Curved Planar Reformation: A Useful Method for Screening Dental Pathologies in Chronic Rhinosinusitis via Paranasal Sinus Computed Tomography.

(1) Background: Curved planar reformation (CPR) is a multiplanar reformatting technique of computed tomography (CT) commonly used during dental cone-beam CT (CBCT) to generate panorex-like images for dental evaluation. Here, we evaluated the utility of an additional CPR sequence in detecting dental pathologies in patients with chronic rhinosinusitis (CRS). (2) Methods: CRS patients who underwent paranasal sinus CT were enrolled retrospectively. The CT images featured three orthogonal sequences and a reconstructed CPR sequence. Additional dental CBCT was performed in patients with pathologies with a strongly suspected odontogenic origin. Dental pathologies detected by CT, CPR, and CBCT were analyzed. (3) Results: A total of 82 CRS patients (37 females and 45 males; mean age 47.3 ± 13.7 years) were included, of whom 23 underwent dental CBCT. In total, 1058 maxillary teeth were evaluated. Compared with paranasal sinus CT, CPR identified greater frequencies of dental pathologies, particularly caries (p < 0.001), periapical lesions (p < 0.001), and fistulae (p = 0.014). CBCT identified greater frequencies of periodontal dental pathologies (p = 0.046) and premolar caries (p = 0.002) compared with CPR. CBCT and CPR detected molar dental pathologies at similar frequencies. (4) Conclusions: CPR could increase the diagnostic rate of odontogenic pathologies compared with standard CT orthogonal views, especially when the sinusitis is caused by caries, periapical lesions, or fistulae. The addition of a CPR sequence allows for simple screening of dental pathologies in CRS patients without a need for additional radiation.

Novel airway-cartilage combined model for medialization laryngoplasty and laryngotracheal reconstruction surgery planning.

BACKGROUND: The clinical outcomes of surgical treatments for vocal cord paralysis and tracheal stenosis, such as medialization laryngoplasty and laryngotracheal reconstruction, vary owing to the complex anatomy and physiology of the human upper airway. However, advances in three-dimensional (3D) simulation and printing ushered its use on an office-based workstation to aid in several surgical areas. METHODS: The preoperation neck computed tomography image was loaded into the InVesalius 3.0 software for manual segmentation of airway and nearby important anatomic landmarks including hyoid bone, thyroid cartilage, and cricoid cartilage. The 3D model of the desired anatomy structure was manufactured and used for presurgical planning and rehearsal of the surgery. RESULTS: We review cases of four patients: two cases of unilateral vocal palsy undergoing medialization laryngoplasty and two cases of tracheal stenosis patients who used the air-cartilage combined model. CONCLUSION: Preoperation planning of the medialization thyroplasty could be more precise by prevision of the paralyzed vocal cord plane. Tracheal surgery could benefit from a preoperative design of segmented length. The novel airway-cartilage combined model offers new insight into vocal cord and trachea surgery.

Mechanical tension mobilizes Lgr6+ epidermal stem cells to drive skin growth.

Uniquely among mammalian organs, skin is capable of marked size change in adults, yet the mechanisms underlying this notable capacity are unclear. Here, we use a system of controlled tissue expansion in mice to uncover cellular and molecular determinants of skin growth. Through machine learning-guided three-dimensional tissue reconstruction, we capture morphometric changes in growing skin. We find that most growth is driven by the proliferation of the epidermis in response to mechanical tension, with more limited changes in dermal and subdermal compartments. Epidermal growth is achieved through preferential activation and differentiation of Lgr6+ stem cells of the epidermis, driven in part by the Hippo pathway. By single-cell RNA sequencing, we uncover further changes in mechanosensitive and metabolic pathways underlying growth control in the skin. These studies point to therapeutic strategies to enhance skin growth and establish a platform for understanding organ size dynamics in adult mammals.

Rapid prototyping-assisted tooth autotransplantation is associated with a reduced root canal treatment rate: a retrospective cohort study.

BACKGROUND: Autotransplantation is a beneficial treatment with a high success rate for young patients. However, most adult patients require root canal treatment (RCT) of the donor teeth after the autotransplantation procedure, which causes a prolonged treatment time and additional expenses and increases the rate of future tooth fracture. Rapid prototyping (RP)-assisted autotransplantation shortens the extra-alveolar time and enables a superior clinical outcome. However, no cohort studies of the application of this method on adult populations have been reported. METHODS: This study is a retrospective cohort study. All patients underwent autotransplantation from 2012 to 2020 in the Kaohsiung and Chia-Yi branches of Chang Gung Memorial Hospital, and the procedure and clinical outcomes were analysed. Differences in clinical outcomes, age, sex, extra-alveolar time, fixation method, and RCT rate were compared between the two groups. RESULTS: We enrolled 21 patients, 13 treated using the conventional method and 8 treated using the RP-based technique. The RCT rates of the conventional group and RP group were 92.3% and 59%, respectively. The mean age of the two groups was significantly different (28.8 ± 10 vs. 21.6 ± 2.1); after performing subgroup analysis by excluding all of the patients aged > 40 years, we found that the RCT rates were still significantly different (91.0% vs. 50%). The mean extra-alveolar time was 43 s in the RP group, and the autotransplantation survival rate in both groups was 100%. CONCLUSIONS: Rapid prototyping-assisted autotransplantation was successfully adopted for all patients in our study population. By shortening the extra-alveolar time, only 50% of the patients required a root canal treatment with a 100% autotransplantation survival rate. TRIAL REGISTRATION: Retrospectively registered.

The Role of the Visor Flap in Scalp Reconstruction: A Case Series of 21 Patients.

BACKGROUND: Full-thickness scalp defects pose a reconstructive problem, especially in the setting of infection, chemotherapy/radiation, and underlying cranial defects. Current options include dermal matrices, skin grafts, and local flaps. Local flaps often fail, requiring subsequent microvascular free flap reconstruction. OBJECTIVE: To describe the visor flap, a novel bipedicled advancement flap design, and its role in reconstruction of scalp defects. METHODS: A retrospective review of 21 adult patients who developed scalp defects reconstructed using the visor flap from 2013 to 2017. The visor flap is a large bipedicled advancement flap design with a triangular extension at the base, which allows redistribution of a large surface area of the scalp. RESULTS: All 21 patients achieved complete and viable soft tissue coverage of the recipient site, but 19.0% developed complications unrelated to flap viability, requiring reoperation (infected bone flap, epidural hematoma, and recurrent glioblastoma with subdural abscess). Only 1 patient required conversion to free flap reconstruction due to cerebrospinal fluid leak. Etiologies included cancer (76.1%), cerebrovascular disease (19.0%), and traumatic brain injury (4.8%). Preoperative radiation (42.9%), bone/hardware exposure (57.1%), and previous craniotomy (85.7%) were widely prevalent. Defect size ranged from 3 to 50 cm2 (mean, 16.9 cm2), and flap size ranged from 90 to 500 cm2 (mean, 222 cm2). CONCLUSION: The visor flap provides an innovative solution for closure of scalp defects. This technique optimizes immediate closure of tissue compromised by infection or chemotherapy/radiation without burning bridges to more complex reconstructive options.

Preoperative Use of Neuromodulators to Optimize Surgical Outcomes in Upper Blepharoplasty and Brow Lift.

BACKGROUND: Upper eyelid dermatochalasis often triggers frontalis hyperactivity in an effort to elevate the upper lids away from the visual axis. Similarly, prior neuromodulator treatment of the brow depressors may cause false elevation of the brows, diminishing the extent of preoperative brow ptosis or dermatochalasis. Studies have quantified postoperative brow ptosis and recurrent dermatochalasis following upper blepharoplasty, but a methodology to predict the postoperative brow position remains to be elucidated. OBJECTIVES: The authors present our comprehensive perioperative protocol utilizing neuromodulators to optimize results of upper blepharoplasty and brow lift. METHODS: In patients presenting with upper lid dermatochalasis and frontalis hyperactivity, who request upper blepharoplasty, the authors apply a neuromodulator treatment protocol. Patients with prior neuromodulator treatment of brow depressors wait four months after the last treatment to allow for product attrition. Two weeks prior to surgery, the authors treat the frontalis with 15 to 20 units of Botox Cosmetic. RESULTS: From 2002 to 2016, the authors treated 521 patients (458 women, 63 men) with frontalis hyperactivity who presented for periorbital rejuvenation. This method has led to neither excessive resection of upper eyelid skin tissue nor lagophthalmos. Preoperatively, the authors have unveiled upper eyelid ptosis in 39 patients (31 women, 8 men) and brow ptosis in 131 patients (97 women, 34 men). CONCLUSIONS: Brow position and frontalis hyperactivity should be taken into consideration during preoperative evaluation for upper blepharoplasty and brow lift. Routine preoperative treatment of the hyperactive frontalis with neuromodulator, along with attrition of prior neuromodulator in the brow depressors, reveals the true anatomic brow position to optimize surgical planning.

Autotransplantation of Odontoma-Associated Impacted Teeth-A Treatment Strategy for Satisfying Immediate Esthetic Demands: A Case Report.

Compound odontomas are common odontogenic tumors associated with permanent tooth impaction in the premaxilla. This report describes the case of a 14-year-old girl with an odontoma-associated impaction over the premaxilla that was treated using autotransplantation to satisfy an immediate esthetic demand. At postoperative follow-up conducted in the 14th month, a satisfactory cosmetic appearance with a healthy periodontal status was observed. In addition, the authors discuss the possible complications of autotransplantation and different treatment strategies for odontoma-associated impaction and for correcting bone defects in this case report. Autotransplantation for treating odontoma-associated impaction can be an alternative solution for satisfying an immediate cosmetic demand and providing a favorable outcome.

The Visor Flap: A Novel Design for Scalp Wound Closure.

Full-thickness scalp defects pose a reconstructive problem in the setting of infection, radiation, and underlying calvarial defects. Current options include dermal matrices, skin grafts, and local fasciocutaneous flaps. Free tissue transfer is frequently required when scalp-based flaps fail or the wound is significantly large or complex. The authors present 7 patients of complex scalp defect reconstruction using the novel visor flap. The visor flap is a bipedicled advancement flap with a triangular posterior extension. The flap was designed to redistribute tension over a large surface area that prioritizes tension-free closure of the wound over a relatively small remote donor site. This method achieved complete primary healing of the recipient site in all patients. This flap design is a durable adjunct to minimize donor site morbidity and avoid microsurgical reconstruction of hostile scalp wounds.

Comparison of Extruded and Sonicated Vesicles for Planar Bilayer Self-Assembly.

Lipid vesicles are an important class of biomaterials that have a wide range of applications, including drug delivery, cosmetic formulations and model membrane platforms on solid supports. Depending on the application, properties of a vesicle population such as size distribution, charge and permeability need to be optimized. Preparation methods such as mechanical extrusion and sonication play a key role in controlling these properties, and yet the effects of vesicle preparation method on vesicular properties and integrity (e.g., shape, size, distribution and tension) remain incompletely understood. In this study, we prepared vesicles composed of 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC) lipid by either extrusion or sonication, and investigated the effects on vesicle size distribution over time as well as the concomitant effects on the self-assembly of solid-supported planar lipid bilayers. Dynamic light scattering (DLS), quartz crystal microbalance with dissipation (QCM-D) monitoring, fluorescence recovery after photobleaching (FRAP) and atomic force microscopy (AFM) experiments were performed to characterize vesicles in solution as well as their interactions with silicon oxide substrates. Collectively, the data support that sonicated vesicles offer more robust control over the self-assembly of homogenous planar lipid bilayers, whereas extruded vesicles are vulnerable to aging and must be used soon after preparation.

The role of stem cells in the treatment of diabetic foot ulcers.

Diabetic foot ulcers (DFUs) are a significant and rapidly growing complication of diabetes and its effects on wound healing. Over half of diabetic patients who develop a single ulcer will subsequently develop another ulcer of which the majority will become chronic non-healing ulcers. One-third will progress to lower extremity amputation. Over the past decade, the outcomes for patients with DFUs ulcers have not improved, despite advances in wound care. Successful treatment of diabetic foot ulcers is hindered by the lack of targeted therapy that hones in on the healing processes dysregulated by diabetes. Stem cells are a promising treatment for DFUs as they are capable of targeting, as well as bypassing, the underlying abnormal healing mechanisms and deranged cell signaling in diabetic wounds and promote healing. This review will focus on existing stem cell technologies and their application in the treatment of DFUs.

Preparation and characterization of glycoacrylate-based polymer-tethered lipid bilayers on benzophenone-modified substrates.

Polymer-tethered lipid bilayers are promising models for biological membranes as they may provide a soft, lubricating environment with sufficient spacing between the substrate and bilayer for incorporating transmembrane proteins. We present such a system that uses a glycoacrylate-based telechelic lipopolymer in combination with a lipid analogue. Characterization of the mixed monolayers of lipopolymers and free lipids at the air-water interface is used to examine the molecular organization that dictates the final assembly properties. Isotherms indicate that the source of the dominating interactions, whether polymer interactions in the subphase or alkyl chain interactions, depends on both the tethering density and area per molecule. Moreover, a critical composition exists at which the alkyl chain interactions dominate the monolayer behavior regardless of the area per molecule. Isobaric creep and hysteresis experiments suggest that permanent states due to irreversible polymer-polymer interactions are not created as the monolayer is compressed. These data, combined with theoretical polymer predictions, are used to understand the organization of the monolayers at the air-water interface and, hence, the separation distance between the bottom of the bilayer and substrate in the water-swollen state of the final bilayer assembly. Atomic force microscopy is used to confirm that the measured separation distance of 11.2 nm is on the order of what would be predicted using a theoretical analysis for a representative 5 mol % lipopolymer-tethered bilayer. Next, the homogeneity of the final bilayer is probed at multiple scales. Fluorescence microscopy is used to demonstrate that homogeneous and continuous bilayers can be formed (within the optical resolution limit of 500 nm) with all polymer tethering densities used in this study. Atomic force microscopy studies demonstrate that homogeneity comparable to that of a solid-supported lipid bilayer can be achieved for a representative 5 mol % lipopolymer-tethered bilayer. Langmuir-Blodgett transfer conditions for depositing monolayers that can be used to create homogeneous, fluid bilayers are also discussed. Finally, the distal leaflet lateral mobility is measured using fluorescence recovery after photobleaching experiments and shown to be a function of the tethering density. A possible model for the mobility data is developed in which the tethered lipids in the proximal leaflet act as immobile lipid obstacles that couple to distal leaflet lipids.

Glyco-acrylate copolymers for bilayer tethering on benzophenone-modified substrates.

Model biological membranes are becoming increasingly important for studying fundamental biophysical phenomena and developing membrane-based devices. To address the anticipated problem of non-physiological interactions between membrane proteins and substrates seen in "solid-supported lipid bilayers" that are formed directly on hydrophilic substrates, we have developed a polymer-tethered lipid bilayer system based on a random copolymer with multiple lipid analogue anchors and a glyco-acrylate backbone. This system is targeted at applications that, most importantly, require stability and robustness since each copolymer has multiple lipid analogues that insert into the bilayer. We have combined this copolymer with a flexible photochemical coupling scheme that covalently attaches the copolymer to the substrate. The Langmuir isotherms of mixed copolymer/free lipid monolayers measured at the air-water interface indicate that the alkyl chains of the copolymer lipid analogues and the free lipids dominate the film behavior. In addition, no significant phase transitions are seen in the isotherms, while hysteresis experiments confirm that no irreversible states are formed during the monolayer compression. Isobaric creep experiments at the air-water interface and AFM experiments of the transferred monolayer are used to guide processing parameters for creating a fluid, homogeneous bilayer. Bilayer homogeneity and fluidity are monitored using fluorescence microscopy. Continuous bilayers with lateral diffusion coefficients of 0.6 microm(2)/s for both leaflets of the bilayer are observed for a 5% copolymer system.

Engineering an arginine catabolizing bioconjugate: Biochemical and pharmacological characterization of PEGylated derivatives of arginine deiminase from Mycoplasma arthritidis.

Arginine is an important metabolite in the normal function of several biological systems, and arginine deprivation has been investigated in animal models and human clinical trials for its effects on inhibition of tumor growth, angiogenesis, or nitric oxide synthesis. In order to design an optimal arginine-catabolizing enzyme bioconjugate, a novel recombinant arginine deiminase (ADI) from Mycoplasma arthritidis was prepared, and multi-PEGylated derivatives were examined for enzymatic and biochemical properties in vitro, as well as pharmacokinetic and pharmacodynamic behavior in rats and mice. ADI bioconjugates constructed with 12 kDa or 20 kDa monomethoxy-poly(ethylene glycol) polymers with linear succinimidyl carbonate linkers were investigated via intravenous, intramuscular, or subcutaneous administration in rodents. The selected PEG-ADI compounds have 22 +/- 2 PEG strands per protein dimer, providing an additional molecular mass of about 0.2-0.5 x 10(6) Da and prolonging the plasma mean residence time of the enzyme over 30-fold in mice. Prolonged plasma arginine deprivation was demonstrated with each injection route for these bioconjugates. Pharmacokinetic analysis employed parallel measurement of enzyme activity in bioassays and enzyme assays and demonstrated a correlation with the pharmacodynamic analysis of plasma arginine concentrations. Either ADI bioconjugate depressed plasma arginine to undetectable levels for 10 days when administered intravenously at 5 IU per mouse, while the subcutaneous and intramuscular routes exhibited only slightly reduced potency. Both bioconjugates exhibited potent growth inhibition of several cultured tumor lines that are deficient in the anabolic enzyme, argininosuccinate synthetase. Investigations of structure-activity optimization for PEGylated ADI compounds revealed a benefit to constraining the PEG size and number of attachments to both conserve catabolic activity and streamline manufacturing of the experimental therapeutics. Specifically, ADI with either 12 kDa or 20 kDa PEG attachments on 33% of the primary amines retained about 60% or 48% of enzyme activity, respectively; the Km and pH profiles were nearly unchanged; IC50 values were diminished by less than 30%; while stability studies demonstrated full retention of activity at 4 degrees C for 5 months. A comparison of the enzymatic properties of a second ADI from Pseudomonas putida illustrated the superior characteristics of the M. arthritidis ADI enzyme.

Influence of mobile phase composition and thermodynamics on the normal phase chromatography of echinocandins.

In the normal phase preparative HPLC of fermentation derived echinocandins, resolution of key impurities from the product of interest, pneumocandin B(o), is accomplished using a ternary ethyl acetate/methanol/water mobile phase with silica gel as the sorbent. In this work, previous characterization of the system is extended to define the impact and role of water content on the separation efficiency and retention of pneumocandin B(o). Experimental results indicate that column efficiency, measured using both the product of interest and small molecule tracers (compounds used for pulse tests), is good despite the use of an irregular silica and unusually high levels (greater than 6%) of water in the mobile phase. In contrast to column efficiency measurements using small molecules (MEK and toluene), measurements performed with the product itself indicate improved efficiency with increasing water content of the mobile phase. Building on these results, a scale-up/scale-down protocol was developed based on measurements of column efficiency using theoretical plate counts determined with pneumocandin B(o). Since the solubility of pneumocandin B(o) in the ternary mobile phase is relatively low, a higher strength solvent with higher levels of methanol and water is employed for dissolution of the crude product at concentrations of up to 40g/L. The mismatch between the high strength solvent used for the feed introduction and the mobile phase has the potential to affect column performance. The impact of this mismatch using plate count measurements with the product at both analytical and semi-preparative scales was found not to be significant. Finally, a van't Hoff analysis was performed to characterize the thermodynamics of adsorption of pneumocandin B(o) on silica. The analysis shows that the adsorption process for pneumocandin B(o) on silica in the ternary solvent system is endothermic (DeltaH(ads)>0), implying that the adsorption is entropically driven. Results from an overall water balance across the column indicate significant enrichment of adsorbed water on the silica surface. These results further emphasize the importance of selective partitioning of water between the bulk mobile phase and the silica as a dominant factor in controlling retention.