Major histocompatibility complex class I molecules protect motor neurons from astrocyte-induced toxicity in amyotrophic lateral sclerosis

Astrocytes isolated from individuals with amyotrophic lateral sclerosis (ALS) are toxic to motor neurons (MNs) and play a non–cell autonomous role in disease pathogenesis. The mechanisms underlying the susceptibility of MNs to cell death remain unclear. Here we report that astrocytes derived from either mice bearing mutations in genes associated with ALS or human subjects with ALS reduce the expression of major histocompatibility complex class I (MHCI) molecules on MNs; reduced MHCI expression makes these MNs susceptible to astrocyte-induced cell death. Increasing MHCI expression on MNs increases survival and motor performance in a mouse model of ALS and protects MNs against astrocyte toxicity. Overexpression of a single MHCI molecule, HLA-F, protects human MNs from ALS astrocyte–mediated toxicity, whereas knockdown of its receptor, the killer cell immunoglobulin-like receptor KIR3DL2, on human astrocytes results in enhanced MN death. Thus, our data indicate that, in ALS, loss of MHCI expression on MNs renders them more vulnerable to astrocyte-mediated toxicity

Interventions for reducing readmissions – are we barking up the right tree?

<p>Abstract</p> <p>Readmission reduction is at the focus of health care systems worldwide in efforts to improve efficiency across care settings. Yet, setting targets for readmission reduction is complicated due to inconsistencies in evidence pointing to effective organization-wide interventions and because of inverse incentives (such as maintaining high occupancy rates). Nonetheless, readmission reduction is one of the few quality measures that, if implemented properly, can serve as a catalyst for system integration. Appropriate mechanisms should be applied to hospitals as well as ambulatory settings to ensure that accountability is assigned to all stakeholders.</p