Considerations in the Surgical Management of Unicuspid Aortic Stenosis.

Unicuspid aortic valve (UAV) stenosis is a rare condition accounting for 5% of non-rheumatic aortic stenosis. The diagnosis can be difficult to make prior to surgical intervention and transesophageal echocardiography has been demonstrated to be more accurate in making the diagnosis compared to transthoracic echocardiography. The presence of a posteriorly located aortic orifice on the short-axis views, with one or two visible raphe anteriorly; the absence of commissures (acommissural); or the presence of a lone commissure (unicommissural) between the left and noncoronary, or the left and right cusps suggests the diagnosis. Patients with UAV are predominantly males and present with stenosis about a decade earlier than those with the more prevalent bicuspid aortic valves (BAV). They more commonly present with aortic annular dilatation and have fewer comorbidities at presentation compared to patients with BAV. Surgical management of UAV stenosis includes aortic valve replacement through standard open heart surgery or percutaneous transcatheter aortic valve replacement (TAVR), aortic valve repair either by bicuspidization, tricuspidization or trileaflet reconstruction, or the Ross procedure. Patients with UAV stenosis require less concomitant coronary or other cardiac procedures when they need surgical intervention, but are about a decade younger at the time of their death. UAV stenosis is a distinct congenital anomaly with a different natural course than BAV. Surgical management should be individualized based on the patient's age at presentation, aortoannular anatomy, and associated cardiac conditions.

Whole transcriptome analysis of smoker palatal mucosa identifies multiple downregulated innate immunity genes.

BACKGROUND: Smoking has significant negative impact on periodontal health and treatment outcomes. The molecular effects of smoking on oral immune homeostasis have not been fully elucidated. The present study aimed to provide a comprehensive assessment of smoking-associated gene expression changes in healthy palatal mucosa and to identify potentially implicated immunologic pathways. METHODS: Palatal biopsies, in the form of connective tissue grafts, were obtained from periodontally healthy smokers and non-smokers. Smoking status was biochemically verified (exhaled air CO and serum cotinine). Tissue samples were processed for next generation sequencing, quantitative real-time polymerase chain reaction (qPCR), and immunohistochemistry. Gene set enrichment/pathway analysis and correlation analysis between gene expression and serum cotinine levels were also performed. RESULTS: Analysis of palatal tissues from 12 non-smokers and 10 smokers identified 830 significantly (P <0.05) differentially expressed genes (DEGs), 249 with fold change (FC) >2. Most increased in expression (≥5-FC) were CYP1A1, CYP1B1, and USP17L9P; most decreased (≥6-FC) were IL36A, DEFB4A, DEFB4B, SPRR2F, CCL20, KLK6, and ADH4. 203 DEGs (FC >2) were significantly correlated with serum cotinine levels. Significant enrichment pathways for cotinine-associated genes include antimicrobial humoral response, regulation of humoral response and various metabolic processes. qPCR and immunohistochemistry confirmed gene and protein expression of selected DEGs. CONCLUSIONS: Smoking has a significant effect on the transcriptome of normal human palatal mucosa and seems to target genes important for innate immune defenses, which may prove to be one of the key mechanisms by which tobacco smoking leads to increased periodontitis susceptibility.

cAMP signaling regulates histone H3 phosphorylation and mitotic entry through a disruption of G2 progression.

cAMP signaling is known to have significant effects on cell growth, either inhibitory or stimulatory depending on the cell type. Study of cAMP-induced growth inhibition in mammalian somatic cells has focused mainly on the combined role of protein kinase A (PKA) and mitogen-activated protein (MAP) kinases in regulation of progression through the G1 phase of the cell cycle. Here we show that cAMP signaling regulates histone H3 phosphorylation in a cell cycle-dependent fashion, increasing it in quiescent cells but dramatically reducing it in cycling cells. The latter is due to a rapid and dramatic loss of mitotic histone H3 phosphorylation caused by a disruption in G2 progression, as evidenced by the inhibition of mitotic entry and decreased activity of the CyclinB/Cdk1 kinase. The inhibition of G2 progression induced through cAMP signaling is dependent on expression of the catalytic subunit of PKA and is highly sensitive to intracellular cAMP concentration. The mechanism by which G2 progression is inhibited is independent of both DNA damage and MAP kinase signaling. Our results suggest that cAMP signaling activates a G2 checkpoint by a unique mechanism and provide new insight into normal cellular regulation of G2 progression.