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.

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.

Lavender Oil Reduces Depressive Mood in Healthy Individuals and Enhances the Activity of Single Oxytocin Neurons of the Hypothalamus Isolated from Mice: A Preliminary Study.

BACKGROUND: The aim of the present study was to assess the effects of lavender oil inhalation on blood pressure, pulse measurements, cortisol levels, depressive mood, and anxiety in healthy male adults. The mechanism was investigated by the action on oxytocin single neurons in the hypothalamus of rodents. METHODS: The participants (n = 7) were aged 20-40 years. After randomisation, they received an inhaled dose of lavender oil or distilled water for 20 min. They received the other treatment after a washout period of one week. We assessed the outcomes using the Self-Rating Depression Scale, State-Trait Anxiety Inventory, and self-rated unidimensional Visual Analogue Scale for depression; anxiety; and hunger, thirst, and appetite, respectively. Blood pressure, pulse rate, and cortisol concentration in the peripheral blood were assessed before and after inhalation. In the rodent study (n = 4), oxytocin single neurons were isolated from the mouse hypothalamus. Intracellular Ca2+ concentration in the oxytocin neurons isolated from the hypothalamus was measured following direct administration of lavender oil. RESULTS: Seven participants completed the study. Lavender inhalation decreased Self-Rating Depression Scale score and systolic and diastolic blood pressure. Ex vivo administration of lavender oil increased intracellular Ca2+ concentration in the hypothalamic oxytocin neurons. CONCLUSIONS: Lavender oil might be a useful therapy for stress relief, and its mechanism of action may include activation of the central oxytocin neurons.

Helicobacter pylori Vacuolating Cytotoxin A Causes Anorexia and Anxiety via Hypothalamic Urocortin 1 in Mice.

Helicobacter pylori (Hp) infection is related to the pathogenesis of chronic gastric disorders and extragastric diseases. Here, we examined the anorexigenic and anxiogenic effects of Hp vacuolating cytotoxin A (VacA) through activation of hypothalamic urocortin1 (Ucn1). VacA was detected in the hypothalamus after peripheral administration and increased Ucn1 mRNA expression and c-Fos-positive cells in the hypothalamus but not in the nucleus tractus solitarius. c-Fos and Ucn1-double positive cells were detected. CRF1 and CRF2 receptor antagonists suppressed VacA-induced anxiety and anorexia, respectively. VacA activated single paraventricular nucleus neurons and A7r5 cells; this activation was inhibited by phospholipase C (PLC) and protein kinase C (PKC) inhibitors. VacA causes anorexia and anxiety through the intracellular PLC-PKC pathway, migrates across the blood-brain barrier, and activates the Ucn1-CRF receptor axis.

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.

Survival advantage of lanthanum carbonate for hemodialysis patients with uncontrolled hyperphosphatemia.

BACKGROUND: Lanthanum carbonate is a non-calcium phosphate binder that is effective for the treatment of hyperphosphatemia. However, it is unknown whether treatment with lanthanum affects survival. METHODS: We retrospectively collected data on maintenance hemodialysis patients at 22 facilities (n = 2292) beginning in December 2008, a time point immediately prior to the commercial availability of lanthanum in Japan. We compared 3-year all-cause mortality among patients who initiated lanthanum (n = 560) and those who were not treated with lanthanum during the study period (n = 560) matched by the propensity score of receiving lanthanum. Several sensitivity analyses were performed to test the robustness of the primary analysis. RESULTS: After the market introduction of lanthanum, the percentage of patients receiving the binder increased gradually to 27%. In the propensity score-matched analysis, the mortality rate for the lanthanum group was not significantly lower than the non-lanthanum group [hazard ratio (HR), 0.71; 95% confidence interval (CI), 0.47-1.09). However, stratification by serum phosphorus disclosed significant survival benefit of lanthanum for patients with serum phosphorus >6.0 mg/dL (HR, 0.52; 95% CI, 0.28-0.95), but not in patients with serum phosphorus ≤6.0 mg/dL (HR, 1.00; 95% CI, 0.55-1.84). The survival benefit of lanthanum in patients with serum phosphorus >6.0 mg/dL was consistent across subgroups and robust in different analytical approaches. CONCLUSIONS: Treatment with lanthanum was independently associated with a significant survival benefit in hemodialysis patients with inadequately controlled hyperphosphatemia. Further studies are required to confirm these findings.

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.

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.

Zinc as an appetite stimulator - the possible role of zinc in the progression of diseases such as cachexia and sarcopenia.

Zinc is required by humans and animals for many physiological functions, such as growth, immune function, and reproduction. Zinc deficiency induces a number of physiological problems, including anorexia, growth retardation, dermatitis, taste disorder, and hypogonadism. Although it is clear that zinc deficiency produces specific and profound anorexia in experimental animals, the connection between zinc deficiency and anorexia is less certain. We were the first to show that orally, but not intraperitoneally, administered zinc rapidly stimulates food intake through orexigenic peptides coupled to the afferent vagus nerve using rats during early-stage zinc deficiency without decreased zinc concentrations in plasma and tissues. We confirmed that a zinc-sufficient diet containing zinc chloride acutely stimulated food intake after short-term zinc deprivation. We also found that orally administered zinc sulfate increased the expression of NPY and orexin mRNA after administration. Using vagotomized rats, we tested whether the increase in food intake after oral administration of zinc was mediated by the vagus nerve. In sham-operated rats, the oral administration of zinc stimulated food intake, whereas zinc and saline administrations did not exhibit differing effects in vagotomized rats. We conclude that zinc stimulates food intake in short-term zinc-deficient rats through the afferent vagus nerve with subsequent effects on hypothalamic peptides associated with food intake regulation. In this review, we describe recent research investigating the roles of zinc as an appetite stimulator in food intake regulation, along with research about hypothalamus, ghrelin, leptin and zinc receptor, and clinical application about anorexia nervosa, cachexia and sarcopenia. The article also presents some promising patents on zinc.