Exploration of Insulin Amyloid Polymorphism Using Raman Spectroscopy and Imaging.

We aimed to investigate insulin amyloid fibril polymorphism caused by salt effects and heating temperature and to visualize the structural differences of the polymorphisms in situ using Raman imaging without labeling. The time course monitoring for amyloid formation was carried out in an acidic condition without any salts and with two species of salts (NaCl and Na2SO4) by heating at 60, 70, 80, and 90°C. The intensity ratio of two Raman bands at 1672 and 1657 cm-1 due to antiparallel ß-sheet and α-helix structures, respectively, was revealed to be an indicator of amyloid fibril formation, and the relative proportion of the ß-sheet structure was higher in the case with salts, especially at a higher temperature with Na2SO4. In conjunction with the secondary structural changes of proteins, the S-S stretching vibrational mode of a disulfide bond (∼514 cm-1) and the ratio of the tyrosine doublet I850/I826 were also found to be markers distinguishing polymorphisms of insulin amyloid fibrils by principal component analysis. Especially, amyloid fibrils with Na2SO4 media formed the gauche-gauche-gauche conformation of disulfide bond at a higher rate, but without any salts, the gauche-gauche-gauche conformation was partially transformed into the gauche-gauche-trans conformation at higher temperatures. The different environments of the hydroxyl groups of the tyrosine residue were assumed to be caused by fibril polymorphism. Raman imaging using these marker bands also successfully visualized the two- and three- dimensional structural differences of amyloid polymorphisms. These results demonstrate the potential of Raman imaging as a diagnostic tool for polymorphisms in tissues of amyloid-related diseases.

Fundamental knowledge taught in compulsory education for effective genetic counseling: a qualitative study of descriptions in textbooks.

In genetic counseling, information must be provided in ways that the client and general public can understand to ensure that decisions are made autonomously. To realize this, we must assess the extent of knowledge held by the general public regarding genetics. To identify the client's original knowledge before genetic counseling, we explored the fundamental knowledge related to genetic counseling that is taught in Japanese compulsory education. A qualitative study was conducted. We selected 50 textbooks for compulsory education (Japanese, social studies, science, health and physical education, technology and home economics, morality, and life) that had been used in more than half of the districts in Japan. The text data were analyzed using qualitative content analysis, and quantitative data were analyzed for methodological triangulation. Codes, subcategories, and categories were generated from the contexts that met the following criteria: the contents included in the official textbook for clinical geneticists, contents derived from such descriptions that were related to genetic counseling, and contents clearly related to genetics. Among the 50 textbooks, 33 textbooks contained fundamental knowledge regarding genetic counseling. A qualitative content analysis identified four major categories: (1) basics of genetics, (2) understanding and control of diseases, (3) efforts and barriers to the realization of a harmonious society, and (4) technology and humans. We found that fundamental knowledge related to genetic counseling is directly or indirectly taught in compulsory education. Our results are an important resource for understanding the client's knowledge baseline and will be helpful for effective genetic counseling.

Severity of Child Autistic Symptoms and Parenting Stress in Mothers of Children with Autism Spectrum Disorder in Japan and USA: Cross-Cultural Differences.

The purpose of this study was to compare the relationship between parenting stress and autistic symptom severity in the U.S. and Japan. Fifty-two U.S. and 51 Japanese mothers of children aged 2-12 with autism completed measures of parenting stress and child characteristics, including the parenting stress index (PSI), the social communication questionnaire (SCQ), and social responsiveness scale-2 (SRS-2). There was a nonlinear relationship between the child's autistic symptom severity and parenting stress in both countries. We also found some cultural differences: in the parent domain, the relationships between children's SCQ scores and PSI scores differed significantly between the U.S. and Japan. Our findings suggest that autistic severity symptom scores may reflect cross-cultural differences in parenting beliefs, views toward autism, and response styles for evaluating children's behavior. The findings also suggest that parents need support regardless of the child's autism severity, including those with mild to moderate symptoms. Expanding on this line of research and understanding cultural influences on parenting stress may help service providers and agencies offer more culturally sensitive services, parent-education courses, and intervention programs.

Coronavirus outbreak from early career psychiatrists' viewpoint: What we have learned so far.

PURPOSE: Since the World Health Organization declared the coronavirus outbreak a global pandemic several million cases and more than three million deaths have been already confirmed worldwide due to COVID-19. DESIGN AND METHODS: Early Career Psychiatrists from all over the world present an overview of what happened in their own countries and what they have learned so far by this experience in everyday clinical practice. PRACTICE IMPLICATION: We tried to take a real time picture of this unexpected situation, drawing useful hints for now and the future.

An attempt to create a treatment algorithm of central adrenal insufficiency using CRH test, DHEA-S and clinical evaluation.

Objective : To examine diagnostic performance of corticotropin-releasing hormone (CRH) test combined with baseline dehydroepiandrosterone sulfate (DHEA-S) in patients with a suspect of central adrenal insufficiency. Methods : Patients (n=215) requiring daily or intermittent hydrocortisone replacement, or no replacement were retrospectively checked with their peak cortisol after CRH test and baseline DHEA-S. Results :  None of 106 patients with the peak cortisol ≥ 17.5 µg / dL after CRH test required replacement, and all 64 patients with the peak cortisol < 10.0 µg / dL required daily replacement. Among 8 patients with 10.0 µg / dL ≤ the peak cortisol < 17.5 µg / dL and baseline DHEA-S below the reference range, 6 patients required daily replacement and 1 patient was under intermittent replacement. Among 37 patients with 10.0 µg / dL ≤ the peak cortisol < 17.5 µg / dL and baseline DHEA-S within the reference range, 10 and 6 patients were under intermittent and daily replacement, respectively. Conclusions : No patients with the peak cortisol ≥ 17.5 µg / dL required hydrocortisone replacement, and all patients with the peak cortisol below 10.0 µg / dL required daily replacement. Careful clinical evaluation was required to determine requirement for replacement in patients with 10.0 µg / dL ≤ the peak cortisol < 17.5 µg / dL even in combination with baseline DHEA-S. J. Med. Invest. 69 : 287-293, August, 2022.

Child and adolescent psychiatry training curriculum: a global trainee's perspective.

This article is a summary of perspectives on training curricula from child and adolescent psychiatry trainees globally. We aimed to identify the relative strengths, weaknesses and gaps in learning needs from a trainee's perspective. The 20 early-career child psychiatrists who contributed are from 16 countries and represent all the five continents. We could identify some global challenges as well as local/regional challenges that need to be addressed to develop competent child psychiatrists.

Remarkable Shrinkage of a Growth Hormone (GH)-secreting Macroadenoma Induced by Somatostatin Analogue Administration: A Case Report and Literature Review.

Acromegaly is caused by excessive growth hormone secretion, usually from pituitary adenomas. Somoatostatin analogues are widely used as primary or adjunctive therapy in the management of acromegaly. In this report, we present a case with remarkable shrinkage of a tumor after relatively short-term octreotide long-acting release (LAR) administration. During the 30-month follow-up after starting octreotide LAR, there was no recurrence of acromegaly with remarkable shrinkage of the tumor on pituitary magnetic resonance imaging. A literature review of the predictors for tumor shrinkage after the administration of somatostatin analogues in patients with acromegaly is also discussed in relation to this case.

The Role of Heparin Cofactor â ¡ in the Regulation of Insulin Sensitivity and Maintenance of Glucose Homeostasis in Humans and Mice.

AIM: Accelerated thrombin action is associated with insulin resistance. It is known that upon activation by binding to dermatan sulfate proteoglycans, heparin cofactor Ⅱ(HCⅡ) inactivates thrombin in tissues. Because HCⅡ may be involved in glucose metabolism, we investigated the relationship between plasma HCⅡ activity and insulin resistance. METHODS AND RESULTS: In a clinical study, statistical analysis was performed to examine the relationships between plasma HCⅡ activity, glycosylated hemoglobin (HbA1c), fasting plasma glucose (FPG), and homeostasis model assessment-insulin resistance (HOMA-IR) in elderly Japanese individuals with lifestyle-related diseases. Multiple regression analysis showed significant inverse relationships between plasma HCⅡ activity and HbA1c (p=0.014), FPG (p=0.007), and HOMA-IR (p= 0.041) in elderly Japanese subjects. In an animal study, HCⅡ＋/＋ mice and HCⅡ＋/- mice were fed with a normal diet or high-fat diet (HFD) until 25 weeks of age. HFD-fed HCⅡ＋/- mice exhibited larger adipocyte size, higher FPG level, hyperinsulinemia, compared to HFD-fed HCⅡ＋/＋ mice. In addition, HFD-fed HCⅡ＋/- mice exhibited augmented expression of monocyte chemoattractant protein-1 and tumor necrosis factor, and impaired phosphorylation of the serine/threonine kinase Akt and AMP-activated protein kinase in adipose tissue compared to HFD-fed HCⅡ＋/＋ mice. The expression of phosphoenolpyruvate carboxykinase and glucose-6-phosphatase was also enhanced in the hepatic tissues of HFD-fed HCⅡ＋/- mice. CONCLUSIONS: The present studies provide evidence to support the idea that HCⅡ plays an important role in the maintenance of glucose homeostasis by regulating insulin sensitivity in both humans and mice. Stimulators of HCⅡ production may serve as novel therapeutic tools for the treatment of type 2 diabetes.

Suppression of the Hypothalamic-pituitary-adrenal Axis by Maximum Androgen Blockade in a Patient with Prostate Cancer.

A 78-year-old Japanese man showed suppression of the hypothalamic-pituitary-adrenal axis during maximum androgen blockade (MAB) therapy including chlormadinone acetate (CMA) for prostate cancer. After stopping the MAB therapy, both the basal ACTH level and the response to CRH recovered. While no reports have indicated that CMA suppresses the hypothalamic-pituitary-adrenal axis in patients with prostate cancer, CMA has been shown to inhibit this axis in animals. These observations suggest that we must monitor the hypothalamic-pituitary-adrenal axis in patients treated with CMA, especially under stressful conditions.