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Sodium-glucose cotransporter-2 (SGLT2) inhibitors are increasingly recommended as first-line treatment for type 2 diabetes mellitus (T2DM), but head-to-head data comparing them with metformin, the canonical biguanide, remain sparse in Japan. To compare the long-term effectiveness and cost of initiating treatment with a biguanide versus an SGLT2 inhibitor, excluding the alternative class for 12 months but permitting other antidiabetic drugs, on a composite of major cardio-cerebrovascular events and all-cause death, and a composite of diabetic complications. We emulated a new-user cohort trial using the Shizuoka Kokuho Database (2014-2021). Patients initiating treatment with either a biguanide or an SGLT2 inhibitor, while avoiding the alternative class during the first 12 months but allowing other glucose-lowering agents, were included. Follow-up began at treatment initiation; those who received the comparator drug within 12 months were excluded. After 1:1 propensity-score matching on demographic, clinical, laboratory, and lifestyle variables, cause-specific Cox models estimated hazard ratios (HRs). Daily medication costs were compared. After matching, 1,246 patients (623 per group) were followed for a median of 2.9 years (maximum 7.2 years). Cardio-cerebrovascular composite: 44/623 biguanide users (7.1%) and 35/623 SGLT2 inhibitor users (5.6%) experienced a first event (HR 0.80, 95% CI 0.51-1.24). Diabetic complications: 86/623 (13.8%) vs. 78/623 (12.5%) (HR 0.88, 95% CI 0.70-1.13). Median daily drug cost was 124.7 JPY for biguanides and 184.0 JPY for SGLT2 inhibitors (P < 0.001). Using a large-scale regional database from Japan, we found that among adults with type 2 diabetes without prior major cardiac or renal disease, first-line treatment with an SGLT2 inhibitor did not reduce risks of cardio-cerebrovascular events, mortality, or complications compared with metformin, and cost about 50% more.

Western guidelines often recommend biguanides as the first-line treatment for diabetes. However, dipeptidyl peptidase-4 (DPP-4) inhibitors, alongside biguanides, are increasingly used as the first-line therapy for type 2 diabetes (T2DM) in Japan. However, there have been few studies comparing the effectiveness of biguanides and DPP-4 inhibitors with respect to diabetes-related complications and cardio-cerebrovascular events over the long term, as well as the costs associated. We aimed to compare the outcomes of patients with T2DM who initiate treatment with a biguanide versus a DPP-4 inhibitor and the long-term costs associated. We performed a cohort study between 2012 and 2021 using a new-user design and the Shizuoka Kokuho database. Patients were included if they were diagnosed with T2DM. The primary outcome was the incidence of cardio-cerebrovascular events or mortality from the initial month of treatment; and the secondary outcomes were the incidences of related complications (nephropathy, renal failure, retinopathy, and peripheral neuropathy) and the daily cost of the drugs used. Individuals who had experienced prior events during the preceding year were excluded, and events within 6 months of the start of the study period were censored. Propensity score matching was performed to compare between two groups. The matched 1:5 cohort comprised 529 and 2,116 patients who were initially treated with a biguanide or a DPP-4 inhibitor, respectively. Although there were no significant differences in the incidence of cardio-cerebrovascular events or mortality and T2DM-related complications between the two groups (p = 0.139 and p = 0.595), daily biguanide administration was significantly cheaper (mean daily cost for biguanides, 61.1 JPY; for DPP-4 inhibitors, 122.7 JPY; p<0.001). In patients with T2DM who initiate pharmacotherapy, there were no differences in the long-term incidences of cardio-cerebrovascular events or complications associated with biguanide or DPP-4 use, but the former was less costly.

Background Guidelines worldwide recommend that physicians should not treat their family members. However, studies in the U.S. have shown that approximately 74–83% of physicians have experience of treating family members. Primary care physicians were more likely to have such experiences than other specialists. In Japan, physicians do not have any guidelines regarding treating family members, and little is known about the experiences of primary care physicians. Therefore, we investigated the experience of treating family members or relatives among primary care physicians in Japan. Methods This cross-sectional study used an online questionnaire. We recruited 2,000 physicians who were members of the Japan Primary Care Association using random sampling. Data were collected from February 10 to March 10, 2021. We compare the experiences of treating family members between clinic-based doctors and hospital-based doctors using the chi-square test. We performed logistic regression analysis to adjust for gender, age, presence of a doctor in family, and physician’s geographic location (rural or not rural). Results A total of 466 physicians (response rate = 23.3%) completed the survey. Of the sample, 79.8% had experience of treating family members or relatives. In the univariate analysis, being a clinic-based physician was associated with experience in treating family members compared to hospital-based physicians (87.6% vs. 74.9%, p  = 0.001). Multivariable analysis showed that being a clinic-based physician (odds ratio 2.30, 95% confidence interval 1.31–4.04) and age of 45–64 years (odds ratio 2.93, 95% confidence interval 1.74–4.93) were significantly related to experience treating family. Gender and geographic location were not statistically significant factors. Conclusions A high percentage of Japanese primary care physicians, especially those who worked in clinics, reported experience treating family members or relatives. These findings will serve as basic data for future studies regarding the care of families and relatives of physicians in Japan.

The Aharonov-Casher (AC) effect is theoretically examined in a mesoscopic ring with an embedded quantum dot in a multi-terminal geometry. We examine a realistic model for such a system with spin-orbit interaction in the ring. A spin-polarized current can be generated in a three-terminal device even in the absence of magnetic field, whereas it cannot in a two-terminal device. The spin polarization is enhanced by the resonant tunneling around the Coulomb peak and Kondo effect in the Coulomb blockade regime. The efficiency for the spin polarization is discussed in realistic devices.

BackgroundSodium-glucose cotransporter-2 (SGLT2) inhibitors are increasingly recommended as first-line treatment for type 2 diabetes mellitus (T2DM), but head-to-head data comparing them with metformin, the canonical biguanide, remain sparse in Japan.ObjectiveTo compare the long-term effectiveness and cost of initiating treatment with a biguanide versus an SGLT2 inhibitor, excluding the alternative class for 12 months but permitting other antidiabetic drugs, on a composite of major cardio-cerebrovascular events and all-cause death, and a composite of diabetic complications.MethodsWe emulated a new-user cohort trial using the Shizuoka Kokuho Database (2014-2021). Patients initiating treatment with either a biguanide or an SGLT2 inhibitor, while avoiding the alternative class during the first 12 months but allowing other glucose-lowering agents, were included. Follow-up began at treatment initiation; those who received the comparator drug within 12 months were excluded. After 1:1 propensity-score matching on demographic, clinical, laboratory, and lifestyle variables, cause-specific Cox models estimated hazard ratios (HRs). Daily medication costs were compared.ResultsAfter matching, 1,246 patients (623 per group) were followed for a median of 2.9 years (maximum 7.2 years). Cardio-cerebrovascular composite: 44/623 biguanide users (7.1%) and 35/623 SGLT2 inhibitor users (5.6%) experienced a first event (HR 0.80, 95% CI 0.51-1.24). Diabetic complications: 86/623 (13.8%) vs. 78/623 (12.5%) (HR 0.88, 95% CI 0.70-1.13). Median daily drug cost was 124.7 JPY for biguanides and 184.0 JPY for SGLT2 inhibitors (P < 0.001).ConclusionUsing a large-scale regional database from Japan, we found that among adults with type 2 diabetes without prior major cardiac or renal disease, first-line treatment with an SGLT2 inhibitor did not reduce risks of cardio-cerebrovascular events, mortality, or complications compared with metformin, and cost about 50% more.

Acquisition of pluripotency by somatic cells is a striking process that enables multicellular organisms to regenerate organs. This process includes silencing of genes to erase original tissue memory and priming of additional cell type specification genes, which are then poised for activation by external signal inputs. Here, through analysis of genome-wide histone modifications and gene expression profiles, we show that a gene priming mechanism involving LYSINE-SPECIFIC DEMETHYLASE 1-LIKE 3 (LDL3) specifically eliminates H3K4me2 during formation of the intermediate pluripotent cell mass known as callus derived from Arabidopsis root cells. While LDL3-mediated H3K4me2 removal does not immediately affect gene expression, it does facilitate the later activation of genes that act to form shoot progenitors when external cues lead to shoot induction. These results give insights into the role of H3K4 methylation in plants, and into the primed state that provides plant cells with high regenerative competency. Plant regeneration can occur via formation of a mass of pluripotent cells known as callus. Here, Ishihara et al. show that acquisition of regenerative capacity of callus-forming cells requires a lysine-specific demethylase that removes H3K4me2 to prime gene expression in response to regenerative cues.

In recent years, a concept of renal rehabilitation has become widely known among nephrology specialists, dialysis specialists, kidney transplantation specialists, rehabilitation specialists, nutrition specialists, guideline specialists, nurses, physiotherapists, and representatives of patients. Therefore, in order to make it clear the definition, methods, and effectiveness of renal rehabilitation in Japan, we launched Renal Rehabilitation Guideline Preparation Committee in 2016 as a part of works in the Japanese Society of Renal Rehabilitation, and created a guideline in accordance to the “Minds Handbook for Clinical Practice Guideline Development 2014”. Here, we report systematic reviews and recommendations of exercise therapies in patients with kidney diseases based on the guideline preparation committee works. Six recommendations for the condition of each kidney disorder, groups addressing nephritis/nephrosis, chronic kidney diseases, dialysis therapy, and kidney transplantation were created. All the recommendation grades were determined by a consensus conference participated in by representatives of patients and various professionals. The purpose of this report is to provide an evidence-based, best practice summary to optimize the quality, safety and efficacy, and availability of renal rehabilitation service, and to provide care for maximum patient prognosis, quality of life, and satisfaction.

INTRODUCTION: Partial splenic torsion in polysplenia syndrome is an extremely rare condition. We encountered and performed surgery for a case of partial splenic torsion in a patient with polysplenia syndrome coexisting with agenesis of the dorsal pancreas.CASE PRESENTATION: A 30-year-old woman with heterotaxy syndrome presented with intermittent epigastric and right lateral abdominal pain persisting for 2 weeks. She was referred to our hospital. Abdominal contrast-enhanced CT revealed multiple spleens on the right side, a right-sided stomach, and agenesis of the dorsal pancreas. One of the 5 spleens showed no contrast enhancement. Suspecting torsion or infarction, we opted for surgical intervention. Intraoperative findings revealed a small spleen with poor coloration and 180-degree torsion, which we removed. Additionally, we identified another poorly anchored spleen and performed splenopexy to secure this wandering spleen.CONCLUSIONS: Polysplenia syndrome is a rare condition involving multiple spleens in the setting of heterotaxy syndrome—a defect in the left–right axis of the thoracic or abdominal organs without a complete mirror image. Several reports have described polysplenia syndrome coexisting with agenesis of the dorsal pancreas. Including our case, 11 instances of splenic torsion associated with polysplenia syndrome have been reported in English, with the current patient being the oldest. Furthermore, this is the 1st reported case of splenic torsion occurring in the context of polysplenia syndrome with agenesis of the dorsal pancreas. Our patient had 2 notable anatomical characteristics: first, a vascular variation in which the right celiac artery lacked a common hepatic artery and instead formed a common trunk with the superior mesenteric artery and common hepatic artery, resembling Adachi type VI (group 24); and second, a centrally located, unfixed dorsal spleen that underwent torsion. We hypothesize that splenic torsion occurred due to the central spleen’s mobility and its slightly elongated splenic artery.

The lineage of periodontal ligament (PDL) stem cells contributes to alveolar bone (AB) and cementum formation, which are essential for tooth-jawbone attachment. Leptin receptor (LepR), a skeletal stem cell marker, is expressed in PDL; however, the stem cell capacity of LepR + PDL cells remains unclear. We used a Cre/LoxP-based approach and detected LepR-cre-labeled cells in the perivascular around the root apex; their number increased with age. In the juvenile stage, LepR + PDL cells differentiated into AB-embedded osteocytes rather than cementocytes, but their contribution to both increased with age. The frequency of LepR + PDL cell-derived lineages in hard tissue was < 20% per total cells at 1-year-old. Similarly, LepR + PDL cells differentiated into osteocytes following tooth extraction, but their frequency was < 9%. Additionally, both LepR + and LepR − PDL cells demonstrated spheroid-forming capacity, which is an indicator of self-renewal. These results indicate that both LepR + and LepR − PDL populations contributed to hard tissue formation. LepR − PDL cells increased the expression of LepR during spheroid formation, suggesting that the LepR − PDL cells may hierarchically sit upstream of LepR + PDL cells. Collectively, the origin of hard tissue-forming cells in the PDL is heterogeneous, some of which express LepR.