Linking the 1940 US Census to the NSHAP: Novel Opportunity to Understand the Effects of Childhood Residential Environment on Cognitive Aging.

OBJECTIVE: The 1940 Census is a valuable resource for understanding various aspects of historical populations in the United States. Recently, the National Social Life, Health and Aging Project (NSHAP) integrated 1940 Census data into its extensive dataset, providing researchers with an opportunity to explore new avenues of life course investigation. We leverage the newly-introduced measures of childhood residential environment and evaluate their potential predictive utility in older adult cognitive functioning net of childhood and adulthood characteristics known to be key risk factors for poor cognition. METHOD: We analyzed 777 respondents who were children in 1940 (age<17) that have been linked to the 1940 U.S. Census. We used childhood geographic location, homeownership status, household composition, and parental nativity as predictors. Cognitive function was measured using the Montreal Cognitive Assessment. RESULTS: Regression analysis showed that growing up in an urban area was associated with better cognitive function, while being born in the South was linked to poorer cognitive function, even after controlling for childhood health, parental education, educational attainment, stroke, and smoking status. Additionally, childhood multigenerational household was associated with better cognitive function, and childhood family size was associated with poorer cognitive function. However, these associations became statistically insignificant with the inclusion of educational attainment. We did not find homeownership and parental nativity to be associated with cognitive function. DISCUSSION: The findings may shed light on the potential long-term effects of childhood circumstances on cognitive aging processes. Implications for current literature and directions for future research are discussed.

A dietary commensal microbe enhances antitumor immunity by activating tumor macrophages to sequester iron.

Innate immune cells generate a multifaceted antitumor immune response, including the conservation of essential nutrients such as iron. These cells can be modulated by commensal bacteria; however, identifying and understanding how this occurs is a challenge. Here we show that the food commensal Lactiplantibacillus plantarum IMB19 augments antitumor immunity in syngeneic and xenograft mouse tumor models. Its capsular heteropolysaccharide is the major effector molecule, functioning as a ligand for TLR2. In a two-pronged manner, it skews tumor-associated macrophages to a classically active phenotype, leading to generation of a sustained CD8+ T cell response, and triggers macrophage 'nutritional immunity' to deploy the high-affinity iron transporter lipocalin-2 for capturing and sequestering iron in the tumor microenvironment. This process induces a cycle of tumor cell death, epitope expansion and subsequent tumor clearance. Together these data indicate that food commensals might be identified and developed into 'oncobiotics' for a multi-layered approach to cancer therapy.

Synthesis of 1,4-Dialkoxynaphthalene-Based Imidazolium Salts and Their Cytotoxicity in Cancer Cell Lines.

In this study, we designed and synthesized novel 1,4-dialkoxynaphthalene-2-alkyl imidazolium salt (IMS) derivatives containing both 1,4-dialkoxynaphthalene and imidazole, which are well known as pharmacophores. The cytotoxicities of these newly synthesized IMS derivatives were investigated in order to explore the possibility of using them to develop anticancer drugs. It was found that some of the new IMS derivatives showed good cytotoxic activities. In addition, an initial, qualitative structure-activity relationship is presented on the basis of observations of activity changes corresponding to structural changes.

Harnessing the bioresponsive adhesion of immuno-bioglue for enhanced local immune checkpoint blockade therapy.

Despite the great promise of immune checkpoint blockade (ICB) therapy for cancer treatment, the currently available options for ICB treatment pose major clinical challenges, including the risk of severe systemic autoimmune responses. Here, we developed a novel localized delivery platform, immuno-bioglue (imuGlue), which is inspired by the intrinsic underwater adhesion properties of marine mussels and can allow the optimal retention of anti-PD-L1 drugs at tumor sites and the on-demand release of drugs in response to the tumor microenvironment. Using a triple-negative breast cancer and melanoma models, we found that imuGlue could significantly enhance anti-tumor efficacy by eliciting a robust T cell-mediated immune response while reducing systemic toxicity by preventing the rapid diffusion of anti-PD-L1 drugs into the systemic circulation and other tissues. It was also demonstrated that imuGlue could be successfully utilized for combination therapy with other immunomodulatory drugs to enhance the anti-tumor efficacy of ICB-based immunotherapy, demonstrating its versatility as a new treatment option for cancer immunotherapy.

A life course approach to total tooth loss: Testing the sensitive period, accumulation, and social mobility models in the Health and Retirement Study.

OBJECTIVES: Childhood socio-economic status (SES) has long been associated with later-life oral health, suggesting that childhood is a sensitive period for oral health. Far less attention has been given to the long-term impact of childhood trauma, abuse, and smoking on later-life oral health. This study fills the gap in the literature by examining how adverse childhood experiences-social, psychological, and behavioral-shape total tooth loss over the life course, with an assessment of the sensitive period, accumulation, and social mobility models from life course research. METHODS: Data are drawn from the 2012 Health and Retirement Study (HRS) merged with multiple HRS data sources to obtain childhood information (N = 6,427; age > 50). Adverse childhood experiences include childhood financial hardship, trauma, abuse, and smoking. Total tooth loss is measured to assess poor oral health in later life. Educational attainment and poverty status (since age 51) are measured as adult adversity. Current health conditions and health behaviors are assessed to reflect the correlates of oral health in later life. RESULTS: The sensitive period model indicates that childhood trauma such as parental death or divorce (odds ratio [OR] = 1.37, 95% confidence interval [CI] = 1.04, 1.80), physical abuse (OR = 1.17, 95% CI = 1.03, 1.34), and low educational attainment (≤ high school; OR = 1.52, 95% CI = 1.04, 2.22) are associated with higher odds of total tooth loss in later life. Poverty status was not associated with the outcome. There was a clear graded relationship between accumulation of adverse experiences and oral health, which supports the accumulation model. In the social mobility model, older adults who occupied a stable disadvantageous position were more likely to be toothless (OR = 1.77, 95% CI = 1.08, 2.90) compared to those who did not face adversity in any case. Neither upward nor downward mobility mattered. CONCLUSIONS: Failing oral health in older adults, especially total tooth loss, may have its roots in adverse experiences such as childhood trauma, abuse, and low educational attainment. Findings also suggest that oral health in later life may be more influenced by accumulation of adversity rather than changes in social and economic position over the life course.