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Brown adipose tissue (BAT) plays a role in energy expenditure and is involved in nutrient metabolism. C-X-C chemokine ligand 12 (CXCL12)-CXCR4 pathway regulates the immune, nervous, and cardiovascular systems and affects the adipose tissue. Here, we investigated the role of this pathway as an activator of BAT. Uncoupling protein 1 mRNA and protein levels and oxygen consumption increased in the brown adipocytes treated with 100 nM CXCL12 peptide. CXCL12-mediated upregulation in P38 and extracellular signal-regulated kinase (ERK) levels was reduced by each inhibitor. Thus, the CXCL12-CXCR4 pathway activated the brown adipocytes through P38 and ERK that acted downstream of this pathway. Mice with CXCR4 defects only in the brown adipocytes were generated and fed with high-fat diet (HFD). Body weight and blood glucose after glucose injection increased in these mice. Long-term exposure to HFD deteriorated blood glucose level after glucose injection. Insulin sensitivity was exacerbated in the knockout mice fed with HFD. Serum lipid parameters and CXCL12 level in knockout mice were similar to those in control mice. These results suggest that the CXCL12-CXCR4 pathway induces brown adipocyte activity and affects nutrient metabolism under HFD load.

Coaching in medical education is a valuable method for enhancing the well‐being and job satisfaction of medical professionals, particularly through interactive conversations that foster self‐awareness and independent action. A 90‐min coaching training program, incorporating lectures and role‐plays, was conducted to equip medical professionals with essential coaching skills. The program was well received, and there are plans to expand and tailor future programs to further develop these skills among various healthcare educators.

Background The COVID-19 pandemic has created a need for educational materials and methods that can replace clinical clerkships (CCs) for online simulated clinical practice (online-sCP). This study evaluates the impact of using simulated electronic health records (sEHR) for inpatients, and electronic problem-based learning (e-PBL) and online virtual medical interviews (online-VMI) for outpatients, for an online-sCP using a learning management system (LMS) and online meeting system facilitated by a supervising physician. Methods The sEHR was reviewed by medical students and subsequently discussed with a supervising physician using an online meeting system. In the e-PBL, medical students reviewed the simulated patients and discussed on the LMS. For the online-VMI, a faculty member acted as an outpatient and a student acted as the doctor. Small groups of students discussed the clinical reasoning process using the online meeting system. A mixed-method design was implemented. Medical students self-assessed their clinical competence before and after the online-sCP. They answered questionnaires and participated in semi-structured focus group interviews (FGIs) regarding the advantages and disadvantages of the practice. Results Forty-three students completed the online-sCP during May and June 2020. All students indicated significant improvement in all aspects of self-evaluation of clinical performance after the online-sCP. Students using sEHR reported significant improvement in writing daily medical records and medical summaries. Students using e-PBL and online-VMI reported significant improvement in medical interviews and counseling. Students also indicated CCs as more useful for learning associated with medical interviews, physical examinations, and humanistic qualities like professionalism than the online-sCP. Eight FGIs were conducted ( n  = 42). The advantages of online-sCP were segregated into five categories (learning environment, efficiency, accessibility, self-paced learning, and interactivity); meanwhile, the disadvantages of online-sCP were classified into seven categories (clinical practice experience, learning environment, interactivity, motivation, memory retention, accessibility, and extraneous cognitive load). Conclusions Online-sCP with sEHR, e-PBL, and online-VMI could be useful in learning some of the clinical skills acquired through CC. These methods can be implemented with limited preparation and resources.

Background The coronavirus disease 2019 (COVID-19) pandemic has led to considerable advances in medical education through technological integration. The crisis generated by the pandemic in medical practice, education, and evolving technology has led to changes in the skills of medical professionals. This study aimed to examine the competencies required of medical students in the post-pandemic era. Methods We conducted 2 mixed-methods studies. Study 1 explored medical students’ necessary competencies after the COVID-19 pandemic. We conducted group work with faculty members and students from the Chiba University School of Medicine, captured proposed competencies, discussed them, and qualitatively analyzed the group work data using content analysis to extract the competencies. Study 2 was a secondary data analysis that compared the categories identified in Study 1 with the competencies required prior to the COVID-19 pandemic, which were extracted from the websites of all 82 medical schools and colleges in Japan, to identify the differences in competencies before and after the pandemic. Results Study 1 resulted in the identification of 12 categories and 62 subcategories. The results of Study 2 showed that the increased occurrence of competencies was related to the utilization of information and communication technology (ICT) and artificial intelligence (AI), self-management, information gathering and explanation, liberal arts and generic skills, and exploring medicine and medical care/research presentations. The prevalence rates of these factors prior to the COVID-19 outbreak were 17.1%, 28.0%, 39.0%, 41.5%, and 48.8%, respectively. Conclusions Competency-based medical education in ICT, self-management, and medical exploration has become increasingly important after the pandemic. Therefore, it is necessary to develop an educational curriculum to enable medical students to acquire these competencies. The study findings contribute to the literature on medical education and offer valuable insight into setting effective academic goals and designing suitable curricula for undergraduate medical students in the post-pandemic era.

Introduction To compare the effects of ipragliflozin, a sodium-glucose transporter 2 inhibitor, with those of metformin on visceral fat (as well as muscles and bones) in Japanese elderly patients with type 2 diabetes (T2D), we conducted a sub-analysis of a prospective, multicenter, blinded-endpoint randomized-controlled study. Methods In total, 103 patients with T2D (body mass index ≥ 22 kg/m 2 ; glycated hemoglobin, 7–10%) and being treated with sitagliptin (a dipeptidyl peptidase-4 inhibitor) were included and randomized to receive ipragliflozin or metformin. The primary outcome was the change in visceral fat area measured using computed tomography 24 weeks following treatment. The secondary outcomes included changes in subcutaneous and total fat area, muscle volume, bone density measured using computed tomography, handgrip strength, bone markers, plasma glucose, insulin, homeostasis model assessment (HOMA)2-beta, HOMA2-R, glycated hemoglobin, lipid panel, uric acid, blood pressure, adiponectin, and high-sensitivity C-reactive protein. All patients aged 65–74 years were selected for sub-analysis. Results The sub-analysis included 15 and 14 patients in the ipragliflozin and metformin groups, respectively. The patients’ backgrounds were well balanced. Visceral fat area reduction was greater in the ipragliflozin group than in the metformin group (− 10.58% vs. − 6.93%; P  = 0.034). There were significant differences in the changes in bone absorption markers, uric acid, and total cholesterol levels between the groups. Conclusion Ipragliflozin significantly reduced the visceral fat area compared with metformin when added to sitagliptin in elderly patients with T2D. Long-term and large-scale studies are required to elucidate whether ipragliflozin is suitable for elderly patients. Trial Registration The study was registered at https://www.umin.ac.jp/ctr/ (UMIN-ID: UMIN 000015170).

IntroductionSodium glucose cotransporter-2 (SGLT2) inhibitors are widely used for diabetes treatment. Although SGLT2 inhibitors have been clinically observed to increase food intake, roles or even the presence of SGLT2 in the central nervous system (CNS) has not been established. We aimed to elucidate potential functions of SGLT2 in the CNS, and the effects of CNS-targeted SGLT2 inhibitors on food intake.Research design and methodsWe administered three kinds of SGLT2 inhibitors, tofogliflozin, dapagliflozin, and empagliflozin, into the lateral ventricle (LV) in rats and evaluated their effects on food intake. We also evaluated the effects of tofogliflozin administration in the third (3V) and fourth ventricle (4V). Intraperitoneal administration of liraglutide, a glucagon-like peptide-1 (GLP-1) receptor agonist known to suppress food intake, was combined with central tofogliflozin to elucidate whether GLP-1 signaling antagonizes the effect of central SGLT2 inhibitors on food intake. To elucidate potential molecular mechanisms mediating changes in feeding, hypothalamic areas associated with food intake regulation were harvested and analyzed after intracerebroventricular administration (ICV) of tofogliflozin.ResultsBolus ICV injection of tofogliflozin induced a robust increase in food intake starting at 1.5 hours postinjection, and lasting for 5 days. No effect was observed when the same dose of tofogliflozin was administered intraperitoneally. ICV dapagliflozin and empagliflozin significantly enhanced food intake, although the strength of these effects varied among drugs. Food intake was most markedly enhanced when tofogliflozin was infused into the LV. Fewer or no effects were observed with infusion into the 3V or 4V, respectively. Systemic administration of liraglutide suppressed the effect of ICV tofogliflozin on food intake. ICV tofogliflozin increased phosphorylation of AMPK and c-fos expression in the lateral hypothalamus.ConclusionsSGLT2 inhibitors in the CNS increase food intake. SGLT2 activity in the CNS may regulate food intake through AMPK phosphorylation in the lateral hypothalamic area.

In undergraduate medical education, clinical clerkships (CC) serve as a platform for acquiring the integrated competencies essential to physicians. Simultaneously, CC plays a crucial role in facilitating a smooth transition to postgraduate training and preventing burnout. This study aims to elucidate the effects of coaching on medical students during CC, with particular focus on self-efficacy and resilience. This was a mixed-methods study based on an explanatory sequential design. The participants were fifth-year medical students who underwent CC at Chiba University Hospital in Japan between June and October 2021. They received four weeks of one-on-one coaching during one department's CC by other attending physicians trained as coaches. The participants answered self-assessment web questionnaires using the Japanese version of the Generalised Self-Efficacy Scale (GSE-J) and the Brief Resilience Scale Japanese version (BRS-J) before and after coaching. In addition, they participated in semi-structured focus group interviews related to the effects of coaching. Narrative data were analysed using qualitative content analysis. Fifteen medical students participated in the study. The mean GSE-J and BRS-J scores (n = 13) significantly increased after coaching (from 71.0 (11.7) to 77.5 (16.2), = 0.018, = 0.76, = 0.71 and from 18.5 (4.7) to 21.4 (4.1), = 0.019, = 0.75, = 0.70, respectively). Four focus group interviews were conducted. The effects of coaching were classified into eight categories (goal setting and milestones, positiveness, verbalisation, self-confidence, proactivity, good communication, dealing with difficulties, and reflection and metacognition) related to self-efficacy and resilience. Medical students who receive coaching during CC improved their self-efficacy and resilience. Combining coaching with regular training in CC might serve as a useful educational strategy in terms of a smooth transition to postgraduate training and preventing burnout.

Aims/Introduction Recent randomized clinical trials have suggested that sodium–glucose cotransporter 2 inhibitors might reduce cardiovascular events and heart failure, and have renal protective effects. Despite these remarkable benefits, the effects of sodium–glucose cotransporter 2 inhibitors on bone and muscle are unclear. Materials and Methods A subanalysis of a randomized controlled study was carried out to evaluate the effects of the sodium–glucose cotransporter 2 inhibitor, ipragliflozin, versus metformin on bone and muscle in Japanese patients with type 2 diabetes mellitus (baseline body mass index ≥22 kg/m2 and hemoglobin A1c 7–10%) who were already receiving sitagliptin. These patients were randomly administered ipragliflozin 50 mg or metformin 1,000–1,500 mg daily. The effects of these medications on the bone formation marker, bone alkali phosphatase; the bone resorption marker, tartrate‐resistant acid phosphatase 5b (TRACP‐5b); handgrip strength; abdominal cross‐sectional muscle area; and bone density of the fourth lumbar vertebra were evaluated. Results After 24 weeks of treatment, the changes in bone density of the fourth lumbar vertebra, handgrip strength and abdominal cross‐sectional muscle area were not significantly different between the two groups. However, TRACP‐5b levels increased in patients treated with ipragliflozin compared with patients treated with metformin (median 11.94 vs −10.30%, P < 0.0001), showing that ipragliflozin can promote bone resorption. Conclusions There were no adverse effects on bone or muscle when sitagliptin was used in combination with either ipragliflozin or metformin. However, ipragliflozin combination increased the levels of TRACP‐5b. A long‐term study is required to further understand the effects of this TRACP‐5b increase caused by ipragliflozin. Ipragliflozin in combination with sitagliptin did not affect bones or muscles adversely compared to metformin. However, ipragliflozin increased the levels of the bone resorption marker, tartrate‐resistant acid phosphatase 5b.

Aims/Introduction Impaired glucose tolerance (IGT) is a subtype of prediabetes, a condition having high risk for development to diabetes mellitus, but its pathophysiology is not fully understood. In the present study, we examined metabolic changes in IGT by using two types (D‐glucose [Glc] and partial hydrolysate of starch [PHS]) of oral glucose tolerance tests (OGTTs), with emphasis on serum incretins and metabolites. Materials and Methods We carried out the two types of OGTT (Glc/OGTT and PHS/OGTT) in 99 young Japanese individuals who had tested either positive (GU+; n = 48) or negative (GU−; n = 51) for glycosuria. After OGTT, they were sub‐grouped into five categories: normal glucose tolerance (NGT) in the GU− group (GU−/NGT; n = 49), NGT in the GU+ group (GU+/NGT; n = 28), IGT (n = 12), diabetes mellitus (n = 1) and renal glycosuria (n = 9). Serum incretin and metabolites of GU−/NGT and IGT were then measured. Results When the serum insulin level at each time‐point during PHS/OGTT was expressed as its ratio relative to Glc/OGTT, it was increased time‐dependently in GU−/NGT, but not in IGT. Such an increase in the ratio was also detected of serum incretin levels in GU−/NGT, but not in IGT, suggesting a lack of deceleration of oligosaccharide absorption in IGT. Metabolome analysis showed a difference in the serum levels of two metabolites of unknown function in mammals, methylcysteine and sedoheptulose 1,7‐bisphosphate, between GU−/NGT and IGT. Conclusions Comparison of PHS/OGTT and Glc/OGTT showed that oligosaccharide absorption was accelerated in IGT. Methylcysteine and sedoheptulose 1,7‐bisphosphate could be novel markers for dysregulated glucose metabolism. The physiological and metabolic changes of young Japanese with IGT was evaluated using two types (D‐glucose [Glc] and partial hydrolysate of starch [PHS]) of oral glucose tolerance tests (OGTT). By comparing two OGTTs, we found that oligosaccharide absorption was accelerated in IGT. Metabolome analysis identified two metabolites as novel markers for dysregulated glucose metabolism.

Aims/Introduction To assess the efficacy and safety of sitagliptin compared with α‐glucosidase inhibitors in Japanese patients with type 2 diabetes inadequately controlled by metformin or pioglitazone alone. Materials and Methods In the present multicenter, randomized, open‐label, parallel‐group, active‐controlled, non‐inferiority trial, 119 patients aged 20–79 years with type 2 diabetes who had glycated hemoglobin 6.9–8.8% on stable metformin (500–1,500 mg/day) or pioglitazone (15–30 mg/day) alone were randomly assigned (1:1) to receive the addition of sitagliptin (50 mg/day) or an α‐glucosidase inhibitor (0.6 mg/day voglibose or 150 mg/day miglitol) for 24 weeks. The primary end‐point was change in glycated hemoglobin from baseline to week 12. All data were analyzed according to the intention‐to‐treat principle. Results After 12 weeks, reductions in adjusted mean glycated hemoglobin from baseline were −0.70% in sitagliptin and −0.21% in the α‐glucosidase inhibitor groups respectively; between‐group difference was −0.49% (95% confidence interval −0.66 to −0.32, P < 0.0001), meeting the predefined non‐inferiority criterion (0.25%) and showing statistical significance. This statistical significance also continued after 24 weeks. Although sitagliptin did not affect bodyweight, α‐glucosidase inhibitors decreased bodyweight significantly from baseline (−0.39 kg; P = 0.0079). Gastrointestinal disorders were significantly lower with sitagliptin than with an α‐glucosidase inhibitor (6 [10.3%] patients vs 23 [39.7%]; P = 0.0003). Minor hypoglycemia occurred in two patients (3.5%) in each group. Conclusions Sitagliptin showed greater efficacy and better tolerability than an α‐glucosidase inhibitor when added to stable doses of metformin or pioglitazone. These findings support the use of sitagliptin in Japanese patients with type 2 diabetes inadequately controlled by insulin‐sensitizing agents. This trial was registered with UMIN (no. 000004675).