 0.7% of all newborn infants. Jacobsen syndrome (11q-) is a rare chromosomal disorder caused by deletions in distal 11q. We have previously determined that a wide spectrum of the most common congenital heart defects occur in 11q-, including an unprecedented high frequency of hypoplastic left heart syndrome (HLHS). We identified an approximately 7 Mb 'cardiac critical region' in distal 11q that contains a putative causative gene(s) for congenital heart disease. In this study, we utilized chromosomal microarray mapping to characterize three patients with 11q- and congenital heart defects that carry interstitial deletions overlapping the 7 Mb cardiac critical region. We propose that this 1.2 Mb region of overlap harbors a gene(s) that causes at least a subset of the congenital heart defects that occur in 11q-. We demonstrate that one gene in this region, ETS-1 (a member of the ETS family of transcription factors), is expressed in the endocardium and neural crest during early mouse heart development. Gene-targeted deletion of ETS-1 in mice in a C57/B6 background causes, with high penetrance, large membranous ventricular septal defects and a bifid cardiac apex, and less frequently a non-apex-forming left ventricle (one of the hallmarks of HLHS). Our results implicate an important role for the ETS-1 transcription factor in mammalian heart development and should provide important insights into some of the most common forms of congenital heart disease.

Background The worldwide spread of SARS-CoV-2 has infected millions of people leading to over 0.3 million mortalities. The disruption of sodium homeostasis, tends to be a common occurrence in patients with COVID-19. Methods and results A total of 1,254 COVID-19 patients comprising 124 (9.9%) hyponatremic patients (under 135 mmol/L) and 30 (2.4%) hypernatremic patients (over 145 mmol/L) from three hospitals in Hubei, China, were enrolled in the study. The relationships between sodium balance disorders in COVID-19 patients, its clinical features, implications, and the underlying causes were presented. Hyponatremia patients were observed to be elderly, had more comorbidities, with severe pneumonic chest radiographic findings. They were also more likely to have a fever, nausea, higher leukocyte and neutrophils count, and a high sensitivity C-reactive protein (HS-CRP). Compared to normonatremia patients, renal insufficiency was common in both hyponatremia and hypernatremia patients. In addition, hyponatremia patients required extensive treatment with oxygen, antibiotics, and corticosteroids. The only significant differences between the hypernatremia and normonatremia patients were laboratory findings and clinical complications, and patients with hypernatremia were more likely to use traditional Chinese medicine for treatment compared to normonatremia patients. This study indicates that severity of the disease, the length of stay in the hospital of surviving patients, and mortality were higher among COVID-19 patients with sodium balance disorders. Conclusion Sodium balance disorder, particularly hyponatremia, is a common condition among hospitalized patients with COVID-19 in Hubei, China, and it is associated with a higher risk of severe illness and increased in-hospital mortality.

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Background-PINCH proteins are 5 LIM domain-only adaptor proteins that function as key components of the integrin signaling pathway and play crucial roles in multiple cellular processes. Two PINCH proteins, PINCH1 and PINCH2, have been described in mammals and share high homology. Both PINCH1 and PINCH2 are ubiquitously expressed in most tissues and organs, including myocardium. Cardiac-specific PINCH1 knockout or global PINCH2 knockout mice exhibit no basal cardiac phenotype, which may reflect a redundant role for these 2 PINCH proteins in myocardium. A potential role for PINCH proteins in myocardium remains unknown. Methods and Results-To define the role of PINCH in myocardium, we generated mice that were doubly homozygous null for PINCH1 and PINCH2 in myocardium. Resulting mutants were viable at birth but developed dilated cardiomyopathy and died of heart failure within 4 weeks. Mutant hearts exhibited disruptions of intercalated disks and costameres accompanied by fibrosis. Furthermore, multiple cell adhesion proteins exhibited reduced expression and were mislocalized. Mutant cardiomyocytes were significantly smaller and irregular in size. In addition, we observed that the absence of either PINCH1 or PINCH2 in myocardium leads to exacerbated cardiac injury and deterioration in cardiac function after myocardial infarction. Conclusions-These results demonstrate essential roles for PINCHs in myocardial growth, maturation, remodeling, and function and highlight the importance of studying the role of PINCHs in human cardiac injury and cardiomyopathy. (Circulation. 2009;120:568-576.)Key Words: cardiomyopathy Ⅲ cell adhesion molecules Ⅲ heart failure Ⅲ pinch protein, mouse Ⅲ remodeling C ells communicate with their microenvironment and neighbors by several specialized cell membrane-associated structures. In myocardium, these include costameres and intercalated disks, which provide mechanical and electric coupling between myocytes and enable myocardium to function as a syncytium. Dysfunction of cell adhesions in both animal models and human diseases is implicated in the pathogenesis of cardiomyopathy, heart failure, and injury repair. [1][2][3][4][5] Clinical Perspective on p 576Myocardial cell-matrix adhesion at the costamere is mediated by integrin-␤1 receptor and its associated complex and plays vital roles in morphogenesis and tissue integrity by regulating multiple cellular processes such as cell adhesion, proliferation, differentiation, and survival. 6 -10 Engagement of integrin with extracellular matrix leads to recruitment and formation of a cytoplasmic focal adhesion complex composed of integrin-linked kinase (ILK), Parvin, and PINCH, which links integrins to the actin cytoskeleton and other intracellular pathways. 6 In contrast to Drosophila and Caenorhabditis elegans, which have only 1 PINCH protein, 2 PINCH proteins, PINCH1 and PINCH2, have been described in mammals and share high sequence and structural similarity. 11 PINCH1 is expressed in the blastocyst, whereas PINCH2 expression starts on embryonic d...