Parameters Governing the Formation of Photopolymerized Silica Sol-Gel Monoliths in PDMS Microfluidic Chips.

Although polydimethylsiloxane (PDMS) microfluidic chips provide an alternative to more expensive microfabricated glass chips, formation of monolithic stationary phases in PDMS is not a trivial task. Photopolymerized silica sol-gel monoliths were fabricated in PDMS based microfluidic devices using 3-trimethoxysilylpropylmethacrylate (MPTMOS) and glycidyloxypropyltrimethoxysilane (GPTMOS). The monolith formation was optimized by identifying a suitable porogen, controlling monomer concentration, functional additives, salts, porogen, wall attachment methods, and rinsing procedures.

A standardized approach to the Fugl-Meyer assessment and its implications for clinical trials.

Background: Standardizing scoring reduces variability and increases accuracy. A detailed scoring and training method for the Fugl-Meyer motor assessment (FMA) is described and assessed, and implications for clinical trials considered.

Methods: A standardized FMA scoring approach and training materials were assembled, including a manual, scoring sheets, and instructional video plus patient videos.

Evidence for high translational potential of mesenchymal stromal cell therapy to improve recovery from ischemic stroke.

Although ischemic stroke is a major cause of morbidity and mortality, current therapies benefit only a small proportion of patients. Transplantation of mesenchymal stromal cells (MSC, also known as mesenchymal stem cells or multipotent stromal cells) has attracted attention as a regenerative therapy for numerous diseases, including stroke. Mesenchymal stromal cells may aid in reducing the long-term impact of stroke via multiple mechanisms that include induction of angiogenesis, promotion of neurogenesis, prevention of apoptosis, and immunomodulation.

Case study of ecstatic meditation: fMRI and EEG evidence of self-stimulating a reward system.

We report the first neural recording during ecstatic meditations called jhanas and test whether a brain reward system plays a role in the joy reported. Jhanas are Altered States of Consciousness (ASC) that imply major brain changes based on subjective reports: (1) external awareness dims, (2) internal verbalizations fade, (3) the sense of personal boundaries is altered, (4) attention is highly focused on the object of meditation, and (5) joy increases to high levels. The fMRI and EEG results from an experienced meditator show changes in brain activity in 11 regions shown to be associated with the subjective reports, and these changes occur promptly after jhana is entered.

Photopolymerized sol-gel monoliths for separations of glycosylated proteins and peptides in microfluidic chips.

Photopolymerized silica sol-gel monoliths, functionalized with boronic acid ligands, have been developed for protein and peptide separations in polydimethylsiloxane microfluidic devices. Pore size characterization of the monoliths was carried out with SEM, image analysis, and differential scanning calorimetry to evaluate both the micron-sized macropores and the nanometer-sized mesopores. Monoliths were functionalized with boronic acid using three different immobilization techniques.

High-throughput screening for the development of a monoclonal antibody affinity precipitation step using ELP-z stimuli responsive biopolymers.

This study provides a detailed investigation into the performance of a stimuli responsive ELP-Z based process for monoclonal antibody (mAb) affinity precipitation. A multidimensional high-throughput screening (HTS) protocol was developed and employed to investigate the effects of a variety of operating conditions on mAb yield and aggregation during the process. Precipitation efficiency of ELP-Z in the absence of mAb was first determined as a function of temperature and sodium sulfate concentration and conditions producing high yields were identified.

Genetic variation in the human brain dopamine system influences motor learning and its modulation by L-Dopa.

Dopamine is important to learning and plasticity. Dopaminergic drugs are the focus of many therapies targeting the motor system, where high inter-individual differences in response are common. The current study examined the hypothesis that genetic variation in the dopamine system is associated with significant differences in motor learning, brain plasticity, and the effects of the dopamine precursor L-Dopa.

Design of peptide affinity ligands for S-protein: a comparison of combinatorial and de novo design strategies.

Design of peptide affinity ligands against biological targets is important for a broad range of applications. Here, we report on de novo and combinatorial strategies for the design of high-affinity and high-specificity peptides against S-protein as a target. The peptide libraries employed in this study contain (1) consensus motif (CM) sequences identified from high-throughput phage combinatorial screening, (2) point mutations of CM sequences, and (3) de novo sequences rationally designed based on stereo-chemical information of the complex between S-protein and its natural ligand, S-peptide.

Safety, pharmacokinetics, and pharmacodynamics of escalating repeat doses of GSK249320 in patients with stroke.

Background And Purpose: Restorative therapies have the potential to improve function and reduce disability after stroke with a wide therapeutic window. The current study evaluated GSK249320, a monoclonal antibody that blocks the axon outgrowth inhibition molecule myelin-associated glycoprotein and also protects oligodendrocytes.

Methods: Patients with mild-moderate stroke were randomized to intravenous GSK249320 (1, 5, or 15 mg/kg per infusion, in escalating cohorts of 8-9 subjects) versus placebo (n=17).

Patient-reported measures provide unique insights into motor function after stroke.

Background And Purpose: Patient-reported outcome measures have been found useful in many disciplines but have received limited evaluation after stroke. The current study investigated the relationship that patient-reported measures have with standard impairment and disability scales after stroke.

Methods: Patients with motor deficits after stroke were scored on standard assessments including the National Institutes of Health Stroke Scale, modified Rankin Scale, and Fugl-Meyer motor scale, and on 2 patient-reported measures, the hand function domain of the Stroke Impact Scale, which documents difficulty of hand motor usage, and the amount of use portion of the Motor Activity Log, which records amount of arm motor usage.

A Spatial Augmented Reality rehab system for post-stroke hand rehabilitation.

This paper features a Spatial Augmented Reality system for rehabilitation of hand and arm movement. The table-top home-based system tracks a subject's hand and creates a virtual audio-visual interface for performing rehabilitation-related tasks that involve wrist, elbow, and shoulder movements. It measures range, speed, and smoothness of movements locally and can send the real-time photos and data to the clinic for further assessment.

Brain-computer interface controlled functional electrical stimulation device for foot drop due to stroke.

Gait impairment due to foot drop is a common outcome of stroke, and current physiotherapy provides only limited restoration of gait function. Gait function can also be aided by orthoses, but these devices may be cumbersome and their benefits disappear upon removal. Hence, new neuro-rehabilitative therapies are being sought to generate permanent improvements in motor function beyond those of conventional physiotherapies through positive neural plasticity processes.

Biomarkers and predictors of restorative therapy effects after stroke.

Many restorative therapies that promote brain repair are under development. Stroke is very heterogeneous, highlighting the need to identify target populations and to understand intersubject differences in treatment response. Several neuroimaging measures have shown promise as biomarkers and predictors, including measures of structure and function, in gray matter and white matter.

Influence of hematoma location on acute mortality after intracerebral hemorrhage.

Background And Purpose: This study aimed to identify predictors of acute mortality after intracerebral hemorrhage (ICH), including voxel-wise analysis of hematoma location.

Methods: In 282 consecutive patients with acute ICH, clinical and radiological predictors of acute mortality were identified. Voxel-based lesion-symptom mapping examined spatial correlates of acute mortality, contrasting results in basal ganglia ICH and lobar ICH.

Predictors of Gains During Inpatient Rehabilitation in Patients with Stroke- A Review.

Stroke remains a major cause of disability. The cost of stroke rehabilitation is substantial. Understanding the factors that predict response to inpatient stroke rehabilitation may be useful, for example, to best individualize the content of therapy, or to maximize the efficiency with which resources are directed.

The BDNF val(66)met polymorphism is not related to motor function or short-term cortical plasticity in elderly subjects.

The brain derived neurotrophic factor (BDNF) val(66)met polymorphism affects function of the motor system in young subjects, but little is known about motor system effects in the elderly. The current study assessed motor system physiology and behavior, plus a measure of short-term motor cortex plasticity using transcranial magnetic stimulation, in 38 elderly subjects, then examined whether findings varied in relation to BDNF genotype. Baseline data were also collected from 14 young subjects.

Comparison of three-dimensional, assist-as-needed robotic arm/hand movement training provided with Pneu-WREX to conventional tabletop therapy after chronic stroke.

Objectives: Robot-assisted movement training can help individuals with stroke reduce arm and hand impairment, but robot therapy is typically only about as effective as conventional therapy. Refining the way that robots assist during training may make them more effective than conventional therapy. Here, the authors measured the therapeutic effect of a robot that required individuals with a stroke to achieve virtual tasks in three dimensions against gravity.

ELP-z and ELP-zz capturing scaffolds for the purification of immunoglobulins by affinity precipitation.

The increasing demand of monoclonal antibodies for therapeutic applications along with the high manufacturing cost have made it necessary to evaluate better process options and technologies for their purification. Affinity precipitation is an attractive alternative to traditional chromatographic methods by affording effective purification using a simple environmental trigger. The feature of elastin-like-protein (ELP) fused with antibody binding domains has already been explored for the purification of antibodies.

The influence of genetic factors on brain plasticity and recovery after neural injury.

Purpose Of Review: The fields of clinical genetics and pharmacogenetics are rapidly expanding. Genetic factors have numerous associations with injury and with treatment effects in the setting of neural plasticity and recovery.

Recent Findings: Evidence is reviewed that established genetic variants, as well as some more recently described variants, are related to outcome after neural injury and in some cases are useful for predicting clinical course.

Improving selectivity in multimodal chromatography using controlled pH gradient elution.

Externally generated pH gradients are employed on a multimodal cation exchange chromatographic resin to improve the selectivity for a mixture of model proteins. By combining controlled pH gradients with the unique selectivities arising from the multiple interaction types exhibited by the multimodal resin, the separation of the protein mixture is significantly improved as compared to linear salt gradient operation. Several gradient conditions are explored and a shallow gradient from pH 3.

Organization of a United States county system for comprehensive acute stroke care.

Background And Purpose: Organized systems of care have the potential to improve acute stroke care delivery. The current report describes the experience of implementing a county-wide system of spoke-and-hub stroke neurology receiving centers (SNRC) that incorporated several comprehensive stroke center recommendations.

Methods: Observational study of patients with suspected stroke of <5 hours duration transported by emergency medical system personnel to an SNRC during the first year of this system.

Probing multimodal ligand binding regions on ubiquitin using nuclear magnetic resonance, chromatography, and molecular dynamics simulations.

Site-directed mutagenesis, nuclear magnetic resonance (NMR) chemical shift perturbation experiments, and molecular dynamics (MD) simulations are employed in concert with chromatographic experiments to provide insight into protein-ligand interactions in multimodal chromatographic systems. In previous studies, a preferred binding region was identified on the surface of the protein ubiquitin for binding with a multimodal ligand. In this study, site-directed mutagenesis is used to enable direct NMR evaluation of the mutant protein as compared to the wild type.