Meningeal lymphatics stem cognitive decline in craniosynostosis.

Craniosynostosis is a congenital craniofacial disorder where premature fusion of cranial sutures causes elevated intracranial pressure and neurological deficits. In this issue of Cell Stem Cell, Ma et al. demonstrate that replenishing skull progenitor cells alleviates intracranial pressure elevations in craniosynostosis by restoring the meningeal lymphatic system, improving neurocognitive function.

Emergency department use of an electronic differential diagnosis generator in the evaluation of critically ill patients.

BACKGROUND: Accurate diagnosis is an essential component of managing critically ill emergency department (ED) patients. Electronic diagnosis generators (EDGs) are software tools which assist clinicians in their diagnosis generation; however, they have not been evaluated for use for critical ED patients. We aimed to evaluate the use of an EDG for this population to determine its impact on diagnosis generation and diagnostic testing. METHODS: We performed an observational study on usage of an EDG in the high-acuity area of a tertiary care ED. The EDG was used by residents evaluating each patient in the area. The resident used the EDG when the case was felt to have diagnostic uncertainty and completed a data collection tool. Data were summarized by frequencies. Chi-squared or Fisher's exact tests were used to assess the association of added value of the EDG for diagnosis generation and diagnostic testing. RESULTS: Over the 8-month study period, the EDG was utilized to evaluate 98 critical ED patients, of whom 60% were female, 7% were pediatric, and 46% were elderly. It was used most commonly for gastroenterological, infectious disease/immunologic, metabolic/renal, and neuropsychiatric presentations, and was least used for trauma presentations. Use of the EDG led to a diagnosis not initially considered in 47% of cases and led to additional diagnostic testing in 4% of cases. CONCLUSION: EDGs have some potential to improve diagnosis in critical EM patients by expanding the differential diagnosis and, to a lesser extent, altering diagnostic testing.

The Gαq/phospholipase Cß signaling system represses tau aggregation.

Alzheimer's disease is typified by calcium dysfunction and neurofibrillary tangles of tau aggregates along with mitotic proteins. Using PC12 cells as a model system, we determined whether the Gαq/PLCß/ calcium signaling pathway impacts the manifestation of Alzheimer's disease. Down-regulating PLCß significantly increases tau protein expression and causes a large increase in tau aggregation. Stimulating Gαq to activate PLCß results in a modest reduction in tau aggregation while inhibiting PLCß activity results in a modest enhancement of tau aggregation. These results suggest that PLCß may effect tau aggregation by an additional mechanism that is independent of its ability to transduce calcium signals. To this end, we found that a cytosolic population of PLCß binds to a mitotic protein found in neurofibrillary tangles, CDK18, which promotes tau phosphorylation and aggregation. Taken together, our studies show that the loss of PLCß1 can promote Alzheimer's disease by a combination of its catalytic activity and its interaction with mitotic proteins thus offering an orthogonal method to control tau aggregation.

Alternative remedies for insomnia: a proposed method for personalized therapeutic trials.

Insomnia is a common symptom, with chronic insomnia being diagnosed in 5-10% of adults. Although many insomnia patients use prescription therapy for insomnia, the health benefits remain uncertain and adverse risks remain a concern. While similar effectiveness and risk concerns exist for herbal remedies, many individuals turn to such alternatives to prescriptions for insomnia. Like prescription hypnotics, herbal remedies that have undergone clinical testing often show subjective sleep improvements that exceed objective measures, which may relate to interindividual heterogeneity and/or placebo effects. Response heterogeneity can undermine traditional randomized trial approaches, which in some fields has prompted a shift toward stratified trials based on genotype or phenotype, or the so-called n-of-1 method of testing placebo versus active drug in within-person alternating blocks. We reviewed six independent compendiums of herbal agents to assemble a group of over 70 reported to benefit sleep. To bridge the gap between the unfeasible expectation of formal evidence in this space and the reality of common self-medication by those with insomnia, we propose a method for guided self-testing that overcomes certain operational barriers related to inter- and intraindividual sources of phenotypic variability. Patient-chosen outcomes drive a general statistical model that allows personalized self-assessment that can augment the open-label nature of routine practice. The potential advantages of this method include flexibility to implement for other (nonherbal) insomnia interventions.