Severe fibromyalgia alleviated by the unique muscle relaxation method of applying low force: A case report.

RATIONALE: Fibromyalgia (FM) is characterized by idiopathic persistent chronic pain in the ligaments or musculoskeletal system, and more than half of the patients with FM might have migraine headaches. Direct musculoskeletal intervention could be a non-pharmacological management to relieve symptoms. However, patients with severe FM often have intense pain from only a soft touch, thereby rendering musculoskeletal intervention challenging. PATIENT CONCERNS: A 47-year-old man had progressing intense pain, and this affected his everyday life. There were no abnormal physical findings on laboratory examination such as levels of complement, antinuclear antibodies, and C-reactive protein, which were within normal limits. Magnetic resonance imaging did not indicate abnormalities. DIAGNOSES, INTERVENTIONS, AND OUTCOMES: The patient satisfied the American College of Rheumatology criteria. Finally, we made a final diagnosis of fibromyalgia. The therapeutic intervention of Kanshoho, the unique muscle relaxation technique with low force, relieved his pain. LESSONS: If Kanshoho is carefully applied in a state of hospitalization under surveillance by an experienced physician, it could be a promising muscle relaxation method. Relaxing the trapezius muscle and reducing its intramuscular pressure might be key in treating patients with severe FM. However, it needs elucidation of its mechanism.

Exercise Suppresses Head and Neck Squamous Cell Carcinoma Growth via Oncostatin M.

Major advances have been made in cancer treatment, but the prognosis for elderly cancer patients with sarcopenia and frailty remains poor. Myokines, which are thought to exert preventive effects against sarcopenia, have been reported to be associated with the prognosis of various cancers, but their effect on head and neck squamous cell carcinoma (HNSCC) is unknown. The aim of this study was to clarify the influence of exercise on the control of HNSCC and to examine the underlying mechanism involved. Mice were injected with HSC-3-M3 cells, a human cell line of highly metastatic and poorly differentiated tongue cancer, at the beginning of the study. Just prior to transplantation, blood was collected from the mice, and the levels of myokines were measured by ELISA. Oncostatin M (OSM), a selected myokine, was added to HSC-3-M3 cells, after which the cell proliferation ability, cell cycle, and protein expression were analyzed in vitro. Tumor cell viability was lower (control: 100%, exercise: 75%), tumors were smaller (control: 26.2 mm3, exercise: 6.4 mm3), and survival was longer in the exercise group than in the control group in vivo. OSM inhibited HSC-3-M3 cell proliferation in a concentration-dependent manner in vitro. The addition of OSM increased the proportion of cells in the G0/G1 phase, decreased the proportion of cells in the G2/M phase, and increased the expression of the CDK inhibitors p21 and p27. These results indicate that exercise may directly inhibit the proliferation of HNSCC cell lines via OSM.

Musclin prevents depression-like behavior in male mice by activating urocortin 2 signaling in the hypothalamus.

Introduction: Physical activity is recommended as an alternative treatment for depression. Myokines, which are secreted from skeletal muscles during physical activity, play an important role in the skeletal muscle-brain axis. Musclin, a newly discovered myokine, exerts physical endurance, however, the effects of musclin on emotional behaviors, such as depression, have not been evaluated. This study aimed to access the anti-depressive effect of musclin and clarify the connection between depression-like behavior and hypothalamic neuropeptides in mice. Methods: We measured the immobility time in the forced swim (FS) test, the time spent in open arm in the elevated-plus maze (EPM) test, the mRNA levels of hypothalamic neuropeptides, and enumerated the c-Fos-positive cells in the paraventricular nucleus (PVN), arcuate nucleus (ARC), and nucleus tractus solitarii (NTS) in mice with the intraperitoneal (i.p.) administration of musclin. Next, we evaluated the effects of a selective corticotropin-releasing factor (CRF) type 1 receptor antagonist, selective CRF type 2 receptor antagonist, melanocortin receptor (MCR) agonist, and selective melanocortin 4 receptor (MC4R) agonist on changes in behaviors induced by musclin. Finally we evaluated the antidepressant effect of musclin using mice exposed to repeated water immersion (WI) stress. Results: We found that the i.p. and i.c.v. administration of musclin decreased the immobility time and relative time in the open arms (open %) in mice and increased urocortin 2 (Ucn 2) levels but decreased proopiomelanocortin levels in the hypothalamus. The numbers of c-Fos-positive cells were increased in the PVN and NTS but decreased in the ARC of mice with i.p. administration of musclin. The c-Fos-positive cells in the PVN were also found to be Ucn 2-positive. The antidepressant and anxiogenic effects of musclin were blocked by central administration of a CRF type 2 receptor antagonist and a melanocortin 4 receptor agonist, respectively. Peripheral administration of musclin also prevented depression-like behavior and the decrease in levels of hypothalamic Ucn 2 induced by repeated WI stress. Discussion: These data identify the antidepressant effects of musclin through the activation of central Ucn 2 signaling and suggest that musclin and Ucn 2 can be new therapeutic targets and endogenous peptides mediating the muscle-brain axis.

Macrocytic anemia induced by selenium deficiency in the course of anorexia nervosa: A case report.

RATIONALE: Anorexia nervosa is characterized by an extreme fear of weight gain. Clinicians often prescribe meal replacement shakes if patients are unable or unwilling to consume typical foods. However, these shakes sometimes lack essential micronutrients, such as selenium, which may lead to health risks. Moreover, selenium deficiency induces macrocytic anemia. Herein, we present a case of a patient with anorexia nervosa with macrocytic anemia due to selenium deficiency, which was alleviated by selenium supplementation. PATIENT CONCERNS: An 18-year-old female was admitted to our hospital. The patient was diagnosed with anorexia nervosa. Ultimately, she was unable to walk independently because of fatigue and electrolyte disturbances. CLINICAL FINDINGS: On admission, the height, weight, and body mass index of the patient were 158.5 cm, 27.1 kg, and 10.8, respectively. Our treatment for anorexia nervosa showed relative effectiveness, and the patient's body weight recovered to 29.2 kg by day 60. However, the mean corpuscular volume increased from day 20, suggesting macrocytic anemia. DIAGNOSES, INTERVENTIONS, AND OUTCOMES: Despite our vitamin B12 and folic acid supplementation interventions, the mean corpuscular volume continued to rise. On day 60, the patient was diagnosed with selenium deficiency, and selenium administration of 100 µg/day was initiated. OUTCOMES: The macrocytic anemia in the patient was alleviated, and treatment for anorexia nervosa was continued in our hospital. LESSONS: To the best of our knowledge, this is the first case of macrocytic anemia induced by selenium deficiency with anorexia nervosa comorbidity, underscoring the importance of selenium supplementation in patients with anorexia nervosa, especially in those with macrocytic anemia.

The effect of lavender aroma for anxiety disorder: a study protocol for a multicenter, double-masked, randomized, placebo-controlled clinical trial.

BACKGROUND: Anxiety disorder is the most prevalent psychiatric disorder. Benzodiazepines, which are often used for anxiety in patients with anxiety disorder, have various side effects. Lavender, one of the most commonly used essential oils in aromatherapy, has the potential to reduce benzodiazepine use for anxiety disorders. METHODS: This study is a multicenter, double-masked, randomized, placebo-controlled clinical trial. The study will recruit patients aged 20-59 years old with generalized anxiety disorder and panic disorder among anxiety disorders. The bottle containing the test solution (lavender aroma essential oil or distilled water) will be given to the patients. Patients will carry the bottles with them in their daily life and use the drops on tissue paper when anxious. The primary endpoint is the number of times anxiolytics used in 28 days. DISCUSSION: If the use of benzodiazepines could be reduced by sniffing lavender aroma, which is inexpensive and safe, it would contribute not only to the risks associated with benzodiazepine use but also to the health care economy and could even be added as a standard treatment. TRIAL REGISTRATION: University hospital Medical Information Network Clinical Trials Registry (UMIN-CTR), ID: UMIN000034422 Registered 17 January 2019.

Correlation between trait emotional intelligence and prefrontal activation during a verbal fluency task: A functional near-infrared spectroscopy study.

Stress is inevitable in humans and stress changes our physical and mental states. Stress has been studied epidemiologically, biologically, and psychologically. First defined in 1990, emotional intelligence (EI) affects psychological stress management. In contrast, the prefrontal cortex (PFC) is suggested to play a vital role in stress management. Human PFC activity can be inferred from the balance of oxygenated and deoxygenated hemoglobin in cerebral blood flow, which can be measured and calculated using functional near-infrared spectroscopy (fNIRS). An important cognitive activation task to activate the PFC is the verbal fluency task (VFT). Therefore, if the PFC is activated by the VFT and monitored by fNIRS, and the activity correlates with EI, fNIRS can be used to measure EI. In this study, Psychological tests using the self-rating depression scale, state-trait anxiety inventory (STAI), and trait emotional intelligence questionnaire-short form (TEIQue-SF) were conducted to evaluate the correlation with VFT performance. Relative oxygenated and deoxygenated hemoglobin concentrations were measured using an fNIRS device, and their correlation with VFT performance was tested. Spearman correlation coefficient was used to determine correlations. Results were as follows. Although VFT performance did not correlate with the oxygenated hemoglobin concentration ([Oxy-Hb]) changes, [Oxy-Hb] was elevated in all channels. VFT performance was significantly negatively correlated with the Zung self-rating depression scale (ρ = 0.063, P = .759), trait anxiety or anxiety level as a personal characteristic of STAI (ρ = 0.243, P = .232), and state anxiety or anxiety about an event of STAI (ρ = -0.138, P = .500), whereas no correlation was found with the TEIQue-SF (ρ = 0.303, P = .132). Healthy individuals PFC activity is not severely affected by their mental state and cognitive activation successfully activates the PFC, supporting the hypothesis that EI is correlated with frontal cortical activation during the VFT in a nonclinical population. EI may play a vital role in reducing stress associated with depression and anxiety in our social lives. Although we failed to show a statistical correlation between TEIQue-SF and [Oxy-Hb] due to a sample size shortage, our preliminary study was the first to attempt to show the PFC activity of EI through a hemodynamic response. Future research may elucidate the role of EI in reducing psychological stress in social life.

Unpredictable refeeding syndrome with severe hypophosphatemia in borderline personality disorder comorbidity: A case report.

RATIONALE: Refeeding syndrome (RS) is a fatal condition caused by rapid calorie intake during starvation. Self-neglected fasting in psychiatric disorders is associated with RS. However, overeating resulting from circumventing the clinician's instructions does not have a reportedly high risk of RS. PATIENT CONCERNS: A 47-year-old undernourished woman with borderline personality disorder was hospitalized for nausea, vomiting, and diarrhea. CLINICAL FINDINGS: She had not eaten much for 10 days and had lost weight (56.5-51.1 kg) over 3 weeks. No abnormalities were indicated on physical examination and imaging examinations. DIAGNOSES, INTERVENTIONS, AND OUTCOMES: Infectious diseases and malignancies were excluded from the differential diagnosis. On the third day of admission, the patient's serum phosphorus level significantly decreased to 0.7 mg/dL, and additional sodium phosphate was administered intravenously. On the fourth day, despite our instructions, the patient was found to be eating nonhospital food from the first day of admission. In conjunction with her history, a final diagnosis of RS was made. After appropriate treatments, the patient was discharged on the 15th day of hospitalization. The patient's nausea, vomiting, and diarrhea were improved. LESSONS: When undernourished patients have psychiatric disorders, including borderline personality disorder or schizophrenia, the occurrence of RS should be considered based on the patients' poor adherence to physicians' instructions.

Malocclusion impairs cognitive behavior via AgRP signaling in adolescent mice.

Introduction: Occlusal disharmony induced by deteriorating oral health conditions, such as tooth loss and decreased masticatory muscle due to sarcopenia, is one of the causes of cognitive impairment. Chewing is an essential oral function for maintaining cognitive function not only in the elderly but also in young people. Malocclusion is an occlusal disharmony that commonly occurs in children. The connection between a decline in cognitive function and malocclusion in children has been shown with chronic mouth breathing, obstructive sleep apnea syndrome, and thumb/digit sucking habits. However, the mechanism of malocclusion-induced cognitive decline is not fully understood. We recently reported an association between feeding-related neuropeptides and cognitive decline in adolescent mice with activity-based anorexia. The aim of the present study was to assess the effects of malocclusion on cognitive behavior and clarify the connection between cognitive decline and hypothalamic feeding-related neuropeptides in adolescent mice with malocclusion. Methods: Four-week-old mice were randomly assigned to the sham-operated solid diet-fed (Sham/solid), sham-operated powder diet-fed (Sham/powder), or malocclusion-operated powder diet-fed (Malocclusion/powder) group. We applied composite resin to the mandibular anterior teeth to simulate malocclusion. We evaluated cognitive behavior using a novel object recognition (NOR) test, measured hypothalamic feeding-related neuropeptide mRNA expression levels, and enumerated c-Fos-positive cells in the hypothalamus 1 month after surgery. We also evaluated the effects of central antibody administration on cognitive behavior impairment in the NOR test. Results: The NOR indices were lower and the agouti-related peptide (AgRP) mRNA levels and number of c-Fos-positive cells were higher in the malocclusion/powder group than in the other groups. The c-Fos-positive cells were also AgRP-positive. We observed that the central administration of anti-AgRP antibody significantly increased the NOR indices. Discussion: The present study suggests that elevated cerebral AgRP signaling contributes to malocclusion-induced cognitive decline in adolescents, and the suppression of AgRP signaling can be a new therapeutic target against cognitive decline in occlusal disharmony.

Possible effect of natural light on emotion recognition and the prefrontal cortex: A scoping review of near-infrared (NIR) spectroscopy.

Near-infrared (NIR) spectroscopy, also known as functional NIR spectroscopy (fNIRS), is a tool for measuring the hemodynamic response of the prefrontal cortex (PFC) by using NIR light, enabling a noninvasive indirect neural activity assessment. The application of fNIRS in emotion recognition or the differential diagnosis of psychiatric disorders of depressive patients, including major depressive disorder, bipolar disorder and schizophrenia, has previously been reported. Although the use of fNIRS has gradually expanded in cognitive neuroscience studies, few researchers have focused on the effects of light exposure in fNIRS studies. In addition, to the best of our knowledge, there are no scoping reviews of fNIRS studies on light exposure. Because light is an important topic in cognitive neuroscience and psychiatry, we evaluated fNIRS studies on light exposure in humans. We reviewed 10 papers in their entirety. Bright light (BR) modulates fear, and the color differences showed no significance in 1 study, whereas other studies delved extensively into the effects of colored light, finding some individual hemodynamic responses. In our study, we highlighted that the effects of natural light have not been studied using fNIRS. Light is becoming a critical topic in cognitive neuroscience and psychiatry, and fNIRS is critical for improving public health and managing psychiatric disorders.

Esophageal achalasia, diagnosed through the repeated manometry, alleviated using benzodiazepine: A case report.

RATIONALE: Idiopathic achalasia is an esophageal peristaltic dysfunction of the lower esophageal sphincter (LES). The initial symptom is progressive dysphagia. However, due to its rarity, it is often misdiagnosed as an esophageal disorder. High LES pressure on esophageal manometry is an essential finding for the diagnosis. PATIENT CONCERNS: A 55-year-old man was hospitalized with saliva-like vomitus, stuck-in-throat feeling of dysphagia, and weight loss. CLINICAL FINDINGS: On initial admission, gastrointestinal endoscopy, esophageal manometry, laboratory tests, and physical examination results were within normal limits. DIAGNOSES, INTERVENTIONS, AND OUTCOMES: Initially, the patient was diagnosed with globus sensation and recovered with medication. However, the symptoms recurred. He requested another examination on the second admission and was diagnosed with achalasia based on repeat esophageal manometry. The patient recovered after surgical treatment. LESSONS: When patients still suffer from these symptoms, there is a need to reconsider achalasia, even if it is initially excluded from the differential diagnosis. Medication is not a radical treatment; however, it sometimes ameliorates symptoms. Moreover, the psychosomatic approach can be useful in such cases.

Intraperitoneal administration of nesfatin­1 stimulates glucagon­like peptide­1 secretion in fasted mice.

Increasing endogenous secretion of glucagon­like peptide (GLP)­1 is considered a promising therapeutic approach for type 2 diabetes because decreased GLP­1 plasma concentrations have been observed in patients with this condition. Nesfatin­1, which is a central and peripheral anorexigenic peptide, has been reported to release GLP­1 from enteroendocrine STC­1 cells, although whether nesfatin­1 stimulates GLP­1 secretion in vivo remains to be elucidated. Previous studies have indicated that nesfatin­1 has glucose­lowering and insulinotropic effects in mice and rats; however, the in vivo mechanism remains unclear. The present study aimed to investigate whether peripheral administration of nesfatin­1 increased blood concentrations of GLP­1 and insulin in food­deprived mice. Nesfatin­1 was administered intraperitoneally to 18­h fasted mice. Plasma GLP­1 and insulin concentrations in the mice administered 2.5 µmol/kg nesfatin­1 were higher than those in saline­treated mice. Blood glucose concentrations in mice treated with 1.25 and 2.5 µmol/kg nesfatin­1 were lower than those in saline­treated mice. The mRNA expression of preproglucagon in mouse ilea after treatment with 1.25 µmol/kg nesfatin­1 was higher than that in saline­treated mice. The administration of 1.25 µmol/kg nesfatin­1 raised GLP­1 concentrations at 30 and 60 min and insulin concentrations at 30 and 60 min after injection. Furthermore, the higher level of nesfatin­1­induced insulin was diminished by pre­administration of anti­GLP­1 antiserum. Intraperitoneally administered nesfatin­1 increased insulin concentrations by accelerating GLP­1 secretion. The results are the first in vivo demonstration of promotion of GLP­1 secretion by nesfatin­1 in the mouse, suggesting the developmental potential of nesfatin­1 for GLP­1 release.

Rubiscolin­6 rapidly suppresses the postprandial motility of the gastric antrum and subsequently increases food intake via δ­opioid receptors in mice.

Rubiscolin­6 is a food­derived opioid peptide found in Spinacia oleracea that has anti­nociceptive, memory­enhancing, anxiolytic­like and anti­depressant effects. Rubiscolin­6 has been reported to have two opposing effects on food intake. Food intake is closely connected to gut motility; however, to the best of our knowledge, the effect of rubiscolin­6 on gut motility has not been reported. The present study aimed to investigate the effect of rubiscolin­6 on postprandial motility of the gastric antrum in conscious mice. A catheter was implanted in the gastric antrum of male C57BL/6J mice. Manometric measurements were performed in fasted male mice and chow was then provided to assess motility in the fed state. Rubiscolin­6, the δ­opioid receptor antagonist naltrindole, a mixture of rubiscolin­6 and naltrindole, or vehicle was administered intraperitoneally 30 min after eating. The percentage motor index (%MI) was then calculated. Cumulative food intake was measured in both ad libitum­fed and overnight­fasted mice. The %MI was significantly lower in mice treated with rubiscolin­6 compared with that in the other groups, but normalized by treatment with the rubiscolin­6/naltrindole mixture. The decrease in %MI induced by rubiscolin­6 remained for 1 h after administration. Cumulative food intake was significantly higher 4 and 6 h after rubiscolin­6 administration in ad libitum­fed mice but was normalized by the rubiscolin­6/naltrindole mixture. Food intake 30 min after rubiscolin­6 administration was normal, but was higher in mice treated with the rubiscolin­6/naltrindole mixture. Thus, rubiscolin­6 may have a rapid effect to reduce postprandial antral motility and may subsequently increase food intake after this inhibitory effect disappears. These effects were revealed to be mediated through δ­opioid receptors. The orexigenic effect of rubiscolin­6 may be applicable to the treatment of anorexia and cachexia.

The Effect of Mindfulness Yoga in Children With School Refusal: A Study Protocol for an Exploratory, Cluster-Randomized, Open, Standard Care-Controlled, Multicenter Clinical Trial.

Background: School refusal occurs in about 1-2% of young people. Anxiety and depression are considered to be the most common emotional difficulties for children who do not attend school. However, at present, no definitive treatment has been established for school refusal, although interventions such as cognitive behavioral therapy have been used. This paper reports a protocol for a cluster-randomized controlled trial of a mindfulness yoga intervention for children with school refusal. Methods: This study is a multicenter, exploratory, open cluster-randomized controlled trial. This study will recruit children aged 10-15 years with school refusal. After a 2-week baseline, participants for each cluster will be randomly assigned to one of two groups: with or without mindfulness yoga for 4 weeks. Mindfulness yoga will be created for schoolchildren for this protocol and distributed to the participants on DVD. The primary outcome is anxiety among children with school refusal using the Spence Children's Anxiety Scale-Children. Discussion: For this study, we developed a mindfulness yoga program and protocol, and examine whether mindfulness yoga can improve anxiety in children with school refusal. Our mindfulness yoga program was developed based on the opinions of children of the same age, and is a program that children can continue to do every day without getting bored. In this way, we believe that we can contribute to the smooth implementation of support to reduce the anxiety of children with school refusal, and to the reduction of the number of children who refuse to go to school.

Application of objective structured clinical examination (OSCE) for the evaluation of Kampo medicine training.

BACKGROUND: The purpose of this study was to develop an objective, content-valid, and reliable assessment method for Kampo medicine using an objective structured clinical examination (OSCE) for the assessment of clinical competence in Kampo medicine. METHODS: We developed a blueprint followed by a list of 47 assessment items and three task scenarios related to clinical competence in Kampo medicine. An eight-member test committee checked the relevance of the assessment items on a Likert scale. We calculated a content validity index and content validity ratio, and used the Angoff method to set the passing threshold. We trained a total of nine simulated patients with three assigned to each scenario. We conducted an OSCE for 11 candidates with varying medical abilities, and conducted three stations per person, which were evaluated by one evaluator in one room by direct observation. We used video recordings to test the inter-rater reliability of the three raters. We used the test results to verify the reliability of the assessment chart. RESULTS: The inter-rater reliability (intraclass correlation coefficient [2,1]) was 0.973. The reliability of the assessment chart for each scenario (Cronbach's α) was 0.86, 0.89, and 0.85 for Scenarios 1, 2, and 3, respectively. The reliability of the assessment chart for the whole OSCE (Cronbach's α) was 0.90. CONCLUSIONS: We developed a content-valid new OSCE assessment method for Kampo medicine and obtained high inter-rater and test reliabilities. Our findings suggest that this is one of the most reliable evaluation methods for assessing clinical competence in Kampo medicine.

Evidence-based clinical practice guidelines for functional dyspepsia 2021.

BACKGROUND: Functional dyspepsia (FD) is a disorder that presents with chronic dyspepsia, which is not only very common but also highly affects quality of life of the patients. In Japan, FD became a disease name for national insurance in 2013, and has been gradually recognized, though still not satisfactory. Following the revision policy of Japanese Society of Gastroenterology (JSGE), the first version of FD guideline was revised this time. METHOD: Like previously, the guideline was created by the GRADE (grading of recommendations assessment, development and evaluation) system, but this time, the questions were classified to background questions (BQs, 24 already clarified issues), future research questions (FRQs, 9 issues cannot be addressed with insufficient evidence), and 7 clinical questions that are mainly associated with treatment. RESULTS AND CONCLUSION: These revised guidelines have two major features. The first is the new position of endoscopy in the flow of FD diagnosis. While endoscopy was required to all cases for diagnosis of FD, the revised guidelines specify the necessity of endoscopy only in cases where organic disease is suspected. The second feature is that the drug treatment options have been changed to reflect the latest evidence. The first-line treatment includes gastric acid-secretion inhibitors, acetylcholinesterase (AChE) inhibitors (acotiamide, a prokinetic agent), and Japanese herbal medicine (rikkunshito). The second-line treatment includes anxiolytics /antidepressant, prokinetics other than acotiamide (dopamine receptor antagonists, 5-HT4 receptor agonists), and Japanese herbal medicines other than rikkunshito. The patients not responding to these treatment regimens are regarded as refractory FD.

Survey of problems in Kampo curriculum and the need for interdisciplinary collaboration education in Japanese medical, pharmacy, dental, and nursing departments.

In recent years, there has been a lot of research on the effectiveness of Kampo medicine. New findings from modern medicine are also being delivered in addition to traditional education in Japanese University. Kampo treatment covers a wide range of disorders. To achieve multidisciplinary cooperation in Kampo treatment, it is necessary to have an education system in which pharmacy, nursing, medicine and dentistry collaborate. The purpose of this study was to investigate the current status of Kampo classes in Japanese universities to clarify the problems experienced by each department and the needs for a system of interdisciplinary collaboration, and to examine what a new curriculum should encompass. We conducted a questionnaire survey of the Kampo curriculum at all medical, pharmaceutical, dental and nursing schools at universities in Japan. The target respondents were faculty members and administrators in charge of Kampo lectures. Multivariate analysis and correspondence analysis were conducted for multiple response items. Fisher's exact test and Cochrane's Q test were used to compare response frequency among departments and desired collaborators in each faculty, respectively. The results showed that the lack of instructors and the number of hours in the curriculum were problems in the departments of medicine, dentistry, and nursing. Medical, nursing, and dental departments cited the lack of time in their curriculum as a problem. The departments of medicine and pharmacy wished to further incorporate experiential learning (active learning) and problem-based learning/tutorial teaching methods. Incorporating an interdisciplinary collaboration system in the Kampo curriculum was required by a large percentage of respondents from all four academic departments. We identified trends in the problems and needs of each individual department, and this has given us direction for the development of Kampo curriculum in the future. Based on these findings, a new curriculum that includes interdisciplinary collaboration is required.

Activation of α7 nicotinic receptors suppresses sucrose addiction in mice.

The mesolimbic dopamine system is important for the rewarding and motivational aspects of consuming rewarding and palatable food. Nicotinic receptors are present in the mesolimbic dopamine system and enhance the reinforcement of drugs of abuse. In this study, we examined the involvement of nicotine receptor subtypes in sucrose addiction in a sucrose preference paradigm. Sucrose preference and intake in mice increased in proportion to stepwise increases in sucrose concentrations. Moreover, sucrose preference and intake following sucrose withdrawal in mice were increased in comparison with the first set of trials. In the present study, α7, but not α4 and ß2, nicotinic receptor subunit mRNA was decreased in the nucleus accumbens, but not in the hypothalamus, after sucrose withdrawal and subsequent sucrose intake. Administration of an agonist for α7, but not α4 and ß2, nicotinic receptors suppressed the enhancement of sucrose preference and intake following sucrose withdrawal. These findings indicate that α7 nicotinic receptor activation suppresses sucrose addiction in a sucrose preference test in mice.

Atractylenolide-III suppresses lipopolysaccharide-induced inflammation via downregulation of toll-like receptor 4 in mouse microglia.

Atractylenolide-III (AIII), a sesquiterpene compound isolated from the rhizome of Atractylodes macrocephala, has been reported to have anti-inflammatory effects in the peripheral organs. However, its effects on brain inflammation remain elusive. The present study investigated the effects of AIII on the response to lipopolysaccharide (LPS) in mouse microglia and clarified the underlying mechanism. In this study, treatment of MG6 cells with AIII (100 µM) significantly decreased the mRNA expression and protein levels of toll-like receptor 4 (TLR4). In addition, pretreatment of MG6 cells and primary cultured microglia cells with AIII (100 µM) significantly decreased the mRNA expression and protein levels of tumor necrosis factor-α, interleukin-1ß, interleukin-6, inducible nitric oxide synthase, and cyclooxygenase-2 induced by LPS (5 ng/mL) without cytotoxicity. Subsequently, pretreatment with AIII significantly suppressed the phosphorylation of p38 mitogen-activated protein kinase (p38 MAPK) and c-Jun NH2-terminal kinase (JNK) after LPS stimulation in MG6 cells. These results showed that AIII downregulated TLR4 expression, leading to suppression of the p38 MAPK and JNK pathways, which in turn inhibited the production of pro-inflammatory cytokines and enzymes in LPS-stimulated microglia. Our findings, therefore, suggest the potential for AIII as a therapeutic agent for the treatment of brain inflammation, particularly in microglia-associated inflammation.

The relationship between premorbid intelligence and symptoms of severe anorexia nervosa restricting type.

The purposes of this study were as follows: to compare premorbid IQ with present IQ in patients with more severe anorexia nervosa restricting type (AN-R) and to investigate the relationship between decreasing IQ and symptoms in patients with severe AN-R. Twenty-two participants were recruited (12 were AN-R patients; 10 were healthy controls). The average BMI in AN-R patients and healthy controls was 12.65 and 19.82, respectively. We assessed the outcomes using the Wechsler Adult Intelligence Scale-Third Edition (WAIS-III), the Japanese Adult Reading Test, The Eating Disorders Inventory-2 (EDI-2), Beck Depression Scale-2 (BDI-2) and State-Trait Anxiety Index. In two-way ANOVA, there were significant interactions for the FIQ and PIQ. Only in the AN-R group, a significant single main effect of time was evidenced for the FIQ and PIQ. In the AN-R group, a significantly high positive correlation was found between changes in the PIQ and the body dissatisfaction subscale of the EDI-2. These findings raise the possibility that in patients with severe AN-R, an excessive decrease in body weight induces decreased PIQ; as a result, they have worse dissatisfaction with their body shape.