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Purpose: The present multicenter randomized controlled trial explored the effectiveness of a person-centered care program (intervention group) and a dementia-type-specific program (control group) for nurses in acute-care hospitals., Methods: Seven hospitals in Prefecture A were randomly allocated to two groups (an intervention group and a control group), and a study of these groups was conducted from July 2021 to January 2022., Results: A total of 158 participants were included in the study: 58 in the control group and 100 in the intervention group. In a comparison of assessment values immediately after the course, three months later, and six months later for both the intervention and control groups, "expertise in dementia nursing," "medical expertise in dementia, " and "confidence in nursing older people with dementia" were all significantly higher than before the course. Significant improvements in the intervention group's "knowledge of dementia" and "sense of dignity" on the ethical sensitivity scale were found immediately after the course compared to baseline, three months later, and six months later and were also significantly greater than the control group in terms of the amount of change. In the control group's "unique care tailored to cognitive function and the person," there were significant improvements in the ratings immediately after the course and three and six months after the course compared to baseline, with significantly greater amounts of change than in the intervention group., Conclusion: The person-centered care program for nurses led to improvements in the knowledge about dementia and awareness of the dignity of ethical sensitivity. In addition, the type of dementia program had a significant influence on medical knowledge and unique care tailored to the cognitive function and the individual patient. Further outcome evaluations of physical restraint rates as a quality of care in nursing practice are needed.

Immune checkpoint inhibitor therapy has been attracting attention as a new cancer treatment and is likely to be widely used in combination with radiotherapy. Therefore, examination of the effects of X-ray irradiation on sentinel lymph nodes and lymphatic vessels, which are involved in antigen presentation, is important for therapy. The hindlimbs of mice were irradiated with X-rays (total radiation doses: 2, 10, and 30 Gy), and X-ray computed tomography (CT) imaging was performed using 15-nm or 2-nm gold nanoparticles (AuNPs) as contrast agents on days 7, 14, and 28 after irradiation to evaluate the diameter of the collecting lymph vessels and lymph flow within the irradiated area. X-ray CT imaging data using 15-nm AuNPs on day 28 after irradiation showed that the diameter of the collecting lymph vessels was significantly larger in all irradiated groups compared to the control group (p ≤ 0.01). CT imaging with 2-nm AuNPs showed that lymphatic drainage was significantly reduced in the lymph nodes irradiated with 10 Gy and 30 Gy compared to the lymph nodes irradiated with 2 Gy (p ≤ 0.05). Additionally, immunohistochemical analyses were conducted to evaluate the area density and morphology of high endothelial venules (HEVs) in the lymph nodes, which are important vessels for naive T cells to enter the lymph nodes. The expression level of MECA-79, which specifically localized to HEVs, was significantly decreased in the 10 Gy and 30 Gy irradiation groups compared to the control group (p ≤ 0.05). There was a significant decrease in normal HEV morphology (p ≤ 0.05) and a significant increase in abnormal HEV morphology (p ≤ 0.05) in all irradiated groups. These results also showed that X-ray irradiation induced a time- and radiation dose-dependent increase in the diameter of the collecting lymph vessels, stagnation of intralymphatic lymph flow, and a reduction in the area density of HEVs and their abnormal morphology, demonstrating that X-ray irradiation affected the immune responses. Therefore, these findings suggest that X-ray irradiation to lymph nodes may impair the opportunity for antigen presentation in the lymph nodes, which is the key to cancer immunity, and that for this reason, it is important to carefully plan irradiation of sentinel lymph nodes and develop treatment strategies according to future treatment options., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Inc. All rights reserved.)

An inhibitor of the complex of factor VIIa and tissue factor (fVIIa/TF), 2-substituted-4-amidinophenylpyruvic acid 1a, was structurally modified with the aim of increasing its potency and selectivity. The lead compound 1a was originally found in our factor Xa (fXa) inhibitor library on the basis of structural similarity of the primary binding sites of fVIIa and fXa. The design was based on computational docking studies using the extracted active site of fVIIa. Compound 1j was found to inhibit factor VIIa/TF at nanomolar concentration with improved selectivity versus fXa and thrombin and it preferentially prolonged the clotting time in the TF-dependent extrinsic pathway.

An inhibitor of factor Xa (fXa), the m-substituted benzamidine AXC1578 (1a), was structurally modified with the aim of increasing its potency. In particular, pyruvic acid and propionic acid substituents were incorporated into the P1 benzamidine moiety to introduce a favorable interaction with the oxy-anion hole in the catalytic triad region of fXa. This strategy was based on computational docking studies using the extracted active site of fXa. The validity of the computational model was supported by the acquisition of X-ray crystal structures of the 1a-trypsin and 3b-trypsin complexes (the homology around the active sites of fXa and trypsin is high). The above modifications significantly increased the inhibitory activity toward fXa, whereas the high selectivity for fXa versus thrombin was maintained or enhanced. Compounds 3b, 3c, 3e, and 4b are considered to be potential lead compounds for the development of orally active anticoagulant drugs because they demonstrated potent activity when administered orally to cynomolgus monkeys.

We have investigated metabolite profiles and gene expression in two chemo-varietal forms, red and green forms, of Perilla frutescens var. crispa. Striking difference in anthocyanin content was observed between the red and green forms. Anthocyanin, mainly malonylshisonin, was highly accumulated in the leaves of the red form but not in the green form. Less obvious differences were also observed in the stems. However, there was no remarkable difference in the contents and patterns of flavones and primary metabolites such as inorganic anions, organic anions and amino acids. These results suggest that only the regulation of anthocyanin production, but not that of other metabolites, differs in red and green forms. Microscopic observation and immunohistochemical studies indicated that the epidermal cells of leaves and stems are the sites of accumulation of anthocyanins and localization of anthocyanidin synthase protein. By differential display of mRNA from the leaves of red and green forms, we could identify several genes encoding anthocyanin-biosynthetic enzymes and presumptive regulatory proteins. The possible regulatory network leading to differential anthocyanin accumulation in a form-specific manner is discussed.

This study was conducted to obtain information about the critical temperature of the spinal cord in hyperthermia produced by radiofrequency waves applied to the spine. The first component of the spinal cord evoked potential was analyzed as an indicator of spinal cord function. The spinal cords were heated by radiofrequency waves to a maximum of 47 degrees C momentarily or for 30 minutes. The temperatures were measured with a thermosensor in the epidural space. In momentary heating, the reductions in amplitude were almost parallel with the increases in temperature. In maintained heating for 30 minutes, at 44 degrees C and below, the amplitudes decreased by one-quarter to three-quarters of the control value in the first 5 minutes and recovered to over three-quarters of the control value in 30 minutes. The amplitudes returned to almost the control value after restoration of normal spinal cord temperatures. At 45 degrees C and above, however, the amplitudes were prominently reduced or disappeared in the first 5 minutes and remained depressed during the remainder of the heating. On normalizing the temperature, the amplitudes did not return to the control value. These results suggest that 44 degrees C in the epidural space is the highest tolerable temperature for normal spinal cord function.

Since 1960 isolation perfusion chemotherapy has been performed as a preoperative procedure combined with surgery in 226 patients with malignant tumor of the extremities in our department. In this report we presented the result of isolation perfusion chemotherapy using cisplatin (CDDP) for 27 patients since 1983. The histologic classification of the malignant tumor was osteosarcoma in 17 patients, malignant fibrous histiocytoma (MFH) of bone in 8, and other tumor in 2. The extremity was perfused with CDDP (100 micrograms/ml) for 60 minutes. Of 27 patients, 11 were treated with hyperthermic isolation perfusion. The two-year survival rate of the 15 patients with osteosarcoma was 80%, and that of the 7 patients with MFH of bone 71%. The tumor was microscopically analyzed, and the ratio of necrotic to viable tumor cells was calculated. The degree of tumor necrosis was classified as excellent (greater than or equal to 95%), good (80-94%), fair (50-79%), and poor (less than 50%). Of 16 patients, 7 were excellent, 5 good, 3 fair and 1 poor. We concluded that isolation perfusion chemotherapy using CDDP is an effective procedure combined with surgery for malignant tumor of the extremities.