Roles of participation in social activities in the association between adverse childhood experiences and health among older Japanese adults

Adverse childhood experiences (ACEs) have shown strong associations with later-life health such as depression and subjective health. Social participation is also associated with later-life health but it is unclear to what extent this could contribute to alleviating harmful impacts of ACEs, nor is it clear whether ACEs are themselves associated with later-life social participation. Thus, this study aims to understand: (1) the influence of ACEs on social participation in later life and (2) whether social participation can alleviate the harmful influences of ACEs on depression and subjective health among Japanese older adults. Data were from 5,671 Japanese older adults (aged 65+) in surveys in 2013 and 2016 as part of the Japan Gerontological Evaluation Study (JAGES). Logistic regression analyses were conducted to estimate the relations between ACEs and later-life social participation, adjusting for potential confounders and mediators. Inverse probability weighting was used to estimate average effects of ACEs on later-depression and subjective health, adjusting for potential confounders, and these were compared against controlled direct effect (CDE) estimates from marginal structural models based on all respondents experiencing weekly social participation. We found that ACEs were associated with reduced later-life social participation (OR for >1 ACEs = 0.88, 95% CI = 0.79, 0.99). The estimated effect of ACEs on depression ( adjusted total effect estimates: OR = 1.23, 95% CI = 1.05, 1.45) was marginally alleviated in estimates assuming weekly social participation for everyone (CDE = 1.18, 95% CI = 0.98, 1.43). A similar tendency was seen for poor subjective heath. Negative impacts of ACEs on depression may be marginally mitigated through social participation, but mitigating effects were moderate. Further investigation on other potential later-life mitigating factors is needed

Impact of the COVID-19 Pandemic on Cancer Death Locations in Japan: An Analysis of Excess Mortality Through February 2023

Background: The novel coronavirus disease 2019 (COVID-19) pandemic has significantly impacted end-of-life decisions for cancer patients in Japan, with disparities existing between preferred and actual care settings. Our study investigates the potential shifts in cancer death locations during the pandemic and if there were excess cancer deaths. Methods: Utilizing national mortality data from the Ministry of Health, Labour and Welfare from January 2012 to February 2023, we identified cancer deaths using International Classification of Disease, 10th revision codes. We assessed death locations, including medical institutions, nursing facilities, and homes. The Farrington algorithm was employed to estimate expected death counts, and the differences between observed and expected counts were denoted as excess deaths. Results: From January 2018 to February 2023, there was consistently increase in the weekly observed cancer deaths. The presence of a definitive excess during the pandemic period remains uncertain. The percentage of deaths in medical institutions declined from 83.3% to 70.1%, while home deaths increased from 12.1% to 22.9%. Between April 2020 and February 2023, deaths in medical institutions frequently fell below the 95% prediction lower limit. Home deaths consistently exceeded the 95% prediction upper limit, with significant excess deaths reported annually. Conclusion: Our study found a shift in cancer death locations from medical institutions to homes in Japan during the COVID-19 pandemic. Our study did not confirm an overall increase in cancer deaths during this period. As with global trends, the profound shift from hospitals to homes in Japan calls for a comprehensive exploration to grasp the pandemic’s multifaceted impact on end-of-life cancer care decisions

Sendai Virus, a Murine Parainfluenza Virus Type 1, Replicates to a Level Similar to Human PIV1 in the Upper and Lower Respiratory Tract of African Green Monkeys and Chimpanzees

AbstractHuman parainfluenza virus type 1 (HPIV1), a major cause of croup in infants and young children, accounts for 6% of hospitalizations for pediatric respiratory tract disease. The antigenically related Sendai virus, referred to here as murine PIV1 (MPIV1), is being considered for use as a live-attenuated vaccine to protect against HPIV1 (J. L. Hurwitz, K. F. Soike, M. Y., Sangster, A. Portner, R. E. Sealy, D. H. Dawson, and C. Coleclough, 1997, Vaccine 15(5), 533–540) and also as a recombinant vaccine vector expressing antigens to protect against viral disease in humans. However, in the 1950s MPIV1 was reported to have been isolated from humans, suggesting that zoonotic transmission might have occurred. It is therefore important to examine the ability of MPIV1 to replicate in nonhuman primates, i.e., surrogate hosts for humans. In the present study the level of replication of MPIV1 and HPIV1 was compared in African green monkeys and chimpanzees. Surprisingly, MPIV1 replicated as efficiently as HPIV1 in the upper and lower respiratory tract of African green monkeys at doses of 104 and 106 and replicated only slightly less efficiently at both sites in chimpanzees. African green monkeys immunized with MPIV1 were highly resistant to subsequent challenge with HPIV1 even though MPIV1 did not induce a detectable HPIV1-neutralizing antibody response. The high level of replication of MPIV1 observed in the upper and lower respiratory tract of these primates suggests that MPIV1 likely would require significant attenuation before it could be given to humans as a vaccine against HPIV1 or as a vaccine vector. Its ability to efficiently replicate in nonhuman primates suggests that MPIV1 lacks a significant host range restriction in primates and could theoretically cause zoonotic disease in humans

Factors for Differential Outcome Across Cancers in Clinical Molecule-Targeted Fluorescence Imaging

Clinical imaging performance using a fluorescent antibody was compared across 3 cancers to elucidate physical and biologic factors contributing to differential translation of epidermal growth factor receptor (EGFR) expression to macroscopic fluorescence in tumors. Methods: Thirty-one patients with high-grade glioma (HGG, n = 5), head-and-neck squamous cell carcinoma (HNSCC, n = 23), or lung adenocarcinoma (LAC, n = 3) were systemically infused with 50 mg of panitumumab-IRDye800 1-3 d before surgery. Intraoperative open-field fluorescent images of the surgical field were acquired, with imaging device settings and operating room lighting conditions being tested on tissue-mimicking phantoms. Fluorescence contrast and margin size were measured on resected specimen surfaces. Antibody distribution and EGFR immunoreactivity were characterized in macroscopic and microscopic histologic structures. The integrity of the blood-brain barrier was examined via tight junction protein (Claudin-5) expression with immunohistochemistry. Stepwise multivariate linear regression of biologic variables was performed to identify independent predictors of panitumumab-IRDye800 concentration in tissue. Results: Optimally acquired at the lowest gain for tumor detection with ambient light, intraoperative fluorescence imaging enhanced tissue-size dependent tumor contrast by 5.2-fold, 3.4-fold, and 1.4-fold in HGG, HNSCC, and LAC, respectively. Tissue surface fluorescence target-to-background ratio correlated with margin size and identified 78%-97% of at-risk resection margins ex vivo. In 4-μm-thick tissue sections, fluorescence detected tumor with 0.85-0.89 areas under the receiver-operating-characteristic curves. Preferential breakdown of blood-brain barrier in HGG improved tumor specificity of intratumoral antibody distribution relative to that of EGFR (96% vs. 80%) despite its reduced concentration (3.9 ng/mg of tissue) compared with HNSCC (8.1 ng/mg) and LAC (6.3 ng/mg). Cellular EGFR expression, tumor cell density, plasma antibody concentration, and delivery barrier were independently associated with local intratumoral panitumumab-IRDye800 concentration, with 0.62 goodness of fit of prediction. Conclusion: In multicancer clinical imaging of a receptor-ligand-based molecular probe, plasma antibody concentration, delivery barrier, and intratumoral EGFR expression driven by cellular biomarker expression and tumor cell density led to heterogeneous intratumoral antibody accumulation and spatial distribution whereas tumor size, resection margin, and intraoperative imaging settings substantially influenced macroscopic tumor contrast