Clinical Effect of Virtual Reality to Relieve Anxiety During Impacted Mandibular Third Molar Extraction Under Local Anesthesia.

PURPOSE: Many patients undergoing dental treatment have experienced pain associated with the treatment and become anxious and/or fearful of treatment. Anxiety and fear have conventionally been managed with the use of inhalation anesthesia or tranquilizers. However, their physical effects must also be considered, and they will not be suitable for all patients. The purpose of the present study was to assess the clinical effect of virtual reality (VR) to relieve anxiety during impacted mandibular third molar extraction under local anesthesia. MATERIALS AND METHODS: We used VR to alleviate anxiety concerning surgical treatment for 51 patients undergoing impacted mandibular third molar extraction under local anesthesia. Fear and anxiety before and after treatment were evaluated by a questionnaire that included a visual analog scale (VAS). The post-treatment questionnaire asked patients to evaluate their satisfaction on a 5-level Likert scale. Heart rate variability (HRV) was also analyzed in the VR group using acceleration plethysmography. RESULTS: Anxiety had decreased among the patients who had used VR (VR group), with a difference of -13.3 ± 28.7 mm in anxiety measured using a VAS before and during treatment. In contrast, it had increased by 4.0 ± 22.3 mm in the 49 patients who had not used VR. Furthermore, the post-treatment questionnaire administered to the VR group revealed that 92% had reported that their anxiety had decreased. Objective evaluation by HRV measurement also showed a sympathetic nerve-predominant state before treatment. However, with VR use during treatment, parasympathetic nervous activity was predominant, with a stable balance between the 2. No patient showed symptoms suggestive of cybersickness. CONCLUSIONS: These results have shown that the use of VR could be valuable during dental treatment, especially extractions and surgical treatment.

[Clinical Efficacy of Cepharanthin(R)for Radiotherapy-Induced Leukopenia - A Nationwide, Multicenter, and Observational Study].

The clinical efficacy and safety of cepharanthin for the treatment of radiotherapy-induced leukopenia were reevaluated at multiple institutions.Clinical data of cancer patients aged over 20 years old, who received a total radiotherapy dose above 40 Gy, and who were treated with cepharanthin for more than 2 weeks between April 2007 and November 2012, were evaluated. Data from 65 patients(males: 31, females: 34)from 7 facilities were analyzed to assess efficacy and adverse events.The mean leukocyte count was significantly higher at the end of the treatment compared with the initial data.However, no significant differences were observed in erythrocyte and platelet counts.No adverse events attributed to cepharanthin were reported.Although this was a retrospective study, cepharanthin was found to be safe and significantly effective for the management of leukopenia caused by radiotherapy.

Clinical effects of different virtual reality presentation content on anxiety and pain: a randomized controlled trial.

Many patients are frightened of or anxious about dental treatment. We have recently reported our use of virtual reality (VR) to alleviate the fear and anxiety experienced during oral surgical procedures However, the effectiveness of VR in alleviating anxiety varies greatly between individuals. We therefore investigated whether the content of the VR presentation made any difference to its effect in alleviating anxiety, and whether it had any analgesic effect. The study subjects experienced one of two different types of VR presentation and were asked to complete a questionnaire about any changes in their anxiety during the procedure, including a visual analog scale (VAS) score. As an objective evaluation, changes in pain threshold during the VR presentation were investigated using PainVision. For those patients who experienced a presentation showing a natural landscape, the change in VAS score was - 13.3 ± 28.7 mm, whereas for those who experienced a presentation showing a video game the change was - 22.2 ± 32.1 mm, an even greater reduction. In a pain questionnaire completed by individuals who had experienced the video game presentations, approximately 70% reported that their pain had diminished. An objective evaluation of pain threshold also showed that the pain threshold of individuals increased by around 3% while experiencing the natural landscape VR presentation, but that while experiencing the video game presentation, it increased significantly by around 15% compared with baseline. These results show that the content of the presentation affected not only the rate of decrease in anxiety, but also the pain threshold.

Clinical evaluation of steroid ointment for the treatment of mucoceles.

OBJECTIVE: We examined whether steroid ointment (0.1% dexamethasone) is an effective treatment for mucoceles. STUDY DESIGN: Using a retrospective cohort study design, a statistical study was conducted of 91 patients diagnosed with mucoceles at the Department of Dental and Oral Surgery, Saga University Hospital, Saga, Japan, between January 2006 and December 2016. The patients' age and sex; shape, size, and site of the lesion; duration; and treatment response rate were evaluated. RESULTS: The most frequent site of mucoceles was the lower labial mucosa, and several were <10 mm in size. The age of onset was often <20 years, with no sex-based differences. The treatment response rate was 65.8% for steroid ointment and 100% for surgical removal. In the subgroup analysis according to each clinical factor, some subgroups showed statistically nonsignificant differences compared with the surgery group. Among them, the older age and short disease duration subgroups showed small risk differences, suggesting that application of ointment may lead to a response in these subgroups. CONCLUSIONS: Although its response rate was lower than that of surgical removal, topical steroid application is a noninvasive and useful treatment method that can be used for patients in whom surgical treatment is infeasible.

Development of an application for management of drug holidays in perioperative periods.

Before surgery and other invasive treatments, decisions must be made on whether to discontinue drugs and provide appropriate drug holidays especially for antithrombotic drugs, and this is made difficult by the large number of available drugs and associated guidelines. We have therefore developed an online application for perioperative drug discontinuation and resumption management, named Saga Application for Management of Drug Holidays in PeriOperative Periods (SAMPOP).Multidisciplinary medical staff at Saga University Hospital (SUH) worked together to build an evidence-based Perioperative Drug Discontinuation Management Database (PDDMD) and developed the user-friendly SAMPOP online application via preliminary verification at SUH. From September 2018 to February 2020, 420 medical staff at SUH, including physicians, nurses, and pharmacists, installed and tested SAMPOP.Rate per surgical procedure for forgetting to discontinue antithrombotic drugs preoperatively decreased from 0.18% to 0.09% as of August 2019, 12 months after the introduction of SAMPOP (P = .1359). In addition, six months later, it decreased further to 0.03% as of February 2020 (P = .0436). Forgetting to resume antithrombotic drugs postoperatively decreased from 0.20% to 0.02% as of August 2019, 12 months after the introduction of SAMPOP (P = .0008). There was no case of forgetting to resume the medication in the last 6 months.SAMPOP may be useful for management of drug holidays in the clinic and warrants further evaluation of its safety and efficacy.

TRPV2 expression in rat oral mucosa.

The oral mucosa is a highly specialised, stratified epithelium that confers protection from infection and physical, chemical and thermal stimuli. The non-keratinised junctional epithelium surrounds each tooth like a collar and is easily attacked by foreign substances from the oral sulcus. We found that TRPV2, a temperature-gated channel, is highly expressed in junctional epithelial cells, but not in oral sulcular epithelial cells or oral epithelial cells. Dual or triple immunolabelling with immunocompetent cell markers also revealed TRPV2 expression in Langerhans cells and in dendritic cells and macrophages. Electron microscopy disclosed TRPV2 immunoreactivity in the unmyelinated and thinly myelinated axons within the connective tissue underlying the epithelium. TRPV2 labelling was also observed in venule endothelial cells. The electron-dense immunoreaction in junctional epithelial cells, macrophages and neural axons occurred on the plasma membrane, on invaginations of the plasma membrane and in vesicular structures. Because TRPV2 has been shown to respond to temperature, hypotonicity and mechanical stimuli, gingival cells expressing TRPV2 may act as sensor cells, detecting changes in the physical and chemical environment, and may play a role in subsequent defence mechanisms.

Distribution of substance P and neurokinin-1 receptors in the peri-implant epithelium around titanium dental implants in rats.

We examined the distribution of substance P and neurokinin-1 (NK1) receptors and substance-P-containing nerve fibers in the peri-implant mucosa around titanium dental implants in rats. Immunohistochemistry and immunocytochemistry revealed that substance-P-immunoreactive nerve fibers abundantly innervated the peri-implant epithelium (PIE) compared with other epithelia of the peri-implant mucosa. NK1 receptor mRNA and protein expression in the peri-implant mucosa were confirmed by reverse transcription with the polymerase chain reaction and immunoblotting. Immunoelectron microscopy revealed that NK1 receptor immunoreactivity was preferentially localized in peri-implant epithelial cells. NK1-receptor-positive products were found on the plasma membrane and in vesicles and granules in PIE cells. Neutrophils and intraepithelial nerve axons in the PIE were positive for the NK1 receptor. NK1 receptor immunoreactivity was also detected in endothelial cells, fibroblasts, and nerve fibers in the connective tissue beneath the PIE. These findings suggest that peri-implant tissue receives sensory information through regenerated nerves expressing substance P and the NK1 receptor. In the peri-implant mucosa, the substance P/NK1 receptor system may play a role in pain transmission, the endocytosis of neutrophils, the extravasation of crevicular fluid, and the migration of macrophages and neutrophils in response to neurogenic inflammation, as in healthy gingiva.

Impaired Junctions and Invaded Macrophages in Oral Epithelia With Oral Pain.

Recurrent or chronic oral pain is a great burden for patients. Recently, the links between epithelial barrier loss and disease were extended to include initiation and propagation. To explore the effects of pathohistological changes in oral epithelia on pain, we utilized labial mucosa samples in diagnostic labial gland biopsies from patients with suspected Sjögren's syndrome (SS), because they frequently experience pain and discomfort. In most labial mucosa samples from patients diagnosed with SS, disseminated epithelial cellular edema was prevalent as ballooning degeneration. The disrupted epithelia contained larger numbers of infiltrating macrophages in patients with oral pain than in patients without pain. Immunohistochemistry revealed that edematous areas were distinct from normal areas, with disarranged cell-cell adhesion molecules (filamentous actin, E-cadherin, ß-catenin). Furthermore, edematous areas were devoid of immunostaining for transient receptor potential channel vanilloid 4 (TRPV4), a key molecule in adherens junctions. In an investigation on whether impaired TRPV4 affect cell-cell adhesion, calcium stimulation induced intimate cell-cell contacts among oral epithelial cells from wild-type mice, while intercellular spaces were apparent in cells from TRPV4-knockout mice. The present findings highlight the relationship between macrophages and epithelia in oral pain processing, and identify TRPV4-mediated cell-cell contacts as a possible target for pain treatment.

Exogenous nitric oxide stimulates the odontogenic differentiation of rat dental pulp stem cells.

Nitric oxide (NO) is thought to play a pivotal regulatory role in dental pulp tissues under both physiological and pathological conditions. However, little is known about the NO functions in dental pulp stem cells (DPSCs). We examined the direct actions of a spontaneous NO gas-releasing donor, NOC-18, on the odontogenic capacity of rat DPSCs (rDPSCs). In the presence of NOC-18, rDPSCs were transformed into odontoblast-like cells with long cytoplasmic processes and a polarized nucleus. NOC-18 treatment increased alkaline phosphatase activity and enhanced dentin-like mineralized tissue formation and the expression levels of several odontoblast-specific genes, such as runt related factor 2, dentin matrix protein 1 and dentin sialophosphoprotein, in rDPSCs. In contrast, carboxy-PTIO, a NO scavenger, completely suppressed the odontogenic capacity of rDPSCs. This NO-promoted odontogenic differentiation was activated by tumor necrosis factor-NF-κB axis in rDPSCs. Further in vivo study demonstrated that NOC-18-application in a tooth cavity accelerated tertiary dentin formation, which was associated with early nitrotyrosine expression in the dental pulp tissues beneath the cavity. Taken together, the present findings indicate that exogenous NO directly induces the odontogenic capacity of rDPSCs, suggesting that NO donors might offer a novel host DPSC-targeting alternative to current pulp capping agents in endodontics.

Anaplastic Lymphoma Kinase-Positive Anaplastic Large Cell Lymphoma with Cardiac Metastasis and Arterial Tumor Embolisms during First-Course Chemotherapy.

We described an 11-year-old boy suffering from pediatric anaplastic lymphoma kinase-positive anaplastic large cell lymphoma with heart metastasis at diagnosis and arterial tumor embolisms during chemotherapy. Both the heart metastasis and pericardial effusion showed improvement with prednisolone, but numbness and pallor sequentially developed in his lower extremities during the first course of chemotherapy. Contrast-enhanced imaging revealed occlusion of the right anterior tibial artery and left popliteal artery. These symptoms were spontaneously remitted due to the compensation of other arteries. Arterial tumor embolism is a rare but possible complication when a lymphoma shows intracardiac infiltration.

Milk basic protein supplementation enhances fracture healing in mice.

OBJECTIVES: There is an unmet need for agents that can stimulate bone healing. The goal of this study was to evaluate the effects of basic proteins from milk whey (milk basic protein [MBP]) on fracture healing in mice. METHODS: Closed tibial transverse fractures were generated in 6-wk-old male C3 H/HeJ mice given either tap water or MBP-supplemented water for 3, 7, 14, 28, and 56 d after fracture generation. The tibial tissues were analyzed by radiography, µCT, and a three-point bending test. The expression levels of genes associated with bone metabolism were analyzed by real-time reverse transcription-polymerase chain reaction. RESULTS: Quantitative µCT analysis showed that MBP-treated fractured tibiae had a larger hard callus in the sectional area and a larger volume compared with fractured tibiae without MBP treatment. The expression levels of genes associated with chondrogenesis and osteogenesis showed greater increases in fractured tibiae with MBP treatment. Significant increases in the callus mechanical properties were found in MBP-treated tibiae. CONCLUSIONS: MBP supplementation has the potential to improve fracture healing and bone strength in mouse tibiae. MBP could be a potential safe, low-cost, and easily administered nutritional element to prevent secondary fractures in patients with bone fractures.

Sequential expression of endothelial nitric oxide synthase, inducible nitric oxide synthase, and nitrotyrosine in odontoblasts and pulp cells during dentin repair after tooth preparation in rat molars.

Nitric oxide (NO) stimulates osteoblast differentiation, but whether NO contributes to odontoblast differentiation during dentin repair is unknown. By using reverse transcription/polymerase chain reaction and immunostaining, we investigated the gene expression and/or immunolocalization of endothelial NO synthase (eNOS), inducible NOS (iNOS), and nitrotyrosine (a biomarker for NO-derived peroxinitrite), and alkaline phosphatase (ALP) and osteocalcin (early and terminal differentiation markers of odontoblasts, respectively) in dental pulp tissue after rat tooth preparation. At the early stage (1-3 days) post-preparation, markedly increased expression of iNOS and nitrotyrosine was found in odontoblasts and pulp cells beneath the cavity, whereas eNOS expression was significantly decreased. ALP mRNA expression was significantly increased after 1 day but decreased after 3 days, whereas ALP activity was weak in the dentin-pulp interface under the cavity after 1 day but strong after 3 days. Osteocalcin mRNA expression was significantly increased at this stage. At 7 days post-preparation, tertiary dentin was formed under the cavity. All the molecules studied were expressed at control levels in odontoblasts/pulp cells beneath the cavity. These findings show that abundant NO is released from odontoblasts and pulp cells at an early stage after tooth preparation and indicate that, after tooth preparation, the up-regulation of iNOS and nitrotyrosine in odontoblasts is synchronized with increased cellular expression of ALP and osteocalcin. Therefore, the NO synthesized by iNOS after tooth preparation probably participates in regulating odontoblast differentiation during tertiary dentinogenesis.

Cystatin C stimulates the differentiation of mouse osteoblastic cells and bone formation.

Cystatin C (CysC) is a natural cysteine proteinase inhibitor that suppresses the differentiation and bone-resorptive function of osteoclasts. By contrast, the effect of CysC on the differentiation and bone-formative function of osteoblasts has not been elucidated thoroughly. We examined the effects of CysC on mouse osteoblastic cells using in vitro cultures from bone marrow and calvaria and ex vivo calvarial cultures. CysC-stimulated cells showed increased alkaline phosphatase (ALP) activity, mineralization of the new bone matrix, and calvarial bone formation. The cells treated with CysC immunodepleted by anti-CysC antibody (iCysC) and a chemical papain-like cysteine proteinase inhibitor, E-64, did not induce mineralization. Elevated mRNA levels of bone morphogenetic protein (BMP)-2, the differentiation marker osteocalcin, and a master osteogenic transcription factor, Runx2, were observed in CysC-treated cells. These results suggest that CysC affects the BMP signaling cascades in osteoblastic cells and then promotes osteoblast differentiation, mineralization, and bone formation.

Immunocytochemical localization of the neurokinin 1 receptor in rat dental pulp.

The dentin-pulp complex is a peripheral end-organ supplied by dense sensory nerve fibers. Substance P, a representative neuropeptide widely distributed in the dental pulp, has been reported to play roles in pain transmission and the amplification of inflammation. We analyzed here the expression of the neurokinin 1 (NK1) receptor, preferentially activated by substance P, using immunocytochemistry in rat dental pulp at both the light and electron microscopic levels. Conspicuous NK1 receptor immunoreactivity was found in the odontoblasts; immunolabelings were present at their plasma membrane and endosomal structures, especially in their cytoplasmic processes. Immunoreactions for NK1 receptor were also detectable in a part of the nerve terminals associated with the cytoplasmic processes of the odontoblasts. Furthermore, the endothelial cells of capillaries and post-capillary venules and the fibroblasts were labeled with the NK1 receptor in the subodontoblast layer. These findings suggest that pulpal cells and nerve fibers are targets for substance P that mediate multiple functions, including a vasoactive function and the regulation of vascular permeability as well as the modulation of pain transmission.