A Post-Synaptic Scaffold at the Origin of the Animal Kingdom

The evolution of complex sub-cellular structures such as the synapse requires the assembly of multiple proteins, each conferring added functionality to the integrated structure. Tracking the early evolution of synapses has not been possible without genomic information from the earliest branching animals. As the closest extant relatives to the Eumetazoa, Porifera (sponges) represent a pivotal group for understanding the evolution of nervous systems, because sponges lack neurons with clearly recognizable synapses, in contrast to eumetazoan animals.We show that the genome of the demosponge Amphimedon queenslandica possesses a nearly complete set of post-synaptic protein homologs whose conserved interaction motifs suggest assembly into a complex structure. In the critical synaptic scaffold gene, dlg, residues that make hydrogen bonds and van der Waals interactions with the PDZ ligand are 100% conserved between sponge and human, as is the motif organization of the scaffolds. Expression in Amphimedon of multiple post-synaptic gene homologs in larval flask cells further supports the existence of an assembled structure. Among the few post-synaptic genes absent from Amphimedon, but present in Eumetazoa, are receptor genes including the entire ionotropic glutamate receptor family.Highly conserved protein interaction motifs and co-expression in sponges of multiple proteins whose homologs interact in eumetazoan synapses indicate that a complex protein scaffold was present at the origin of animals, perhaps predating nervous systems. A relatively small number of crucial innovations to this pre-existing structure may represent the founding changes that led to a post-synaptic element

Home videophones improve direct observation in Tuberculosis treatment: a mixed methods evaluation

BACKGROUND: The use of direct observation to monitor tuberculosis treatment is controversial: cost, practical difficulties, and lack of patient acceptability limit effectiveness. Telehealth is a promising alternative delivery method for improving implementation. This study aimed to evaluate the clinical and cost-effectiveness of a telehealth service delivering direct observation, compared to an in-person drive-around service. METHODOLOGY/PRINCIPAL FINDINGS: The study was conducted within a community nursing service in South Australia. Telehealth patients received daily video calls at home on a desktop videophone provided by the nursing call center. A retrospective cohort study assessed the effectiveness of the telehealth and traditional forms of observation, defined by the proportion of missed observations recorded in case notes. This data was inputted to a model, estimating the incremental cost-effectiveness ratio (ICER) of telehealth. Semi-structured interviews were conducted with current patients, community nursing and Chest Clinic staff, concerning service acceptability, usability and sustainability. The percentage of missed observations for the telehealth service was 12.1 (n = 58), compared to 31.1 for the in-person service (n = 70). Most of the difference of 18.9% (95% CI: 12.2 – 25.4) was due to fewer pre-arranged absences. The economic analysis calculated the ICER to be AUD$1.32 (95$0.51 – $2.26) per extra day of successful observation. The video service used less staff time, and became dominant if implemented on a larger scale and/or with decreased technology costs. Qualitative analysis found enabling factors of flexible timing, high patient acceptance, staff efficiency, and Chest Clinic support. Substantial technical problems were manageable, and improved liaison between the nursing service and Chest Clinic was an unexpected side-benefit. CONCLUSIONS/SIGNIFICANCE: Home video observation is a patient-centered, resource efficient way of delivering direct observation for TB, and is cost-effective when compared with a drive-around service. Future research is recommended to determine applicability and effectiveness in other settings.Victoria A. Wade, Jonathan Karnon, Jaklin A. Eliott and Janet E. Hille

Conceptualisation of self-management intervention for people with early stage dementia

Dementia is a major challenge for health and social care services. People living with dementia in the earlier stages experience a "care-gap". Although they may address this gap in care, self-management interventions have not been provided to people with dementia. It is unclear how to conceptualise self-management for this group and few published papers address intervention design. Initial focusing work used a logic mapping approach, interviews with key stakeholders, including people with dementia and their family members. An initial set of self-management targets were identified for potential intervention. Self-management for people living with dementia was conceptualised as covering five targets: (1) relationship with family, (2) maintaining an active lifestyle, (3) psychological wellbeing, (4) techniques to cope with memory changes, and (5) information about dementia. These targets were used to focus literature reviewing to explore an evidence base for the conceptualisation. We discuss the utility of the Corbin and Strauss (Unending work and care: managing chronic illness at home. Jossey-Bass, Oxford, 1988) model of self-management, specifically that self-management for people living with dementia should be conceptualised as emphasising the importance of "everyday life work" (targets 1 and 2) and "biographical work" (target 3), with inclusion of but less emphasis on specific "illness work" (targets 4, 5). We argue that self-management is possible for people with dementia, with a strengths focus and emphasis on quality of life, which can be achieved despite cognitive impairments. Further development and testing of such interventions is required to provide much needed support for people in early stages of dementia