Background Adults with congenital heart disease (CHD) have been considered potentially high risk for novel coronavirus disease-19 (COVID-19) mortality or other complications. Objectives This study sought to define the impact of COVID-19 in adults with CHD and to identify risk factors associated with adverse outcomes. Methods Adults (age 18 years or older) with CHD and with confirmed or clinically suspected COVID-19 were included from CHD centers worldwide. Data collection included anatomic diagnosis and subsequent interventions, comorbidities, medications, echocardiographic findings, presenting symptoms, course of illness, and outcomes. Predictors of death or severe infection were determined. Results From 58 adult CHD centers, the study included 1,044 infected patients (age: 35.1 ± 13.0 years; range 18 to 86 years; 51% women), 87% of whom had laboratory-confirmed coronavirus infection. The cohort included 118 (11%) patients with single ventricle and/or Fontan physiology, 87 (8%) patients with cyanosis, and 73 (7%) patients with pulmonary hypertension. There were 24 COVID-related deaths (case/fatality: 2.3%; 95% confidence interval: 1.4% to 3.2%). Factors associated with death included male sex, diabetes, cyanosis, pulmonary hypertension, renal insufficiency, and previous hospital admission for heart failure. Worse physiological stage was associated with mortality (p = 0.001), whereas anatomic complexity or defect group were not. Conclusions COVID-19 mortality in adults with CHD is commensurate with the general population. The most vulnerable patients are those with worse physiological stage, such as cyanosis and pulmonary hypertension, whereas anatomic complexity does not appear to predict infection severity.

SGK-1 (serum- and glucocorticoid-regulated kinase-1) is a stress-induced serine/threonine kinase that is phosphorylated and activated downstream of PI3K (phosphoinositide 3-kinase). SGK-1 plays a critical role in insulin signalling, cation transport and cell survival. SGK-1 mRNA expression is transiently induced following cellular stress, and SGK-1 protein levels are tightly regulated by rapid proteasomal degradation. In the present study we report that SGK-1 forms a complex with the stress-associated E3 ligase CHIP [C-terminus of Hsc (heat-shock cognate protein) 70-interacting protein]; CHIP is required for both the ubiquitin modification and rapid proteasomal degradation of SGK-1. We also show that CHIP co-localizes with SGK-1 at or near the endoplasmic reticulum. CHIP-mediated regulation of SGK-1 steady-state levels alters SGK-1 kinase activity. These data suggest a model that integrates CHIP function with regulation of the PI3K/SGK-1 pathway in the stress response.

OBJECTIVE The objective of this study was to examine similarities and differences in Caucasian and African-American patients with Bicuspid Aortic Valve (BAV) with respect to morphology, severity of aortic stenosis/insufficiency, and aortic dilatation. BACKGROUND Bicuspid aortic valve is a common congenital valve abnormality accounting for a large number of valve replacements. METHODS 229 patients with the diagnostic code “BAV” were identified retrospectively from our computerized adult echocardiographic database consisting of 91,896 studies performed at the University of Chicago Medical Center from 1998–2009, entailing 40.878 patients. Of those, 183 patients with BAV were included in this retrospective BAV single center cohort study, and reanalyzed with a comprehensive assessment of aortic dimensions, aortic valve morphology and function, clinical cardiovascular risk factors and patient characteristics. RESULTS Of the 183 patients with BAV, 138 were Caucasians (C) and 45 were African Americans (AA). Our Echo database encompasses approximately 65% AA, 31% C and 4% other races, for an estimated frequency of BAV in AA of 0.17 % and a frequency of BAV in C of 1.1 % (p=0.001). There were no significant inter-racial differences regarding gender, height, weight, hyperlipidemia, diabetes, tobacco use, cardiac medications, and left ventricular ejection fraction. The AA cohort was older (50±17 vs. 43±17, p<0.05) and had a higher prevalence of hypertension (51% vs. 24%, p <0.05). After adjusting for comorbidities, aortic dimensions were larger in C (C vs. AA: annulus 2.4±0.4 vs. 2.1±0.4, sinuses of Valsalva 3.4±0.7 vs. 3.1±0.6, sino-tubular junction 3.0±0.6 vs. 2.6±0.5, and ascending aorta 3.5±0.7 vs. 3.2±0.5, all p<0.05). CONCLUSIONS This is the first study to report racial differences among patient with BAV with reduced aortic dimensions in AA despite the presence of more risk factors, suggestive of marked heterogeneity in the BAV population, and indicating race as a potential disease modifier in BAV.

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This study defines the in vitro phenomenon of ciliated bovine bronchial epithelial cell (BBEC) detachment from the basal epithelium and regulation of cilia motility mediated through protein kinase C epsilon (PKCε). The authors determined the time course of activation and downregulation of PKCε by the known PKC activator phorbol 12-myristate 13-acetate (PMA) and demonstrate that chemical inhibition of PKC by calphostin C or the novel PKC isoform inhibitor Ro 31-8220 induced striking detachment of ciliated BBECs from the basal cell monolayer within 1 hour, independent of apoptosis or necrotic cell death. The results of this study support a possible novel PKCε-mediated signaling pathway through which ciliated cell attachment is maintained. Keywords airway epithelium; bronchial epithelial cell; cell detachment; cilia; kinase; protein kinase C epsilonThe protein kinase C (PKC) family of serine/threonine kinases transmits cellular signals via phosphorylation in response to diverse stimuli, regulating biological processes such as proliferation and differentiation. PKCε has been shown in multiple cell types to be activated by second messengers such as diacylglyercerol (DAG), fatty acids, and phosphatidylinositol 3,4,5,-triphosphate (PIP3). The activated kinase translocates from the cytoplasm to the membrane or cytoskeleton in response to DAG or PIP3, whereas binding of certain fatty acids causes translocation to the Golgi network [1]. Specific subcellular localization of PKCε is also enhanced by association with the selective adaptor protein beta'-COP (also called RACK2) within the Golgi apparatus [2], whereas binding to the scaffolding protein receptor of activated C kinase 1 (RACK1) at the cellular membrane can enhance focal adhesion assembly and induce migration and spreading of certain mammalian cell types [3,4]. Phosphorylation by PKCε has been implicated in the regulation of several diverse mammalian systems such as (1) modulation of stress signals via heat-shock proteins [5]; (2) induction of neurite outgrowth [6] MATERIALS AND METHODS Cell Culture and TreatmentsPrimary bovine bronchial epithelial cells (BBECs) were prepared from bovine lung as described previously [18]. Briefly, bronchi were dissected from the lung and digested overnight at 4°C in 0.1% bacterial protease type IV in minimum essential medium (M199 with Earl's salts; Gibco, Carlsbad, CA). The following day, the bronchi were repeatedly rinsed in M199 containing 10% fetal bovine serum (FBS; Gibco) to collect a mixture >95% viable ciliated and basal epithelial cells lining the lumen. These cells were then washed in M199 medium, counted with a hemacytometer, and 3×10 6 cells were plated on 60-mm tissue culture dishes coated with 1% type I collagen (Vitrogen; Cohesion, Palo Alto, CA). BBECs were grown in M199 complete medium containing 10% FBS, 50 U/mL penicillin and streptomycin (Gibco), and 2 μg/mL fungizone (Gibco) in a humidified 95% air/5% CO 2 incubator at 37°C. Confluent monolayers of primary BBECs (a mixed cell population of clumped, ci...