Anti-inflammatory reprogramming of microglia cells by metabolic modulators to counteract neurodegeneration; a new role for Ranolazine.

Microglia chronic activation is a hallmark of several neurodegenerative diseases, including the retinal ones, possibly contributing to their etiopathogenesis. However, some microglia sub-populations have anti-inflammatory and neuroprotective functions, thus making arduous deciphering the role of these cells in neurodegeneration. Since it has been proposed that functionally different microglia subsets also rely on different metabolic routes, we hypothesized that modulating microglia metabolism might be a tool to enhance their anti-inflammatory features. This would have a preventive and therapeutic potential in counteracting neurodegenerative diseases. For this purpose, we tested various molecules known to act on cell metabolism, and we revealed the anti-inflammatory effect of the FDA-approved piperazine derivative Ranolazine on microglia cells, while confirming the one of the flavonoids Quercetin and Naringenin, both in vitro and in vivo. We also demonstrated the synergistic anti-inflammatory effect of Quercetin and Idebenone, and the ability of Ranolazine, Quercetin and Naringenin to counteract the neurotoxic effect of LPS-activated microglia on 661W neuronal cells. Overall, these data suggest that using the selected molecules -also in combination therapies- might represent a valuable approach to reduce inflammation and neurodegeneration while avoiding long term side effects of corticosteroids.

Medicare Beneficiary Factors Associated with Skilled Nursing Facility Lengths of Stay.

The objectives of this study are (1) to identify beneficiary-level characteristics associated with skilled nursing facility (SNF) length of stay (LOS), and (2) to determine if significant differences in LOS exist for vulnerable populations at the individual level or among nursing homes that serve a disproportionate share of vulnerable populations. This study employed 2014-2015 Medicare Long-Term Care Minimum Data Set (MDS v3.0) assessment, fee-for-service claims and enrollment, and 2014 Nursing Home Compare data to examine SNF LOS in Medicare beneficiaries. We used a hierarchical linear model to identify which beneficiary-level characteristics are associated with SNF LOS, while controlling for facility-level characteristics. After controlling for beneficiary-and facility-level characteristics, we found dual eligibility, racial or ethnic minority, depression, and Alzheimer's disease to be associated with longer Medicare covered SNF stays. We found that facilities that served higher proportions of dually eligible individuals tended to have higher average LOS compared to other facilities.