Genome editing to define the function of risk loci and variants in rheumatic disease.

Discoveries in human genetic studies have revolutionized our understanding of complex rheumatic and autoimmune diseases, including the identification of hundreds of genetic loci and single nucleotide polymorphisms that potentially predispose individuals to disease. However, in most cases, the exact disease-causing variants and their mechanisms of action remain unresolved. Functional follow-up of these findings is most challenging for genomic variants that are in non-coding genomic regions, where the large majority of common disease-associated variants are located, and/or that probably affect disease progression via cell type-specific gene regulation. To deliver on the therapeutic promise of human genetic studies, defining the mechanisms of action of these alleles is essential. Genome editing technology, such as CRISPR-Cas, has created a vast toolbox for targeted genetic and epigenetic modifications that presents unprecedented opportunities to decipher disease-causing loci, genes and variants in autoimmunity. In this Review, we discuss the past 5-10 years of progress in resolving the mechanisms underlying rheumatic disease-associated alleles, with an emphasis on how genomic editing techniques can enable targeted dissection and mechanistic studies of causal autoimmune risk variants.

Language-enriched exercise plus socialization for older adults with dementia: translation to rural communities.

Interventions that stimulate and engage individuals with dementia physically, cognitively, and socially offer promise for improving health and well-being and for potentially slowing functional losses with disease progression. We describe a volunteer-based intervention that combines physical exercise, cognitive-linguistic stimulation, and social outings for older persons living with dementia in rural communities. One-year follow-up data, although clearly preliminary (n = 8), suggest stability in global cognition, mood, and aspects of physical fitness. Challenges to implementing dementia interventions in rural areas are discussed.