No moderating effect of coping skills on the association between bullying experience and self-esteem: Results from K-CHILD study

IntroductionFew studies have investigated the moderating effect of coping skills on the association between bullying experience and low self-esteem. The aim of this study was to examine whether coping skills have a moderating effect on the association between bullying experience and self-esteem among Japanese students.MethodsData from the population-based Kochi Child Health Impact of Living Difficulty (K-CHILD) study conducted in 2016 were analyzed. Participants included fifth-and eighth-grade students living in Kochi Prefecture, Japan. A questionnaire for the students (n = 5,991) assessed the bullying experience, self-esteem (the Japanese Edition of the Harter’s Perceived Competence Scale for Children), and coping skills that comprised six types (The shortened version of coping skills for elementary school children). Multivariate linear regression analyses were conducted to examine the association between bullying experience and self-esteem and then the moderating effects of six types of coping as interaction terms on the association were considered.ResultsBullying experience was inversely associated with self-esteem. All six types of coping did not moderate the relationship between bullying experience and low self-esteem even after adjusting for cofounders (all P for interaction > 0.15).ConclusionCoping skills did not moderate the association between bullying experience and self-esteem, suggesting that intervention to boost coping skills to mitigate the adverse effect of bullying experience may not be promising

Development of the Intimate Partner Violence During Pregnancy Instrument (IPVPI)

Background: Intimate partner violence (IPV) during pregnancy can lead to negative consequences for both the mother and offspring. Although IPV is recognized as a worldwide public health issue, its prevalence is considered to be underestimated because cases are likely underreported, suggesting that there might be unmeasured IPV. The aim of this study was to develop an instrument to detect IPV in pregnant women.Methods: A total of 6,590 women in Aichi prefecture, Japan, who took part in a 3 or 4 month infant health checkup program, participated in the study. Questionnaires assessing history of IPV during pregnancy (physical abuse and verbal abuse), maternal characteristics, partner's characteristics, and household characteristics were mailed to women before, or distributed at, the checkup. Women returned the questionnaires to the checkup sites or mailed them back to the health centers. A prediction model for history of IPV was then generated using potential risk factors selected based on the literature.Results: Among 6,530 women who responded to either question on IPV during pregnancy (response rate = 67.3%), the rate of participants who experienced any IPV during pregnancy was 11.1% (physical IPV = 1.2%; verbal IPV = 10.8%). Multiple logistic regression analyses showed that maternal age (<25 years old), multiparity, history of artificial abortion, negative feelings when the pregnancy was confirmed (e.g., confused), having no one to provide support during pregnancy, having relationship problems with their partner, paternal smoking during pregnancy, and difficult financial status were associated with any abuse from the partner. Based on the analysis, the Intimate Partner Violence during Pregnancy Instrument (IPVPI) was developed, comprising of eight questions to detect unmeasured IPV in pregnant women, and showed moderate predictive power (area under receiver operating characteristic curve = 0.719, 95% confidence interval: 0.698 to 0.740) ranging from 0 to 16 with a cut-off point of 2 (sensitivity = 79.5%, specificity = 47.1%).Conclusion: The IPVPI, which allows to ask indirect questions rather that asking directly about experience of IPV, might be helpful to detect unmeasured IPV in pregnant women in fields of primary healthcare and obstetrics. Further research longitudinal studies are needed to improve the sensitivity and specificity of the IPVPI

Pathway of the Association Between Child Poverty and Low Self-Esteem: Results From a Population-Based Study of Adolescents in Japan

Child poverty leads to various negative consequences, including low self-esteem, which is a risk factor for mental illness, suicide, or poor academic achievement. However, little is known about why child poverty leads to low self-esteem. We aimed to elucidate the association of child poverty and low self-esteem based on the ecological model, which includes family-level, school-level, and community-level factors. Data were obtained from the Adachi Child Health Impact of Living Difficulty (A-CHILD) study in 2016, and participants included 1,652 children in fourth grade (534 pairs), sixth grade (530 pairs), and eighth grade (588 pairs) living in Adachi City, Tokyo, Japan. A questionnaire survey was implemented to assess child poverty, parental mental health, parental involvement with children, parental social capital by caregivers, and self-esteem and school social capital by children. The structural equation model was applied to elucidate the association between child poverty and low self-esteem, using family-level (parental mental health and parental involvement with children), school-level (school social capital), and community-level (parental social capital) factors. Child poverty was associated with low self-esteem. Child poverty leads to poor parental involvement, which can be indirectly associated with poor parental mental health and poor parental social capital, and poor parental involvement was directly or indirectly associated with low self-esteem through poor school social capital. To mitigate the impact of child poverty on low self-esteem, comprehensive health policies targeting family-level (parental mental health and parental involvement with children), school-level (school social capital), and community-level (parental social capital) factors may be effective

Development and Characterization of Novel Molecular Probes for Ca2+/Calmodulin-Dependent Protein Kinase Kinase, Derived from STO-609

Ca2+/calmodulin-dependent protein kinase kinase (CaMKK) activates particular multifunctional kinases, including CaMKI, CaMKIV, and 5′AMP-activated protein kinase (AMPK), resulting in the regulation of various Ca2+-dependent cellular processes, including neuronal, metabolic, and pathophysiological pathways. We developed and characterized a novel pan-CaMKK inhibitor, TIM-063 (2-hydroxy-3-nitro-7H-benzo[de]benzo[4,5]imidazo[2,1-a]isoquinolin-7-one) derived from STO-609 (7H-benzimidazo[2,1-a]benz[de]isoquinoline-7-one-3-carboxylic acid), and an inactive analogue (TIM-062) as molecular probes for the analysis of CaMKK-mediated cellular responses. Unlike STO-609, TIM-063 had an inhibitory activity against CaMKK isoforms (CaMKKα and CaMKKβ) with a similar potency (Ki = 0.35 μM for CaMKKα, and Ki = 0.2 μM for CaMKKβ) in vitro. Two TIM-063 analogues lacking a nitro group (TIM-062) or a hydroxy group (TIM-064) completely impaired CaMKK inhibitory activities, indicating that both substituents are necessary for the CaMKK inhibitory activity of TIM-063. Enzymatic analysis revealed that TIM-063 is an ATP-competitive inhibitor that directly targets the catalytic domain of CaMKK, similar to STO-609. TIM-063 suppressed the ionomycin-induced phosphorylation of exogenously expressed CaMKI, CaMKIV, and endogenous AMPKα in HeLa cells with an IC50 of ∼0.3 μM, and it suppressed CaMKK isoform-mediated CaMKIV phosphorylation in transfected COS-7 cells. Thus, TIM-063, but not the inactive analogue (TIM-062), displayed cell permeability and the ability to inhibit CaMKK activity in cells. Taken together, these results indicate that TIM-063 could be a useful tool for the precise analysis of CaMKK-mediated signaling pathways and may be a promising lead compound for the development of therapeutic agents for the treatment of CaMKK-related diseases

Capability and Limitations of Recent Diagnostic Criteria for Autoimmune Pancreatitis

Because a diagnostic serological marker is unavailable, autoimmune pancreatitis (AIP) is diagnosed based on unique features. The diagnostic capabilities and potential limitations of four sets of diagnostic criteria for AIP (Japanese diagnostic criteria 2006 and 2011, Asian diagnostic criteria, and international consensus diagnostic criteria (ICDC)) were compared among 85 patients who were diagnosed AIP according to at least one of the four sets. AIP was diagnosed in 87%, 95%, 95%, and 95% of the patients according to the Japanese 2006, Asian, ICDC, and Japanese 2011 criteria, respectively. The ICDC can diagnose types 1 and 2 AIP independently and show high sensitivity for diagnosis of AIP. However, as the ICDC are rather complex, diagnostic criteria for AIP should perhaps be revised and tailored to each country based on the ICDC

Nivolumab Versus Gemcitabine or Pegylated Liposomal Doxorubicin for Patients With Platinum-Resistant Ovarian Cancer: Open-Label, Randomized Trial in Japan (NINJA)

PURPOSE: This phase III, multicenter, randomized, open-label study investigated the efficacy and safety of nivolumab versus chemotherapy (gemcitabine [GEM] or pegylated liposomal doxorubicin [PLD]) in patients with platinum-resistant ovarian cancer. MATERIALS AND METHODS: Eligible patients had platinum-resistant epithelial ovarian cancer, received ≤ 1 regimen after diagnosis of resistance, and had an Eastern Cooperative Oncology Group performance score of ≤ 1. Patients were randomly assigned 1:1 to nivolumab (240 mg once every 2 weeks [as one cycle]) or chemotherapy (GEM 1000 mg/m2 for 30 minutes [once on days 1, 8, and 15] followed by a week's rest [as one cycle], or PLD 50 mg/m2 once every 4 weeks [as one cycle]). The primary outcome was overall survival (OS). Secondary outcomes included progression-free survival (PFS), overall response rate, duration of response, and safety. RESULTS: Patients (n = 316) were randomly assigned to nivolumab (n = 157) or GEM or PLD (n = 159) between October 2015 and December 2017. Median OS was 10.1 (95% CI, 8.3 to 14.1) and 12.1 (95% CI, 9.3 to 15.3) months with nivolumab and GEM or PLD, respectively (hazard ratio, 1.0; 95% CI, 0.8 to 1.3; P = .808). Median PFS was 2.0 (95% CI, 1.9 to 2.2) and 3.8 (95% CI, 3.6 to 4.2) months with nivolumab and GEM or PLD, respectively (hazard ratio, 1.5; 95% CI, 1.2 to 1.9; P = .002). There was no statistical difference in overall response rate between groups (7.6% v 13.2%; odds ratio, 0.6; 95% CI, 0.2 to 1.3; P = .191). Median duration of response was numerically longer with nivolumab than GEM or PLD (18.7 v 7.4 months). Fewer treatment-related adverse events were observed with nivolumab versus GEM or PLD (61.5% v 98.1%), with no additional or new safety risks. CONCLUSION: Although well-tolerated, nivolumab did not improve OS and showed worse PFS compared with GEM or PLD in patients with platinum-resistant ovarian cancer

Time-resolved serial femtosecond crystallography reveals early structural changes in channelrhodopsin

X線自由電子レーザーを用いて、光照射によるチャネルロドプシンの構造変化の過程を捉えることに成功. 京都大学プレスリリース. 2021-03-26.Channelrhodopsins (ChRs) are microbial light-gated ion channels utilized in optogenetics to control neural activity with light . Light absorption causes retinal chromophore isomerization and subsequent protein conformational changes visualized as optically distinguished intermediates, coupled with channel opening and closing. However, the detailed molecular events underlying channel gating remain unknown. We performed time-resolved serial femtosecond crystallographic analyses of ChR by using an X-ray free electron laser, which revealed conformational changes following photoactivation. The isomerized retinal adopts a twisted conformation and shifts toward the putative internal proton donor residues, consequently inducing an outward shift of TM3, as well as a local deformation in TM7. These early conformational changes in the pore-forming helices should be the triggers that lead to opening of the ion conducting pore