Down syndrome and Alzheimer\u27s disease: A scoping review of functional performance and fall risk

INTRODUCTION: Alzheimer\u27s disease (AD) occurs in aging adults with Down syndrome (DS) at a higher prevalence and an earlier age than in typical aging adults. As with the general aging adult population, there is an urgent need to understand the preclinical and early phases of AD progression in the adult population with DS. The aim of this scoping review was to synthesize the current state of the evidence and identify gaps in the literature regarding functional activity performance and falls and their significance to disease staging (i.e., mild, moderate, and severe defined staging criteria) in relation to Alzheimer\u27s disease and related dementias (ADRD) in adults with DS. METHODS: This scoping review included six electronic databases (e.g., PsycInfo, Academic Search Complete, CINAHL, COCHRANE Library, MEDLINE, and PubMed). Eligible studies included participants with DS ≥25 years of age, studies with functional measures and/or outcomes (e.g., activities of daily living, balance, gait, motor control, speech, behavior, and cognition; falls; and fall risks), and studies that investigated AD pathology and implications. RESULTS: Fourteen eligible studies were included and categorized through a thematic analysis into the following themes: (1) physical activity and motor coordination (PAMC), (2) cognition, (3) behavior, and (4) sleep. The studies indicated how functional activity performance and engagement may contribute to early identification of those at risk of cognitive decline and AD development and/or progression. DISCUSSION: There is a need to expand the research regarding ADRD pathology relative to functional outcomes in adults with DS. Functional measures related to disease staging and cognitive impairment are essential to understanding how AD progression is characterized within real-world settings. This scoping review identified the need for additional mixed-methods research to examine the use of assessment and intervention related to function and its detection of cognitive decline and AD progression

Environmental Modifications and Supports for Participation Among Adults Aging With Intellectual and Developmental Disabilities: A Scoping Review

Importance: Adults aging with intellectual and developmental disabilities (IDD) continue to face barriers to participation in meaningful occupation; moreover, the increased life expectancy of adults with IDD intensifies the need for age- and environment-specific support. Objective: To map and categorize transdisciplinary literature on environmental modifications and supports for adults aging with IDD. Data Sources: Studies published between January 1, 2000, and January 1, 2019, identified through PubMed and Scopus. Study Selection and Data Collection: Eleven articles met the inclusion criteria and contained information specific to occupational participation based on environmental modification (e.g., physical space, technology, universal design, type of living setting), social supports (e.g., family members, caretakers, peer groups, health care professionals, policies, organizational infrastructure), or both and adults age ≥35 yr with IDD. Findings: Eleven studies met the criteria for this scoping review. Thematic coding was used to examine the articles within one or more themes: definition of need, environmental risk and assessment, environmental setting, intervention and program planning, use of technology, and bureaucracy. Conclusions and Relevance: This review highlights collective and individual outcomes in the areas of assessment, intervention, and advocacy. Further research is needed within the scope of occupational therapy and disability studies that examines environmental factors and participation outcomes in this population. What This Article Adds: The authors define the interconnectedness of adults aging with IDD and environmental factors, identify barriers to participation, and guide occupational therapy practitioners’ logic on how to positively affect environmental change and supports through intervention

NTR 2.0: a rationally engineered prodrug-converting enzyme with substantially enhanced efficacy for targeted cell ablation.

Transgenic expression of bacterial nitroreductase (NTR) enzymes sensitizes eukaryotic cells to prodrugs such as metronidazole (MTZ), enabling selective cell-ablation paradigms that have expanded studies of cell function and regeneration in vertebrates. However, first-generation NTRs required confoundingly toxic prodrug treatments to achieve effective cell ablation, and some cell types have proven resistant. Here we used rational engineering and cross-species screening to develop an NTR variant, NTR 2.0, which exhibits ~100-fold improvement in MTZ-mediated cell-specific ablation efficacy, eliminating the need for near-toxic prodrug treatment regimens. NTR 2.0 therefore enables sustained cell-loss paradigms and ablation of previously resistant cell types. These properties permit enhanced interrogations of cell function, extended challenges to the regenerative capacities of discrete stem cell niches, and novel modeling of chronic degenerative diseases. Accordingly, we have created a series of bipartite transgenic reporter/effector resources to facilitate dissemination of NTR 2.0 to the research community