Search

We investigate bifurcations of periodic solutions observed in the forced Wilson-Cowan neuron pair by both the brute-force computation and the shooting method. By superimposing the results given by both methods, a detailed topological classification of periodic solutions is achieved that includes tori and chaos attractors in the parameter space is achieved. We thoroughly explore the parameter space composed of threshold values, amplitude, and angular velocity of an external forcing term. Many bifurcation curves that are invisible when using brute-force method are solved by the shooting method. We find out a typical bifurcation structure including Arnold tongue in the angular velocity and the amplitude of the external force parameter plane, and confirm its fractal structure. In addition, the emergence of periodic bursting responses depending on these patterns is explained.

Predictive processing in the brain, involving interaction between interoceptive (bodily signal) and exteroceptive (sensory) processing, is essential for understanding music as it encompasses musical temporality dynamics and affective responses. This study explores the relationship between neural correlates and subjective certainty of chord prediction in both musically appropriate chord progressions and random chord sequences. Participants were asked to predict the final chord in sequences while their brain activity was measured using electroencephalography (EEG). We found that the stimulus preceding negativity (SPN), an EEG component associated with predictive processing of sensory stimuli, was larger for random chord sequences than for chord progressions. Additionally, the heartbeat evoked potential (HEP), an EEG component related to interoceptive processing, was larger for random chord sequences and correlated with prediction certainty ratings. HEP also correlated with the N5 component, found while listening to the final chord. Our results suggest that SPN may be linked to the emotional detection of chord sequences, while HEP may reflect motivational differences during the task. These findings offer new insights into the neural mechanisms underlying music perception and prediction, emphasizing the importance of considering auditory prediction certainty when examining the neural basis of music cognition.

Supplementary Figure S3. (A and B) The graphs compare beta-endorphin levels in the supernatant of oral SCC (HSC-3) cells re-expressing mu-opioid receptor and control oral SCC cells, with and without naloxone treatment. Cells transduced with Ad-OPRM1 at 200 MOI secreted an average of 400pg/ml beta-endorphin, which was significantly higher than non-transduced cells (*p < 0.05, One-way ANOVA, Holm-Sidak test). When treated with naloxone (10-6 to 10-12 mol/L) Ad-OPRM1 HSC-3 cells secreted significantly less beta-endorphin than the control vehicle-treated Ad-OPRM1 HSC-3 cells at all naloxone concentrations (p

Purpose: In this study, we evaluated the analgesic potential of demethylating drugs on oral cancer pain. Although demethylating drugs could affect expression of many genes, we focused on the mu-opioid receptor (OPRM1) gene pathway, because of its role in pain processing. We determined the antinociceptive effect of OPRM1 re-expression in a mouse oral cancer model.Experimental Design: Using a mouse oral cancer model, we determined whether demethylating drugs produced antinociception through re-expression of OPRM1. We then re-expressed OPRM1 with adenoviral transduction and determined if, and by what mechanism, OPRM1 re-expression produced antinociception. To determine the clinical significance of OPRM1 on cancer pain, we quantified OPRM1 methylation in painful cancer tissues and nonpainful contralateral normal tissues of patients with oral cancer, and nonpainful dysplastic tissues of patients with oral dysplasia.Results: We demonstrated that OPRM1 was methylated in cancer tissue, but not normal tissue, of patients with oral cancer, and not in dysplastic tissues from patients with oral dysplasia. Treatment with demethylating drugs resulted in mechanical and thermal antinociception in the mouse cancer model. This behavioral change correlated with OPRM1 re-expression in the cancer and associated neurons. Similarly, adenoviral-mediated OPRM1 re-expression on cancer cells resulted in naloxone-reversible antinociception. OPRM1 re-expression on oral cancer cells in vitro increased β-endorphin secretion from the cancer, and decreased activation of neurons that were treated with cancer supernatant.Conclusion: Our study establishes the regulatory role of methylation in cancer pain. OPRM1 re-expression in cancer cells produces antinociception through cancer-mediated endogenous opioid secretion. Demethylating drugs have an analgesic effect that involves OPRM1. Clin Cancer Res; 20(18); 4882–93. ©2014 AACR.

Objective The dental treatment such as local anesthetic injections are a common source of anxiety and fear during dental procedures. One of the causes of these anxiety and fear are regarded as taste and tactile sensory input. The purpose of this study was to investigate the effects of inhalation sedation with nitrous oxide (IS–N2O) on intraoral taste and tactile sensory input in human. Materials and methods We performed taste testing using electrogustometry and the filter paper disc test in the proglossis region, and precise tactile function testing using the Semmes-Weinstein monofilaments (SWM) test was performed on the mandibular incisor interdental gingival papilla of healthy male and female volunteers. Results On electrogustometry, the 50% IS-N2O threshold was significantly higher than those of other conditions (vs. room air [RA], 100% O2, Recovery, vs. 30% IS-N2O). In the filter paper disc test, the 30%/50% IS-N2O thresholds were significantly higher than those of other conditions (vs. RA, 100% O2, Recovery) for all tastes. However, no significant difference in the recognition threshold was noted between 30% IS-N2O and 50% IS-N2O. In the SWM test, the 30%/50% IS-N2O thresholds were significantly higher than those of other conditions (vs. RA, 100% O2, Recovery), but the 50% IS-N2O threshold was higher than the 30% IS-N2O threshold. Conclusion IS-N2O inhibit the input of taste and tactile sensations and may be an effective tool for patients undergoing dental procedures.

Purpose Consensus is lacking regarding the optimal antibiotic treatment for pediatric complicated appendicitis. This study determined the optimal first-line antibiotic treatment for pediatric patients with complicated appendicitis based on peritoneal fluid cultures. Methods This retrospective study examined the cases of pediatric patients who underwent appendectomy for complicated appendicitis at our institution between 2013 and 2019. Peritoneal fluid specimens obtained during appendectomy were cultured for the presence of bacteria. Results Eighty-six pediatric patients were diagnosed with complicated appendicitis. Of them, bacteria were identified in 54 peritoneal fluid samples. The major identified bacteria were Escherichia coli (n=36 [66.7%]), Bacteroides fragilis (n=28 [51.9%]), α-Streptococcus (n=25 [46.3%]), Pseudomonas aeruginosa (n=10 [18.5%]), Enterococcus avium (n=9 [16.7%]), γ-Streptococcus (n=9 [16.7%]), and Klebsiella oxytoca (n=6 [11.1%]). An antibiotic susceptibility analysis showed E. coli was inhibited by sulbactam/ampicillin in 43.8% of cases versus cefmetazole in 100% of cases. Tazobactam/piperacillin and meropenem inhibited the growth of 96.9-100% of the major identified bacteria. E. coli (100% vs. 84.6%) and P. aeruginosa (100% vs. 80.0%) were more susceptible to amikacin than gentamicin. Conclusion Tazobactam/piperacillin or meropenem is a reasonable first-line antibiotic treatment for pediatric complicated appendicitis. In the case of aminoglycoside use, amikacin is recommended.

In 2019, several aquarium-reared fish died at a sea life park in Japan. Necropsy revealed micronodules on the spleen in the dotted gizzard shad (Konosirus punctatus). Seven of 16 fish exhibited microscopic multifocal granulomas associated with acid-fast bacilli in the spleen, kidney, liver, alimentary tract, mesentery, gills, and/or heart. Bacterial cultures yielded isolates from the dotted gizzard shad and a Japanese sardine (Sardinops melanostictus). Microbiological examination, multilocus sequence typing analysis, and variable number of tandem repeats analysis with a newly proposed 6-loci set revealed the isolates as Mycobacterium pseudoshottsii. To our knowledge, this is the first isolation of M. pseudoshottsii from aquarium-reared fish.

The aim of this study is to investigate effects of cisplatin preadministration on oral ulcerative mucositis-induced nociception by using an experimental model of rats.After two rounds of cisplatin administration, oral ulcers developed with topical acetic acid treatment in rats. Spontaneous mouth rubbing behavior was observed as spontaneous nociceptive behavior in a plastic cage. Head-withdrawal behavior was observed as mechanical allodynia by using von Frey test in the oral mucosa of conscious rats. Bacterial invasion and inflammatory cell infiltration into oral ulcerative region and systemic leukocyte phagocytic activity were assessed.Following cisplatin preadministration, oral ulcerative mucositis-induced spontaneous nociceptive behavior was not observed in the model. The preadministration enhanced leukocyte phagocytic activity, leading to reduce bacterial invasion and inflammatory cell infiltration in the oral ulcerative region. In contrast, oral ulcerative mucositis-induced mechanical allodynia was induced. The exaggerated mechanical allodynia in the oral ulcerative region was largely inhibited by topical treatment with the antioxidative drug, ɑ-lipoic acid, or the blocker of N-formyl peptide receptor 1, N-t-butoxycarbonyl-methionyl-leucyl-phenylalanine.These results suggest that cisplatin preadministration suppresses spontaneous nociception in oral ulcerative region, due to antiinflammatory effects by enhancement of leukocyte phagocytic activity, but exaggerates mechanical allodynia due to oxidative stress with N-formyl peptide receptor 1 activation. The suppression of spontaneous nociception is one of the advantages of cisplatin treatment for head and neck cancer patients although the exaggerated allodynia is a serious symptom.

Objectives Previous studies have indicated that xerostomia is a critical factor affecting periodontitis; nonetheless, it is controversial whether xerostomia impairs peri-implant tissue. The objective of this experimental study was to evaluate the effect of xerostomia on the peri-implant hard and soft tissues in the rat model. Materials and methods Implants were placed in bilateral maxillae of male Wistar rats. The animals underwent submandibular and sublingual gland resection on both sides (DRY group) or sham operation (CTR group). Silk ligatures were placed around one side of abutments, which were randomly selected in each animal. The effects of xerostomia were assessed using micro-CT, histological analysis, real-time PCR, and 16S rRNA-based metagenomic analysis. Results Ligation with silk thread caused bone resorption around implants. Although xerostomia itself did not induce bone resorption, it significantly enhanced silk ligature-mediated bone resorption around implants. Histological analysis and real-time PCR indicated that xerostomia induced inflammation and osteoclastogenesis around implants with silk ligatures. Furthermore, it altered the microbiota of the plaque on the silk thread around implants. Conclusion Xerostomia accelerates mucosal inflammation and osteoclastogenesis, which aggravates bone resorption around implants.

Two cases of pediatric lung cancer (in 23-month-old and 6-year-old boys) resulting from mother-to-infant transmission of uterine cervical tumors were incidentally detected during routine next-generation sequencing of paired samples of tumor and normal tissue. Spontaneous regression of some lesions in the first child and slow growth of the tumor mass in the second child suggested the existence of alloimmune responses against the transmitted tumors. Immune checkpoint inhibitor therapy with nivolumab led to a strong regression of all remaining tumors in the first child. (Funded by the Japan Agency for Medical Research and Development and others; TOP-GEAR UMIN Clinical Trials Registry number, UMIN000011141.).

Glycyrrhiza extract has been used for the treatment of oral and gastric ulcers, but the analgesic mechanism remains unknown. In the present study, we investigated the effects of isoliquiritigenin, an active ingredient of Glycyrrhiza, on Nav channels in vitro and nociceptive behaviors in vivo. In an autopatch-clamp study, isoliquiritigenin inhibited the currents of Nav1.1, Nav1.3, Nav1.6, Nav1.7, and Nav1.8 in a channel expression system. In small- and medium-sized cultured trigeminal ganglion neurons, the compound suppressed Nav currents in many neurons (78%) and Kv currents in all neurons, dose-dependently. In current-clamp mode, isoliquiritigenin blocked action potential generation in many neurons (64%), but it conversely accelerated action potential generation in the remaining neurons. The opposing effects on action potentials were reproduced in a computational simulation of a modified Hodgkin-Huxley-based model, based on the electrophysiological data. In behavioral experiments, local treatment with isoliquiritigenin suppressed nociceptive behaviors in response to oral ulcer development or nociceptive TRP channel agonists in the oral mucosa and hind paw. These results suggest that isoliquiritigenin exerts an analgesic effect predominantly via inhibitory action on Nav channels on sensory nociceptive fibers. This pharmacological mechanism indicates that isoliquiritigenin is useful for pain relief and provides scientific evidence for Glycyrrhiza at the ingredient level.

To determine the features which predict torsion and the pre-operative indicators of malignancy in cases of ovarian torsion in ovarian tumors (OTs) in children. The medical records of 35 pediatric patients who underwent surgery for OT, except for neonate cases, from 1997 to 2018 at our institution were reviewed retrospectively. The pathological diagnosis was mature teratoma in 17, immature teratoma in 9, yolk sac tumor in 3, and others in 6. The preoperative diagnosis, which was made based on the imaging findings and the serum tumor marker values, matched with the pathological diagnosis in 29/35 (83%). Ovarian torsion occurred in 14/35 (40%). All but one case that presented with torsion had intermittent abdominal pain as the primary symptom. The preoperative white blood cell count was significantly higher in cases where ovary preservation was impossible than where it was possible (p = 0.01) among the cases presenting with torsion. Preoperative imaging findings and the serum tumor marker values enabled us to make an accurate preoperative diagnosis. Patients with intermittent abdominal primary symptoms were more likely to have ovarian torsion than those without such symptoms, and leukocytosis may indicate irreversible ischemic changes in the affected ovary.

Purpose We assessed the effects of hyperglycaemia induced by streptozotocin (STZ) on peri-implantitis developing after implant osseointegration. Methods Thirty-six male Wistar rats (4 weeks old) were used. We placed titanium implants 4 weeks after extraction of the maxillary first molars. Healing abutments were attached 4 weeks later. After osseointegration was confirmed, the rats were divided into control, hyperglycaemia (STZ), and STZ with insulin (STZ + INS) groups. Hyperglycaemia was induced by a single injection of 50 mg/kg STZ. Silk ligatures were placed on only the right sides (i.e. ligature sides), not on the left sides. Peri-implant tissues extracted at 4 weeks post-ligation were analysed both radiologically (via micro-computed tomography) and histologically (via toluidine blue staining). Total RNA was also extracted and analysed by quantitative PCR to detect TNF-α, IL-1β and the receptor of advanced glycation end products (RAGE). Additionally, advanced glycation end products (AGEs) were measured by ELISA. Results Radiological and histological analyses showed that bone loss on the non-ligature sides was significantly greater in the STZ than the control group. However, on the ligature sides, bone loss was greater than on the non-ligature sides, and no significant difference was evident among the three groups. The levels of mRNAs encoding TNF-α, IL-1β, RAGE, and AGEs on the ligature sides were significantly upregulated (all P Conclusions Although hyperglycaemia could be associated with bone loss around implants with increased AGE production and RAGE expression, hyperglycaemia does not become a triggering factor of ligature induced peri-implantitis.

Orthodontic patients complain of pain for the first few days after insertion of appliances. Mechanical force has been reported to produce oxidants in periodontal ligament (PDL) cells. It has not been studied whether orthodontic force-induced oxidative stress elicits nociception. Herein, we focused on the role of the oxidant-sensitive channel TRPA1 on nociception in orthodontic pain. In a rat model of loaded orthodontic force between the maxillary first molar and incisor, the behavioral signs of orofacial nociception, facial rubbing and wiping, increased to a peak on day 1 and gradually diminished to the control level on day 5. Administration of free radical scavengers (Tempol and PBN) and TRPA1 antagonist (HC-030031) inhibited nociceptive behaviors on day 1. In the PDL, the oxidative stress marker 8-OHdG was highly detected on day 1 and recovered on day 5 to the sham-operated level. The dental pulp showed similar results as the PDL. TRPA1 mRNA was abundantly expressed in the trigeminal ganglion relative to PDL tissue, and there were TRPA1-immunopositive neuronal fibers in the PDL and pulp. In dissociated trigeminal ganglion neurons, H2O2 at 5 mM induced a Ca2+ response that was inhibited by HC-030031. Although H2O2 at 100 μM did not yield any response, it enhanced the mechanically activated TRPA1-dependent Ca2+ response. These results suggest that oxidative stress in the PDL and dental pulp following orthodontic force activates and/or mechanically sensitizes TRPA1 on nociceptive fibers, resulting in orthodontic nociception. Later, the disappearance of nociception seems to be related to a decrease in oxidative stress, probably due to tissue remodeling.

Background/Aim: Ascorbate peroxidase (APX) derived from Cyanidioschyzon merolae, a primitive red alga living in high temperature and acidic environments, has greater anti-oxidative capacity than similar peroxidases occurring in other plants. In the present study, we examined whether expression of Cyanidioschyzon merolae-derived APX (cAPX) in mammalian cells increases cellular anti-oxidative capacity. Materials and Methods: The cAPX gene was introduced into the mouse fibroblast-like cell line C3H10T1/2. Production of reactive oxygen species (ROS) and/or cell viability was assessed after heat, H(2)O(2 )and acid stimulation. Results: Heat and H(2)O(2) stimulation resulted in ROS production. cAPX-expressing cells were more tolerant to oxidative stress induced by heat, H(2)O(2) and acid stimulations than control cells lacking cAPX. Conclusion: Introduction of cAPX increases the anti-oxidative capacity in mammalian cells.

Chemotherapy often induces oral ulcerative mucositis (OUM) in patients with cancer, characterized by severe painful inflammation. Mouth-washing with the Japanese herbal medicine hangeshashinto (HST) ameliorates chemotherapy-induced OUM in patients with colorectal cancer. Previously, we demonstrated that HST decreased interleukin 1β-induced prostaglandin E2 production in human oral keratinocytes (HOKs) and OUM-induced mechanical or spontaneous pain in rats. However, HST effects on tissue repair functions in HOKs remain unclear. Here, we examined the effects of HST on scratch-induced wound healing in vitro and in vivo. In vitro, HST enhanced wound healing mainly through scratch-induced HOK migration. Screening of the seven constituent medicinal herbs and their major components revealed that Scutellaria root, processed ginger, and Glycyrrhiza components mainly induced the scratch-induced HOK migration. Pharmacokinetic analyses indicated that the active ingredient concentrations in rat plasma following oral HST administration were below the effective doses for HOK migration, suggesting direct effects of HST in OUM. Mitogen-activated protein kinase and C-X-C chemokine receptor 4 inhibitors significantly suppressed HST-induced HOK migration. Moreover, HST enhanced tissue repair in our OUM rat model. Thus, HST likely enhanced OUM tissue repair through oral keratinocyte migration upon MAPK and CXCR4 activation and may be useful in patients with cancer-associated OUM.

It is known that the value of an object can be increased by forming an image of owning the object without actually possessing it. However, the detailed mechanism behind this phenomenon remains unknown. In this study, we conducted two experiments using newly created three-dimensional abstract objects to examine whether the formation of a mental image of ownership increases the value of an object when a participant has a haptic experience of the object. The results suggest that when participants’ mental visual imagery ability was relatively high, having a haptic experience increased the value of the object through their image of ownership. For others, however, imagining ownership lowered the value of the object. The results also indicate that obtaining spatial information about an object through a haptic experience increases the value of the object. This study suggests that haptic information about an object contributes to the mechanism modulating how the value of an object is influenced by individual differences in visuospatial imagery ability.

Despite the long history of use of steroid ointments for oral mucositis, the analgesic mechanism has not been fully elucidated. In this study, we examined the effects of triamcinolone acetonide (Tmc) on oral ulcerative mucositis-induced pain in conscious rats by our proprietary assay system. Based on evaluations of the physical properties and retention periods in the oral mucosa of human volunteers and rats, we selected TRAFUL® ointment as a long-lasting base. In oral ulcerative mucositis model rats, TRAFUL® with Tmc suppressed cyclooxygenase-dependent inflammatory responses with upregulations of glucocorticoid receptor-induced anti-inflammatory genes and inhibited spontaneous nociceptive behavior. When an ointment with a shorter residual period was used, the effects of Tmc were not elicited or were induced to a lesser extent. Importantly, TRAFUL® with Tmc also improved oral ulcerative mucositis-induced mechanical allodynia, which has been reported to be independent of cyclooxygenase. Ca2+ imaging in dissociated trigeminal ganglion neurons showed that long-term preincubation with Tmc inhibited the hypertonic stimulation-induced Ca2+ response. These results suggest that the representative steroid Tmc suppresses oral ulcerative mucositis-induced pain by general anti-inflammatory actions and inhibits mechanical sensitivity in peripheral nerves. For drug delivery, long-lasting ointments such as TRAFUL® are needed to sufficiently induce the therapeutic effects.

Precise temporal synchronisation between action and perception is crucial in daily life. Interestingly, synchronised tapping for every other tone or more (1:n tapping) is more precise than that for each tone (1:1 tapping), and this phenomenon is called 'subdivision benefit'. One hypothesis to explain this phenomenon is that there is a tendency to underestimate an empty interval, but the subdivision is used as an additional temporal reference and causes an illusionary longer intertap interval (ITI). The other hypothesis is based on strong/weak beats in a tone sequence made by subdivision. Because the strong beat improves the sensitivity of duration perception, synchronisation with strong beats should be better compared with other beats. Instead, the first hypothesis suggests that the subdivision benefit occurs irrespective of beat strength. The present study aimed to clarify this discrepancy using a 1:3 tapping task for a sequence of three-tone patterns and a 1:1 tapping task for a sequence of a single tone repetition. A further aim was to clarify the effect of musical experience. When the ITI was 900 ms or more, the variability of tapping showed the subdivision benefit, irrespective of beat strength. This result supports the first hypothesis, and musicians obtained more benefits than non-musicians. Instead, the timing of tap did not shorten by subdivision, except for the ITI of 900 ms. The findings implicate that the subdivision benefit is due to the additional temporal reference by the subdivided tones, and the benefit is dependent on the ITI length.

Stable synchronization with external auditory/visual events is important for cooperative behavior, such as playing music in an orchestra. One way to enhance synchronization in the auditory domain is by inserting different tones between tones to synchronize. Synchronized tapping for every other tone or more (1: n tapping) is less variable than that for each tone (1:1 tapping). This phenomenon is called the "subdivision benefit," which is interpreted as that additional temporal references by subdivided tones make synchronization more stable. However, it is unclear whether visuomotor synchronization becomes more stable by subdividing a stimulus sequence. To clarify this, the present study compared 1:3 tapping with a sequence of three-picture patterns and 1:1 tapping with a single picture repetition. When the inter-tap interval (ITI) was 1200 ms or more, the tapping variability showed a subdivision benefit, irrespective of the position of the pictures (1st, 2nd, or 3rd picture) in the three-picture pattern. However, when the ITI was1000 ms, subdivision did not have any significant effect. These results imply that the subdivision benefit is due to the additional temporal reference provided by the subdivided stimuli, and the benefit depends on the ITI length.