Myomucosal composite graft: A simple technique for full-thickness vermilion defects of the lower lip.

Reconstruction of vermillion defects of the lower lip requires careful consideration of functional and aesthetic aspects. Traditionally, various local flap methods involving tissue advancement from the corner of the mouth, lateral chin, and medial cheek have been commonly employed to fill lower lip defects. However, these approaches have inherent limitations, which include technical complexity, disruption of the orbicularis oris muscle, lip tightening, microstomia, and visible scarring. To overcome these limitations, we employed a free myomucosal composite graft from the lower lip to reconstruct small to medium vermilion defects. Our technique is based on a simple and reproducible surgical approach that facilitates natural volume rearrangement of tissues. Moreover, this method enables precise inset and tension-free repair, prevents lip tightening, and offers excellent aesthetic outcomes with no vertical scarring and appropriate color matching with surrounding tissues.

Epidemiological characteristics and importance of lobulation of giant epidermal cysts: An 18-year retrospective review of 19 cases.

Giant epidermal cysts, which have a diameter of ≥5 cm, have rarely been reported. Giant epidermal cysts that have multiple lobules are referred to as multilocular giant epidermal cysts. This study aims to establish the epidemiological characteristics and statistically determine the significance of lobulation in giant epidermal cysts. Data on 19 patients who developed giant epidermal cysts between January 2003 and February 2021 were retrospectively reviewed. Patients were divided into 2 groups based on the presence of septa and the differences in characteristics were analyzed. Among the 19 patients, 16 (84.2%) were male, and the mean age was 57.7 ±â€…10.6 years. The mean patient-reported tumor duration was 14.8 ±â€…12.5 years. Seven (36.8%) patients had multilocular giant epidermal cysts, whereas 12 (63.2%) had unilocular giant epidermal cysts. Compared with unilocular giant epidermal cysts, multilocular giant epidermal cysts had a significantly larger mean diameter (6.0 ±â€…0.7 vs 8.2 ±â€…1.8 cm, P = .02) and estimated volume (91.8 ±â€…43.3 vs 250.0 ±â€…157.0 mL, P = .02). Giant epidermal cysts have distinctive epidemiologic characteristics with predominance among males, those in their 50s, and a long tumor duration. Multilocular giant epidermal cysts are significantly larger in diameter and volume than unilocular ones.

Staged Excision Technique to Reduce Scar Length.

Patients and surgeons are often disappointed with the scar length after conventional staged excision of large disfiguring skin lesions. We have developed an alternative approach to facilitate scar length reduction. We aimed to report the efficacy of our staged excision method, which includes a hexagonal-pattern excision, wide undermining, and purse-string suture. Sixty-five patients, each with one lesion, were included in the current study. The lesion length and width were recorded, and the scar area was calculated at each stage. The final scar length after performing the altered staged excision method was compared with that obtained after the conventional staged excision method, which was calculated using a theoretical scar model. Patient satisfaction was also evaluated. The mean longest axis length was 9.41 ± 3.83 cm preoperatively, 9.50 ± 3.92 cm after the first stage postoperatively, and 10.19 ± 3.98 cm after the final stage. The mean lesion width was 6.50 ± 3.48 cm preoperatively, 3.60 ± 1.77 cm after the first stage postoperatively, and 0.42 ± 0.31 cm after the final stage. The final scar length obtained using the altered procedure was much shorter than what would be obtained using conventional staged excision. The patient satisfaction score was 8.8 ± 1.1 out of a possible 10.0 rating. Staged excision with a hexagonal-pattern excision, wide undermining, and purse-string closure may improve aesthetic results.

Long-Term Resorption Rate of Autogenous Onlay Graft in East Asian Rhinoplasty: A Retrospective Study.

BACKGROUND: Autologous material remains the preferred graft material for use in rhinoplasty. However, resorption rates of autografts remain controversial. In addition, long-term follow-up studies on autografts are rare. Thus, the objective of the present study was to access long-term resorption rates of various autologous grafts on the upper nasal third. METHODS: Medical records of patients who had undergone septorhinoplasty with dorsal augmentation using autologous tissues between 2009 and 2018 were retrospectively reviewed. Autogenous grafts applied on the nasal dorsum were categorized into three groups: rolled superficial mastoid fascia, diced cartilage wrapped with superficial mastoid fascia, and rolled sacral dermis. Preoperative and postoperative photographs were used to evaluate resorption rates and projection. RESULTS: The rolled sacral dermis group showed a steep increase in postoperative projection but a sharp decrease in long-term follow-up projection compared to the other two groups. Among these three groups, there were statistically significant trend differences in rhinion (p < 0.001) and ½ nasion-rhinion point (p < 0.001), but not in nasion. Of these three groups, the rolled sacral dermis group showed the most projection, followed by the diced cartilage wrapped with superficial mastoid fascia group. The resorption rate was the highest in the rolled superficial mastoid fascia group (p < 0.001). Regarding resorption rates in the other two groups, the rolled sacral dermis group had a higher rate than the diced cartilage wrapped with superficial mastoid fascia group. CONCLUSIONS: At least 50 percent of resorption was observed in almost all groups in the long term. The choice of graft material and proper decision-making could determine success or failure. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, III.

Late-Onset Inflammation in Asian Rhinoplasty Using Alloplastic Implants.

BACKGROUND: Late-onset inflammation is a rare complication that may occur several months to years after undergoing an uneventful rhinoplasty using alloplastic implants and an uneventful postoperative course. Studies to determine the pathophysiological mechanisms of late-onset inflammation related to implants used in rhinoplasty are limited. The purpose of the study was to analyze differences between non-healthy capsules (NHC) with late-onset inflammation and healthy capsules (HC) without inflammation as controls to determine the possible cause of the inflammation. METHODS: Between April 2009 and May 2018, 39 patients who underwent rhinoplasty with alloplastic implants underwent histological studies. Twenty-one patients in the NHC group showed late-onset inflammation, while 18 patients in the HC group did not display late-onset inflammation. Capsules around the alloplastic implants were harvested, and histological studies using hematoxylin and eosin, Masson's trichrome, colloidal iron, and CD31 staining were performed and compared between the NHC and HC groups. RESULTS: In hematoxylin and eosin and Masson's trichrome staining, edematous granulation tissues, inflammatory cellular contents, and a disorganized collagen layer were increased in the NHC group compared to the HC group. The colloidal iron staining revealed mucin deposition in the NHC group. CD31-positive cells were observed lining the capsule in both groups; however, the lining cells were damaged in the NHC group. CONCLUSION: Granulation tissues, inflammatory reaction, collagen degeneration, mucin deposition, and endothelial lining cell damage were greater in the NHC group compared to the HC group. Damaged capsules may play a crucial role in late-onset inflammation. LEVEL OF EVIDENCE IV: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

CHARMM-GUI 10 years for biomolecular modeling and simulation.

CHARMM-GUI, http://www.charmm-gui.org, is a web-based graphical user interface that prepares complex biomolecular systems for molecular simulations. CHARMM-GUI creates input files for a number of programs including CHARMM, NAMD, GROMACS, AMBER, GENESIS, LAMMPS, Desmond, OpenMM, and CHARMM/OpenMM. Since its original development in 2006, CHARMM-GUI has been widely adopted for various purposes and now contains a number of different modules designed to set up a broad range of simulations: (1) PDB Reader & Manipulator, Glycan Reader, and Ligand Reader & Modeler for reading and modifying molecules; (2) Quick MD Simulator, Membrane Builder, Nanodisc Builder, HMMM Builder, Monolayer Builder, Micelle Builder, and Hex Phase Builder for building all-atom simulation systems in various environments; (3) PACE CG Builder and Martini Maker for building coarse-grained simulation systems; (4) DEER Facilitator and MDFF/xMDFF Utilizer for experimentally guided simulations; (5) Implicit Solvent Modeler, PBEQ-Solver, and GCMC/BD Ion Simulator for implicit solvent related calculations; (6) Ligand Binder for ligand solvation and binding free energy simulations; and (7) Drude Prepper for preparation of simulations with the CHARMM Drude polarizable force field. Recently, new modules have been integrated into CHARMM-GUI, such as Glycolipid Modeler for generation of various glycolipid structures, and LPS Modeler for generation of lipopolysaccharide structures from various Gram-negative bacteria. These new features together with existing modules are expected to facilitate advanced molecular modeling and simulation thereby leading to an improved understanding of the structure and dynamics of complex biomolecular systems. Here, we briefly review these capabilities and discuss potential future directions in the CHARMM-GUI development project. © 2016 Wiley Periodicals, Inc.

The prediction of hole mobility in organic semiconductors and its calibration based on the grain-boundary effect.

A new reliable computational model to predict the hole mobility of poly-crystalline organic semiconductors in thin films was developed. Site energy differences and transfer integrals in crystalline morphologies of organic molecules were obtained from quantum chemical calculations, in which periodic boundary conditions were efficiently applied to capture the interactions with the surrounding molecules in the crystalline organic layer. Then the parameters were employed in kinetic Monte Carlo (kMC) simulations to estimate the carrier mobility. Carrier transport in multiple directions has been considered in the kMC simulation to mimic poly-crystalline characteristics under thin-film conditions. Furthermore, the calculated mobility was corrected using a calibration equation based on microscopy images of the thin films to take the effect of grain boundaries into account. As a result, good agreement was observed between the predicted and measured hole mobility values for 21 molecular species: the coefficient of determination (R(2)) was estimated to be 0.83 and the mean absolute error was 1.32 cm(2) V(-1) s(-1). This numerical approach can be applied to any molecules for which crystal structures are available and will provide a rapid and precise way of predicting device performance.

Langevin dynamics simulations of charged model phosphatidylinositol lipids in the presence of diffusion barriers: toward an atomic level understanding of corralling of PIP2 by protein fences in biological membranes.

BACKGROUND: The polyvalent acidic lipid phosphatidylinositol, 4,5-bisphosphate (PIP2) is important for many cellular functions. It has been suggested that different pools of PIP2 exist in the cytoplasmic leaflet of the plasma membrane, and that such pooling could play a role in the regulation of PIP2. The mechanism of fencing, however, is not understood. RESULTS: This study presents the results of Langevin dynamics simulations of PIP2 to elucidate some of the molecular level considerations that must be applied to models for fencing. For each simulation, a pool of PIP2 (modeled as charged spheres) was placed in containments with boundaries modeled as a single row of rods (steric or electrostatic) or rigid protein filaments. It is shown that even a small gap (20 Å, which is 1.85 times larger than the diameter of a PIP2 sphere) leads to poor steric blocking, and that electrostatic blockage is only effective at very high charge density. Filaments of human septin, yeast septin, and actin also failed to provide adequate blockage when placed on the membrane surface. The two septins do provide high blockage consistent with experiment and with phenomenological considerations of permeability when they are buried 9 Å and 12 Å below the membrane surface, respectively. In contrast, burial does not improve blockage by the "arch-shaped" actin filaments. Free energy estimates using implicit membrane-solvent models indicate that burial of the septins to about 10 Å can be achieved without penetration of charged residues into the hydrophobic region of the membrane. CONCLUSIONS: These results imply that a functioning fence assembled from protein filaments must either be buried well below the membrane surface, have more than a single row, or contain additional components that fill small gaps in the filaments.

Influence of hydrophobic mismatch on structures and dynamics of gramicidin a and lipid bilayers.

Gramicidin A (gA) is a 15-amino-acid antibiotic peptide with an alternating L-D sequence, which forms (dimeric) bilayer-spanning, monovalent cation channels in biological membranes and synthetic bilayers. We performed molecular dynamics simulations of gA dimers and monomers in all-atom, explicit dilauroylphosphatidylcholine (DLPC), dimyristoylphosphatidylcholine (DMPC), dioleoylphosphatidylcholine (DOPC), and 1-palmitoyl-2-oleoyl-phosphatidylcholine (POPC) bilayers. The variation in acyl chain length among these different phospholipids provides a way to alter gA-bilayer interactions by varying the bilayer hydrophobic thickness, and to determine the influence of hydrophobic mismatch on the structure and dynamics of both gA channels (and monomeric subunits) and the host bilayers. The simulations show that the channel structure varied little with changes in hydrophobic mismatch, and that the lipid bilayer adapts to the bilayer-spanning channel to minimize the exposure of hydrophobic residues. The bilayer thickness, however, did not vary monotonically as a function of radial distance from the channel. In all simulations, there was an initial decrease in thickness within 4-5 Å from the channel, which was followed by an increase in DOPC and POPC or a further decrease in DLPC and DMPC bilayers. The bilayer thickness varied little in the monomer simulations-except one of three independent simulations for DMPC and all three DLPC simulations, where the bilayer thinned to allow a single subunit to form a bilayer-spanning water-permeable pore. The radial dependence of local lipid area and bilayer compressibility is also nonmonotonic in the first shell around gA dimers due to gA-phospholipid interactions and the hydrophobic mismatch. Order parameters, acyl chain dynamics, and diffusion constants also differ between the lipids in the first shell and the bulk. The lipid behaviors in the first shell around gA dimers are more complex than predicted from a simple mismatch model, which has implications for understanding the energetics of membrane protein-lipid interactions.

Web interface for Brownian dynamics simulation of ion transport and its applications to beta-barrel pores.

Brownian dynamics (BD) based on accurate potential of mean force is an efficient and accurate method for simulating ion transport through wide ion channels. Here, a web-based graphical user interface (GUI) is presented for carrying out grand canonical Monte Carlo (GCMC) BD simulations of channel proteins: http://www.charmm-gui.org/input/gcmcbd. The webserver is designed to help users avoid most of the technical difficulties and issues encountered in setting up and simulating complex pore systems. GCMC/BD simulation results for three proteins, the voltage dependent anion channel (VDAC), α-Hemolysin (α-HL), and the protective antigen pore of the anthrax toxin (PA), are presented to illustrate the system setup, input preparation, and typical output (conductance, ion density profile, ion selectivity, and ion asymmetry). Two models for the input diffusion constants for potassium and chloride ions in the pore are compared: scaling of the bulk diffusion constants by 0.5, as deduced from previous all-atom molecular dynamics simulations of VDAC, and a hydrodynamics based model (HD) of diffusion through a tube. The HD model yields excellent agreement with experimental conductances for VDAC and α-HL, while scaling bulk diffusion constants by 0.5 leads to underestimates of 10-20%. For PA, simulated ion conduction values overestimate experimental values by a factor of 1.5-7 (depending on His protonation state and the transmembrane potential), implying that the currently available computational model of this protein requires further structural refinement.

Brownian dynamics simulations of ion transport through the VDAC.

It is important to gain a physical understanding of ion transport through the voltage-dependent anion channel (VDAC) because this channel provides primary permeation pathways for metabolites and electrolytes between the cytosol and mitochondria. We performed grand canonical Monte Carlo/Brownian dynamics (GCMC/BD) simulations to explore the ion transport properties of human VDAC isoform 1 (hVDAC1; PDB:2K4T) embedded in an implicit membrane. When the MD-derived, space-dependent diffusion constant was used in the GCMC/BD simulations, the current-voltage characteristics and ion number profiles inside the pore showed excellent agreement with those calculated from all-atom molecular-dynamics (MD) simulations, thereby validating the GCMC/BD approach. Of the 20 NMR models of hVDAC1 currently available, the third one (NMR03) best reproduces both experimental single-channel conductance and ion selectivity (i.e., the reversal potential). In addition, detailed analyses of the ion trajectories, one-dimensional multi-ion potential of mean force, and protein charge distribution reveal that electrostatic interactions play an important role in the channel structure and ion transport relationship. Finally, the GCMC/BD simulations of various mutants based on NMR03 show good agreement with experimental ion selectivity. The difference in ion selectivity between the wild-type and the mutants is the result of altered potential of mean force profiles that are dominated by the electrostatic interactions.

Molecular dynamics studies of ion permeation in VDAC.

The voltage-dependent anion channel (VDAC) in the outer membrane of mitochondria serves an essential role in the transport of metabolites and electrolytes between the cell matrix and mitochondria. To examine its structure, dynamics, and the mechanisms underlying its electrophysiological properties, we performed a total of 1.77 µs molecular dynamics simulations of human VDAC isoform 1 in DOPE/DOPC mixed bilayers in 1 M KCl solution with transmembrane potentials of 0, ±25, ±50, ±75, and ±100 mV. The calculated conductance and ion selectivity are in good agreement with the experimental measurements. In addition, ion density distributions inside the channel reveal possible pathways for different ion species. Based on these observations, a mechanism underlying the anion selectivity is proposed; both ion species are transported across the channel, but the rate for K(+) is smaller than that for Cl(-) because of the attractive interactions between K(+) and residues on the channel wall. This difference leads to the anion selectivity of VDAC.

SIMULATION OF ION CONDUCTION IN α-HEMOLYSIN NANOPORES WITH COVALENTLY ATTACHED ß-CYCLODEXTRIN BASED ON BOLTZMANN TRANSPORT MONTE CARLO MODEL.

Ion channels, as natures' solution to regulating biological environments, are particularly interesting to device engineers seeking to understand how natural molecular systems realize device-like functions, such as stochastic sensing of organic analytes. What's more, attaching molecular adaptors in desired orientations inside genetically engineered ion channels, enhances the system functionality as a biosensor. In general, a hierarchy of simulation methodologies is needed to study different aspects of a biological system like ion channels. Biology Monte Carlo (BioMOCA), a three-dimensional coarse-grained particle ion channel simulator, offers a powerful and general approach to study ion channel permeation. BioMOCA is based on the Boltzmann Transport Monte Carlo (BTMC) and Particle-Particle-Particle-Mesh (P(3)M) methodologies developed at the University of Illinois at Urbana-Champaign. In this paper, we have employed BioMOCA to study two engineered mutations of α-HL, namely (M113F)(6)(M113C-D8RL2)(1)-ß-CD and (M113N)(6)(T117C-D8RL3)(1)-ß-CD. The channel conductance calculated by BioMOCA is slightly higher than experimental values. Permanent charge distributions and the geometrical shape of the channels gives rise to selectivity towards anions and also an asymmetry in I-V curves, promoting a rectification largely for cations.

Simulation of charge transport in ion channels and nanopores with anisotropic permittivity.

Ion channels are part of nature's solution for regulating biological environments. Every ion channel consists of a chain of amino acids carrying a strong and sharply varying permanent charge, folded in such a way that it creates a nanoscopic aqueous pore spanning the otherwise mostly impermeable membranes of biological cells. These naturally occurring proteins are particularly interesting to device engineers seeking to understand how such nanoscale systems realize device-like functions. Availability of high-resolution structural information from X-ray crystallography, as well as large-scale computational resources, makes it possible to conduct realistic ion channel simulations. In general, a hierarchy of simulation methodologies is needed to study different aspects of a biological system like ion channels. Biology Monte Carlo (BioMOCA), a three-dimensional coarse-grained particle ion channel simulator, offers a powerful and general approach to study ion channel permeation. BioMOCA is based on the Boltzmann Transport Monte Carlo (BTMC) and Particle-Particle-Particle-Mesh (P(3)M) methodologies developed at the University of Illinois at Urbana-Champaign. In this paper we briefly discuss the various approaches to simulating ion flow in channel systems that are currently being pursued by the biophysics and engineering communities, and present the effect of having anisotropic dielectric constants on ion flow through a number of nanopores with different effective diameters.