Informal Caregiving in Adolescents from 10 to 16 Years Old: A Longitudinal Study Using Data from the Tokyo Teen Cohort

There is growing evidence of the impact of informal caregiving on adolescent mental health, and its role is often hidden unintentionally or intentionally, which may hamper early identification and support for young informal caregivers. However, the quantitative evidence regarding household factors relating to informal caregiving has mostly been based on cross-sectional findings. This study examines the longitudinal associations between household characteristics and the duration of informal caregiving in adolescents from 10 to 16 years of age. Child–household respondent pairs (n = 2331) from the Tokyo Teen Cohort in Japan were followed every 2 years from 10 to 16 years of age. Informal caregiving was assessed repeatedly based on the household respondent’s survey responses. Persistent caregiving was defined as daily caregiving at two or more waves. There were 2.2% of children who gave daily care at two or more waves. Cross-sectional associations with daily informal caregiving at each wave were found with girls, low household income, and cohabiting with grandparents. A significant association with persistent caregiving was found only in cohabiting with grandparents at 10 years of age after adjusting for sex, number of siblings, single parent, and household income. Our longitudinal examination highlighted cohabiting with grandparents as a preceding factor for persistent caregiving. Identification and support for young informal caregivers should be integrated into social care service systems for older adults. The mechanism of persistent caregiving requires clarification

Neighborhood Social Cohesion and Dementia-Related Stigma Among Mothers of Adolescents in the Pre- and Current COVID-19 Period: An Observational Study Using Population-Based Cohort Data

BACKGROUND: Middle-aged adults may be the ideal target group for dementia-related stigma reduction interventions to encourage the utilization of services among those who may become family caregivers. Neighborhood social cohesion may diminish dementia-related stigma, particularly in terms of perceived public attitudes. The COVID-19 pandemic can further negatively impact perceived public stigma. OBJECTIVE: To investigate the association between neighborhood social cohesion and dementia-related stigma during the pre- and current COVID-19 period. METHODS: We employed a cross-sectional design using data from a large population-based cohort, the Tokyo Teen Cohort, in Japan. Overall, 2,469 mothers of 16-year-old adolescents self-completed a questionnaire comprising nine dementia-related stigma questions evaluating perceived public and personal attitudes. Neighborhood social cohesion was assessed using a five-item instrument. The participants were divided into two groups according to the time of assessment: prior to the pandemic’s onset (February 2019–March 2020) and during the pandemic (April 2020–July 2021). A multiple regression analysis of stigma was performed using neighborhood social cohesion as an independent variable, and caring experience, age, educational level, and working status as covariates. RESULTS: Personal and perceived public stigma were significantly lower in participants who perceived greater neighborhood social cohesion. However, level of personal and perceived public stigma did not differ between pre- and during the pandemic period. CONCLUSIONS: Neighborhood social cohesion may be a modifiable factor for dementia-related stigma. A localized intervention to enhance social cohesion in the neighborhood community would promote the utilization of services among those who may become family caregivers

「乳児保育」における食事援助の学びについての検討―Eating-Feeding相互模擬演習を体験した学生の気づきから―

　　The authors examined the ways in which students in a nursery teacher-training course learn appropriate dietary assistance and analyzed 65 students engaging in eating-feeding simulation exercises. As a result of taking part in these exercises, students experienced increased consciousness of the act of eating. They experienced both negative and positive ways of eating-feeding, including: feeding leading to discomfort due to bad timing of the feeding, or the carer being hurried or impatient during the feeding. 　　These exercises helped both students who played the role of the child being fed and those who played the role of the carer to understand the eating-feeding processes. The students noted that proper feeding has a positive effect on chewing and eating and may impart a sense of peace to the children being fed. Throughout the exercise, participants came to understand that the role of a carer was not to mechanically carry food to the child’s mouth, but to behave as if they enjoy eating with the children they are feeding. The authors will continue to explore better ways of nursery teacher-training

離乳期における保育者の援助特性に関する一考察 ―自食移行期の言語的調整と身体的調整に着目した事例的検討―

The authors recorded digital videos of eight one-to-one interactions between nursery teachers and infants who were in the process of being weaned, and analyzed the movements of the infants and the teachers, paying attention especially to verbal and physical adjustments made by the two nursery teachers and four infants involved in this case study. The infants were in the early stage of mastering self-feeding to eat.The two teachers showed sympathy for the infants, and invited and encouraged them to eat. Two contrasting ways of helping the infants were noted: making verbal adjustments centered on helping them eat, and making physical adjustments centered on the infants’ eating behavior. The authors assume that the latter might lead to better results for teachers if the teachers synchronize their bodily movements with those of the infants

The effects of group work using strength cards on resilience

本研究では，自身のストレングスを認識することでレジリエンスが向上するという観点から，集団活動のレジリエンス・プログラムとして，ストレングスカードを用いたグループワークを実施し，その効果を検証することを目的とした。参加者は大学生であり，ストレングスカードを用いたグループワークを行った介入群22名（男性9名，女性13名，平均年齢20.72歳，SD=1.07），トランプ・UNO を用いたグループワークを行った対照群22名（男性9名，女性13名，平均年齢21.23歳，SD=0.92）であった。日本語版強み認識尺度における群と時期の二要因混合分散分析の結果，有意な交互作用が認められた。時期について，介入群では事前よりも事後，事後よりもフォローアップ，対照群では事前よりもフォローアップのほうが，有意に得点が高かった。群間の単純主効果は，フォローアップにおいて介入群が対照群より高い傾向だった。二次元レジリエンス要因尺度における二要因混合分散分析の結果では，資質的レジリエンス要因において時期にのみ主効果が見られ，獲得的レジリエンス要因においては時期にのみ有意傾向が見られた。どちらも，事前よりも事後，事前よりもフォローアップの方が，有意に得点が高かった。今回のグループワークでは，介入群で，よりストレングスが向上していた。また，介入群・対照群ともに，レジリエンスが向上していた。このことから，ストレングスカードを用いるグループワークでストレングスは高まるが，レジリエンスをさらに向上させるためには，グループワークの内容の精査が必要であることが示唆された。Based on the view that recognition of one’s own strengths can increase resilience, the aim of this study was to hold a group work session using strength cards as a resilience program for a group activity and assess the effects. Participants were university students who were divided into an intervention group (n=22, 9 men, 13 women, mean age 20.72) and a control group (n=22, 9 men, 13 women, mean age 21.23). Two-way mixed ANOVA of group and time point in the SKS revealed a significant interaction. For time point, scores in the intervention group were significantly higher after than before group work and at follow-up than after group work. Two-way mixed ANOVA of scores in the BRS showed a main effect only. With this group work, strength increased more in the intervention group. Resilience increased in both the intervention and control groups. This suggests that taking part in group work using strength cards increases strength, but that a careful consideration of the content of group work is required for a greater increase in resilience.departmental bulletin pape

キサンチンオキシダーゼ阻害薬febuxostatはNrf2を活性化し脂肪細胞分化を抑制する

Xanthine oxidoreductase (XOR) is a rate-limiting enzyme in purine catabolism that acts as a novel regulator of adipogenesis. In pathological states, xanthine oxidoreductase activity increases to produce excess reactive oxygen species (ROS). The nuclear factor erythroid 2-related factor 2 (Nrf2) is a critical inducer of antioxidants, which is bound and repressed by a kelch-like ECH-associated protein 1 (Keap1) in the cytoplasm. The Keap1-Nrf2 axis appears to be a major mechanism for robust inducible antioxidant defenses. Here, we demonstrate that febuxostat, a xanthine oxidase inhibitor, alleviates the increase in adipose tissue mass in obese mouse models with a high-fat diet or ovariectomy. Febuxostat disrupts in vitro adipocytic differentiation in adipogenic media. Adipocytes appeared at day 7 in absence or presence of febuxostat were 160.8 ± 21.2 vs. 52.5 ± 12.7 (p < 0.01) in 3T3–L1 cells, and 126.0 ± 18.7 vs. 55.3 ± 13.4 (p < 0.01) in 10T1/2 cells, respectively. Adipocyte differentiation was further enhanced by the addition of hydrogen peroxide, which was also suppressed by febuxostat. Interestingly, febuxostat, but not allopurinol (another xanthine oxidase inhibitor), rapidly induced the nuclear translocation of Nrf2 and facilitated the degradation of Keap1, similar to the electrophilic Nrf2 activator omaveloxolone. These results suggest that febuxostat alleviates adipogenesis under oxidative conditions, at least in part by suppressing ROS production and Nrf2 activation. Regulation of adipocytic differentiation by febuxostat is expected to inhibit obesity due to menopause or overeating

Correlations of survival with progression-free survival, response rate, and disease control rate in advanced biliary tract cancer: a meta-analysis of randomised trials of first-line chemotherapy

Background: The need to promote novel drug development for advanced biliary tract cancer (ABTC) has emphasised the importance of determining whether various efficacy end points can act as surrogates for overall survival (OS).Methods: We conducted a literature search of randomised trials of first-line chemotherapy for ABTC and investigated correlations between efficacy end points and OS using weighted linear regression analysis. The ratios of the median OS, median progression-free survival (PFS), response rate, and disease control rate in each trial were used to summarise treatment effects. The surrogate threshold effect (STE), which was the minimum treatment effect on PFS required to predict a non-zero treatment effect on OS, was calculated.Results: Seventeen randomised trials with 36 treatment arms were identified, and a sample size of 2148 patients with 19 paired arms was analysed. The strongest correlation between all evaluated efficacy end points was observed between median OS and median PFS ratios (r2=0.66). In trials with gemcitabine-containing therapies and targeted agents, the r2-values were 0.78. The STE was estimated at 0.83 for all trials and 0.81 for trials with gemcitabine-containing therapies, and was not calculated for trials with targeted agents.Conclusions: The median PFS ratio correlated well with the median OS ratio, and may be useful for planning a clinical trial for novel drug development

Human NK cell development in hIL-7 and hIL-15 knockin NOD/SCID/IL2rgKO mice.

The immune system encompasses acquired and innate immunity that matures through interaction with microenvironmental components. Cytokines serve as environmental factors that foster functional maturation of immune cells. Although NOD/SCID/IL2rgKO (NSG) humanized mice support investigation of human immunity in vivo, a species barrier between human immune cells and the mouse microenvironment limits human acquired as well as innate immune function. To study the roles of human cytokines in human acquired and innate immune cell development, we created NSG mice expressing hIL-7 and hIL-15. Although hIL-7 alone was not sufficient for supporting human NK cell development in vivo, increased frequencies of human NK cells were confirmed in multiple organs of hIL-7 and hIL-15 double knockin (hIL-7xhIL-15 KI) NSG mice engrafted with human hematopoietic stem cells. hIL-7xhIL-15 KI NSG humanized mice provide a valuable in vivo model to investigate development and function of human NK cells

Being Praised for Prosocial Behaviors Longitudinally Reduces Depressive Symptoms in Early Adolescents: A Population-Based Cohort Study

BackgroundDepression is highly prevalent and causes a heavy burden in adolescent life. Being praised for prosocial behavior might be a preventive factor because both being praised and prosocial behavior are protective against depression. Here, we investigated the longitudinal relationship between being praised for prosocial behavior and depressive symptoms in adolescents.MethodsIn Tokyo Teen Cohort study (TTC), an ongoing prospective population-based cohort study, we collected 3,171 adolescents' data on self-reported experiences of being praised for prosocial behavior, depressive symptoms, and caregiver-evaluated prosocial behavior. Ten-year-old children were asked to freely describe answers to the question “What are you praised for?”. Only children who clearly answered that they were praised for their prosocial behavior were designated the “prosocial praise group.” The degree of depression at ages 10 and 12 was measured with the Short Mood and Feelings Questionnaire (SMFQ), a self-report questionnaire about depression. Objective prosocial behavior of the 10 year-old children was assessed by the Strength and Difficulty Questionnaire (SDQ). Multiple linear regression analysis was performed using the SMFQ score at age 12 as the objective variable and being praised for prosocial behavior as the main explanatory variable, and the SMFQ score at age 10 and the objective prosocial behavior at age 10 were included as confounders.ResultsDepressive symptoms (SMFQ scores) in the “prosocial praise group” were significantly lower than those in the other group both at age 10 (4.3 ± 4.4 vs. 4.9 ± 4.6, p &lt; 0.001) and at age 12 (3.4 ± 4.2 vs. 4.0 ± 4.6, p &lt; 0.01). In the single regression analysis, the children who reported being praised for prosocial behavior at age 10 had significantly lower depressive symptoms at age 12 (partial regression variable: −0.57, 95% confidence interval (CI) [−0.96, −0.17]). This association remained significant after adjusting for confounders, including baseline depressive symptoms (partial regression variable: −0.44, 95% CI [−0.80, −0.08]). Prosocial behavior alone was not associated with depressive symptoms.ConclusionsBeing praised for prosocial behavior rather than objective prosocial behavior at 10 years of age predicted lower depressive symptoms 2 years later. Praise for adolescents' prosocial behavior can be encouraged to prevent depression

Effective impairment of myeloma cells and their progenitors by hyperthermia

Multiple myeloma (MM) remains incurable, and MM-initiating cells or MM progenitors are considered to contribute to disease relapse through their drug-resistant nature. In order to improve the therapeutic efficacy for MM, we recently developed novel superparamagnetic nanoparticles which selectively accumulate in MM tumors and extirpate them by heat generated with magnetic resonance. We here aimed to clarify the therapeutic effects on MM cells and their progenitors by hyperthermia. Heat treatment at 43°C time-dependently induced MM cell death. The treatment upregulated endoplasmic reticulum (ER) stress mediators, ATF4 and CHOP, while reducing the protein levels of Pim-2, IRF4, c-Myc and Mcl-1. Combination with the proteasome inhibitor bortezomib further enhanced ER stress to potentiate MM cell death. The Pim inhibitor SMI-16a also enhanced the reduction of the Pim-2-driven survival factors, IRF4 and c-Myc, in combination with the heat treatment. The heat treatment almost completely eradicated “side population” fractions in RPMI8226 and KMS-11 cells and suppressed their clonogenic capacity as determined by in vitro colony formation and tumorigenic capacity in SCID mice. These results collectively demonstrated that hyperthermia is able to impair clonogenic drug-resistant fractions of MM cells and enhance their susceptibility to chemotherapeutic drugs