Quality of life and physical/psychosocial factors in children and adolescents with orthostatic intolerance.

BACKGROUND: Orthostatic intolerance (OI), which is common in children and adolescents, negatively impacts their quality of life (QOL) due to physical symptoms that limit work, school, and daily activities. The purpose of this study is to explore the association of physical and psychosocial factors with QOL scores in children and adolescents with OI. METHODS: A cross sectional observational study was conducted. The study participants included 95 Japanese pediatric patients of age 9-15 years who were diagnosed with OI from April 2010 to March 2020. The QOL scores and the QOL T-scores of children with OI assessed using the KINDL-R questionnaire at the initial visit were compared with conventional normative data. The associations of physical and psychosocial factors with the QOL T-scores were examined using multiple linear regression. RESULTS: Pediatric patients with OI had significantly lower QOL scores than healthy children in both elementary (50.7 ± 13.5 vs. 67.9 ± 13.4, p < 0.001) and junior high schools (51.8 ± 14.6 vs. 61.3 ± 12.6, p < 0.001). This finding was observed in the physical, mental, self-esteem, friends, and school domains. Total QOL scores were significantly associated with school nonattendance (ß = - 3.2, 95% confidence interval [CI] = - 5.8 to - 0.5, p = 0.022) and poor relationship with school (ß = - 5.0, 95% CI = - 9.8 to - 0.4, p = 0.035). CONCLUSIONS: These results suggest that the assessment of QOL, including both physical and psychosocial aspects, especially school factors, needs to be implemented earlier in children and adolescents with OI.

Evaluating the Coping Behavior of Children with Psychosomatic Disorders under Frustrating Situations Simulated Using the Rosenzweig Picture-Frustration Study.

Psychosomatic disorders are influenced by psychosocial factors such as interpersonal relationships. Coping behaviors, especially in frustrating situations, reflect a patient's ability to cope with stress, and it is important to assess these behaviors for the treatment of psychosomatic diseases. This study aimed to clarify the interpersonal relationships and coping behaviors of pediatric patients with psychosomatic diseases during frustrating situations simulated using the Rosenzweig Picture-Frustration study. This retrospective study included 126 patients (41 male, 85 female) with an average age of 12.9 (6-16) years who were consulted at the Department of Pediatric Psychosomatic Medicine at Okayama University Hospital from 2013 to 2018 and underwent the P-F study. Each score was compared with a standardization sample. The mean group conformity rating did not differ significantly between the participants and healthy children. Compared with healthy children, those with psychosomatic diseases were less likely to explain their perspective. The children with psychosomatic disorders responded to frustrating situations in a sensible and age-appropriate manner. However, they were less likely to respond by explaining their perspective to protect themselves.

Eleven years of data on the Jefferson Scale of Empathy - medical student version: Japanese norm data and tentative cutoff scores.

BACKGROUND: More and more studies investigate medical students' empathy using the Jefferson Scale of Empathy (JSE). However, no norm data or cutoff scores of the JSE for Japanese medical students are available. This study therefore explored Japanese norm data and tentative cutoff scores for the Japanese translation of the JSE-medical student version (JSE-S) using 11 years of data obtained from matriculants from a medical school in Japan. METHODS: Participants were 1,216 students (836 men and 380 women) who matriculated at a medical school in Japan from 2011 to 2021. The JSE-S questionnaire was administered to participants prior to the start of the program. Data were summarized using descriptive statistics and statistical tests were performed to show the norm data and tentative cutoff scores for male and female students separately. RESULTS: The score distributions of the JSE-S were moderately skewed and leptokurtic for the entire sample, with indices -0.75 and 4.78, respectively. The mean score (standard deviation) for all participants was 110.8 (11.8). Women had a significantly higher mean score (112.6) than men (110.0; p < 0.01). The effect size estimate of gender difference was 0.22, indicating a small effect size. The low and high cutoff scores for men were ≤ 91 and ≥ 126, respectively, and the corresponding scores for women were ≤ 97 and ≥ 128, respectively. CONCLUSIONS: This study provides JSE-S norm data and tentative cutoff scores for Japanese medical school matriculants, which would be helpful in identifying those who may need further training to enhance their empathy.

Adolescent Health Promotion Interventions Using Well-Care Visits and a Smartphone Cognitive Behavioral Therapy App: Randomized Controlled Trial.

BACKGROUND: Adolescent health promotion is important in preventing risk behaviors and improving mental health. Health promotion during adolescence has been shown to contribute to the prevention of late onset of the mental health disease. However, scalable interventions have not been established yet. OBJECTIVE: This study was designed to test the efficacy of two adolescent health promotion interventions: a well-care visit (WCV) with a risk assessment interview and counseling and self-monitoring with a smartphone cognitive behavioral therapy (CBT) app. Our hypothesis was that participants who had received both WCV and the CBT app would have better outcomes than those who had received only WCV or those who had not received any intervention. We conducted a prospective multi-institutional randomized controlled trial. METHODS: Participants were 217 adolescents aged 13-18 years. They were randomly divided into two intervention groups (WCV group and WCV with CBT app group) and a nonintervention group. WCV comprised a standardized physical examination along with a structured interview and counseling for youth risk assessment, which was designed with reference to the Guideline for Health Supervision of Adolescents of Bright Futures. A smartphone-based CBT program was developed based on the CBT approach. The CBT app comprised a 1-week psychoeducation component and a 1-week self-monitoring component. During the CBT program, participants created several self-monitoring sheets based on the CBT model with five window panels: event, thoughts, feelings, body response, and actions. The primary outcome was the change in scores for depressive symptoms. Secondary outcomes included changes in scores for self-esteem, quality of life, self-monitoring, and an adolescent health promotion scale. These outcomes were evaluated at baseline and at 1, 2, and 4 months after baseline. The exploratory outcome was the presence of suicidal ideation during the observation period. Intervention effects were estimated using mixed effect models. RESULTS: In total, 94% (204/217) of the participants completed the 4-month evaluation. Both intervention groups showed a significant effect in the form of reduced scores for depressive symptoms at 1 month in high school students; however, these effects were not observed at 2 and 4 months. The intervention effect was significantly more predominant in those scoring above cutoff for depressive symptoms. There was significantly less suicidal ideation in the intervention groups. As for secondary outcomes, there was significant increase in health promotion scale scores at the 4-month follow-up among junior high school students in the WCV group. Moreover, the CBT app was significantly effective in terms of obtaining self-monitoring skills and reducing depressive symptoms. CONCLUSIONS: Although adolescent health promotion interventions may have short-term benefits, the frequency of WCV and further revision of the CBT app should be considered to evaluate long-term effectiveness. TRIAL REGISTRATION: University Hospital Medical Information Network Clinical Trials Registry UMIN 000036343; https://center6.umin.ac.jp/cgi-open-bin/ctr/ctr_view.cgi?recptno=R000041246.

The effect of Humanitude care methodology on improving empathy: a six-year longitudinal study of medical students in Japan.

BACKGROUND: Empathy, which involves understanding another person's experiences and concerns, is an important component for developing physicians' overall competence. This longitudinal study was designed to test the hypothesis that medical students' empathy can be enhanced and sustained by Humanitude Care Methodology, which focuses on perception, emotion and speech. METHODS: This six-year longitudinal observational study examined 115 students who entered Okayama University Medical School in 2013. The study participants were exposed to two empathy-enhancing programs: (1) a communication skills training program (involving medical interviews) and (2) a Humanitude training program aimed at enhancing their empathy. They completed the Jefferson Scale of Empathy (JSE) seven times: when they entered medical school, before participation in the first program (medical interview), immediately after the first program, before the second program (Humanitude exercise), immediately after the second program, and in the 5th and 6th year (last year) of medical school. A total of 79 students (69% of the cohort) completed all seven test administrations of the JSE. RESULTS: The mean JSE scores improved significantly after participation in the medical interview program (p < 0.01) and the Humanitude training program (p = 0.001). However, neither program showed a sustained effect. CONCLUSIONS: The Humanitude training program as well as medical interview training program, had significant short-term positive effects for improving empathy among medical students. Additional reinforcements may be necessary for a long-term sustained effect.

Prevalence of autism spectrum disorder and autistic traits in children with anorexia nervosa and avoidant/restrictive food intake disorder.

BACKGROUND: Autism spectrum disorder (ASD) and feeding and eating disorders (FEDs) such as anorexia nervosa (AN) are strongly linked as evidenced by frequent comorbidity and overlapping traits. However, eating and social behaviors are shaped by culture, so it is critical to examine these associations in different populations. Moreover, FEDs are heterogeneous, and there has been no examination of autistic traits in avoidant/restrictive food intake disorder (ARFID). METHODS: Therefore, we investigated the prevalence of ASD and autistic traits among Japanese children with AN (n = 92) or ARFID (n = 32) from a prospective multicenter cohort study using the Autism Spectrum Quotient Children's version (AQC) and Children's Eating Attitudes Test (ChEAT26). RESULTS: ASD prevalence was high in both AN and ARFID (16.3 and 12.5%, respectively). The AN group exhibited significantly higher scores on all AQC subscales than an age-matched healthy control (HC) group, but there were no significant correlations between AQC scores and ChEAT26 scores. In the AFRID group, AQC scores did not differ from HCs, but significant correlations were found between total AQC and ChEAT26 scores and between several AQC and ChEAT26 subscales. CONCLUSIONS: Both the AN and ARFID groups had high prevalence rates of ASD. The AN group showed a significantly higher degree of autistic traits than the HC group; however, no difference was found between the ARFID and HC groups. Clinicians need to be aware of these rates when working with children with ED.

Validation of a childhood eating disorder outcome scale.

We developed and validated a childhood eating disorder outcome scale based on outcomes associated with body mass index standard deviation score (BMI-SDS). This prospective observational study included 131 children with eating disorders (aged 5-15 years). Participants' outcomes scales were completed at the first visit and at 1, 3, 6, and 12 months. The scale evaluated 12 outcomes: body weight change (BW), eating attitude (EA), fear of being fat (FF), body image distortion (BD), menstruation (ME), perceived physical condition (PC), attending school (AS), disease recognition by school (RS), family function (FA), disease recognition by parent (RP), social adaptation (SA), and relationships with friends (RF). Responses to all items were on a four-point Likert scale. Exploratory factor analysis was used to determine the number of factors based on the 12 outcomes. The relation between outcome scale scores and BMI-SDS over the 12-month follow-up period was analyzed. Two types of factors were extracted: disease-specific factors (EA, FF, BD) and biopsychosocial factors (BW, PC, AS, FA, SA, RF). Three items (ME, RS, RP) were excluded because they showed no significant loading effect. There was a significant negative correlation between the outcome scale and BMI-SDS, and changes in outcome scale scores from baseline to 12 months were significantly associated with improvement in BMI-SDS. We developed a childhood eating disorder outcome scale characterized by disease-specific and biopsychosocial factors. Biopsychosocial management combined with a therapeutic approach for disease-specific symptoms may support body weight recovery for children with eating disorders.

Ghrelin treatment improves physical decline in sarcopenia model mice through muscular enhancement and mitochondrial activation.

Chronic kidney disease (CKD) impairs physical performance in humans, which leads to a risk of all-cause mortality. In our previous study, we demonstrated that a reduction in muscle mitochondria rather than muscle mass was a major cause of physical decline in 5/6 nephrectomized CKD model mice. Because ghrelin administration has been reported to enhance oxygen utilization in skeletal muscle, we examined the usefulness of ghrelin for a recovery of physical decline in 5/6 nephrectomized C57Bl/6 mice, focusing on the epigenetic modification of peroxisome proliferator activated receptor gamma coactivator-1α (PGC-1α), a master regulator of mitochondrial biogenesis. The mice were intraperitoneally administered acylated ghrelin (0.1 nmol/gBW; three times per week) for a month. Muscle strength and exercise endurance were measured by using a dynamometer and treadmill, respectively. Mitochondrial DNA copy number was determined by quantitative PCR. The methylation levels of the cytosine residue at 260 base pairs upstream of the translation initiation point (C-260) of PGC-1α, which has been demonstrated to decrease the expression, was evaluated by methylation-specific PCR and bisulfite genomic sequencing methods after the ghrelin administration. Ghrelin administration improved both muscle strength and exercise endurance in the mice and was associated with an increase in muscle mass and muscle mitochondrial content. Ghrelin administration decreased the methylation ratio of C-260 of PGC-1α in the skeletal muscle and increased the expression. Therefore, ghrelin administration effectively reduced the physical decline in 5/6 nephrectomized mice and was accompanied with an increased mitochondrial content through de-methylation of the promoter region of PGC-1α in the muscle.

Treatment of sarcopenia and glucose intolerance through mitochondrial activation by 5-aminolevulinic acid.

Recently, sarcopenia has attracted attention as therapeutic target because it constitutes a risk factor for metabolic and cardiovascular diseases. We focused 5-aminolevulinic acid (ALA) which act as electron carriers in the mitochondrial electron transport system. The mice that received ALA for 8 weeks gained muscle strength and endurance, and exhibited increased muscle mass and mitochondrial amount. Administration of ALA to sarcopenia mice aged 100 weeks and chronic kidney disease (CKD) model mice also increased muscle mass and improved physical performance. Metabolome analysis revealed increased branched-chain amino acids (BCAAs) levels in the skeletal muscle of ALA-treated mice. Quantitative PCR analysis revealed decreased expression levels in branched-chain amino acid transaminases (BCATs) that degrade BCAAs and other muscle-degrading factors, and increased levels of mitochondria-activating factors. We also studied in cultured myocytes and obtained compatible results. ALA-treated mice tended to increase body weight, but reduced blood glucose level. These suggested that ALA treatment not only activated muscle mitochondria but also enhanced muscle mass through an increase in BCAAs contents, as to improve muscle strength, endurance and glucose tolerance in mice. In these ways, muscle mitochondrial activation with ALA is suggested to be useful for the treatment of sarcopenia and glucose intolerance.

Relationships between Composition of Major Fatty Acids and Fat Distribution and Insulin Resistance in Japanese.

Objective. The aim of this study was to evaluate the relationships between the composition of free fatty acids (FFAs) and metabolic parameters, including body fat distribution, in Japanese. Methods. The study subjects were 111 Japanese patients (54 males, 57 females). Metabolic parameters and visceral and subcutaneous fat areas as determined by CT scanning at the umbilical level were measured. Glucose tolerance test (GTT) was performed by administering 75 g glucose orally. Results. The percentage of linoleic acid (C18:2), the greatest constituent among FFAs, was negatively correlated with visceral fat area (r = -0.411, p < 0.0001), fasting glucose (r = -0.330, p < 0.0001), HbA1c (r = -0.231, p = 0.0146), and systolic blood pressure (r = -0.224, p = 0.0184). Linoleic acid percentage was also significantly negatively correlated with HOMA-IR (r = -0.416, p < 0.0001) by simple correlation. Based on the findings of OGTT, the 111 subjects were classified into three groups: 33 with normal glucose tolerance, 71 with impaired glucose tolerance (IGT), and 7 diabetic subjects. The percentage of serum linoleic acid in diabetic subjects was significantly lower than that in normal subjects. Conclusion. We conclude that serum linoleic acid level is negatively correlated with the accumulation of visceral fat in relation to a reduction of insulin resistance in Japanese subjects.

Heterologous production of kasugamycin, an aminoglycoside antibiotic from Streptomyces kasugaensis, in Streptomyces lividans and Rhodococcus erythropolis L-88 by constitutive expression of the biosynthetic gene cluster.

Kasugamycin (KSM), an aminoglycoside antibiotic isolated from Streptomyces kasugaensis cultures, has been used against rice blast disease for more than 50 years. We cloned the KSM biosynthetic gene (KBG) cluster from S. kasugaensis MB273-C4 and constructed three KBG cassettes (i.e., cassettes I-III) to enable heterologous production of KSM in many actinomycetes by constitutive expression of KBGs. Cassette I comprised all putative transcriptional units in the cluster, but it was placed under the control of the P neo promoter from Tn5. It was not maintained stably in Streptomyces lividans and did not transform Rhodococcus erythropolis. Cassette II retained the original arrangement of KBGs, except that the promoter of kasT, the specific activator gene for KBG, was replaced with P rpsJ , the constitutive promoter of rpsJ from Streptomyces avermitilis. To enhance the intracellular concentration of myo-inositol, an expression cassette of ino1 encoding the inositol-1-phosphate synthase from S. avermitilis was inserted into cassette II to generate cassette III. These two cassettes showed stable maintenance in S. lividans and R. erythropolis to produce KSM. Particularly, the transformants of S. lividans induced KSM production up to the same levels as those produced by S. kasugaensis. Furthermore, cassette III induced more KSM accumulation than cassette II in R. erythropolis, suggesting an exogenous supply of myo-inositol by the ino1 expression in the host. Cassettes II and III appear to be useful for heterologous KSM production in actinomycetes. Rhodococcus exhibiting a spherical form in liquid cultivation is also a promising heterologous host for antibiotic fermentation.

Analysis of the synthetic house-tree-person drawing test for developmental disorder.

BACKGROUND: Some patients cannot draw three subjects on the same page during the synthetic house-tree-person drawing test (S-HTP). We call this phenomenon "no synthetic sign". The aim of this study was to clarify the pathological meaning of no synthetic sign and investigate its use for the early detection of developmental disorders at a pediatric primary care center. METHODS: We administered the S-HTP to 283 people who consulted the child psychosomatic medical clinic of Okayama University Hospital in 2007-2012. We diagnosed developmental disability based on DSM-IV-TR criteria and compared findings between the different diagnostic groups. RESULTS: A total of 241 patients completed the S-HTP (S-HTP group) and 22 patients were not able to complete the S-HTP, but did complete the HTP (an original version of the S-HTP) or tree test (HTP group). Significantly more people in the HTP group had autism spectrum disorder (ASD) compared with the S-HTP group. Full-scale intelligence quotient was significantly lower in the HTP group compared with the S-HTP group. CONCLUSIONS: There were two types of patients with no synthetic sign. The first involved patients with a suspected mental age younger than 5 years 11 months. The second type consisted of patients with ASD. Although drawing ability reflects multiple domains, it may help in early identification of children with developmental problems and facilitate earlier initiation of interventions.

Palmitic acid-rich diet suppresses glucose-stimulated insulin secretion (GSIS) and induces endoplasmic reticulum (ER) stress in pancreatic islets in mice.

The objective was to clarify whether dietary palmitic acid supplementation affects glucose-stimulated insulin secretion (GSIS) and the endoplasmic reticulum (ER) stress pathway in pancreatic islets in mice. Eight-week-old male C57BL/6J mice were randomly divided into three treatment diet groups: control diet, palmitic acid-supplemented diet (PAL) and oleic acid-supplemented diet (OLE). After 2 weeks of treatment, intraperitoneal glucose tolerance test and intraperitoneal insulin tolerance test were performed. GSIS was assessed by pancreatic perfusion in situ with basal (100 mg/dL) glucose followed by a high (300 mg/dL) glucose concentration. We measured mRNA levels of ER stress markers such as C/EBP homologous protein (CHOP), immunoglobulin heavy-chain binding protein (BIP) and X-box binding protein (XBP)-1 using real-time polymerase chain reaction (PCR) analyses in isolated islets. Immunohistochemical staining was also performed. Mice fed PAL showed significantly decreased glucose tolerance (p < 0.05). In the perfusion study, GSIS was significantly suppressed in the PAL group (p < 0.05). Semi-quantitative RT-PCR revealed that islet CHOP, BIP, and XBP-1 mRNA expression were significantly increased in the PAL group (p < 0.05). TUNEL-positive ß-cells were not detected in all groups. Dietary palmitic acid-supplementation for 2 weeks might suppress GSIS and induce ER stress in pancreatic islets in mice, in the early stage of lipotoxicity.

Improvement of Physical Decline Through Combined Effects of Muscle Enhancement and Mitochondrial Activation by a Gastric Hormone Ghrelin in Male 5/6Nx CKD Model Mice.

Because a physical decline correlates with an increased risk of a wide range of disease and morbidity, an improvement of physical performance is expected to bring significant clinical benefits. The primary cause of physical decline in 5/6 nephrectomized (5/6Nx) chronic kidney disease model mice has been regarded as a decrease in muscle mass; however, our recent study showed that a decrease in muscle mitochondria plays a critical role. In the present study, we examined the effects of a gastric hormone ghrelin, which has been reported to promote muscle mitochondrial oxidation, on the physical decline in the chronic kidney disease model mice, focusing on the epigenetic modulations of a mitochondrial activator gene, peroxisome proliferator-activated receptor-γ coactivator-1α (PGC-1α). Ghrelin treatment improved a decline in exercise endurance of 5/6Nx mice, associated with an increase in both of the muscle mass and mitochondrial amount. The expression level of PGC-1α was decreased in the skeletal muscle of 5/6Nx mice, which was associated with an increase in the methylation ratio of the cytosine residue at 260 base pairs upstream of the initiation point. Conversely, ghrelin treatment de-methylated the cytosine residue and increased the expression of PGC-1α. A representative muscle anabolic factor, IGF-1, did not affect the expression of PGC-1α and muscle mitochondrial amount, although it increased muscle mass. As a result, IGF-1 treatment in 5/6Nx mice did not increase the decreased exercise endurance as effectively as ghrelin treatment did. These findings indicate an advantage of ghrelin treatment for a recovery of physical decline.

Importance and usefulness of evaluating self-esteem in children.

Self-esteem is the "feeling of self-appreciation" and is an indispensable emotion for people to adapt to society and live their lives. For children, in particular, the environment in which they are raised contributes profoundly to the development of their self-esteem, which in turn helps them to adapt better to society. Various psychologists have provided definitions of self-esteem, and examined methods of objectively evaluating self-esteem. Questionnaire-style assessment methods for adult include Rosenberg Self-Esteem Scale and Janis-Field Feeling of Inadequacy Scale, and these for children include Coopersmith Self-Esteem Inventory, Pope's 5-Scale Test of Self-Esteem for children, and Kid- KINDL®. Other methods include Ziller Social Self-Esteem Scale and Implicit Association Test. The development of children's self-esteem is heavily influenced by their environment, that is, their homes, neighborhoods, and schools. Children with damaged self-esteem are at risk of developing psychological and social problems, which hinders recovery from low self-esteem. Thus, to recover low self-esteem, it is important for children to accumulate a series of successful experiences to create a positive concept of self. Evaluating children's self-esteem can be an effective method for understanding their past and present circumstances, and useful to treat for children with psychosomatic disorders.