By using International WHO and standard Indonesia classification systems, general and central obesity were associated with hypertension in Indonesia women. Thus, not only general obesity but also central obesity should be used to assess obesity in Indonesian women.
Recently, the first series of small molecule inhibitors of PD-1/PD-L1 were reported by Bristol-Myers Squibb (BMS), which were developed using a homogeneous time-resolved fluorescence (HTRF)-based screening investigation of the PD-1/PD-L1 interaction. Additional crystallographic and biophysical studies showed that these compounds inhibited the interaction of PD-1/PD-L1 by inducing the dimerization of PD-L1, in which each dimer binds one molecule of the stabilizer at its interface. However, the immunological mechanism of the antitumor effect of these compounds remains to be elucidated. In the present study, we focused on BMS-202 (a representative of the BMS compounds) and investigated its antitumor activity using in vitro and in vivo experiments. BMS-202 inhibited the proliferation of strongly PD-L1-positive SCC-3 cells (IC 50 15 μM) and anti-CD3 antibody-activated Jurkat cells (IC 50 10 μM) in vitro. Additionally, BMS-202 had no regulatory effect on the PD-1 or PD-L1 expression level on the cell surface of these cells. In an in vivo study using humanized MHC-double knockout (dKO) NOG mice, BMS-202 showed a clear antitumor effect compared with the controls; however, a direct cytotoxic effect was revealed to be involved in the antitumor mechanism, as there was no lymphocyte accumulation in the tumor site. These results suggest that the antitumor effect of BMS-202 might be partly mediated by a direct off-target cytotoxic effect in addition to the immune response-based mechanism. Also, the humanized dKO NOG mouse model used in this study was shown to be a useful tool for the screening of small molecule inhibitors of PD-1/PD-L1 binding that can inhibit tumor growth via an immune-response-mediated mechanism.
BackgroundThe purpose of this paper is to describe the features of the Interaction Rating Scale (IRS) as an evidence-based practical index of children’s social skills and parenting.MethodsThe participants in our study, which was conducted as part of a Japan Science and Technology Agency (JST) project, were 370 dyads of children (aged 18, 30, and 42 month) and 81 dyads of 7-year-old children with their caregivers. The participants completed the five minute interaction session and were observed using the IRS.ResultsThe results indicated that the IRS can measure children’s social skill development and parenting with high validity. Along with the discriminate validity for pervasive development disorder (PDD), attention-deficit/hyperactivity disorder (ADHD), abuse and maltreatment, a high correlation with the SDQ (Strength and Difficulties Questionnaire), and high reliability, the IRS is effective in describing features of social skill development.ConclusionsThe IRS provides further evidence of the fact that in order to study children’s social skill development, it is important to evaluate various features of the caregiver-child interaction as a predictor of social skills.
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