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.

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.

Impact of Ninjin'yoeito on frailty and short life in klotho-hypomorphic (kl/kl) mice.

With the recent aging of society, the prevention of frailty has become an important issue because people desire both a long and healthy lifespan. Klotho-hypomorphic (kl/kl) mice are known to show phenotypes of premature aging. Ninjin'yoeito (NYT) is a traditional Japanese Kampo medicine used to treat patients with vulnerable constitution, fatigue or physical exhaustion caused by aging and illness. Recent studies have reported the potential efficacy of NYT against frailty. We therefore evaluated the effect of NYT on the gait function, activity, the histopathological status of organs and survival using kl/kl mice as a model of aging-related frailty. Two sets of 28-day-old male kl/kl mice were assigned to the vehicle (non-treated; NT), 3% or 5% NYT dietary groups. One set of groups (NT, n = 18; 3% NYT, n = 11; 5% NYT, n = 11) was subjected to the analysis of free walking, rotarod, and spontaneous activity tests at approximately 58 days old. Thereafter, we measured triceps surae muscles weight and myofiber cross-sectional area (CSA), and quantified its telomere content. In addition, we evaluated bone strength and performed histopathological examinations of organs. Survival was measured in the second set of groups (NT, 3% NYT and 5% NYT group, n = 8 each). In the walking test, several indicators such as gait velocity were improved in the NYT 3% group. Similar results were obtained for the latency to fall in the rotarod test and spontaneous motor activity. Triceps muscle mass, CSA and its telomere content were significantly improved in the NYT 3% group. Bone density, pulmonary alveolus destruction and testicular atrophy were also significantly improved in the NYT 3% group. Survival rate and body weight were both significantly improved in the NYT3% group compared with those in the NT group. Continuous administration of NYT from the early stage of aging improved not only gait performance, but also the survival in the aging-related frailty model. This effect may be associated with the improvements in aging-related organ changes such as muscle atrophy. Intervention with NYT against the progression of frailty may contribute to a longer, healthier life span among the elderly individuals.

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.

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.

Medicine and food with particular reference to chinpi, dried citrus peel, and a component of Ninjin'yoeito.

Kampo medicines contain many kinds of herbal drugs. Chinpi and Kippi, dried citrus peels, are components of a substantial number of Kampo medicine. They contain abundant flavonoids and studies on hesperidin, narirutin, and nobiletin as active ingredient have been conducted. Conversely, in Kagoshima prefecture, located in the southwestern part of the Japanese Islands, various citrus products are cultivated. Among them, Tankan and Daimasaki are specialies. In this study, we conducted high- performance liquid chromatography to determine the difference in flavonoid contents among Tankan, Daimasaki, Tankan related product, Chinpi, and Kippi. As a result, several active components, such as hesperidin, narirutin, nobiletin, and tangeretin, in common with crude drug, Chinpi, were detected in local citrus fruits. In addition, some active components little or not found in Chinpi, for example hesperetin and rutin, were detected in the local products. A detailed analysis of active components considering their genetic origin, the time of fruit collection, and different parts of the fruit used (peel, albedo, edible parts, and the whole) will need to be discussed to get the most out of the citrus fruits or make best use of them for health and longevity.

Antagonism for NPY signaling reverses cognitive behavior defects induced by activity-based anorexia in mice.

Patients with AN often express psychological symptoms such as body image distortion, cognitive biases, abnormal facial recognition, and deficits in working memory. However, the molecular mechanisms underlying the impairment of cognitive behaviors in AN remain unknown. In the present study, we measured cognitive behavior using novel object recognition (NOR) tasks and mRNA expressions in hypothalamic neuropeptides in female C57BL/6J mice with activity-based anorexia (ABA). Additionally, we evaluated the effects of antagonists with intracerebroventricular (icv) administration on the impairment of cognitive behavior in NOR tasks. Our results showed that NOR indices were lowered, subsequently increasing mRNA levels of agouti-related peptide (AgRP) and neuropeptide Y (NPY), and c-Fos- and AgRP- or NPY-positive cells in the hypothalamic arcuate nucleus in ABA mice. We also observed that icv administration of anti-NPY antiserum (2 µl), anti-AgRP antibody (0.1 µg), and Y5 receptor antagonist CPG71683 (15 nmol) significantly reversed the decreased NOR indices. Therefore, our results suggest that increased NPY and AgRP signaling in the brain might contribute to the impairment of cognitive behavior in AN.

The Effectiveness of Cognitive Behavioral Therapy With Mindfulness and an Internet Intervention for Obesity: A Case Series.

It is difficult for obese (body mass index of more than 30) and overweight (body mass index of 25-30) people to reduce and maintain their weight. The aim of this case series was to examine the effectiveness of a new cognitive behavioral therapy (CBT) program that combines mindfulness exercises (e.g., the raisin exercise and breathing exercises) and an online intervention to prevent dropout and subsequent weight gain in overweight participants. This case series included three participants, for whom previous weight reduction programs had been unsuccessful. All participants completed the program (60-min, group sessions provided weekly for 9 weeks) and an 18-month follow-up assessment. Results showed that all participants succeeded in losing weight (loss ranged from 5.30 to 8.88% of their total body weight). Although rebound weight gain is commonly observed in the first year following initial weight loss, the follow-up assessment showed that participants achieved further weight loss during the 18-month follow-up period. These results suggest that a CBT program that comprises mindfulness and an online intervention may be an effective method for weight loss and maintenance, and may prevent dropout in obese and overweight individuals. TRIAL REGISTRATION: This case series was registered at www.umin.ac.jp with identifier UMIN000029664.

Herbal Medicine Ninjin'yoeito in the Treatment of Sarcopenia and Frailty.

Frailty and sarcopenia have recently gained considerable attention in terms of preventive care in Japan, which has an ever-increasing aging population. Sarcopenia is defined as atrophy of skeletal muscles caused by the age-related decrease in growth hormone/insulin-like growth factor and sex hormones. The Japanese Ministry of Health, Labor and Welfare reports that frailty can lead to impairment of both mental and physical functioning. Chronic diseases such as diabetes and dementia may underlie frailty. It is important to prevent progression of frailty and extend the healthy lifespan. In herbal medicine practice, including Japanese Kampo medicine, "Mibyo," a presymptomatic state, has long been recognized and may be applicable to frailty. Kampo medicines may include several medicinal plants and are thought to have the potential to improve symptoms of frailty, such as loss of appetite and body weight, fatigue, and sarcopenia, as well as anxiety, depression, and cognitive decline. Ninjin'yoeito (Ren Shen Yang Ying Tang) is the most powerful Kampo medicine and has been widely applied to palliative care of cancer patients. This review includes recent anti-aging studies and describes the effects and mechanisms of Ninjin'yoeito (Ren Shen Yang Ying Tang) when used for frailty or to extend a healthy life expectancy.

A Role of Ginseng and Its Constituents in the Treatment of Central Nervous System Disorders.

Ginseng, a perennial plant belonging to the Panax genus of the Araliaceae family, has been used in China, Korea, and Japan as a traditional herbal medicine for thousands of years. Ginseng is recorded to have exhibited a wide variety of beneficial pharmacological effects and has become a popular and worldwide known health supplement and drug. The protective effects of ginseng on central nervous system are discussed in this review. Ginseng species and ginsenosides and their intestinal metabolism and bioavailability are concisely introduced. The molecular mechanisms of the effects of ginseng on central nervous system, mainly focused on the neuroprotection properties of ginseng, memory, and learning enhanced properties, and the effects on neurodegenerative disorders are presented. Thus, ginseng and its constituents are of potential merits in the treatment of cerebral disorders.

Case Report: A Non-small Cell Lung Cancer Patient Treated with GcMAF, Sonodynamic Therapy and Tumor Treating Fields.

BACKGROUND/AIM: Macrophage activating factor (MAF)-based immunotherapy has a wide application for use in treating many diseases via macrophage activation. Sonodynamic therapy (SDT) using low-intensity ultrasound and tumor treating field (TTF) therapy are novel therapeutic modalities. SDT is usually combined with ozone therapy to improve local hypoxia within the tumor environment. CASE REPORT: We treated a 77-year-old male diagnosed with non-small cell lung cancer ((NSCLC) stage 3B) using second-generation serum GcMAF and oral colostrum MAF-based immunotherapy combined with SDT, TTF and ozone therapies. RESULTS: This case report demonstrates that GcMAF, oral colostrum MAF, SDT, TTF and ozone therapy can be used for NSCLC without adverse effects. CONCLUSION: This case report suggests a new concept of cancer treatment using local destruction of cancer tissue, in this case conducted with SDT and TTF therapy, to be used in combination with serum GcMAF and colostrum MAF immunotherapy as a systemic treatment.

The translational aspect of complementary and alternative medicine for cancer with particular emphasis on Kampo.

Complementary and alternative medicine (CAM) including Japanese Kampo is known to have anticancer potential. An increasing number of cancer survivors are using CAM for disease prevention, immune system enhancement, and symptom control. Although there have been abundant previous clinical reports regarding CAM, scientific investigations aimed at acquiring quantifiable results in clinical trials, as well as basic research regarding CAM, have only recently been undertaken. Recent studies suggest that CAM enhancement of immune function is related to cytokines. This review provides a translational aspect of CAM, particularly Hozai in Kampo from both scientific and clinical points of view for further development of CAM for cancer treatment.

Cancer cachexia pathophysiology and translational aspect of herbal medicine.

About half of all cancer patients show a syndrome of cachexia, characterized by anorexia and loss of adipose tissue and skeletal muscle mass. Numerous cytokines have been postulated to play a role in the etiology of cancer cachexia. Cytokines can elicit effects that mimic leptin signaling and suppress orexigenic ghrelin and neuropeptide Y signaling, inducing sustained anorexia and cachexia not accompanied by the usual compensatory response. Furthermore, cytokines have been implicated in the induction of cancer-related muscle wasting. In particular, tumor necrosis factor-alpha, interleukin-1, interleukin-6 and interferon-gamma have been implicated in the induction of cancer-related muscle wasting. Cytokine-induced skeletal muscle wasting is probably a multifactorial process, which involves a depression in protein synthesis, an increase in protein degradation or a combination of both. Cancer patients suffer from the reduction in physical function, tolerance to anti-cancer therapy and survival, while many effective chemotherapeutic agents for cancer are burdened by toxicities that can reduce patient's quality of life or hinder their effective use. Herbal medicines have been widely used to help improve such conditions. Recent studies have shown that herbal medicines such as rikkunshito enhance ghrelin signaling and consequently improve nausea, appetite loss and cachexia associated with cancer or cancer chemotherapy, which worsens the quality of life and life expectancy of the patients. The multicomponent herbal medicines capable of targeting multiple sites could be useful for future drug discovery. Mechanistic studies and identification of active compounds could lead to new discoveries in biological and biomedical sciences.

Ghrelin and cachexia in chronic kidney disease.

Ghrelin is a growth hormone (GH) secretagogue and a potent orexigenic factor that stimulates feeding by interacting with hypothalamic feeding-regulatory nuclei. Its multifaceted effects are potentially beneficial as a treatment in human disease states. In both adult and pediatric chronic kidney disease (CKD) patients, decreased appetite plays a major role in wasting, which in turn is linked to morbidity and mortality; wasting has also been linked to high levels of leptin and proinflammatory cytokines. The beneficial effects of ghrelin treatment in CKD are potentially mediated by multiple concurrent actions, including the stimulation of appetite-regulating centers, anti-inflammatory effects, and direct kidney effects. Further evaluation of this appetite-regulating hormone in CKD is needed to confirm previous findings and to determine the underlying mechanisms.

The roles of salivary secretion, brain-gut peptides, and oral hygiene in obesity.

Obesity has a prevalence of 15-30% among European and American populations. It is an incurable chronic disease associated with considerable mortality and co-morbidity. The co-morbidity risk can be reduced substantially by a moderate weight loss of 5-15%. Notably, additional weight gain exacerbates the morbidity of any concurrent disease. Obesity is also recognized as the basis for metabolic syndrome. Recent research has shown that adipocytes secrete various hormones and cytokines that contribute to obesity. Leptin is an adipostatic hormone that acts on receptors in the hypothalamus to suppress food intake and increase energy consumption. Reduced sensitivity to this molecule can trigger the onset of obesity. Neuropeptides such as leptin also affect salivary secretion. Various neuropeptides have been identified in saliva; the associated receptors are located in the salivary glands or in the nerves innervating the salivary glands. Obesity is associated with hyposalivation and thereby related to several aspects of oral health, such as caries and periodontitis. Hyposalivation is a severe morbidity that can lead to a precipitous decline in oral hygiene, which further leads to multifocal dental caries and periodontitis, or even cardiac disorders. In this article, we review the relationship between salivary secretion and neuropeptides known to play a role in obesity.

Efficacy of ghrelin in cancer cachexia: clinical trials and a novel treatment by rikkunshito.

Cachexia is characterized by decreased food intake, increased energy expenditure, and muscle wasting. It is observed in 80% of patients with advanced-stage cancer and is a major source of decreased quality of life and increased morbidity and mortality in cancer patients. Ghrelin plays an important role in stimulating hunger and maintaining energy homeostasis and is the first-line treatment option for cancer cachexia. Several studies in rodent models and clinical trials have demonstrated that ghrelin or ghrelin receptor (GHS-R) agonists are effective in the treatment of cancer cachexia; however, further large-scale long-term clinical trials are needed to confirm sustained effects. Recently, the traditional Japanese medicine rikkunshito has been shown to increase food intake in rats with cancer or administered chemotherapeutics. The orexigenic effect of rikkunshito is involved in the stimulation of endogenous ghrelin secretion by blocking the serotonin (5-HT) 2b/2c receptor pathway and the enhancement of GHS-R activity. A potentiator of ghrelin signaling such as rikkunshito may represent a novel approach for the treatment of cancer cachexia.

Cachexia and herbal medicine: perspective.

Kampo, a form of traditional herbal medical practice, has become a substance of interest for scientific research. Although earlier clinical reports concerning Kampo are abundant, the scientific investigation of Kampo has a very short history. However, the process of acquiring quantifiable clinical trial evidence on herbal medicine is now clearly underway. The development of multi-component herbal medicines capable of targeting multiple sites could be useful both for future drug discovery and for the potential management of complex diseases. Additionally, mechanistic studies and the identification of active compounds could lead to new discoveries in the biological and biomedical sciences. Modern translational research on herbal medicines beyond basic science and clinical perspectives will contribute to the development of new medicines. This review covers the translational aspects of herbal medicine with a focus on cancer anorexiacachexia. The review gives perspective on a new horizon for herbal medicine from a scientific point of view and a basis for the further development of complementary and alternative medicine (CAM) for patients.