Metal Ionophore Treatment Restores Dendritic Spine Density and Synaptic Protein Levels in a Mouse Model of Alzheimer's Disease

We have previously demonstrated that brief treatment of APP transgenic mice with metal ionophores (PBT2, Prana Biotechnology) rapidly and markedly improves learning and memory. To understand the potential mechanisms of action underlying this phenomenon we examined hippocampal dendritic spine density, and the levels of key proteins involved in learning and memory, in young (4 months) and old (14 months) female Tg2576 mice following brief (11 days) oral treatment with PBT2 (30 mg/kg/d). Transgenic mice exhibited deficits in spine density compared to littermate controls that were significantly rescued by PBT2 treatment in both the young (+17%, p<0.001) and old (+32%, p<0.001) animals. There was no effect of PBT2 on spine density in the control animals. In the transgenic animals, PBT2 treatment also resulted in significant increases in brain levels of CamKII (+57%, p = 0.005), spinophilin (+37%, p = 0.04), NMDAR1A (+126%, p = 0.02), NMDAR2A (+70%, p = 0.05), pro-BDNF (+19%, p = 0.02) and BDNF (+19%, p = 0.04). While PBT2-treatment did not significantly alter neurite-length in vivo, it did increase neurite outgrowth (+200%, p = 0.006) in cultured cells, and this was abolished by co-incubation with the transition metal chelator, diamsar. These data suggest that PBT2 may affect multiple aspects of snaptic health/efficacy. In Alzheimer's disease therefore, PBT2 may restore the uptake of physiological metal ions trapped within extracellular β-amyloid aggregates that then induce biochemical and anatomical changes to improve cognitive function

Prevalence of metabolic syndrome among patients with schizophrenia in Singapore

Annals of the Academy of Medicine Singapore4110457-462AAMS

Conducting a cost-benefit analysis of transitional care programmes: The key challenges and recommendations

10.5334/ijic.4703International Journal of Integrated Care201

GAD1 gene expression in blood of patients with first-episode psychosis

10.1371/journal.pone.0170805PLoS ONE121e017080

Shifting care from hospital to community, a strategy to integrate care in Singapore: Process evaluation of implementation fidelity

10.1186/s12913-020-05263-wBMC Health Services Research20145

Right-Site Care Programme with a community-based family medicine clinic in Singapore: Secondary data analysis of its impact on mortality and healthcare utilisation

10.1136/bmjopen-2019-030718BMJ Open912e03071

Exploring the dimensions of patient experience for community-based care programmes in a multi-ethnic Asian context

10.1371/journal.pone.0242610PLoS ONE1511-Nove024261

Mixed-method evaluation of CARITAS:a hospital-to-community model of integrated care for dementia

Objectives The capability and capacity of the primary and community care (PCC) sector for dementia in Singapore may be enhanced through better integration. Through a partnership involving a tertiary hospital and PCC providers, an integrated dementia care network (CARITAS: comprehensive, accessible, responsive, individualised, transdisciplinary, accountable and seamless) was implemented. The study evaluated the process and extent of integration within CARITAS. Design Triangulation mixed-methods design and analyses were employed to understand factors underpinning network mechanisms. Setting The study was conducted at a tertiary hospital in the northern region of Singapore. Participants We recruited participants who were involved in the conceptualisation, design, development and implementation of the CARITAS Programme from a tertiary hospital and PCC providers. Intervention We used the Rainbow Model of Integrated Care-Measurement Tool (RMIC-MT) to assess integration from managerial perspectives. RMIC-MT comprises eight dimensions that play interconnected roles on a macro-level, meso-level and micro-level. We administered RMIC-MT to healthcare providers and conducted in-depth interviews with key CARITAS stakeholders. Primary and secondary outcome measures We assessed integration scores across eight dimensions of the RMIC-MT and factors underpinning network mechanisms. Results Compared with other dimensions, functional integration (mechanisms by which information and management modalities are linked) achieved the lowest mean score of 55. Other dimensions (eg, clinical, professional and organisational integration) scored about 70. Presence of inspiring clinical leaders and tacit interdependencies among partners strengthened the network. However, the lack of structured documentation and a shared information-technology platform hindered functional integration. Conclusion CARITAS has reached maturity in micro-levels and meso-levels of integration, while macro-integration needs further development. Integration can be enhanced by assessing service gaps, increasing engagement with stakeholders and providing a shared communication system

Retrospective evaluation of healthcare utilisation and mortality of two post-discharge care programmes in Singapore

10.1136/bmjopen-2018-027220BMJ Open95e02722