The use of the Internet-of-Things has improved glycemic control in individuals with diabetes in several small-scale studies with a short follow-up period. This large-scale randomized controlled trial investigates whether a smartphone-based self-management support system prevents the worsening of glycemic control in individuals with type 2 diabetes. Individuals with type 2 diabetes (age range 20-74 years; n = 2,000) will be recruited, enrolled, and randomly assigned to two groups: the intensive therapy group and the conventional therapy group. Participants in the intensive therapy group will be supervised to use an automated Internet-of-Things system that demonstrates a summary of lifelogging data (e.g., weight, blood pressure, and daily activities) obtained from each measurement device and will receive feedback messages via smartphone applications to encourage them to increase their physical activity and to monitor weight and blood pressure. Participants in the conventional therapy group are allowed to use the same measurement devices as part of the routine diabetes care but without the Internet-of-Things system. The primary endpoint is the between-group difference in HbA1c levels from baseline to 52 weeks. This randomized controlled study will test the hypothesis that an Internet-of-Things-based self-monitoring system could effectively prevent the worsening of diabetes in individuals with type 2 diabetes. The expected results of the study should facilitate the development of novel strategies for both diabetes treatment and social health.
A phase II clinical study of 254-S, a new anticancer platinum complex for advanced breast cancer, was conducted by the 254-S Breast Cancer Study Group consisting of 6 institutions nation-wide. Considering the results of the phase I clinical study, 254-S was administered at 100 mg/m2 by intravenous drip infusion and this administration was repeated at least 2 times at 4-week intervals. Of 19 patients registered, 16 were evaluable for tumor response (complete cases). Partial response (PR) was obtained in 2 patients, for a 12.5% response rate. Major toxic effects observed were hematotoxicity thrombocytopenia and leukopenia, and gastrointestinal toxicity (nausea and vomiting, and anorexia), though there was no case in which the treatment with 254-S had to be discontinued due to the toxic effect.
Abstract Impaired bone formation due to defective osteoblast function, as reflected in a decreased serum osteocalcin (OC) concentration in the patients with diabetes, has been implicated in the development of diabetic osteopenia. The role of hyperglycemia in this decrease in serum OC concentration was investigated. 1,25-dihydroxyvitamin D3 (1,25[OH]2D3), an active form of vitamin D3, stimulated OC secretion from the human osteosarcoma cell line MG-63 in a dose-dependent manner. Exposure of the cells to high concentrations of glucose for 7 days significantly impaired 1,25(OH)2D3-induced OC secretion as compared with that observed with cells maintained under normal glucose (5.5 mM) or high mannitol conditions. The inhibitory effect of glucose was in a dose-dependent manner up to 55 mM. High glucose (55 mM) also attenuated the 1,25(OH)2D3-induced increase in OC mRNA abundance in MG-63 cells, suggesting that the inhibition of the 1,25(OH)2D3-induced increase in OC secretion by exposure to a high concentration of glucose was, at least in part, mediated at the transcriptional level. High glucose significantly decreased the number of 1,25(OH)2D3 receptors in MG-63 cells, without any change in the dissociation constant for 1,25(OH)2D3; this effect was not mimicked by high mannitol, indicating specificity for glucose. These observations suggest that a high glucose concentration significantly impairs the ability of osteoblastic cells to synthesize OC in response to 1,25(OH)2D3 by reducing 1,25(OH)2D3 receptor number, and that impaired cell function caused by sustained exposure to high glucose contributes to the defect in bone formation observed in the patients with diabetic osteopenia. (
BLM has been implicated in DNA double-strand break (DSB) repair, but its precise role remains obscure. To explore this, we generated BLM(-/-) and BLM(-/-)LIG4(-/-) cells from the human pre-B cell line Nalm-6. BLM(-/-) cells exhibited retarded growth, increased mutation rates, and hypersensitivity to agents that block replication fork progression. Interestingly, these phenotypes were significantly suppressed by deletion of LIG4, suggesting that nonhomologous end-joining (NHEJ) is unfavorable for integrity and survival of cells lacking BLM. We propose that the absence of BLM leads to accumulation of replication-associated, one-ended DSBs, which are deleterious to cells and lead to genomic instability when repaired by NHEJ. In addition, the NHEJ pathway per se was marginally affected by BLM deficiency, as evidenced by x-ray sensitivity and I-SceI-based DSB repair assays. More intriguingly, however, these experiments revealed the presence of an alternative, DNA ligase IV-independent end-joining pathway, which was significantly affected by the loss of BLM. Collectively, our results provide the first evidence for genetic interactions between BLM and NHEJ in human cells.
