Helical heart

The voltage-gated calcium channel CaV 1.2 is essential for cardiac and vessel smooth muscle contractility and brain function. Accumulating evidence demonstrates that malfunctions of CaV 1.2 are involved in brain and heart diseases. Pharmacological inhibition of CaV 1.2 is therefore of therapeutic value. Here, we report cryo-EM structures of CaV 1.2 in the absence or presence of the antirheumatic drug tetrandrine or antihypertensive drug benidipine. Tetrandrine acts as a pore blocker in a pocket composed of S6II , S6III , and S6IV helices and forms extensive hydrophobic interactions with CaV 1...

INTRODUCTION: The clinical implementation of deep inspiratory breath-hold (DIBH) radiotherapy to reduce cardiac exposure in patients with left-sided breast cancer is challenging with helical tomotherapy(HT) and has received little attention. We describe our novel approach to DIBH irradiation in HT using a specially designed frame and manual gating, and compare cardiac substructure doses with the free-breathing (FB) technique. MATERIAL AND METHODS: The workflow incorporates staggered junctions and a frame that provides tactile feedback to the patient and monitoring for manual cut-off...

Percutaneous mechanical circulatory support (MCS) devices are designed for short-term treatment in cases of acute decompensated heart failure as a bridge to transplant or recovery. Some of the known complications of MCS treatments are related to their hemodynamics in the aorta. The current study investigates the effect of MCS on the aortic flow. The study uses combined experimental and numerical methods to delineate complex flow structures. Particle image velocimetry (PIV) is used to capture the vortical and turbulent flow characteristics in a glass model of the human aorta...

Protein-protein interactions are at the heart of all cellular processes, with the ribosome emerging as a platform, orchestrating the nascent-chain interplay dynamics. Here, to study the characteristics governing co-translational protein folding and complex assembly, we combine selective ribosome profiling, imaging, and N-terminomics with all-atoms molecular dynamics. Focusing on conserved N-terminal acetyltransferases (NATs), we uncover diverging co-translational assembly pathways, where highly homologous subunits serve opposite functions...

Anthracyclines are highly potent anti-cancer drugs, but their clinical use is limited by severe cardiotoxic side effects. The impact of anthracycline-induced cardiotoxicity (AIC) on left ventricular (LV) microarchitecture and diffusion properties remains unknown. This study sought to characterize AIC by cardiovascular magnetic resonance diffusion tensor imaging (DTI). Mice were treated with Doxorubicin (DOX; n = 16) for induction of AIC or saline as corresponding control (n = 15)...

UNLABELLED: As for all single-stranded, positive-sense RNA (+RNA) viruses, intracellular RNA synthesis relies on extensive remodeling of host cell membranes that leads to the formation of specialized structures. In the case of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) coronavirus causing COVID-19, endoplasmic reticulum membranes are modified, resulting in the formation of double-membrane vesicles (DMVs), which contain the viral dsRNA intermediate and constitute membrane-bound replication organelles...

PURPOSE: The main objective of this study was to develop two-dimensional (2D) phase contrast (PC) methods to quantify the helicity and vorticity of blood flow in the aortic root. METHODS: This proof-of-concept study used four-dimensional (4D) flow cardiovascular MR (4D flow CMR) data of five healthy controls, five patients with heart failure with preserved ejection fraction and five patients with aortic stenosis (AS). A PC through-plane generated by 4D flow data was treated as a 2D PC plane and compared with the original 4D flow...

Bicuspid aortic valve (BAV), the most common congenital heart disease, is prone to develop significant valvular dysfunction and aortic wall abnormalities such as ascending aortic aneurysm. Growing evidence has suggested that abnormal BAV hemodynamics could contribute to disease progression. In order to investigate BAV hemodynamics, we performed 3D patient-specific fluid-structure interaction (FSI) simulations with fully coupled blood flow dynamics and valve motion throughout the cardiac cycle. Results showed that the hemodynamics during systole can be characterized by a systolic jet and two counter-rotating recirculation vortices...

Cardiac magnetic resonance imaging (CMR) often shows discrepancies between right ventricular outflow tract (RVOT) flow and left ventricular outflow tract flow in patients with late-stage repaired tetralogy of Fallot (rTOF), leading to potential errors in pulmonary regurgitation fraction (PRF) assessment. This study aimed to identify the conditions under which RVOT flow can be acutely evaluated using four-dimensional (4D) flow CMR. Twenty-seven consecutive patients with rTOF underwent both two-dimensional phase-contrast (2D PC) and 4D flow CMR between 2016 and 2018, excluding those with peripheral pulmonary artery stenosis, RVOT conduit replacement, unknown surgical method, and an aortic valve regurgitation greater than 20%...

BACKGROUND: Variants in the KCNQ1 gene, encoding the α-subunit of the slow component of delayed rectifier K+ channel, Kv7.1, cause long-QT syndrome type 1 (LQT1). The location of variants may be one of factors in determining prognosis. However, detailed genotype-phenotype relationships associated with C-terminus variants remain unelucidated. OBJECTIVE: We investigated the clinical characteristics and variant-specific arrhythmic risks in LQTS patients carrying Kv7...

BACKGROUND: The use of cardiac CT (CCT) has increased dramatically in recent years among patients with pediatric and congenital heart disease (CHD), but little is known about trends and practice pattern variation in CCT utilization for this population among centers. METHODS: A 21-item survey was created to assess CCT utilization in the pediatric/CHD population in calendar years 2011 and 2021. The survey was sent to all non-invasive cardiac imaging directors of pediatric cardiology centers in North America in September 2022...

BACKGROUND: The impact of lead fixation mechanism on extractability is poorly characterized. OBJECTIVE: We aimed to compare the technical difficulty of transvenous lead extraction (TLE) of active vs passive fixation right ventricular (RV) leads. METHODS: A total of 408 patients who underwent RV TLE by a single expert electrophysiologist at Oregon Health & Science University between October 2011 and June 2022 were identified and retrospectively analyzed; 331 (81%) had active fixation RV leads and 77 (19%) had passive fixation RV leads...

Flexible fiber-shaped strain sensors show tremendous potential in wearable health monitoring and human‒machine interactions due to their compatibility with everyday clothing. However, the conductive and sensitive materials generated by traditional manufacturing methods to fabricate fiber-shaped strain sensors, including sequential coating and solution extrusion, exhibit limited stretchability, resulting in a limited stretch range and potential interface delamination. To address this issue, we fabricate a fiber-shaped flexible capacitive strain sensor (FSFCSS) by direct ink writing technology...

The helical arrangement of cardiac muscle fibres underpins the contractile properties of the heart chamber. Across the heart wall, the helical angle of the aligned fibres changes gradually across the range of 90-180°. It is essential to recreate this structural hierarchy in vitro for developing functional artificial tissue. Ice templating can achieve single-oriented pore alignment via unidirectional ice solidification with a flat base mould design. We hypothesise that the orientation of aligned pores can be controlled simply via base topography, and we propose a scalable base design to recapitulate the transmural fibre orientation...

At the heart of the DNA/ALVAC/gp120/alum vaccine's efficacy in the absence of neutralizing antibodies is a delicate balance of pro- and anti-inflammatory immune responses that effectively decreases the risk of SIVmac251 acquisition in macaques. Vaccine efficacy is linked to antibodies recognizing the V2 helical conformation, DC-10 tolerogenic dendritic cells eliciting the clearance of apoptotic cells via efferocytosis, and CCR5 downregulation on vaccine-induced gut homing CD4+ cells. RAS activation is also linked to vaccine efficacy, which prompted the testing of IGF-1, a potent inducer of RAS activation with vaccination...

Asymmetry plays a major role in biology at all scales. This can be seen in the helix of DNA, the fact that the human heart is on the left side, or that most people use their right hand. A single protein such as Myosin 1D can induce helical motion in another molecule. This causes cells, organs, and even entire bodies to twist in a domino effect, causing left-right behaviour. More generally, athlete movements are often asymmetric and, during the physical rehabilitation after injury, the asymmetry is visually discernible...

BACKGROUND: Long-term re-coarctation of the aorta can cause aortic dilatation, hypertension, and cardiac dysfunction due to increased left ventricular (LV) afterload. It is difficult to detect changes in LV function due to increased afterload if the contractile force of the left ventricle is maintained. Herein, we have reported a case of re-coarctation of the aorta, for which four-dimensional (4D) flow magnetic resonance imaging (MRI) scan was obtained both before and after balloon dilatation for aortic re-coarctation...

The effective dose represents the overall internal radiation exposure to the whole body when exposed to radiation sources. This study aims to compare conventional and software-aided methods to derive the effective dose. In the present study, 8 F-T807 and 18 F-Mefway, specific radiotracers for the paired helical tau and serotonin 1A receptor, were administered to healthy subjects (n = 6, each radiotracer), following which whole-body positron emission tomography (PET) images were obtained for 2 h...

BACKGROUND/AIM: To compare heart, left ventricle (LV) and coronary artery dose-sparing with three-dimensional conformal radiotherapy (3D-CRT) vs. helical tomotherapy (HT) in left-sided breast cancer (BC). PATIENTS AND METHODS: 3D-CRT and HT treatments were planned for 20 patients (pts). Computed tomography (CT) scans without and with intravenous contrast (ic) were performed and co-registered. Left breast and organs at risk (OARs) were contoured. Dose-volume histograms (DVHs) for 3D-CRT and HT treatment plans were evaluated in terms of planning target volume for evaluation (PTVeval) coverage and dose to the OARs...

BACKGROUND: This study aimed to evaluate an a-priori multicriteria plan optimization algorithm (mCycle) for locally advanced breast cancer radiation therapy (RT) by comparing automatically generated VMAT (Volumetric Modulated Arc Therapy) plans (AP-VMAT) with manual clinical Helical Tomotherapy (HT) plans. METHODS: The study included 25 patients who received postoperative RT using HT. The patient cohort had diverse target selections, including both left and right breast/chest wall (CW) and III-IV node, with or without internal mammary node (IMN) and Simultaneous Integrated Boost (SIB)...