Aichi Gakuin University

A simple suspension method is used in medical practice to administer several orexin receptor antagonists for patients with dysphagia; however, detailed suspension and passage through catheter evaluations have not been performed. Therefore, to safely administer orexin receptor antagonists using the simple suspension method in patients with dysphagia, this study evaluated the disintegration, suspension, passage through the catheter, and drug recovery after passage of Belsomra® 20 mg (suvorexant), Dayvigo® 10 mg (lemborexant), and Quviviq® 50 mg (daridorexant) tablets through a catheter. Disintegration and suspension of Belsomra® 20 mg, Dayvigo® 10 mg, and Quviviq® 50 mg tablets, and passage through the catheter were visually confirmed. Drug recovery after passage through the catheter was quantified using liquid chromatography-mass spectrometry. In this study, there was no disintegration and suspension of Belsomra® 20 mg tablets. However, Dayvigo® 10 mg and Quviviq® 50 mg tablets demonstrated disintegration and suspension, including passage through the catheter after rapid and complete disintegration. Drug recovery after catheter passage was >80% for Dayvigo® 10 mg without flushing and for Quviviq® 50 mg after two flushes. As the disintegration and suspension properties of Belsomra® 20 mg tablet could not be confirmed, the conventional simple suspension method is not suitable for this product. However, Dayvigo® 10 mg and Quviviq® 50 mg tablets showed potential suitability for the simple suspension method.

The hyoid lesser horn (LH) forms a transient joint with the greater horn in human fetuses. The chondroglossus muscle attaches to the LH; however, its morphology remains unclear. We hypothesized that the muscles involved in LH accelerate joint formation. We examined 34 human fetuses with crown-rump length of 39-230mm. The LH joint was bilaterally absent in eight fetuses; the largest specimen "without" joints was 110mm crown-rump length, whereas the smallest specimen "with" joints was 55mm. The chondroglossus was identified as oblique muscle fibers attached to the LH medial aspect (23/34). The chondroglossus, Adjacent to the transverse lingual muscle (TLM), the chondroglossus ran supero-antero-medially to join the genioglossus. The TLM (21/34) and middle pharyngeal constrictor (pars chondropharyngica; 21/34) originated from the LH. The latter ran posteriorly from the LH medial to the hypoglossal nerve, whereas the middle constrictor arose largely from the greater horn. Notably, without LH attachment, the anterior margin of the mylohyoideus muscle (MPCM) was connected to the TLM using thick fascia wrapped around the LH. Therefore, LH disrupts the muscular ring surrounding the oropharynx. The variation in joint formation timing (9-16 weeks gestational age) suggests that the chondroglossus, TLM, and MPCM development do not require joint movement. Alternatively, an elongated greater horn may provide joint-like space.

This case report illustrates a technique for fabricating a monolithic computer-aided design (CAD)/computer-aided manufacturing (CAM) zirconia crown by reproducing the morphology of a provisional restoration that had been adapted to the clasp of an existing removable partial denture. A 69-year-old patient presented after endodontic treatment of the mandibular right first and second premolars, which served as abutments for a removable partial denture with a double Akers clasp. To achieve optimal clasp adaptation, occlusal contacts, marginal fit, a rest seat, a guide plane, and undercut areas were intentionally incorporated into the provisional restoration. Models of the abutment teeth, provisional restoration, and opposing dentition were fabricated. A definitive cast was scanned with a digital scanner, and the datasets were superimposed to design and fabricate a monolithic zirconia crown. The crown demonstrated excellent clasp adaptation upon placement. Over a four-year follow-up period, denture movement was minimized, abutment teeth remained unaffected, and periodontal tissues remained stable. This case highlights the clinical effectiveness of using a provisional restoration incorporating clasp adaptation as a guide for the CAD/CAM-based fabrication of definitive monolithic zirconia crowns for abutment teeth.

Aim: Early vancomycin-associated acute kidney injury (AKI) identification is important during the initial dosing period when non–steady-state pharmacokinetic exposure may influence nephrotoxicity risk. We aimed to conduct a multicentre retrospective cohort study of hospitalised adult patients who received vancomycin at three tertiary care hospitals in Japan between April 2019 and March 2024. Methods: Early area under the concentration–time curve (AUC) metrics, trough concentrations, concomitant medications, and comorbidities were used to develop and compare machine learning models to predict vancomycin-associated AKI. Eleven algorithms were evaluated using a nested cross-validation framework to minimise optimistic bias and prevent data leakage. Results: Among 442 patients (median age 72 years), AKI occurred in 5.7%. Across models, day 2 AUC and trough concentration consistently emerged as the most influential predictors, followed by concomitant use of piperacillin/tazobactam, diuretics, and vasopressors. The random forest model showed the best overall discriminative performance (area under the receiver operating characteristic curve 0.89; area under the precision–recall curve 0.47). Shapley additive explanations revealed nonlinear increases in AKI risk at approximately day 2 AUC ≥ 550 mg·h/L and trough concentration ≥ 20 μg/mL. These findings indicate that early vancomycin exposure, particularly cumulative exposure within the first 48 h, is strongly associated with AKI risk. Conclusion: Machine learning models incorporating early AUC metrics with trough concentrations may provide a clinically informative framework for early risk stratification during vancomycin therapy and support further evaluation of early AUC-guided dosing strategies with trough concentrations as complementary exposure markers.

Mannose supplementation has emerged as a promising strategy to exploit the hidden vulnerabilities of cancer cells. However, the mannose-dependent effect on cellular functions remains unclear. Here, we investigated the collateral impact of mannose supplementation on the metastatic potential of osteosarcoma. Analysis of a paired osteosarcoma dataset showed significant upregulation of GPI in tumors compared with matched normal tissue, whereas other glycolysis- and mannose-metabolism genes showed non-significant upward trends. By using osteosarcoma cell lines, MG-63 carrying a pronounced epithelial-to-mesenchymal transition phenotype showed a dose-dependent inhibition of proliferation upon mannose supplementation. We also found that mannose-induced attenuation of cell growth was further enhanced, accompanied by marked reductions in migration and invasion ability. Consistently, qPCR analysis indicated that mannose supplementation downregulated key genes associated with metastasis. Collectively, our data reveal that mannose inhibits osteosarcoma not merely by dampening glycolysis but also by triggering, in part, MPI-linked mannose metabolism, which disrupts key drivers of motility-associated phenotypes. Together, these data show that pharmacologic mannose supplementation modulates cell growth- and motility-associated phenotypes in osteosarcoma cell models, accompanied by changes in epithelial-to-mesenchymal transition-associated transcripts.

This study aimed to investigate differences in responses between groups by comparing online responses via smartphones using various response formats on Google Forms with responses from paper questionnaires among university students. Participants were randomly assigned to either an online group where they responded using one of grid, radio button, or linear scale formats, or a paper-based group. In each group, respondents answered multiple psychological scales and rated the visibility of the survey form. Additionally, response times and the ratio of careless responses were recorded. A total of 1,108 valid responses were analyzed. Results indicated that in the grid group, certain mean values of scale scores and some correlation coefficients differed from those in the paper-based group. Furthermore, there were more careless responses, longer response times, and lower ratings for form visibility in the grid group. Differences in mean values for some scales compared to the paper-based group were also observed in the linear scale group. The radio button group showed the least difference in responses compared to the paper-based group.