Functional screening for compounds that promote remyelination represents a major hurdle in the development of rational therapeutics for multiple sclerosis. Screening for remyelination is problematic, as myelination requires the presence of axons. Standard methods do not resolve cell-autonomous effects and are not suited for high-throughput formats. Here we describe a binary indicant for myelination using micropillar arrays (BIMA). Engineered with conical dimensions, micropillars permit resolution of the extent and length of membrane wrapping from a single two-dimensional image. Confocal imaging acquired from the base to the tip of the pillars allows for detection of concentric wrapping observed as ‘rings’ of myelin. The platform is formatted in 96-well plates, amenable to semiautomated random acquisition and automated detection and quantification. Upon screening 1,000 bioactive molecules, we identified a cluster of antimuscarinic compounds that enhance oligodendrocyte differentiation and remyelination. Our findings demonstrate a new high-throughput screening platform for potential regenerative therapeutics in multiple sclerosis.

Demyelination in MS disrupts nerve signals and contributes to axon degeneration. While remyelination promises to restore lost function, it remains unclear whether remyelination will prevent axonal loss. Inflammatory demyelination is accompanied by significant neuronal loss in the experimental autoimmune encephalomyelitis (EAE) mouse model and evidence for remyelination in this model is complicated by ongoing inflammation, degeneration and possible remyelination. Demonstrating the functional significance of remyelination necessitates selectively altering the timing of remyelination relative to inflammation and degeneration. We demonstrate accelerated remyelination after EAE induction by direct lineage analysis and hypothesize that newly formed myelin remains stable at the height of inflammation due in part to the absence of MOG expression in immature myelin. Oligodendroglial-specific genetic ablation of the M1 muscarinic receptor, a potent negative regulator of oligodendrocyte differentiation and myelination, results in accelerated remyelination, preventing axonal loss and improving functional recovery. Together our findings demonstrate that accelerated remyelination supports axonal integrity and neuronal function after inflammatory demyelination.DOI: http://dx.doi.org/10.7554/eLife.18246.001

The uninsured do not use more ED visits than the insured population as is sometimes argued. Instead, the publicly insured are overrepresented among ED users. Frequent ED users do not appear to use the ED as a substitute for their primary care but, in fact, are a less healthy population who need and use more care overall.

Context Between 1998 and 2008, the number of hospital-based emergency departments (EDs) in the United States declined, while the number of ED visits increased, particularly visits by publicly-insured and uninsured patients. Little is known about the hospital, community, and market factors associated with ED closures. Federal law requiring EDs to treat all in need regardless of a patient’s ability to pay may make EDs more vulnerable to the market forces that govern US health care. Objective To determine hospital, community, and market factors associated with ED closures. Design ED and hospital organizational information from 1990 through 2009 was acquired from the American Hospital Association (AHA) Annual Surveys (annual response rates ranging from 84–92%) and merged with hospital financial and payer mix information available through 2007 from Medicare hospital cost reports. We evaluated 3 sets of risk factors: hospital characteristics (safety-net as defined by hospitals caring for more than double their Medicaid share of discharges, compared with other hospitals within a 15-mile radius) ownership, teaching status, system membership, hospital size, case-mix), county population demographics (race, poverty, uninsurance, elderly), and market factors (ownership mix, profit margin, location in a competitive market, presence of other EDs). Setting All general, acute, non-rural, short-stay hospitals in the US with an operating ED anytime from 1990–2009. Main Outcome Closure of an emergency department anytime during the study period. Results The number of hospitals with EDs in non-rural areas declined from 2446 in 1990 to 1779 in 2009, with 1041 EDs closing and 374 hospitals opening EDs. Based on analysis of 2,814 urban acute care hospitals, constituting 36,335 hospital-year observations over an 18-year study interval (1990–2007), for-profit hospitals and those with low profit margins were more likely to close than their counterparts (26% vs 16%; HR 1.8, 95% CI 1.5 to 2.1 and 36% vs 18%; HR 1.9, 95% CI 1.6 to 2.3, respectively]. Hospitals in more competitive markets had a significantly higher risk of closing their EDs (34% vs 17%; HR 1.3, 95% CI 1.1 to 1.6), as did safety-net hospitals (10% vs 6%; HR 1.4, 95% CI 1.1 to 1.7) and those serving a higher share of populations in poverty (37% vs 31%; HR 1.4, 95% CI 1.1 to 1.7). Conclusion From 1990 to 2009, the number of hospital EDs in non-rural areas declined by 27%, with for-profit ownership, location in a competitive market, safety-net status, and low profit margin associated with increased risk of ED closure.

In this analysis, with data collected from a random sample of 265 employed dual-earner couples, we estimated the association between time spent on housework tasks on one hand and psychological distress on the other. Based on the literature relating job control to mental health outcomes, we hypothesized that hours spent in low-schedule-control tasks, but not total hours spent in housework tasks or hours spent in high-schedule-control tasks, would be associated with psychological distress. Further, we hypothesized that absolute but not proportional time in low-schedule-control tasks would be related to distress. After controlling for age, gender, education, occupational prestige, number of children, preschool children, gender role ideology, marital role quality, and total number of hours in paid employment, all hypotheses were supported. Finally, as hypothesized these relationships were not moderated by gender.