Bioinformatics pipeline to guide late-onset Alzheimer's disease (LOAD) post-GWAS studies: Prioritizing transcription regulatory variants within LOAD-associated regions.

Introduction: As new late-onset Alzheimer's disease (LOAD) genetic risk loci are identified and brain cell-type specific omics data becomes available, there is an unmet need for a bioinformatics framework to prioritize genes and variants for testing in single-cell molecular profiling experiments and validation using disease models and gene editing technologies. Prior work has characterized and prioritized active enhancers located in LOAD-genome-wide association study (GWAS) regions and their potential interactions with candidate genes. The current study extends this work by focusing on single nucleotide polymorphisms (SNPs) within these LOAD enhancers and their impact on altering transcription factor (TF) binding.

If Thymectomy Reduces the Risk of Progression of Ocular to Generalized Myasthenia Gravis, Who Should Receive it?

In this issue of Neurotherapeutics, Li et.al. report a large retrospective study of the beneficial effects of thymectomy on the progression of ocular myasthenia gravis (OMG) to generalized MG (GMG) (Huanhuan et al.

Recent Myocardial Infarction is Associated With Increased Risk in Older Adults With Acute Ischemic Stroke Receiving Thrombolytic Therapy.

Background Intravenous recombinant tissue-type plasminogen activator (rtPA) remains the only medical therapy to improve outcomes for acute ischemic stroke (AIS), but the safety of rtPA in AIS patients with a history of recent myocardial infarction (MI) remains controversial. Methods and Results We sought to determine whether the presence of recent MI would alter the risk of mortality and rtPA-related complications. Multivariate logistic regression models were used to compare in-hospital outcomes between rtPA-treated AIS patients with recent MI within 3 months and those with no history of MI from the Get With The Guidelines-Stroke hospitals between February 2009 and December 2015.

International Comparison of Patient Characteristics and Quality of Care for Ischemic Stroke: Analysis of the China National Stroke Registry and the American Heart Association Get With The Guidelines--Stroke Program.

Background Adherence to evidence-based guidelines is an important quality indicator; yet, there is lack of assessment of adherence to performance measures in acute ischemic stroke for most world regions. Methods and Results We analyzed 19 604 patients with acute ischemic stroke in the China National Stroke Registry and 194 876 patients in the Get With The Guidelines--Stroke registry in the United States from June 2012 to January 2013. Compared with their US counterparts, Chinese patients were younger, had a lower prevalence of comorbidities, and had similar median, lower mean, and less variability in National Institutes of Health Stroke Scale (median 4 [25th percentile-75th percentile, 2-7], mean 5.

Shock Index Predicts Patient-Related Clinical Outcomes in Stroke.

Background The prognostic value of shock index ( SI ), heart rate divided by systolic blood pressure, in stroke for clinical outcomes other than mortality is not well understood. Methods and Results We examined the Get With The Guidelines-Stroke ( GWTG -Stroke) data to explore the usefulness of SI in predicting in-hospital outcomes in 425 808 acute stroke cases (mean age: 71.0±14.

First-in-man allopregnanolone use in super-refractory status epilepticus.

Super-refractory status epilepticus (SRSE) is associated with high morbidity and mortality. Treatment of SRSE is complicated by progressive cortical hyperexcitability believed to result in part from synaptic GABA receptor internalization and desensitization. Allopregnanolone, a neurosteroid that positively modulates synaptic and extrasynaptic GABA receptors, has been proposed as a novel treatment.

Non-Invasive Neuromodulation Using Time-Varying Caloric Vestibular Stimulation.

Caloric vestibular stimulation (CVS) to elicit the vestibulo-ocular reflex has long been used in clinical settings to aid in the diagnosis of balance disorders and to confirm the absence of brainstem function. While a number of studies have hinted at the potential therapeutic applications of CVS, the limitations of existing devices have frustrated that potential. Current CVS irrigators use water or air during short-duration applications; however, this approach is not tenable for longer duration therapeutic protocols or home use.