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Data from the Vietnamese Aging and Care Survey (VACS) showed the high prevalence of disability, depressive symptoms, and cognitive impairment in older Vietnamese immigrants and refugees. We proposed a Community-Engaged Dementia Education Program to examine the Houston Vietnamese American community's literacy on dementia and develop a one-pager educational material. This is a cross-sectional, qualitative study (interviews and focus groups) using the Cultural Exchange Model as a conceptual framework. We interviewed fourteen Vietnamese key informants and assessed the community's knowledge of dementia based on Edwards' 9-stage Community Readiness Model. The community's low literacy on dementia (Stages 2–3: Denial/resistance to vague awareness) was revealed. Approaches to introducing dementia conversations to the community and what to include in the one-pager were discussed. Based on the key informants' insight, we developed a dementia one-pager tailored to the community by using lay language with a representative image of the target population, indicating warning signs of dementia, and encouraging them to see their doctors for cognitive check-ups. The plan for the next steps includes utilizing the local ethnic media, collaborating with the existing pillars of the Cultural Exchange model, leveraging the university students' learning opportunities, and disseminating the culturally and linguistically tailored one-pager. [ABSTRACT FROM AUTHOR]

Although the activator protein‐1 (AP‐1) factor Batf is required for Th17 cell development, its mechanisms of action to underpin the Th17 program are incompletely understood. Here, we find that Batf ensures Th17 cell identity in part by restricting alternative gene programs through its actions to restrain IL‐2 expression and IL‐2‐induced Stat5 activation. This, in turn, limits Stat5‐dependent recruitment of Ets1‐Runx1 factors to Th1‐ and Treg‐cell‐specific gene loci. Thus, in addition to pioneering regulatory elements in Th17‐specific loci, Batf acts indirectly to inhibit the assembly of a Stat5‐Ets1‐Runx1 complex that enhances the transcription of Th1‐ and Treg‐cell‐specific genes. These findings unveil an important role for Stat5‐Ets1‐Runx1 interactions in transcriptional networks that define alternate T cell fates and indicate that Batf plays an indispensable role in both inducing and maintaining the Th17 program through its actions to regulate the competing actions of Stat5‐assembled enhanceosomes that promote Th1‐ and Treg‐cell developmental programs. Synopsis: In addition to its function as a pioneering transcription factor in Th17 development, Batf suppresses alternative T cell fates by down‐regulating IL‐2 receptor components thereby diminishing Stat5 activation and limiting the assembly of a Stat5‐Ets1‐Runx1 enhancer complex that promotes Th1– and Treg–specifying gene expression. Batf inhibits IL‐2 expression early in Th17 development and limits IL‐2R and Stat5 expression in late stage Th17 cells.Batf impairs Stat5‐dependent recruitment of Ets1 and Runx1 to Th1 and Treg‐cell gene loci, thus forming an enhanceosome that promotes lineage‐specifying gene transcription.Sustained Batf expression is essential to prevent deviation to alternative cell fates and stabilize the Th17 phenotype. [ABSTRACT FROM AUTHOR]

Purpose: While familial aggregation of colorectal cancer (CRC) is recognized, the majority of the germline predisposition factors remain unidentified, and many high‐risk CRC pedigrees remain unexplained by known risk variants. Fanconi Anemia genes have been recognized to be associated with cancer risk. Notably, FANCM (OMIM 609644) variants have been reported to confer risk for CRC and breast cancer. Methods: Exome sequencing of CRC‐affected cousins in a set of 47 independent extended high‐risk CRC pedigrees identified a candidate set of rare, shared variants. Variants were tested for association with risk in 744 Utah CRC cases and 1525 controls, and for segregation with CRC in affected relatives. Results: A FANCM stopgain variant was observed in two CRC‐affected cousin pairs, each from an independent Utah high‐risk pedigree, and yielded a nonsignificant, but elevated OR = 2.05 in a set of Utah cases and controls. Segregation of the variant to other related CRC‐affected cases was observed in the two extended pedigrees. Conclusion: A rare stopgain variant in FANCM (rs144567652) that is recognized as a breast cancer predisposition variant, and that has previously been proposed, but not confirmed, as a CRC predisposition variant, is validated here as a risk factor for familial CRC. [ABSTRACT FROM AUTHOR]

A significant limiting factor to the human clinical application of conditionally replicative adenovirus (CRAd)-based virotherapy is the inability to noninvasively monitor these agents and their potential persistence. To address this issue, we proposed a novel imaging approach that combines transient expression of the human somatostatin receptor (SSTR) subtype 2 reporter gene with genetic labeling of the viral capsid with mCherry fluorescent protein. To test this dual modality system, we constructed the Ad5/ 3Δ24pIXcherry/SSTR CRAd and validated its capacity to generate fluorescent and nuclear signals in vitro and following intratumoral injection. Analysis of 64Cu-CB-TE2A-Y3-TATE biodistribution in mice revealed reduced uptake in tumors injected with the imaging CRAd relative to the replication--incompetent, Ad-expressing SSTR2 but significantly greater uptake compared to the negative CRAd control. Optical imaging demonstrated relative correlation of fluorescent signal with virus replication as determined by viral genome quantification in tumors. Positron emission tomography/computed tomography studies demonstrated that we can visualize radioactive uptake in tumors injected with imaging CRAd and the trend for greater uptake by standardized uptake value analysis compared to control CRAd. In the aggregate, the plasticity of our dual imaging approach should provide the technical basis for monitoring CRAd biodistribution and persistence in preclinical studies while offering potential utility for a range of clinical applications. [ABSTRACT FROM AUTHOR]