[Practical pharmacotherapy education "pharmacology role-play": expansion and ingenuity in Medical, Dental, Pharmaceutical and Nursing education.]

Active learning in pharmacology education "pharmacology role-play," in which students pretend to be health professionals and patients and explain diseases and drug treatments. Because pharmacology role-play is based on cases presented in advance and active learning through communication, named Case & Communication based approach (C&C approach). Pharmacology role-play was started in 2010 at the University of Miyazaki, it has been shared by 28 schools in 4 faculties of medicine, pharmacy, dentistry, and nursing (23 medical schools, 1 pharmaceutical school, 2 dental schools, and 2 nursing universities) over the 13 years until 2022. Although it is a common program, it is implemented with diversity while devoting various ingenuity according to the characteristics of the University. Pharmacology role-play is effective in (1) understanding of medical treatment, (2) understanding patient's feelings, (3) improvement of mental attitude and motivation as health professionals (4) positive influence upon study attitude, regardless of universities that conducted the pharmacology role-play. Various efforts include combining with Personal Drugs, developing interprofessional education through joint role-playing by medical students and nursing students, and developing Oriental medicine education through the cases including Kampo medicine. In addition, there are online lectures in response to the Covid-19, and a joint implementation of two universities, all of which are highly effective. The advantage of the multi-institution common program is that a lot of information can be obtained at once, and it is easy to quickly reflect successful ideas. The flexibility and high resilience that can flexibly change the implementation method (face-to-face/remote) according to the situation are also great strengths.

[Nursing pharmacology education and active-learning.]

Comprehensive pharmacology education in nursing based on the "Patient-oriented Pharmacology" is effective against the improvement of quality of pharmacotherapy and patient satisfaction. Two active learning programs of practical pharmacotherapy for nursing students have been performed in School of Nursing, University of Miyazaki; (1) pharmacotherapy role-play for interprofessional education (IPE) and (2) practical excise for Kampo medicine. Pharmacotherapy role-play for IPE was performed as joint lecture both medical students and nursing students. This pharmacotherapy role-play is named Case & Communication based approach (C&C approach), since it is studied through communication between physicians, nurses and patients based on cases presented beforehand. In the practical excise for Kampo medicine, nursing students studied Kampo medicines and tried to taste 9 frequently used Kampo medicines. These active-learning programs in nursing pharmacology education may be effective for better understanding of pharmacotherapy and patient's feeling, and improvement of students' motivation as a nurse.

How was cognitive behavioural therapy for mood disorder implemented in Japan? A retrospective observational study using the nationwide claims database from FY2010 to FY2015.

OBJECTIVES: To clarify the dissemination status of cognitive behavioural therapy (CBT) in Japan under the national health insurance scheme. DESIGN: Retrospective observational study. SETTING: National Database of Health Insurance Claims and Specific Health Checkups of Japan. PARTICIPANTS: Patients who received CBT under the national health insurance scheme from fiscal years (FY) 2010 to 2015. PRIMARY AND SECONDARY OUTCOME MEASURES: We estimated the change rate and the standardised claim ratio (SCR) for the number of patients receiving CBT and analysed the association between the CBT status and several regional factors. RESULTS: We found that (a) a total of 60 304 patients received CBT during the study period; (b) the number of patients receiving CBT was highest in the first year (-1.8% from FY2010 to FY2015); (c) the number of patients who received CBT per 100 000 population decreased (or remained at zero) in most prefectures (32 out of 47); (d) there was a maximum 424.7-fold difference between prefectures in the standardised claim ratio for CBT and (e) the number of registered CBT institutions was significantly associated with the number of patients who received CBT. CONCLUSIONS: The provision of CBT did not increase in the first 6 years (FY2010-2015) after its coverage in Japan's national health insurance scheme. Further studies including a questionnaire survey of registered CBT institutions are required to get more detailed information on the dissemination of CBT in Japan.

Constitutive activity of glycogen synthase kinase-3beta: positive regulation of steady-state levels of insulin receptor substrates-1 and -2 in adrenal chromaffin cells.

In cultured bovine adrenal chromaffin cells, 12-h treatment with 1-20 mM LiCl, an inhibitor of glycogen synthase kinase-3 (GSK-3), increased Ser(9) phosphorylation of GSK-3beta by approximately 44%, while decreasing insulin receptor substrate-1 (IRS-1) and IRS-2 protein levels by approximately 38 and approximately 62% in a concentration-dependent manner. Treatment with SB216763 (0.1-30 microM for 12 h), a selective inhibitor of GSK-3, lowered IRS-1 and IRS-2 levels by approximately 38 and approximately 48%, while increasing beta-catenin protein level by approximately 47%, due to the prevention of GSK-3-induced degradation of beta-catenin by SB216763. Insulin (100 nM for 24 h) increased Ser(9) phosphorylation of GSK-3beta by approximately 104%, while decreasing IRS-1 and IRS-2 levels by approximately 41 and approximately 72%; the insulin-induced Ser(9) phosphorylation of GSK-3beta, as well as down-regulations of IRS-1 and IRS-2 levels were restored to the control levels of nontreated cells at 24 h after the washout of the insulin (100 nM for 12 h)-treated cells. Either clasto-lactacystin beta-lactone or lactacystin (an inhibitor of proteasome) prevented LiCl- or SB216763-induced decreases of IRS-1 and IRS-2 levels by approximately 100 and approximately 69%, respectively. In contrast, calpastatin (an inhibitor of calpain) and leupeptin (an inhibitor of lysosome) failed to prevent the decreases of IRS-1 and IRS-2 levels caused by LiCl or SB216763. LiCl or SB216763 lowered IRS-2 mRNA level, with no effect on IRS-1 mRNA level. These results suggest that constitutive activity of GSK-3beta in quiescent cells positively maintains steady-state levels of IRS-1 and IRS-2 via regulating proteasomal degradation and/or synthesis of IRS-1 and IRS-2 proteins.

New twist on neuronal insulin receptor signaling in health, disease, and therapeutics.

Long after the pioneering studies documenting the existence of insulin (year 1967) and insulin receptor (year 1978) in brain, the last decade has witnessed extraordinary progress in the understanding of brain region-specific multiple roles of insulin receptor signalings in health and disease. In the hypothalamus, insulin regulates food intake, body weight, peripheral fat deposition, hepatic gluconeogenesis, reproductive endocrine axis, and compensatory secretion of counter-regulatory hormones to hypoglycemia. In the hippocampus, insulin promotes learning and memory, independent of the glucoregulatory effect of insulin. Defective insulin receptor signalings are associated with the dementia in normal aging and patients with age-related neurodegenerative diseases (e.g., Alzheimer's disease); the cognitive impairment can be reversed with systemic administration of insulin in the euglycemic condition. Intranasal administration of insulin enhances memory and mood and decreases body weight in healthy humans, without causing hypoglycemia. In the hypothalamus, insulin-induced activation of the phosphoinositide 3-kinase pathway followed by opening of ATP-sensitive K+ channel has been shown to be related to multiple effects of insulin. However, the precise molecular mechanisms of insulin's pleiotropic effects still remain obscure. More importantly, much remains unknown about the quality control mechanisms ensuring correct conformational maturation of the insulin receptor, and the cellular mechanisms regulating density of cell surface functional insulin receptors.