Teikyo Heisei University

Well-known risk factors for soft tissue heterotopic ossification (HO) include aging and mechanical stress, which may be linked to oxidative stress and downstream nucleotide metabolites. Thus, we investigated the involvement of extracellular ATP (ex-ATP) and its metabolites in the oxidative stress-induced mineralization of TT-D6 cells and primary mouse tendon cells. An osteogenic culture with the intermittent addition of hydrogen peroxide was monitored for two weeks using metabolomic and gene expression analyses. Calcium deposition was significantly enhanced by 0.3 mM hydrogen peroxide in the osteogenic media after 2 weeks, with minimal calcification in its absence. Similar results were observed in a medium transfer experiment using 3-day-old hydrogen peroxide-treated conditioned medium, which led to an increased expression of osterix and alkaline phosphatase. Metabolomic analysis revealed a gradual increase in ex-ATP and its metabolites, including ADP, AMP, and adenosine, in the medium. The metabolite increase was enhanced by hydrogen peroxide after 12 h. Moreover, exogenous adenosine (100 μM) increased mineralization in osteogenic media. Additionally, 1 μM dipyridamole, an inhibitor of equilibrative nucleoside transporter 1 (Ent1), also increased it in response to low-dose (0.1 mM) hydrogen peroxide. The enhanced osteogenic calcification of the tendon cell culture by hydrogen peroxide was associated with an increase in extracellular nucleotide metabolites, especially adenosine, with some evidence of causality.

We investigated the protective effects of skipjack tuna (Katsuwonus pelamis) bone-derived biocalcium (Bio) against dexamethasone-induced atrophy in C2C12 myotubes. Bio rescued atrophic morphology, increasing myotube diameter dose-dependently. It mitigated inflammation by suppressing nitric oxide production and the expression and concentration of proinflammatory cytokines (IL-6, TNF-α, IL-1β) significantly and dose-dependently. Bio restored protein turnover balance by downregulating MuRF1 and atrogin-1 while upregulating MTOR. At 5-20µg/mL, Bio downregulated total NF-κB p65, p38 mitogen-activated protein kinase (MAPK), and FoxO3a and upregulated Akt expression. Crucially, Bio dose-dependently downregulated primary-, precursor-, and mature-microRNA-29b. In Bio-treated, dexamethasone-treated C2C12 myotubes, microRNA-29b inhibitor co-transfection significantly increased myogenin and MyoD expression, whereas microRNA-29b mimic co-transfection suppressed these myogenic markers, confirming the inhibitory role of microRNA-29b. Molecular docking simulations confirmed strong binding affinities between microRNA-29b and myogenin/MyoD. These results demonstrate that Bio exerts anti-atrophy effects by disrupting the microRNA-29b-mediated block on myogenesis and modulating inflammatory responses, protein turnover, and key signaling pathways. Collectively, skipjack tuna-derived Bio shows promise as a functional food supplement for sarcopenia prevention and management.

Monitoring and modeling population health is essential for understanding the impact of lifestyle behaviors and pharmacologic therapies on chronic disease management. In this study, we used a nationwide Japanese health insurance claims and health checkup database to investigate the associations between physical activity and glycemic control among 24,830 treatment-naïve adults with type 2 diabetes receiving DPP-4 inhibitors, SGLT2 inhibitors, or metformin. The odds of achieving hemoglobin A1c (HbA1c) < 6.5% at follow-up were assessed according to physical activity status, determined using standardized questionnaires. In this real-world population, physically active individuals had higher odds of achieving glycemic control than sedentary individuals among those treated with DPP-4 inhibitors or SGLT2 inhibitors, whereas no statistically significant association was observed among those treated with metformin. These findings support the potential value of integrating physical activity with pharmacologic therapy in type 2 diabetes management in real-world clinical settings.

HighlightsWhat are the main findings?TRPM2 is functionally enriched in atrial cardiomyocytes and drives stress-evoked Ca2+ influx that triggers ANP secretion.TRPM2 deficiency exacerbates ISO-induced hypertrophy, fibrosis, and systolic dysfunction, with blunted Nppa/ANP induction; exogenous ANP rescues these phenotypes.What are the implications of the main findings?TRPM2 functions as an upstream Ca2+-dependent regulator of the cardiac natriuretic peptide system, extending its known roles beyond oxidative-stress sensing.Therapeutic augmentation of the ANP axis (e.g., ANP administration, neprilysin inhibition) or targeting TRPM2 may mitigate pathological cardiac remodeling in hypertension and heart failure.Transient receptor potential melastatin 2 (TRPM2) channel is a Ca2+-permeable, redox-activated cardiac ion channel protective in ischemia–reperfusion, but whether it regulates atrial endocrine output under stress is unclear. Here, we investigated whether TRPM2 contributes to the atrial natriuretic peptide (ANP) response during β-adrenergic stimulation. We compared how male C57BL/6J wild-type (WT) and TRPM2 knockout (TRPM2−/−) mice (8–12 weeks old) respond to β-adrenergic stress induced by isoproterenol (ISO) using echocardiography, histology, RT-PCR, electrophysiology, Ca2+ imaging, ELISA, and atrial RNA-seq. We detected abundant Trpm2 transcripts in WT atria and measured ADP-ribose (ADPr)-evoked currents and hydrogen peroxide (H2O2)-induced Ca2+ influx characteristic of TRPM2; these were absent in TRPM2−/− cells. Under the ISO-induced hypertrophic model, TRPM2−/− mice developed greater cardiac hypertrophy, fibrosis, and systolic dysfunction compared with WT mice. Atrial bulk RNA-seq showed significant induction of Nppa (ANP precursor gene) in WT + ISO, accompanied by higher circulating ANP; TRPM2−/− + ISO showed blunted Nppa and ANP responses. ISO-treated TRPM2−/− mice exhibited more blunt responses, in both Nppa transcripts and circulating ANP levels. Exogenous ANP attenuated ISO-induced dysfunction, hypertrophy, and fibrosis in TRPM2−/− mice, suggesting that TRPM2 is needed for the cardioprotective endocrine response via ANP to control stress-induced β-adrenergic remodeling.

目的：発達障害児の眼球運動の稚拙さは定型発達児に比較し発生頻度が高い．「気が散りやすい」「文字を飛ばして読んでしまう」などの彼らの困り事の1つに眼球運動の苦手さが挙げられている．問題が顕在化される就学前に発見し治療することが望ましいが，現状，指標となる発達過程の眼球運動は明示されていない．そこで定型発達児の眼球運動の定量的評価の開発を試みた．

To examine longitudinal changes in exercise-induced hormonal responses in adolescent male basketball players. Fifteen adolescent males were assigned to prepeak height velocity (pre-PHV) and post-PHV groups according to the predicted age at PHV. Salivary testosterone, cortisol levels, and the testosterone-to-cortisol ratio were evaluated before (PRE), immediately after (POST), and 15minutes after a bodyweight resistance training session, which was repeated after 1year to analyze longitudinal changes in testosterone and cortisol levels. Resting testosterone levels and acute testosterone responses after bodyweight resistance training increased in both groups after 1year at all measurement points. The POST testosterone levels at initial measurement and PRE and 15-minute postexercise levels at 1year in the post-PHV group were significantly higher than those in the pre-PHV group. Cortisol levels significantly decreased in the post-PHV group at baseline and 1year later. In the post-PHV, the testosterone-to-cortisol ratio after bodyweight resistance training was significantly increased at baseline and 1year later. Although testosterone levels increase with age, no acute response to bodyweight resistance training was observed after 1year. The change in anabolic status indicated by the testosterone-to-cortisol ratio was due to a decrease in cortisol levels.

携帯電話をテレビリモコンのように使う行動は失認のためなのかどうかについて考察した。①携帯電話に対して探索行動を行ったあとテレビに向けた場合：多様式失認の可能性はある。携帯電話の呼称ができるか，使い方や意味を説明できるかを調べるのがよい。②探索せず，携帯電話を手にとってすぐにテレビに向けた場合：注意障害や抑制障害が考えられる。リモコンに形状の似た携帯電話に誘発されて，慣習的動作が脱抑制的に出現したと考えるのが，認知症患者の症状としてはもっとも可能性が高い。さまざまな症状が何なのかを考えるには，DSM-5の6つの認知領域のどれがかかわるかを考えるのがよい。失認は知覚-運動の領域の障害であるが，認知症では通常複数の領域が障害され，失認単独で出現することは稀である。道具の認知という点では，観念性失行の可能性についても考慮する必要がある。

The reproducibility of immobilization is critical in small animal radiotherapy, especially for the head region. We developed a reusable immobilization method using a thermoplastic mask molded with cylinders that can be universally applied, eliminating the need for individual patient-specific masks. We aimed to compare the effectiveness of this method with two conventional techniques, namely immobilization using a cylinder and patient-specific thermoplastic mask immobilization. Five beagle dogs underwent repeated CT scans for each method, and the positional errors of the anatomical landmarks were measured. In addition to the maxilla, we examined the mandible and lymph nodes in the head and neck region, which have rarely been considered in previous studies. The results demonstrated that the accuracy of the new universal immobilization method was comparable with that of the conventional methods, with no significant differences in the positioning of the bony landmarks. Universal immobilization outperformed cylindrical immobilization for the lymph nodes. However, large errors were observed in the positions of the lymph nodes across all tested head immobilization methods. The universal method required the shortest setup time, emphasizing its efficiency. It also eliminated the need for patient-specific individual masks, making it simple and sustainable. Despite certain limitations, such as the exclusive use of beagle dogs and the single-day anesthesia protocol, the study concluded that the cylindrical thermoplastic mask is a promising method that offers precision and efficiency. This study represents a model investigation rather than a validated clinical approach. Further proof-of-principle investigations are required to validate the clinical utility of this approach.

Dispensing audit support systems that authenticate pharmaceuticals via barcodes have been introduced into clinical practice to prevent dispensing errors, yet they occasionally generate false warnings, complicating clinical usage. This study sought to identify drugs prone to weight-error false warnings in the C-correct II® dispensing audit support system and to clarify its operational problems. We investigated the drugs that caused false weight-error warnings in the system, confirming that such errors did occur. Furthermore, the drugs causing weight errors tended to be significantly heavier than those that did not. Accurately identifying and addressing such operational issues within dispensing audit support systems will minimize the risk of dispensing errors and ultimately enhance medical safety.

BackgroundDexrazoxane is used to treat extravascular leakage of anthracycline antitumor agents, but its own extravascular leakage and management remain underreported. This case aimed to highlight both doxorubicin and dexrazoxane leakage during treatment for diffuse large B-cell lymphoma.Case presentationA 55-year-old man with diffuse large B-cell lymphoma developed doxorubicin leakage during rituximab, cyclophosphamide, doxorubicin hydrochloride, vincristine, and prednisolone (R-CHOP) therapy, which was treated with dexrazoxane. Subsequently, dexrazoxane leakage occurred, causing erythema and swelling. Topical clobetasol propionate was applied, leading to symptom resolution without necrosis. The patient successfully completed chemotherapy and achieved long-term remission.ConclusionsThis case report is one of the first to document the management of dexrazoxane extravascular leakage using topical steroids, effectively preventing severe outcomes. The findings suggest that topical steroids may be a desirable treatment approach for dexrazoxane leakage. Prompt intervention and interdisciplinary care contributed to the favorable outcome. This case highlights the need for further research and guideline refinement to optimize the management of inflammatory extravascular leakage.