Valvulogenesis of a living, innervated pulmonary root induced by an acellular scaffold.

Heart valve disease is a major cause of mortality and morbidity worldwide with no effective medical therapy and no ideal valve substitute emulating the extremely sophisticated functions of a living heart valve. These functions influence survival and quality of life. This has stimulated extensive attempts at tissue engineering "living" heart valves. These attempts utilised combinations of allogeneic/ autologous cells and biological scaffolds with practical, regulatory, and ethical issues. In situ regeneration depends on scaffolds that attract, house and instruct cells and promote connective tissue formation. We describe a surgical, tissue-engineered, anatomically precise, novel off-the-shelf, acellular, synthetic scaffold inducing a rapid process of morphogenesis involving relevant cell types, extracellular matrix, regulatory elements including nerves and humoral components. This process relies on specific material characteristics, design and "morphodynamism".

Novel concepts and early results of repairing common arterial trunk.

OBJECTIVES: Common Arterial Trunk (CAT) continues to have a very poor prognosis globally. To address that, we have developed a novel technique targeting key concepts for the correction of all components of the anomaly, using autologous arterial tissue. This aims to enhance results, availability worldwide, and importantly to avoid the need for repeated reoperations. METHODS: From January 2019 to 4 January 2021, all patients with isolated CAT had repair of the defect using autologous arterial trunk tissue with direct right ventricle (RV) to pulmonary artery (PA) connection. Clinical outcomes, follow-up which included multi-slice computed tomography 3D segmentation and 4D cardiovascular magnetic resonance flow, are presented. RESULTS: Twenty patients were included in the study (median age 4.5 months). There were 2 hospital deaths due to systemic infection and pulmonary hypertensive crisis, respectively. Following discharge all patients remained asymptomatic with no signs of heart failure and improved pattern of growth (median follow-up: 8 months). Early postoperative 3D segmentation showed a conical shaped neo-right ventricular outflow chamber connecting the body of the RV to the main PA through a valveless ostium, and normal crossing of PA and neo-aorta. 4D cardiovascular magnetic resonance pattern of flow showed normal rapid laminar flow through the atrioventricular valves followed by a vortex towards the outflow tracts. There was laminar flow through the neo-aorta and neo-PA with velocity not exceeding 2.5 m/s. The PA regurgitant fraction was 25 ± 5% and was limited to early diastole. CONCLUSIONS: The initial results of utilizing the key concepts, using autologous arterial tissue for the repair of CAT, are encouraging, both clinically and by multimodality imaging.

Knockdown of c-MYC Controls the Proliferation of Oral Squamous Cell Carcinoma Cells in vitro via Dynamic Regulation of Key Apoptotic Marker Genes.

Oral squamous cell carcinoma (OSCC) is the most common malignant epithelial cancer occurring in the oral cavity, where it accounts for nearly 90% of all oral cavity neoplasms. The c-MYC transcription factor plays an important role in the control of programmed cell death, normal-to-malignant cellular transformation, and progression of the cell cycle. However, the role of c-MYC in controlling the proliferation of OSCC cells is not well known. In this study, c-MYC gene was silenced in OSCC cells (ORL-136T), and molecular and cellular responses were screened. To identify the pathway through which cell death occurred, cytotoxicity, colony formation, western blotting, caspase-3, and RT-qPCR analyzes were performed. Results indicated that knockdown of c-MYC has resulted in a significant decrease in the cell viability and c-MYC protein synthesis. Furthermore, caspase-3 was shown to be upregulated leading to apoptosis via the intrinsic pathway. In response to c-MYC knockdown, eight cell proliferation-associated genes showed variable expression profiles: c-MYC (-21.2), p21 (-2.5), CCNA1(1.8), BCL2 (-1.4), p53(-3.7), BAX(1.1), and CYCS (19.3). p27 expression was dramatically decreased in c-MYC-silenced cells in comparison with control, and this might indicate that the relative absence of c-MYC triggered intrinsic apoptosis in OSCC cells via p27 and CYCS.

Left Ventricular Remodeling Following Balloon Mitral Valvuloplasty in Rheumatic Mitral Stenosis: Magnetic Resonance Imaging Study.

Background: Rheumatic heart disease affects primarily cardiac valves, it could involve the myocardium either primarily or secondary to heart valve affection. The influence of balloon mitral valvuloplasty (BMV) on left ventricular function has not been sufficiently studied. Aim: To determine the influence of balloon mitral valvuloplasty (BMV) on both global and regional left ventricular (LV) function. Methods: Thirty patients with isolated rheumatic mitral stenosis (MS) were studied. All patients had cardiac magnetic resonance imaging (CMR) before, 6 months and 1 year after successful BMV. LV volumes, ejection fraction (EF), regional and global LV deformation, and LV late gadolinium enhancement were evaluated. Results: At baseline, patients had median EF of 57 (range: 45-69) %, LVEDVI of 74 (44-111) ml/m2 and LVESVI of 31 (14-57) ml/m2 with absence of late gadolinium enhancement in all myocardial segments. Six months following BMV, there was a significant increase in LV peak systolic global longitudinal strain (GLS) (-16.4 vs. -13.8, p < 0.001) and global circumferential strain (GCS) (-17.8 vs. -15.6, p = 0.002). At 1 year, there was a trend towards decrease in LVESVI (29 ml/m2, p = 0.079) with a significant increase in LV EF (62%, p < 0.001). A further significant increase, compared to 6 months follow up studies, was noticed in GLS (-17.9 vs. -16.4, p = 0.008) and GCS (-19.4 vs. -17.8 p = 0.03). Conclusions: Successful BMV is associated with improvement in global and regional LV systolic strain which continues for up to 1 year after the procedure.

A New Technique for Shaping the Aortic Sinuses and Conserving Dynamism in the Remodeling Operation.

BACKGROUND: Preserving dynamism and recreating the sinuses in the Dacron graft are thought to be important for optimizing results of aortic valve-conserving operations. METHODS: We describe a novel technique that preserves dynamism and recreates the sinotubular junction. In addition, it tailors 3 sinuses of defined longitudinal and transverse curvatures in a straight Dacron tube during the operation. The technique has been used in 6 patients with varied aortic root pathology. We performed preoperative and postoperative multimodality imaging using computerized image analysis as well as 3-dimensional models. RESULTS: There was no early or midterm death. Upon discharge, patients were clinically well, with echocardiographic evidence of minimal (3 patients) or mild (3 patients) aortic regurgitation. Computed tomography and cardiac magnetic resonance imaging with extensive image analysis of the aortic root size, shape, and function showed partial or complete normalization of these parameters. This included the shape and dynamism of the aortic annulus and the size and shape of the geometric (effective) orifice. The 4-dimensional magnetic resonance imaging pattern of flow in the sinuses and ascending aorta showed favorable vortices in the sinuses, right-handed helical flow, and marked diminution of energy loss in the ascending aorta. CONCLUSIONS: The novel technique described here is simple, practical, and cost-effective because it uses a widely available straight Dacron tube. The technique does not use rigid internal or external support. The early results are encouraging. Larger series with longer follow-up are required.

The Egyptian Collaborative Cardiac Genomics (ECCO-GEN) Project: defining a healthy volunteer cohort.

The integration of comprehensive genomic and phenotypic data from diverse ethnic populations offers unprecedented opportunities toward advancements in precision medicine and novel diagnostic technologies. Current reference genomic databases are not representative of the global human population, making variant interpretation challenging, especially in underrepresented populations, such as the North African population. To address this, the Egyptian Collaborative Cardiac Genomics (ECCO-GEN) Project launched a study comprising 1000 individuals free of cardiovascular disease (CVD). Here, we present the first 391 Egyptian healthy volunteers recruited to establish a pilot phenotyped control cohort. All individuals underwent detailed clinical investigation, including cardiac magnetic resonance imaging (MRI), and were sequenced using a targeted panel of 174 genes with reported roles in inherited cardiac conditions. We identified 1262 variants in 27 cardiomyopathy genes of which 15.1% were not captured in current global and regional genetic reference databases (here: gnomAD and Great Middle Eastern Variome). The ECCO-GEN project aims at defining the genetic landscape of an understudied population and providing individual-level genetic and phenotypic data to support future studies in CVD and population genetics.

Mechanics of the dicrotic notch: An acceleration hypothesis.

The dicrotic notch is a prominent and distinctive feature of the pressure waveform in the central arteries. It is universally used to demarcate the end of systole and the beginning of diastole in these arteries. Despite its importance clinically, no physical mechanism for the formation of the dicrotic notch has been demonstrated convincingly. We first explore a mechanism based on the reflection of a backward wavefront from the aortic valve at the time of closure. This hypothesis is rejected on the basis of experimental evidence from measurements made in dogs. A new hypothesis is presented involving the acceleration of the aortic valve apparatus at the time of valve closure. This hypothesis is supported by new calculations of the acceleration of the aortic valve apparatus during the cardiac cycle based on computed tomography scans in man.