Interpeduncular cistern intrathecal targeted drug delivery for intractable postherpetic neuralgia: A case report.

BACKGROUND: Intractable postherpetic neuralgia (PHN) can be difficult to manage even with aggressive multimodal therapies. Patients who experience uncontrolled refractory cranial PHN despite conservative treatment may benefit from an intrathecal drug delivery system (IDDS). For craniofacial neuropathic pain, the traditional approach has been to place the intrathecal catheter tip below the level of the cranial nerve root entry zones, which may lead to insufficient analgesia. CASE SUMMARY: We describe a 69-year-old man with a 1-year history of PHN after developing a vesicular rash in the ophthalmic division of cranial nerve V (trigeminal nerve) distribution. The pain was rated 7-8 at rest and 9-10 at breakthrough pain (BTP) on a numeric rating scale. Despite receiving aggressive multimodal therapies including large doses of oral analgesics (gabapentin 150 mg q12 h, oxycodone 5 mg/acetaminophen 325 mg q6 h, and lidocaine 5% patch 700 mg q12 h) and sphenopalatine ganglion block, there was no relief of pain. Subsequently, the patient elected to have an implantable IDDS with the catheter tip placed at the interpeduncular cistern. The frequency of BTP episodes decreased. The patient's continuous daily dose was adjusted to 0.032 mg/d after 3 mo of follow-up and stopped 5 mo later. He did not report pain or other discomfort at outpatient follow-up 6 mo and 1 year after stopping intracisternal hydromorphone. CONCLUSION: The use of interpeduncular cistern intrathecal infusion with low-dose hydromorphone by IDDS may be effective for severe craniofacial PHN.

Lever arm on bracket vs. lever arm on archwire: A 3D finite element method study of mechanics of miniscrew-supported lingual en-masse retraction of maxillary anterior teeth.

OBJECTIVE: To compare the deformation of the main archwire and 3D movements of maxillary anterior teeth during miniscrew-supported en-masse retraction with the lever arm on the archwire and on the brackets in lingual orthodontic treatment in finite element analysis (FEM) simulation. MATERIAL AND METHODS: A 3D dental-alveolar model with bonded 0.018×0.025-inch slot lingual brackets and a 0.017×0.025-inch dimension stainless-steel archwire was created. Four FEM models were created based on a 3D dental-alveolar model: in Models A and C, the lever arms were attached to the lingual bracket, while in Models B and D, the lever arms were attached to the archwire. Meanwhile, in Models A and B, the miniscrews were placed in between the molars, while in Models C and D, the miniscrews were positioned on the palatal roof. After a 1.5N retraction force was applied from the miniscrew to the end of the lever arm, the initial movements in the sagittal, transversal, and vertical planes were recorded and analysed for maxillary anterior teeth. RESULTS: In Models B and D, smaller deformation of the main archwire and less prominent bowing effect were noticed in both sagittal and vertical directions compared to their counter groups. In Models C and D, the central incisors showed less torque loss in the sagittal direction and more canine intrusion vertically. CONCLUSIONS: For the same lever arm-miniscrew retraction configuration, the lever arm on the bracket showed less deformation of the main archwire and more body movement of the teeth than the lever arm on the archwire group. With the same level arm height, the transverse and vertical bowing effect is reduced when the lever arm was placed distal to the central incisor and the miniscrews placed next to the palatal suture.

3D printed PEKK bone analogs with internal porosity and surface modification for mandibular reconstruction: An in vivo rabbit model study.

Polyetheretherketone (PEEK) and its derivative polyetherketoneketone (PEKK) have been used as implant materials for spinal fusing and enjoyed their success for many years because of their mechanical properties similar to bone and their chemical inertness. The osseointegration of PEEKs is datable. Our strategy was to use custom-designed and 3D printed bone analogs with an optimized structure design and a modified PEKK surface to augment bone regeneration for mandibular reconstruction. Those bone analogs had internal porosities and a bioactive titanium oxide surface coating to promote osseointegration between native bone and PEKK analogs. Our workflow was 3D modeling, bone analog designing, structural optimization, mechanical analysis via finite element modeling, 3D printing of bone analogs and subsequently, an in vivo rabbit model study on mandibular reconstruction and histology evaluation. Our results showed the finite element analysis validated that the porous PEKK analogs provided a mechanical-sound structure for functional loadings. The bone analogs offered a perfect replacement for segmented bones in the terms of shape, form and volume for surgical reconstruction. The in vivo results showed that bioactive titanium oxide coating enhanced new bone in-growth into the porous PEKK analogs. We have validated our new approach in surgical mandibular reconstruction and we believe our strategy has a significant potential to improve mechanical and biological outcomes for patients who require mandibular reconstruction procedures.

Experimental validation of a new model for mandibular motions.

Long-term excessive forces loading from muscles of mastication during mandibular motions may result in disorders of temporomandibular joint (TMJ), myofascial pain, and restriction of jaw opening and closing. Current analysis of mandibular movements is generally conducted with a single opening, protrusive and lateral movements rather than composite motions that the three can be combined arbitrarily. The objective of this study was to construct theoretical equations reflecting the correlation between composite motions and muscle forces, and consequently to analyze the mandibular composite motions and the tensions of muscles of mastication in multiple dimensions. The muscle performances such as strength, power, and endurance of mandibular motions were analyzed and the effective motion range of each muscle was derived. The mandibular composite motion model was simplified by calculating muscle forces. An orthogonal rotation matrix based on muscle forces was established. A 3D printed mandible was used for in vitro simulation of mandibular motions on a robot and measurements of force were conducted. The theoretical model and forces were verified through a trajectory tracing experiment of mandibular motions driven by a 6-axis robot with force/torque sensors. Through the analysis of the mandibular composite motion model, the motion form was obtained and transferred to guide the motions of the robot. The error between the experimental data obtained by the 6-axis force/torque sensors and the theoretical data was within 0.6 N. Our system provides excellent visualization for analyzing the changes of muscle forces and locations during various mandibular movements. It is useful for clinicians to diagnose and formulate treatment for patients who suffer from (temporomandibular joint disorders) TMDs and restrict jaw movements. The system can potentially offer the comparison before and after treatment of TMDs or jaw surgery.

The Clinical Significance of Detecting Blood Supply to the Inferior Parathyroid Gland Based on the "Layer of Thymus-Blood Vessel-Inferior Parathyroid Gland" Concept.

Objective: How to preserve the inferior parathyroid gland (IPTG) in situ during central neck dissection (CND) is the major concern of thyroid surgeons. The "layer of thymus-blood vessel-IPTG" (TBP layer) concept showed to be effective in preserving IPTG. The objective of this study was to identify the origin and course of blood supply to IPTG (IPBS) within the TBP layer and to take key points of operation during CND. Design: This is a retrospective control study. Participants. Patients who underwent thyroidectomy plus CND using the TBP layer concept and conventional technique between 2017 and 2019 were enrolled. Measurements. The origin and course of IPBS in relation to recurrent laryngeal nerve (RLN) and thymus and prevalence of hypoparathyroidism were detected. Results: A total of 71.3% of IPTGs (251 of 352) were supplied by ITA branches, defined as type A. Type A was further divided into Types A1 (branches of ITA, coursing laterally to the RLN (53.1%, 187 of 352)) and A2 (branches of ITA, traversing medially to the RLN (18.2%, 64 of 352)). Type A2 was more common on the right side than on the left side (P < 0.001). Fifty-five (15.6%) IPTG feeding vessels originated from the thymus or mediastinum. Nineteen (5.4%) IPTGs were supplied by branches of the superior thyroid artery. The incidence of transient hypoparathyroidism decreased from 45.7% to 3.6% (P < 0.001), in the TBP layer group compared with the conventional technique group. Conclusion: The origin and course of IPBS follow a definite pattern. This mapping and precautions help surgeons optimize intraoperative manipulations for better preservation of IPBS during CND.

3D-printed porous condylar prosthesis for temporomandibular joint replacement: Design and biomechanical analysis.

BACKGROUND: Customized prosthetic joint replacements have crucial applications in severe temporomandibular joint problems, and the combined use of porous titanium scaffold is a potential method to rehabilitate the patients. OBJECTIVE: The objective of the study was to develop a design method to obtain a titanium alloy porous condylar prosthesis with good function and esthetic outcomes for mandibular reconstruction. METHODS: A 3D virtual mandibular model was created from CBCT data. A condylar defect model was subsequently created by virtual condylectomy on the initial mandibular model. The segmented condylar defect model was reconstructed by either solid or porous condyle with a fixation plate. The porous condyle was created by a density-driven modeling scheme with an inhomogeneous tetrahedral lattice structure. The porous condyle, supporting fixation plate, and screw locations were topologically optimized. Biomechanical behaviors of porous and solid condylar prostheses made of Ti-6Al-4V alloy were compared. Finite element analysis (FEA) was used to evaluate maximum stress distribution on both prostheses and the remaining mandibular ramus. RESULTS: The FEA results showed levels of maximum stresses were 6.6%, 36.4% and 47.8% less for the porous model compared to the solid model for LCI, LRM, and LBM loading conditions. Compared to the solid prosthesis, the porous prosthesis had a weight reduction of 57.7% and the volume of porosity of the porous condyle was 65% after the topological optimization process. CONCLUSIONS: A custom-made porous condylar prosthesis with fixation plate was designed in this study. The 3D printed Ti-6Al-4V porous condylar prosthesis had reduced weight and effective modulus of elasticity close to that of cortical bone. The.

Biomechanical behavior of mandible with posterior marginal resection using finite element analysis.

This study aims to characterize biomechanical behavior of various designs of posterior mandibular marginal resection under functional loadings using finite element method. The ultimate goal of this work is to provide clinically relevant information to prevent postoperative fracture and to stipulate prophylactic internal fixation for planning of marginal mandibulectomy. A 3D mandibular master model was reconstructed from cone beam computed tomography images. Different marginal resection models were created based on three design parameters, namely, defect curvilinear radius, anterior-posterior defect width and residual height of the mandibular body. Functional loadings from incisors (60 N) and contralateral first molar area (200 N) were applied to designed models and stress patterns were compared of five groups with curvilinear radius from 0 (conventional rectangular shape), 2.5, 3.5, 5, and 6 mm. Models with 25, 35 and 45 mm defect width mimic defects varied from canine to 3rd molar were tested. Residual height range from 10 to 4 mm was assessed. The results show high stresses predominated in the occlusal area and the posterior inferior border near the resection corner. The average maximum stress decreased by 29.8% (r = 2.5 mm), 51.9% (r = 3.5 mm), 54.4% (r = 5 mm), and 59.3% (r = 6 mm) compared to the baseline of r = 0 mm. The results from the combined defect width/residual height models demonstrate the increase of defect width and the decrease in residual height resulted in the increase of maximum stress. Our data also confirm that the factor of residual height supersedes defect width in terms of prevention of postoperative fracture when considering resection design.

Evaluation of a custom-designed human-robot collaboration control system for dental implant robot.

BACKGROUND: The purpose of this study is to develop a methodology to better control a human-robot collaboration for robotic dental implant placement. We have designed a human-robot collaborative implant system (HRCDIS) which is based on a zero-force hand-guiding concept and a operational task management workflow that can achieve highly accurate and stable osteotomy drilling based on a surgeon's decision and robotic arm movements during implant surgery. METHOD: The HRCDIS brings forth the robot arm positions, exact drilling location, direction and performs automatic drilling. The HRCDIS can also avoid complex programing in the robot. The purpose of the study is to evaluate the accuracy of drilling resulting from our developed operational task management method (OTMM). The OTMM can enable the robot to switch, pause, and resume drilling tasks. The force required for hand-guiding in a zero-force control mode of the robot was detected by a 6D force sensor. We compared our force data to those provided by the manufacturer's manual. The study was conducted on a phantom head with a 3D-printed jaw bone to verify the validity of our HRCDIS. We appraised the discrepancies between free-hand drillings and the HRCDIS controlled drillings at apical centre and head centre of the implant and implant angulation to the baseline data from a virtual surgical planning model. RESULTS: The average required force used by hand-guiding to operate the robot with HRCDIS was near 7 Newton which is much less than the manufacturer's specification (30 Newton). The results from our study showed that the average error at implant head was 1.04 ± 0.37 mm, 1.56 ± 0.52 mm at the implant apex, and deviation of implant angle was 3.74 ± 0.67°. CONCLUSIONS: The results from this study validate the merit of the human-robot collaboration control by the HRCDIS. Based on the improved navigation system using HRCDIS, a robotic implant placement can provide seamless drilling with ease, efficiency and accuracy.

Biomechanical and Mechanostat analysis of a titanium layered porous implant for mandibular reconstruction: The effect of the topology optimization design.

A porous scaffold/implant is considered a potential method to repair bone defects, but its mechanical stability and biomechanics during the repair process are not yet clear. A mandibular titanium implant was proposed and designed with layered porous structures similar to that of the bone tissue, both in structure and mechanical properties. Topology was used to optimize the design of the porous implant and fixed structure. The finite element analysis was combined with bone "Mechanostat" theory to evaluate the stress and osteogenic property of the layered porous implant with 3 different fixation layouts (Model I with 4 screws, Model II with 5 screws and Model III with 6 screws) for mandibular reconstruction. The results showed that Model III could effectively reduce the stress shielding effect, stress within the optimized implant, defective mandible, and screws were respectively dropped 48.18%, 44.23%, and 57.27% compared to Model I, and the porous implant had a significant stress transmission effect and maintained the same stress distribution as the intact mandible after the mandibular defect was repaired. The porous implant also showed a significant mechanical stimulation effect on the growth and healing of the bone tissue according to the bone "Mechanostat" theory. The combination of porous structure with the topology technique is a promising option to improve the mechanical stability and osteogenesis of the implant, and could provide a new solution for mandibular reconstruction.

Experimental validation of finite element simulation of a new custom-designed fixation plate to treat mandibular angle fracture.

BACKGROUND: The objective of the study was to validate biomechanical characteristics of a 3D-printed, novel-designated fixation plate for treating mandibular angle fracture, and compare it with two commonly used fixation plates by finite element (FE) simulations and experimental testing. METHODS: A 3D virtual mandible was created from a patient's CT images as the master model. A custom-designed plate and two commonly used fixation plates were reconstructed onto the master model for FE simulations. Modeling of angle fracture, simulation of muscles of mastication, and defining of boundary conditions were integrated into the theoretical model. Strain levels during different loading conditions were analyzed using a finite element method (FEM). For mechanical test design, samples of the virtual mandible with angle fracture and the custom-designed fixation plates were printed using selective laser sintering (SLS) and selective laser melting (SLM) printing methods. Experimental data were collected from a testing platform with attached strain gauges to the mandible and the plates at different 10 locations during mechanical tests. Simulation of muscle forces and temporomandibular joint conditions were built into the physical models to improve the accuracy of clinical conditions. The experimental vs the theoretical data collected at the 10 locations were compared, and the correlation coefficient was calculated. RESULTS: The results show that use of the novel-designated fixation plate has significant mechanical advantages compared to the two commonly used fixation plates. The results of measured strains at each location show a very high correlation between the physical model and the virtual mandible of their biomechanical behaviors under simulated occlusal loading conditions when treating angle fracture of the mandible. CONCLUSIONS: Based on the results from our study, we validate the accuracy of our computational model which allows us to use it for future clinical applications under more sophisticated biomechanical simulations and testing.

Accuracy of dental implant surgery with robotic position feedback and registration algorithm: An in-vitro study.

BACKGROUND: The purpose of this study was to develop and validate a positioning method with hand-guiding and contact position feedback of robot based on a human-robot collaborative dental implant system (HRCDIS) for robotic guided dental implant surgery. METHODS: An HRCDIS was developed based on a light-weight cooperative robot arm, UR5. A three-dimensional (3D) virtual partially edentulous mandibular bone was reconstructed using the cone bone computed tomography images. After designing the preoperative virtual implant planning using the computer software, a fixation guide worn on teeth for linking and fixing positioning marker was fabricated by 3D printing. The fixation guide with the positioning marker and a resin model mimicking the oral tissues were assembled on a head phantom. The planned implant positions were derived by the coordinate information of the positioning marker. The drilling process using the HRCDIS was conducted after mimicking the experimental set-up and planning the drilling trajectory. Deviations between actual and planned implant positions were measured and analyzed. RESULTS: The head phantom experiments results showed that the error value of the central deviation at hex (refers to the center of the platform level of the implant) was 0.79 ± 0.17 mm, central deviation at the apex was 1.26 ± 0.27 mm, horizontal deviation at the hex was 0.61 ± 0.19 mm, horizontal deviation at the apex was 0.91 ± 0.55 mm, vertical deviation at the hex was 0.38 ± 0.17 mm, vertical deviation at the apex was 0.37 ± 0.20 mm, and angular deviation was 3.77 ± 1.57°. CONCLUSIONS: The results from this study preliminarily validate the feasibility of the accurate navigation method of the HRCDIS.

Topological optimization of 3D printed bone analog with PEKK for surgical mandibular reconstruction.

PURPOSE: The purpose of this study was to analyze mechanical behaviors of a topologically optimized and 3D-printed mandibular bone block with polyetherketoneketone (PEKK) for surgical mandibular reconstruction. MATERIALS AND METHODS: 3D virtual mandibular models were reconstructed from cone beam computed tomography images. A proposed mandibular resection of the mandibular body (40 mm anterior-posteriorly) was segmented. Internal structure of the resected bone was designed with topological optimization. Dental implants and implant-supported crowns were integrated into the design. A second 3D virtual model was created with the same size and location of the defect but was reconstructed with a fibular graft and implant-supported crowns. The biomechanical behaviors of the two models were compared by finite element method (FEM) under the same boundary constraints and three loading locations, namely, central incisors, lower left and right side first molar areas. RESULTS: The FEM results showed the maximum stresses and displacements of the topology optimized model were much lower than those of the model with fibular bone graft. The highest stress of the optimized mandibular model was located on the lower edge of the posterior border of bone analog, and fixation screws. The maximum displacement occurred at the lower edge of the proximal mandibular stump or the lower edge of the distal mandibular body on the contralateral site. Under the same three loading locations, the maximum stress of the optimized model significantly decreased by 67.9%, 71.9% and 68.6% compared to the fibular graft model. CONCLUSIONS: The 3D printed bone analog with topological optimization is patient-specific and has advantages over the conventional fibular bone graft for surgical mandibular reconstruction. The optimized PEKK bone analog model creates more normal stress-strain trajectories than the fibular graft model and likely provides better functional and cosmetic outcomes.

Bionic mechanical design and 3D printing of novel porous Ti6Al4V implants for biomedical applications.

In maxillofacial surgery, there is a significant need for the design and fabrication of porous scaffolds with customizable bionic structures and mechanical properties suitable for bone tissue engineering. In this paper, we characterize the porous Ti6Al4V implant, which is one of the most promising and attractive biomedical applications due to the similarity of its modulus to human bones. We describe the mechanical properties of this implant, which we suggest is capable of providing important biological functions for bone tissue regeneration. We characterize a novel bionic design and fabrication process for porous implants. A design concept of "reducing dimensions and designing layer by layer" was used to construct layered slice and rod-connected mesh structure (LSRCMS) implants. Porous LSRCMS implants with different parameters and porosities were fabricated by selective laser melting (SLM). Printed samples were evaluated by microstructure characterization, specific mechanical properties were analyzed by mechanical tests, and finite element analysis was used to digitally calculate the stress characteristics of the LSRCMS under loading forces. Our results show that the samples fabricated by SLM had good structure printing quality with reasonable pore sizes. The porosity, pore size, and strut thickness of manufactured samples ranged from (60.95± 0.27)% to (81.23±0.32)%, (480±28) to (685±31) µm, and (263±28) to (265±28) µm, respectively. The compression results show that the Young's modulus and the yield strength ranged from (2.23±0.03) to (6.36±0.06) GPa and (21.36±0.42) to (122.85±3.85) MPa, respectively. We also show that the Young's modulus and yield strength of the LSRCMS samples can be predicted by the Gibson-Ashby model. Further, we prove the structural stability of our novel design by finite element analysis. Our results illustrate that our novel SLM-fabricated porous Ti6Al4V scaffolds based on an LSRCMS are a promising material for bone implants, and are potentially applicable to the field of bone defect repair.

Anatomical localization of normal parathyroid glands before thyroidectomy through ultrasonography reduces postoperative hypoparathyroidism.

Postoperative hypoparathyroidism due to dysfunction of the parathyroid gland is the most common complication after thyroidectomy. Our objective was to introduce the method of anatomical localization of normal parathyroid glands before thyroidectomy through ultrasonography and to evaluate its efficiency. The study group included 52 patients subjected to anatomical localization of the parathyroid gland prethyroidectomy through ultrasonography. The control group included 52 sex- and age-matched patients without parathyroid gland localization. The proportion of parathyroid glands preserved in situ and postoperative hypoparathyroidism rates in the 2 groups were compared. The rates of normal parathyroid glands identified according to ultrasonography for left superior, left inferior, right superior, and right inferior glands were 78.8%, 90.4%, 57.7%, and 82.7%, respectively. The rate of parathyroid gland excised inadvertently was significantly decreased (P = .038) in the study group as compared with the control group. The rates of parathyroid gland preservation in situ were significantly improved in the left superior (P = .001), left inferior (P = .002), and right inferior glands (P = .005). Furthermore, the incidence of transient hypoparathyroidism decreased significantly (P = .028). Our study indicated that normal parathyroid glands were identified by ultrasonography, and the anatomical localization improved the rate of parathyroid gland preservation in situ and decreased the incidence of transient hypoparathyroidism.

Biomechanical behavior of mandibles reconstructed with fibular grafts at different vertical positions using finite element method.

BACKGROUND: For large mandibular defects, surgical reconstruction using microvascular fibular grafts has advantages over other alternatives in terms of blood supply and good quality of grafted bone. However, the fibular segment is usually lower in height than that of the original mandible, meaning that the vertical positioning of the fibular graft is variable, with different biomechanical consequences on the reconstructed mandible. OBJECTIVES: To use finite element method (FEM) to evaluate stress distribution and displacement of a reconstructed mandible versus an intact mandible under occlusal loads. METHODS: A three-dimensional intact edentulous mandibular bone (Model I) and a reconstructed mandible bone with fibular graft were created from CBCT images. Calculation models were generated with fibular bone graft extracted from the reconstructed mandible of identical length placed into a mimicked defect area on the right-hand side of the mandible at three different vertical positions: superior (Model II), intermediate (Model III), and inferior (Model IV). Forces were applied at lower left first molar region and lower left central incisor area. Von Mises stresses and mandibular displacement were calculated as outcome measurements during loadings. RESULTS: Maximum stress and strain within the reconstructed mandible were identified at the posterior border of the graft and the contralateral condyle. Maximum displacement occurred near the interface of fibular graft and anterior segment of the mandible. Stress distribution in the graft under functional loads is much higher than that in the residual mandibular segments from Models II to IV. The combined average maximum stress from anterior and posterior loads is 10.66 times higher in the mandible with inferiorly positioned graft (Model IV), 8.72 times for superior graft (Model II), and 3.68 times for intermediate graft (Model III) than that in the control group (Model I). The worst displacement result during functional loadings was in the group with fibular graft located at the inferior border of the mandible. CONCLUSIONS: The position of fibular graft placed in the surgical resection site has significant effects on the mechanical behavior of the reconstructed mandible. The fibular graft aligned with the inferior border of the mandible, the most common site designated location by clinicians, has the worst effects on the stress distribution and displacement to the mandibular under functional loads. The fibular graft placed at the intermediate location has the best biomechanics and provides favorable condition for subsequent prosthetic reconstruction.

Exendin-4 inhibits high-altitude cerebral edema by protecting against neurobiological dysfunction.

The anti-inflammatory and antioxidant effects of exendin-4 (Ex-4) have been reported previously. However, whether (Ex-4) has anti-inflammatory and antioxidant effects on high-altitude cerebral edema (HACE) remains poorly understood. In this study, two rat models of HACE were established by placing rats in a hypoxic environment with a simulated altitude of either 6000- or 7000-m above sea level (MASL) for 72 hours. An altitude of 7000 MASL with 72-hours of hypoxia was found to be the optimized experimental paradigm for establishing HACE models. Then, in rats where a model of HACE was established by introducing them to a 7000 MASL environment with 72-hours of hypoxia treatment, 2, 10 and, 100 µg of Ex-4 was intraperitoneally administrated. The open field test and tail suspension test were used to test animal behavior. Routine methods were used to detect change in inflammatory cells. Hematoxylin-eosin staining was performed to determine pathological changes to brain tissue. Wet/dry weight ratios were used to measure brain water content. Evans blue leakage was used to determine blood-brain barrier integrity. Enzyme-linked immunosorbent assay (ELISA) was performed to measure markers of inflammation and oxidative stress including superoxide dismutase, glutathione, and malonaldehyde values, as well as interleukin-6, tumor necrosis factor-alpha, cyclic adenosine monophosphate levels in the brain tissue. Western blot analysis was performed to determine the levels of occludin, ZO-1, SOCS-3, vascular endothelial growth factor, EPAC1, nuclear factor-kappa B, and aquaporin-4. Our results demonstrate that Ex-4 preconditioning decreased brain water content, inhibited inflammation and oxidative stress, alleviated brain tissue injury, maintain blood-brain barrier integrity, and effectively improved motor function in rat models of HACE. These findings suggest that Ex-4 exhibits therapeutic potential in the treatment of HACE.

Variation in the degree of reciprocal herkogamy affects the degree of legitimate pollination in a distylous species.

Distyly is a widespread floral polymorphism characterized by the flowers within a population showing reciprocal placement of the anthers and stigma. Darwin hypothesizes that distyly evolves to promote precise pollen transfer between morphs. Primula chungensis exhibits two types of anther heights, and these two types of anthers show pollen of two different size classes. To understand whether the stigma could capture more pollen grains from the anthers of the pollen donor as the separation between the stigma of pollen receiver and the anther of pollen donor decreased, the present research assessed the source of the pollen load in a series of open-pollinated flowers with continuous variation of style lengths. Individuals with continuous variation of style length were tagged, and the selected flowers in the tagged plants were emasculated the day before dehiscence. The stigma of the emasculated flowers was fixed in fuchsin gel at the end of blooming. We assessed the pollen sources on each stigma by taking photos under a microscope and measured the diameter of each conspecific pollen grain with ImageJ. We found that a shorter distance from the stigmas to the anthers of a pollen donor gave the flower a higher capacity to receive pollen from those anthers. Our result provides a new evidence that distyly could promote the pollen transfer between morphs, which is consistent with Darwin's hypothesis of disassortative pollination. An alternative hypothesis for the evolution of distyly (e.g. selfing avoidance) might also be true, but less likely, because self-incompatibility would greatly avoid self-fertilization for many distylous species.

Correlation between the timing of autonomous selfing and floral traits: a comparative study from three selfing Gentianopsis species (Gentianaceae).

About 20% of angiosperms employ self-fertilization as their main mating strategy. In this study, we aimed to examine how the selfing timing correlated with floral traits in three Gentianopsis species in which autonomous selfing is achieved through filament elongation. Although the three Gentianopsis species exhibit no significant variation in their capacity for autonomous selfing, flowers of G. grandis last longer, are larger and have a higher corolla biomass, P/O ratios and male biomass allocation than those of G. paludosa, and especially those of G. contorta. Autonomous selfing occurs in the early floral life of G. paludosa and G. contorta and in the later floral life of G. grandis. Seed production mainly results from autonomous selfing in G. paludosa and G. contorta; however, G. grandis could be more described as having a mixed mating system. We suggest that autonomous selfing in later floral life increases the chance of cross-pollination prior to this, while autonomous selfing in early floral life offers a selective advantage to plants by reducing the resource investment in traits that may increase pollinator attraction and visitation.

A finite element analysis of the stress distribution to the mandible from impact forces with various orientations of third molars.

OBJECTIVE: To investigate the stress distribution to the mandible, with and without impacted third molars (IM3s) at various orientations, resulting from a 2000-Newton impact force either from the anterior midline or from the body of the mandible. MATERIALS AND METHODS: A 3D mandibular virtual model from a healthy dentate patient was created and the mechanical properties of the mandible were categorized to 9 levels based on the Hounsfield unit measured from computed tomography (CT) images. Von Mises stress distributions to the mandibular angle and condylar areas from static impact forces (Load I-front blow and Load II left blow) were evaluated using finite element analysis (FEA). Six groups with IM3 were included: full horizontal bony, full vertical bony, full 450 mesioangular bony, partial horizontal bony, partial vertical, and partial 450 mesioangular bony impaction, and a baseline group with no third molars. RESULTS: Von Mises stresses in the condyle and angle areas were higher for partially than for fully impacted third molars under both loading conditions, with partial horizontal IM3 showing the highest fracture risk. Stresses were higher on the contralateral than on the ipsilateral side. Under Load II, the angle area had the highest stress for various orientations of IM3s. The condylar region had the highest stress when IM3s were absent. CONCLUSIONS: High-impact forces are more likely to cause condylar rather than angular fracture when IM3s are missing. The risk of mandibular fracture is higher for partially than fully impacted third molars, with the angulation of impaction having little effect on facture risk.

A customized fixation plate with novel structure designed by topological optimization for mandibular angle fracture based on finite element analysis.

BACKGROUND: The purpose of this study was to design a customized fixation plate for mandibular angle fracture using topological optimization based on the biomechanical properties of the two conventional fixation systems, and compare the results of stress, strain and displacement distributions calculated by finite element analysis (FEA). METHODS: A three-dimensional (3D) virtual mandible was reconstructed from CT images with a mimic angle fracture and a 1 mm gap between two bone segments, and then a FEA model, including volume mesh with inhomogeneous bone material properties, three loading conditions and constraints (muscles and condyles), was created to design a customized plate using topological optimization method, then the shape of the plate was referenced from the stress concentrated area on an initial part created from thickened bone surface for optimal calculation, and then the plate was formulated as "V" pattern according to dimensions of standard mini-plate finally. To compare the biomechanical behavior of the "V" plate and other conventional mini-plates for angle fracture fixation, two conventional fixation systems were used: type A, one standard mini-plate, and type B, two standard mini-plates, and the stress, strain and displacement distributions within the three fixation systems were compared and discussed. RESULTS: The stress, strain and displacement distributions to the angle fractured mandible with three different fixation modalities were collected, respectively, and the maximum stress for each model emerged at the mandibular ramus or screw holes. Under the same loading conditions, the maximum stress on the customized fixation system decreased 74.3, 75.6 and 70.6% compared to type A, and 34.9, 34.1, and 39.6% compared to type B. All maximum von Mises stresses of mandible were well below the allowable stress of human bone, as well as maximum principal strain. And the displacement diagram of bony segments indicated the effect of treatment with different fixation systems. CONCLUSIONS: The customized fixation system with topological optimized structure has good biomechanical behavior for mandibular angle fracture because the stress, strain and displacement within the plate could be reduced significantly comparing to conventional "one mini-plate" or "two mini-plates" systems. The design methodology for customized fixation system could be used for other fractures in mandible or other bones to acquire better mechanical behavior of the system and improve stable environment for bone healing. And together with SLM, the customized plate with optimal structure could be designed and fabricated rapidly to satisfy the urgent time requirements for treatment.