Piton: Investigating the Controllability of a Wearable Telexistence Robot.

The COVID-19 pandemic impacted collaborative activities, travel, and physical contact, increasing the demand for real-time interactions with remote environments. However, the existing remote communication solutions provide limited interactions and do not convey a high sense of presence within a remote environment. Therefore, we propose a snake-shaped wearable telexistence robot, called Piton, that can be remotely used for a variety of collaborative applications. To the best of our knowledge, Piton is the first snake-shaped wearable telexistence robot. We explain the implementation of Piton, its control architecture, and discuss how Piton can be deployed in a variety of contexts. We implemented three control methods to control Piton: HM-using a head-mounted display (HMD), HH-using an HMD and hand-held tracker, and FM-using an HMD and a foot-mounted tracker. We conducted a user study to investigate the applicability of the proposed control methods for telexistence, focusing on body ownership (Alpha IVBO), mental and physical load (NASA-TLX), motion sickness (VRSQ), and a questionnaire to measure user impressions. The results show that both the HM and HH provide relevantly high levels of body ownership, had high perceived accuracy, and were highly favored, whereas the FM control method yielded the lowest body ownership effect and was least favored. We discuss the results and highlight the advantages and shortcomings of the control methods with respect to various potential application contexts. Based on our design and evaluation of Piton, we extracted a number of insights and future research directions to deepen our investigation and realization of wearable telexistence robots.

Synthesis and preclinical evaluation of [11C]MTP38 as a novel PET ligand for phosphodiesterase 7 in the brain.

PURPOSE: Phosphodiesterase (PDE) 7 is a potential therapeutic target for neurological and inflammatory diseases, although in vivo visualization of PDE7 has not been successful. In this study, we aimed to develop [11C]MTP38 as a novel positron emission tomography (PET) ligand for PDE7. METHODS: [11C]MTP38 was radiosynthesized by 11C-cyanation of a bromo precursor with [11C]HCN. PET scans of rat and rhesus monkey brains and in vitro autoradiography of brain sections derived from these species were conducted with [11C]MTP38. In monkeys, dynamic PET data were analyzed with an arterial input function to calculate the total distribution volume (VT). The non-displaceable binding potential (BPND) in the striatum was also determined by a reference tissue model with cerebellar reference. Finally, striatal occupancy of PDE7 by an inhibitor was calculated in monkeys according to changes in BPND. RESULTS: [11C]MTP38 was synthesized with radiochemical purity ≥99.4% and molar activity of 38.6 ± 12.6 GBq/µmol. Autoradiography revealed high radioactivity in the striatum and its reduction by non-radiolabeled ligands, in contrast with unaltered autoradiographic signals in other regions. In vivo PET after radioligand injection to rats and monkeys demonstrated that radioactivity was rapidly distributed to the brain and intensely accumulated in the striatum relative to the cerebellum. Correspondingly, estimated VT values in the monkey striatum and cerebellum were 3.59 and 2.69 mL/cm3, respectively. The cerebellar VT value was unchanged by pretreatment with unlabeled MTP38. Striatal BPND was reduced in a dose-dependent manner after pretreatment with MTP-X, a PDE7 inhibitor. Relationships between PDE7 occupancy by MTP-X and plasma MTP-X concentration could be described by Hill's sigmoidal function. CONCLUSION: We have provided the first successful preclinical demonstration of in vivo PDE7 imaging with a specific PET radioligand. [11C]MTP38 is a feasible radioligand for evaluating PDE7 in the brain and is currently being applied to a first-in-human PET study.

Development and Evaluation of a Treadmill-based Video-see-through and Optical-see-through Mixed Reality Systems for Obstacle Negotiation Training.

Mixed reality (MR) technologies have a high potential to enhance obstacle negotiation training beyond the capabilities of existing physical systems. Despite such potential, the feasibility of using MR for obstacle negotiation on typical training treadmill systems and its effects on obstacle negotiation performance remains largely unknown. This research bridges this gap by developing an MR obstacle negotiation training system deployed on a treadmill, and implementing two MR systems with a video see-through (VST) and an optical see-through (OST) Head Mounted Displays (HMDs). We investigated the obstacle negotiation performance with virtual and real obstacles. The main outcomes show that the VST MR system significantly changed the parameters of the leading foot in cases of Box obstacle (approximately 22 cm to 30 cm for stepping over 7cm-box), which we believe was mainly attributed to the latency difference between the HMDs. In the condition of OST MR HMD, users tended to not lift their trailing foot for virtual obstacles (approximately 30 cm to 25 cm for stepping over 7cm-box). Our findings indicate that the low-latency visual contact with the world and the user's body is a critical factor for visuo-motor integration to elicit obstacle negotiation.

Venous architecture of the glabellar to the forehead region.

The precise venous anatomy of the glabellar to the forehead region remains unknown. This study aimed to detail the venous architecture of the glabellar region to the forehead in conjunction with that of the supratrochlear artery to reduce the risk of venous congestion of flaps in this area. Fifteen fresh human cadavers were examined here. In five specimens, contrast medium was injected only into the venous system; in 10 specimens, two different types of contrast media were injected into the arterial and venous systems, respectively. A total of 30 hemifacial specimens were radiographed stereoscopically and observed microscopically. In all the cadavers, a distinct vein (termed as the "transverse nasal root vein") connected the bilateral angular veins. One or two large ascending veins branched from the transverse nasal root or angular vein, coursing toward the forehead skin. Numerous small veins branched out from the large ascending vein(s), forming a subdermal polygonal venous network. Small ascending veins arose from this network and coursed toward the dermis, draining venous flow from the dermis. Three different-sized valves prevented the reflux of blood in the venous pathway. The large ascending vein(s) and supratrochlear artery ran parallel only in the medial canthal area. Tiny venous vasa vasorum surrounded the adventitia of the supratrochlear artery and anastomosed with the polygonal venous network, while a few small veins from the vasa vasorum ascended toward the dermis. Understanding the venous architecture of this region is expected to facilitate the safe elevation of various flaps in the area.

Palatoplasty for bilateral oblique cleft of the soft palate accompanied by Tessier number 5·7 cleft.

Craniofacial cleft is a rare congenital deformity in which there are fissures of a facial structure classified by Tessier. A palatoplasty to reconstruct the muscle sling and to close the cleft of the velum was performed. Acceptable postoperative appearance of the velum was seen after 6 months. Although further follow-up is still needed for velopharyngeal function, this case report provides details of the anatomical deformities and our surgical approach to this atypical bilateral cleft palate.

MMP-13 plays a role in keratinocyte migration, angiogenesis, and contraction in mouse skin wound healing.

Matrix metalloproteinases (MMPs) have been implicated in wound healing. To analyze the roles of MMP-9 and MMP-13 in wound healing, we generated full-thickness cutaneous wounds in MMP-9 knockout (KO), MMP-13 KO, MMP-9/13 double KO, and wild-type mice. Macroscopic wound closure was delayed in all of the KO mice, as compared with wild-type mice. The rate of re-epithelialization was significantly delayed in MMP-9 KO and MMP-13 KO mice and remarkably delayed in MMP-9/13 double KO mice, as compared with wild-type mice. Both MMP-9 and MMP-13 were expressed by the leading edges of epidermal cells in wild-type mice, and the migration of keratinocytes was suppressed by treatment with an MMP inhibitor or transfection of small interfering RNAs for MMP-9 or MMP-13, as compared with controls. The vascular density in wound granulation was significantly lower in both MMP-13 KO and MMP-9/13 double KO mice than in wild-type mice. Degradation of connective tissue growth factor in wound tissue was transiently prevented in MMP-13 KO mice. Morphometric analyses demonstrated a reduction in both wound contraction and myofibroblast formation in both MMP-13 KO and MMP-9/13 double KO mice. Proliferation and transforming growth factor-beta1-induced myofibroblast differentiation of dermal fibroblasts from MMP-13 KO mice were decreased, as compared with wild-type dermal fibroblasts. These data suggest that MMP-13 plays a role in keratinocyte migration, angiogenesis, and contraction in wound healing, while MMP-9 functions in keratinocyte migration.

Management of craniofacial hyperostosis in Proteus syndrome.

Proteus syndrome is a rare congenital hamartomatous condition that is characterized by a wide range of malformations, occasionally involving the head and the face. Skin and skeletal developmental malformations are common and may be manifested in significant physical anomalies. In this report, we describe the cases of 2 patients affected by this condition. For one patient, a recurrence occurred 4 years after the elimination of cranial hyperostosis. In the second patient, although we observed macrosomia and peculiar countenance in the context of craniofacial hyperostosis, the patient did not visit a clinic for approximately 50 years before seeking treatment. The management of the craniofacial involvement is described, and a literature overview is presented.

A rare case of proboscis lateralis with median cleft lip.

A very rare case of proboscis lateralis is reported. This case is different from previously reported cases due to proboscis lateralis, single nostril, loss of columella, and median cleft lip without holoprosencephaly. In addition, this is considered the first surviving individual with proboscis lateralis accompanied by median cleft lip.

Pyrazolo[4,3-d]pyrimidine Derivatives as a Novel Hypoxia-Inducible Factor Prolyl Hydroxylase Domain Inhibitor for the Treatment of Anemia.

Inhibition of hypoxia-inducible factor prolyl hydroxylase domain (HIF-PHD) promotes erythropoietin (EPO) production by stabilizing the HIFα subunit. Thieno[2,3-d]pyrimidine 8 identified based on X-ray crystal structure analysis was optimized to lead to the discovery of pyrazolo[4,3-d]pyrimidine 13 as the lead compound of orally bioavailable HIF-PHD inhibitors. Conversion of the benzyl moiety in 13 gave pyrazolopyrimidine 19 with high solubility and bioavailability, which increased hemoglobin levels in anemic model rats after repeated oral administration. It was shown that pyrazolo[4,3-d]pyrimidine derivatives are promising therapeutic agents for renal anemia through the inhibition of HIF-PHD.

A new method to quantify subtle morphological deformities in nasal profile curvatures and its application for analysis of unilateral cleft lip noses.

OBJECTIVE: The authors conducted the present study to elucidate what elements characterize the nasal profiles of patients with unilateral cleft lips (CLs). MATERIALS AND METHODS: A total of 40 Japanese unilateral CL patients were studied. For each patient, the nasal profile curve was traced on three-dimensional computer tomography image. Then four points were marked on the contour. The points were NAS (Nasion), MAP (the Most Anterior Point on the nasal profile curve), GPRN (the Genuine Pronasale: the point on the nasal curve at which the curve protrudes most), and SBN (Subnasale: the point at the columellar base). Using specially designed software, the distances between these marking points were measured along the nasal profile curve. RESULTS: In CL patients, the distance between the MAP and GPRN is longer, and the GPRN is located more inferiorly than in non-cleft persons. CONCLUSION: The nasal tip tends to become round and to droop in unilateral CL patients. In order to avoid this deformity pattern, the nasal tip should be reshaped to present a sharper curvature and corrected superiorly.

Analysis of the orbital floor morphology.

INTRODUCTION: For the repair of large orbital floor defects due to blow-out fractures or those involved by tumours, it is necessary to understand the detailed morphology. The purpose of the present study was to elucidate how age and gender affect its three-dimensional morphology. METHODS: The 3-D computer tomography data of 305 orbits of 182 patients were included in the study. Using the CT data, the orbital floor angle (the angle between the orbital floor and the horizontal plane) and the location of the most inferior point of the orbital floor were measured. Patients were classified into subgroups according to their gender and age. Data were compared among the subgroups. RESULTS: The orbital floor angle was greater in males than in females, and in children than in adults. The location of the lowest point of the orbital floor moves postero-inferiorly with increasing age. CONCLUSION: The present study demonstrated that gender and age affects morphology of the orbital floor. These findings should be useful for reconstruction of the orbital floor.

Appropriate diameter for screws to fix the maxilla following Le Fort I osteotomy: an investigation utilizing finite element analysis.

BACKGROUND: After Le Fort I osteotomy, there is sometimes a secondary deformity (relapse), with the lower segment deviating from the intraoperatively fixed position. It is hyopothesized that the structural stability of the reconstructed maxilla is affected by the diameter of the fixation screws. The present study aims to elucidate the relationship between the diameters of the screws and the structural stability of the maxilla after Le Fort I osteotomy. METHODS: 3D models were produced on a workstation from 20 dry skulls and a Le Fort I operation was simulated on them. The upper and lower segments of the divided maxilla in each of the 20 models were connected using four plates and 16 screws. Five different diameters of the fixation screws were tested. Thus altogether 100 models were produced. A 180N load was applied to the molar region for each model. Using finite element analysis, the resultant stresses and deviations of the lower segments were calculated. Finally, referring to these values, the relationships between screw diameters and stability of the lower segment were evaluated. RESULT: The stability of the lower segment was greatest when the diameter of the fixation screws was equal to the thickness of the bone at each fixation site. CONCLUSION: In performing Le Fort I osteotomy, it is recommended that bone thickness is measured at each fixation site in advance, and the diameter of the fixation screws matched accordingly; thereby optimum stability of the reconstructed maxilla can be anticipated.

A tie-over with "untied" parallel stitches: a useful technique for fixation of a bolster after treatment of cryptotia.

We describe a new technique for the treatment of cryptotia by which stitches for bolster fixation are inserted parallel to the auriculartemporal sulcus and temporarily left untied. After the bolster has been inserted into the temporal sulcus, the corresponding ends of the threads are tied to each other. Our technique is easy to use and secures a firm bolster fixation, and we recommend it for the treatment of cryptotia.

A comparative study of most suitable miniplate fixation for mandibular symphysis fracture using a finite element model.

The purpose of this study is to determine the most stable fixation method for mandibular symphysis fractures by comparing the mechanical characteristics of models fixed at different positions with different numbers of plates. Fractures were generated in 3-dimensional finite element models, and were fixed with a single miniplate, parallel double miniplates, or perpendicular double miniplates. A 300 N perpendicular load was then applied on the left molar region, and a finite element analysis was performed. We compared vertical gaps between the fractured surfaces, maximum stress within the screw/plating system, and maximum stress around screw holes in the bone. Compared to the single miniplate, both the parallel and perpendicular double miniplates demonstrated significantly less stress in the screw/plating system and screw holes in the bone. In addition, the perpendicular double miniplateshad significantly smaller vertical gaps between fracture surfaces when compared to the single miniplate. Comparing parallel and perpendicular double miniplate fixations, less stress was found around the screw holes of the perpendicular miniplate models than those of the parallel miniplatemodels. There were no differences in vertical gaps or maximum stress within the screw/plating systems between the 2 double miniplate fixations. These results suggest that perpendicular double miniplate fixation is more suitable for fixing mandibular symphysis fractures.

Adaquate fixation of plates for stability during mandibular reconstruction.

PURPOSE: To determine the most appropriate plate fixation for dispersing the stress around screws in mandibular reconstruction. MATERIAL AND METHODS: Forty-eight three-dimensional reconstructed mandibular models with Central (C) or right Lateral (L) defects were created and divided into three groups, fixed with: (1) two screws on each side, (2) three screws on the left side with the third (middle one) located distally, or (3) three screws on the left side with the third (middle one) located proximally. A 300N vertical load was applied to the left molar region. The maximum stress was calculated using a finite element method and statistically evaluated. RESULTS: Stress was concentrated around the screw at the distal end of the mandibular halves on the loaded side ('crucial screw'). For the C defect, stress concentrated around the 'crucial screw' was greater when there were only two screws for fixation (20.55MPa) than when there were three screws (16.17MPa; p=0.022). No significant difference was found between the two groups with three screws for fixation. For the L defect on the other hand, stress on the 'crucial screw' was relatively greater when there were three screws for fixation (18.9MPa) than when there were only two screws for (12.83MPa; p=0.051). No significant difference was found between the two groups with three screws for fixation. As for the reconstruction plate, the stresses on the plates were not different among the various screw groups for fixation nor among the C and L defects. CONCLUSION: This paradoxical result is explained by plate bowing. Thus in large defects screw positions should take into consideration the potential for plate bowing.

The fetal dermal but not loose fascial mesenchymal cells possess regenerative activity of dermal structure.

Fetal skin possesses a regenerative activity until certain developmental stages. However, the origin of cells that regenerate dermis after wounding has not been clarified yet. In the present study we located the origin of cells that reconstruct fetal dermal structure by histological examination and by marking cells in the loose fascia. Next we evaluated the regenerative activity of fetal dermal mesenchymal cells by cotransplanting with fetal epidermal cells onto the skin defect of scid mice. We conclude that fetal dermal mesenchymal cells but not loose fascial cells possess regenerative activity even on the environment in scid mice.

Transplanted endothelial progenitor cells augment the survival areas of rat dorsal flaps.

Endothelial progenitor cells (EPCs) have been identified in peripheral blood, and have been reported to be incorporated into ischemic regions such as the ischemic hindlimb. In this study, we examined whether or not transplantation of EPCs is useful for salvaging surgical flaps in vivo. At the same time, we quantitatively compared the neovascularization ability of transplanted EPCs and that of mature endothelial cells (ECs). ECs obtained from the aorta of rats by explantation and passaged several times were used in the present study. EPCs were obtained from the blood of rat hearts. The blood samples were separated by density gradient centrifugation. Light-density mononuclear cells (MNCs) were collected and cultured on plastic plates coated with rat plasma vitronectin. Cells attached at day 7 of culture were deemed to be EPCs. Then PBS (control), ECs, or EPCs (3.0 x 10(5) suspended in 1.0 ml PBS) were injected at the middle of a flap. Seven days after surgery, the survival lengths of the flaps were evaluated. EPC-transplanted groups revealed statistically significant augmentation of survival length compared with the other two groups (p < 0.003). EPC-transplanted groups had significantly more angiographically detectable blood vessels (p < 0.003) and significantly higher capillary density (p < 0.03) than the other two groups. Confocal microscopy revealed that EPCs were incorporated into enhanced neovascularization. These results suggest that transplantation of EPCs may be useful for salvaging surgical flaps, and EPCs are superior to ECs in neovascularization ability.

Transplanted mesenchymal stem cells are effective for skin regeneration in acute cutaneous wounds.

Mesenchymal stem cells (MSCs) possess the capacity for site-specific differentiation of cell types in response to cues provided by different organs. This phenomenon suggests that MSCs participate in cutaneous wound regeneration. However, there are no prior reports on the influence of the local application of MSCs on cutaneous wound regeneration. To examine the effects of MSCs on wound regeneration, we cultured bone marrow cells of the femur of rats and treated the plastic adherent cells with a differentiation medium to induce differentiation. After treatment, we found that the bone marrow-derived plastic adherent cells possessed myogenesis, chondrogenesis, and adipogenesis capabilities, indicating that these cells are MSCs. The bone marrow-derived plastic adherent cells were injected intradermally into the skin of rats, and linear full-thickness incisional wounds were made immediately through the injected area. At 14 days after operation, wounds transplanted with bone marrow-derived plastic adherent cells had healed with very fine scars. Collagen architecture was thick and appeared to be similar to normal dermis. Histomorphologic scale analysis demonstrated significant differences between the control and the wounds transplanted with bone marrow-derived plastic adherent cells. These results indicate that transplanted MSCs can respond quite normally to wound healing and regenerate dermal structure.

Basic studies on the clinical applications of platelet-rich plasma.

Platelets, which contain many growth factors such as platelet-derived growth factor (PDGF) and transforming growth factor-beta (TGF-beta), are being used in clinical applications as platelet-rich plasma (PRP). Only a few studies, however, have been conducted on the growth factors present in PRP and on the clinical applications using the drug delivery system (DDS). For the purpose of clinical application, we first modified the PRP preparation method and assessed the amounts of growth factors contained in the human platelet concentrates. Furthermore, we assessed fibrin glue as a DDS of platelet concentrates. Platelet precipitations were made by twice centrifuging human whole blood. The precipitated platelet was resuspended to yield the platelet concentrates. The growth factor concentrations were measured. Fibrin glue sheets containing this platelet concentrate were implanted in rabbit pinna and samples were obtained for immunostaining (anti-PDGF antibody) to assess the use of PRP over time using the fibrin glue as the DDS. The mean concentration of growth factors present in the platelet concentrates was three times or greater than that of conventional PRP. Furthermore, the results indicated that when the platelet concentrate was used with fibrin glue as a carrier, the contents were released over a period of about 1 week. This raises the possibility that this system may be useful in clinical applications.