Feasibility and acceptability of a web-based advance care plan for dementia.

While advance care planning (ACP) can help elicit preferences and is associated with improved end-of-life outcomes, persons living with dementia (PLWD) in nursing homes are rarely included in ACP. Web-based decision aids are a readily available tool to engage PLWD in ACP, but none are designed for the unique needs of PLWD, particularly those residing in nursing homes. Our Memory Care Wishes (OMCW) was adapted from a publicly available web-based ACP tool in collaboration with dementia care experts. This study aimed to explore the acceptability of OMCW. We used a convergent, mixed methods design to describe PLWD and surrogates' experiences using the OMCW website. Participants described ease of use, comfort with viewing, helpfulness for planning, and likelihood to recommend. Overall, OMCW is acceptable, however, PLWD continue to have difficulties understanding and engaging with some website content. Modifications were incorporated based on these findings, setting the stage for implementation and effectiveness testing.

Examining Face Validity of Visual Stimuli Used in Preference Assessments for Older Adults With Communication Impairments.

PURPOSE: Preference assessment is integral to person-centered treatment planning for older adults with communication impairments. There is a need to validate photographs used in preference assessment for this population. Therefore, this study aimed to establish preliminary face validity of photographs selected to enhance comprehension of questions from the Preferences for Everyday Living Inventory-Nursing Home (PELI-NH) and describe themes in older adults' recommendations for revising photographic stimuli. METHOD: This qualitative, cognitive interviewing study included 21 participants with an average age of 75 years and no known cognitive or communication deficits. Photographic stimuli were randomized and evaluated across one to two interview sessions. Participants were asked to describe what the preference stimuli represented to them. Responses were scored to assess face validity. Participants were then shown the PELI-NH written prompt and asked to evaluate how well the photograph(s) represented the preference. A semideductive thematic analysis was conducted on interview transcripts to summarize themes in participant feedback. RESULTS: Forty-six (64%) stimuli achieved face validity criteria without revisions. Six (8%) stimuli achieved face validity after one partial revision. Twenty (28%) stimuli required multiple revisions and reached feedback saturation, requiring team review for finalization. Thematic analysis revealed challenges interpreting stimuli (e.g., multiple meanings) and participant preferences for improving photographs (e.g., aesthetics). CONCLUSIONS: Cognitive interviewing was useful for improving face validity of stimuli pertaining to personal care topics. Abstract and subjective preferences (e.g., cultural traditions) may be more challenging to represent. This study provides a framework for further testing with older adults with cognitive, communication, and hearing impairments.

The long noncoding RNA Morrbid regulates CD8 T cells in response to viral infection.

The transcriptional programs that regulate CD8 T-cell differentiation and function in the context of viral infections or tumor immune surveillance have been extensively studied; yet how long noncoding RNAs (lncRNAs) and the loci that transcribe them contribute to the regulation of CD8 T cells during viral infections remains largely unexplored. Here, we report that transcription of the lncRNA Morrbid is specifically induced by T-cell receptor (TCR) and type I IFN stimulation during the early stages of acute and chronic lymphocytic choriomeningitis virus (LCMV) infection. In response to type I IFN, the Morrbid RNA and its locus control CD8 T cell expansion, survival, and effector function by regulating the expression of the proapoptotic factor, Bcl2l11, and by modulating the strength of the PI3K-AKT signaling pathway. Thus, our results demonstrate that inflammatory cue-responsive lncRNA loci represent fundamental mechanisms by which CD8 T cells are regulated in response to pathogens and potentially cancer.

Disruption of IL-33 Signaling Limits Early CD8+ T Cell Effector Function Leading to Exhaustion in Murine Hemophagocytic Lymphohistiocytosis.

Danger signals mediated through ST2, the interleukin-33 (IL-33) receptor, amplify CD8+ T cell-mediated inflammation in the murine model of familial hemophagocytic lymphohistiocytosis type 2 (FHL2), and blockade of ST2 provides a potential therapeutic strategy in this disease. However, the long-term effects of disrupting IL-33/ST2 signaling on the CD8+ T cell compartment are unknown. Here, we examined the evolution of the T cell response in murine FHL type 2 in the absence of ST2 signaling and found that CD8+ T cells gradually undergo exhaustion, similar to a related nonfatal FHL model. ST2 inhibition indirectly promotes CD8+ T cell exhaustion, and in contrast to other forms of FHL, reversal of exhaustion does not affect mortality. Disruption of IL-33 signaling exerts a more significant impact on the CD8+ T cell compartment early in the course of disease by intrinsically limiting CD8+ T cell proliferative and cytokine production capacity. Our data thus suggest that while ST2 blockade ultimately enables the development of CD8+ T cell exhaustion in late-stage murine FHL2, exhaustion is merely an effect, rather than the cause, of extended survival in these mice. The acute impact of ST2 inhibition on both the quantity and quality of the effector CD8+ T cell response more likely underlies the protective benefits of this treatment. This study provides evidence that redefines the relationship between CD8+ T cell exhaustion and mortality in murine FHL and supports the therapeutic use of ST2 blockade during the acute stage of disease.

Control of Immune Cell Homeostasis and Function by lncRNAs.

The immune system is composed of diverse cell types that coordinate responses to infection and maintain tissue homeostasis. In each of these cells, extracellular cues determine highly specific epigenetic landscapes and transcriptional profiles to promote immunity while maintaining homeostasis. New evidence indicates that long non-coding RNAs (lncRNAs) play crucial roles in epigenetic and transcriptional regulation in mammals. Thus, lncRNAs have emerged as key regulatory molecules of immune cell gene expression programs in response to microbial and tissue-derived cues. We review here how lncRNAs control the function and homeostasis of cell populations during immune responses, emphasizing the diverse molecular mechanisms by which lncRNAs tune highly contextualized transcriptional programs. In addition, we discuss the new challenges faced in interrogating lncRNA mechanisms and function in the immune system.