Endoleak after use of the fenestrated frozen elephant trunk technique to treat acute type A aortic dissection.

Several studies have indicated that the fenestrated frozen elephant trunk (FET) technique enhances early outcomes in cases of acute aortic dissection, although long-term outcomes remain unclear. A case involving a 62-year-old male who experienced endoleak from a fenestration site following total arch replacement using the fenestrated FET technique for a DeBakey type I aortic dissection is reported. The patient underwent successful reoperation involving total arch replacement and reinsertion of the FET. Postoperatively, there was an absence of endoleak from the fenestration, and a noteworthy reduction in the diameter of the aortic arch was observed. It is imperative to recognize that endoleak from a fenestration poses a risk for prompt aortic expansion, thus necessitating vigilant postoperative monitoring. Furthermore, when adopting fenestrated FET, it is crucial to ensure firm fixation around the fenestration to prevent endoleak.

Data on molecular docking and molecular dynamics targeting Mycobacterium tuberculosis shikimic acid kinase.

We have previously performed a hierarchical in silico screening of a Mycobacterium tuberculosis shikimic acid kinase [1]. Specifically, 11 compounds were screened from a library of 154,118 compounds provided by ChemBridge [2] using UCSF DOCK [3] and the GOLD [4] program in the first and second steps, respectively. Molecular dynamic simulations were further performed on compound 2 (2-[(5Z)-5-(1-benzyl-5bromo-2-oxoindol-3-(5Z)-5-(1-benzyl-5-bromo-2-oxoindol-3-(5Z)-4-oxo-2 ylidene)-4oxo-2-sulfanylidene-1,3-thiazolidin-3-yl] acetic acid), which showed antimicrobial efficacy. These processes yielded ligand docking scores and trajectories. In this data article, we have added solvent-accessible surface area and PCA analyses, which were calculated from the raw docking scores and trajectories. Data obtained from molecular docking and molecular dynamic simulations are useful in two ways: (1) Further support for previous work (2) Provides a stepping stone for experimental scientists to conduct in silico studies and research ideas for other drug discovery researchers and computational biologists. We believe that this article will provide an opportunity to develop new Mycobacterium tuberculosis therapeutics through searching for analogs and inhibitors against new targets.

Sutureless Repair for Iliac Vein Bleeding Using an Elastomeric Sealant.

Addressing venous bleeding is a frequent complication of vascular and abdominopelvic surgeries. We present a novel sutureless repair technique using HydrofitⓇ (Terumo, Tokyo, Japan), an elastomeric sealant. In a patient experiencing common iliac vein bleeding during abdominal aortic aneurysm surgery, this technique successfully achieved complete hemostasis. By applying the elastomeric sealant with an autologous arterial patch to the bleeding site, we demonstrate the simplicity and effectiveness of sutureless hemostasis for venous bleeding.

Embolization of left anterior descending artery due to pledget after a redo surgery.

A 53-year-old man underwent aortic root replacement for acute aortic dissection. Following this procedure, the patient developed a pseudoaneurysm at the aortic root, necessitating reoperation. The subsequent surgery was performed routinely, allowing the patient to be weaned from mechanical ventilation on the same day. Postoperative electrocardiography revealed ST-segment elevation, suggesting myocardial ischaemia. Coronary angiography identified 90% stenosis in the left anterior descending artery, and computed tomography revealed a high-density mass. These findings suggested an embolus from a previous surgery. A snare catheter was successfully employed to extract the embolic material, which was identified as a pledget used for aortic valve replacement in the initial operation. This case underscores the potential for complications associated with pledgets used in valve surgeries, illustrating the risk of embolization when the valve is subsequently removed.

Severe right ventricular infarction due to iatrogenic aortocoronary dissection successfully treated by surgical repair and extracorporeal membrane oxygenation.

Iatrogenic aortocoronary dissection (IACD) is a rare but potentially fatal complication of percutaneous coronary intervention or coronary angiography (CAG). In particular, if the condition of the patient is complicated by cardiogenic shock and right ventricular (RV) dysfunction, the mortality rate is high. Herein, we report the case of an 85-year-old woman with IACD who underwent elective CAG of the right coronary artery complicated with cardiogenic shock due to RV infarction. After prompt surgical repair and postoperative extracorporeal membrane oxygenation, the postoperative course was uneventful and the patient was discharged to a rehabilitation facility.

Identification of novel antimicrobial compounds targeting Mycobacterium tuberculosis shikimate kinase using in silico hierarchical structure-based drug screening.

The development of new anti-TB drugs to prevent the spread of multidrug-resistant Mycobacterium tuberculosis (Mtb) strains is imperative. Mtb shikimate kinase (MtSK) was selected as the target protein to screen for new anti-TB drugs. We performed hierarchical in silico screening using a library of 154,118 compounds to search for novel compounds that could bind to the active site of MtSK. The growth-inhibitory effects of the candidate compounds on Mycobacterium smegmatis were evaluated in vitro. Nine of the 11 candidate compounds exhibited inhibitory effects against mycobacteria in vitro. The inhibitory activity of Compound 2 (IC50 = 1.39 µM) was higher than that of isoniazid, the first-line drug for TB treatment. Moreover, Compound 2 did not exhibit toxicity against mammalian cells and Escherichia coli. Molecular dynamics simulations using the MtSK-Compound 2 complex structure in a timeframe of 100 ns suggested that Compound 2 could stably bind to MtSK. The binding free energy of Compound 2 was estimated to be -37.96 kcal/mol using the MM/PBSA method, demonstrating that Compound 2 can stably bind to MtSK. These in silico and in vitro results indicated that Compound 2 is a promising hit compound for the development of novel anti-TB drugs.

SPICA Force Field for Proteins and Peptides.

A coarse-grained (CG) model for peptides and proteins was developed as an extension of the Surface Property fItting Coarse grAined (SPICA) force field (FF). The model was designed to examine membrane proteins that are fully compatible with the lipid membranes of the SPICA FF. A preliminary version of this protein model was created using thermodynamic properties, including the surface tension and density in the SPICA (formerly called SDK) FF. In this study, we improved the CG protein model to facilitate molecular dynamics (MD) simulations with a reproduction of multiple properties from both experiments and all-atom (AA) simulations. An elastic network model was adopted to maintain the secondary structure within a single chain. The side-chain analogues reproduced the transfer free energy profiles across the lipid membrane and demonstrated reasonable association free energy (potential of mean force) in water compared to those from AA MD. A series of peptides/proteins adsorbed onto or penetrated into the membrane simulated by the CG MD correctly predicted the penetration depths and tilt angles of peripheral and transmembrane peptides/proteins as comparable to those in the orientations of proteins in membranes (OPM) database. In addition, the dimerization free energies of several transmembrane helices within a lipid bilayer were comparable to those from experimental estimation. Application studies on a series of membrane protein assemblies, scramblases, and poliovirus capsids demonstrated the good performance of the SPICA FF.

Coarse-grained molecular dynamics study of membrane fusion: Curvature effects on free energy barriers along the stalk mechanism.

The effects of membrane curvature on the free energy barrier for membrane fusion have been investigated using coarse-grained molecular dynamics (CG-MD) simulations, assuming that fusion takes place through a stalk intermediate. Free energy barriers were estimated for stalk formation as well as for fusion pore formation using the guiding potential method. Specifically, the three different geometries of two apposed membranes were considered: vesicle-vesicle, vesicle-planar, and planar-planar membranes. The free energy barriers for the resulting fusion were found to depend importantly on the fusing membrane geometries; the lowest barrier was obtained for vesicular membranes. Further, lipid sorting was observed in fusion of the mixed membranes of dimyristoyl phosphatidylcholine and dioleoyl phosphatidylethanolamine (DOPE). Specifically, DOPE molecules were found to assemble around the stalk to support the highly negative curved membrane surface. A consistent result for lipid sorting was observed when a simple continuum model (CM) was used, where the Helfrich energy and mixing entropy of the lipids were taken into account. However, the CM predicts a much higher free energy barrier than found using CG-MD. This discrepancy originates from the conformational changes of lipids, which were not considered in the CM. The results of the CG-MD simulations reveal that a large conformational change in the lipid takes place around the stalk region, which results in a reduction of free energy barriers along the stalk mechanism of membrane fusion.

Free energy analysis along the stalk mechanism of membrane fusion.

The free energy profile of the stalk model of membrane fusion has been calculated using coarse-grained molecular dynamics simulations. The proposed method guides the lipid configuration using a guiding wall potential to make the transition from two apposed membranes to a stalk and a fusion pore. The free energy profile is obtained with a thermodynamic integration scheme using the mean force working on the guiding wall as a response of the system. We applied the method to two apposed flat bilayers composed of dioleoyl phosphatidylethanolamine/dioleoyl phosphatidylcholine expanding over the simulation box under the periodic boundary conditions. The two transition states are identified as pre-stalk and pre-pore states. The free energy barrier for the latter is confirmed to be in good agreement with that estimated by the pulling method. The present method provides a practical way to calculate the free energy profile along the stalk mechanism.

A guiding potential method for evaluating the bending rigidity of tensionless lipid membranes from molecular simulation.

A new method is proposed to estimate the bending rigidity of lipid membranes from molecular dynamics simulations. An external cylindrical guiding potential is used to impose a sinusoidal deformation to a planar membrane. The bending rigidity is obtained from the mean force acting on the cylinder by calibrating against a discretized Helfrich model that accounts for thermal fluctuations of the membrane surface. The method has been successfully applied to a dimyristoyl phosphatidylcholine bilayer simulated with a coarse-grained model. A well-converged bending rigidity was obtained for the tension-free membrane and showed reasonable agreement with that obtained from the height fluctuation spectrum.

Inverted micelle formation of cell-penetrating peptide studied by coarse-grained simulation: importance of attractive force between cell-penetrating peptides and lipid head group.

Arginine-rich peptide and Antennapedia are cell-penetrating peptides (CPPs) which have the ability to permeate plasma membrane. Deformation of the plasma membrane with CPPs is the key to understand permeation mechanism. We investigate the dynamics of CPP and the lipid bilayer membrane by coarse-grained simulation. We found that the peptide makes inverted micelle in the lipid bilayer membrane, when the attractive potential between the peptide and lipid heads is strong. The inverted micelle is formed to minimize potential energy of the peptide. For vesicle membrane, the peptide moves from the outer vesicle to the inner vesicle through the membrane. The translocation of the peptide suggests inverted micelle model as a possible mechanism of CPPs.