A structured multicomponent intervention adapted to individual risk profiles can increase the quality of life of ethnically diverse dementia caregivers. ClinicalTrials.gov identifier: NCT00177489.

Flavivirus RNA replication occurs within a replication complex (RC) that assembles on ER membranes and comprises both non-structural (NS) viral proteins and host cofactors. As the largest protein component within the flavivirus RC, NS5 plays key enzymatic roles through its N-terminal methyltransferase (MTase) and C-terminal RNA-dependent-RNA polymerase (RdRp) domains, and constitutes a major target for antivirals. We determined a crystal structure of the full-length NS5 protein from Dengue virus serotype 3 (DENV3) at a resolution of 2.3 Å in the presence of bound SAH and GTP. Although the overall molecular shape of NS5 from DENV3 resembles that of NS5 from Japanese Encephalitis Virus (JEV), the relative orientation between the MTase and RdRp domains differs between the two structures, providing direct evidence for the existence of a set of discrete stable molecular conformations that may be required for its function. While the inter-domain region is mostly disordered in NS5 from JEV, the NS5 structure from DENV3 reveals a well-ordered linker region comprising a short 310 helix that may act as a swivel. Solution Hydrogen/Deuterium Exchange Mass Spectrometry (HDX-MS) analysis reveals an increased mobility of the thumb subdomain of RdRp in the context of the full length NS5 protein which correlates well with the analysis of the crystallographic temperature factors. Site-directed mutagenesis targeting the mostly polar interface between the MTase and RdRp domains identified several evolutionarily conserved residues that are important for viral replication, suggesting that inter-domain cross-talk in NS5 regulates virus replication. Collectively, a picture for the molecular origin of NS5 flexibility is emerging with profound implications for flavivirus replication and for the development of therapeutics targeting NS5.

The number of people over the age of 65 is increasing worldwide with the fastest growing subgroup those aged 80+ years. Computer and information technologies hold promise in terms of increasing the quality of life for older people. However, successful use of technology by older adults is predicated on systems that are designed to accommodate the needs and preferences of this user group. This paper discusses the implications of age-related changes in cognition for system design. Generally, the existing literature shows that, although older adults are willing to use technology, many report usability problems with existing systems and these problems may in part be due to the cognitive and perceptual demands placed on the user. These findings are discussed in terms of guidelines for system design.

The CPQ and CPQ-12 are useful tools to gauge computer proficiency for training and research purposes, even among low computer proficient older adults.

The findings indicate that training, experience, and abilities are important when using complex health websites. However, training alone is not sufficient. The complexity of web content needs to be considered to ensure successful use of these websites by those with lower abilities.