Binding of Cholera Toxin B-Subunit to a Ganglioside GM1-Functionalized PEG-Tethered Lipid Membrane.

We report neutron reflectometry (NR) studies of polyethylene glycol (PEG)-tethered model lipid membranes at the solid-liquid interface and of cholera toxin's B-subunit (CTxB) binding to tethered membranes containing ganglioside GM1 receptors. First, tethered polymer brushes were formed by grafting silane-functionalized PEG lipopolymers to quartz from solution. Subsequent deposition of lipids by Langmuir-Blodgett/Langmuir-Schaefer (LB/LS) resulted in a tethered bilayer structure separated from the solid support by a hydrated PEG layer. NR revealed that the tethers formed a highly hydrated polymer brush, uniformly separating the bilayer from the underlying solid substrate. Further, the lipid bilayer did not significantly perturb the brush's conformation relative to a free brush. Biological functionality of the tethered bilayers was verified by interacting CTxB, with ganglioside GM1 receptors incorporated into the bilayer. The surface coverage of CTxB bound to the lipid membrane, θCTB= 0.58 ± 0.08, was consistent with the coverage predicted for random sequential absorption, and toxin binding did not impact the membrane conformation.

The integration of sensations and mental experiences into a unified experience: A neuropsychological model for the "sense of self".

A continued weakness in the cognitive neurosciences is the lack of a model to explain the phenomenological experience of the "self." This article proposes a model that suggests that the right hemisphere association area integrates physical sensations and mental experiences into a unified experience (i.e., a "sense of self") that is best conceptualized and understood as the subjective experience of "mineness." This model presents a unifying framework for neurologic and psychiatric disorders of the self (i.e., dis-integrated sense of "mineness"), as well as a neuropsychological framework to explain several human characteristics and experiences. Research is reviewed that indicates the sense of self can be activated to serve as the neuropsychological foundation of "self-integrated" character traits such as empathy (i.e., experiencing other's thoughts/emotions as "mine"), and conversely, the inhibition of this integrative process which can serve as the foundation of "selfless" experiences such as transcendence and forgiveness. Future research and clinical applications are discussed.

Body-Mounted Robotic System for MRI-Guided Shoulder Arthrography: Cadaver and Clinical Workflow Studies.

This paper presents an intraoperative MRI-guided, patient-mounted robotic system for shoulder arthrography procedures in pediatric patients. The robot is designed to be compact and lightweight and is constructed with nonmagnetic materials for MRI safety. Our goal is to transform the current two-step arthrography procedure (CT/x-ray-guided needle insertion followed by diagnostic MRI) into a streamlined single-step ionizing radiation-free procedure under MRI guidance. The MR-conditional robot was evaluated in a Thiel embalmed cadaver study and healthy volunteer studies. The robot was attached to the shoulder using straps and ten locations in the shoulder joint space were selected as targets. For the first target, contrast agent (saline) was injected to complete the clinical workflow. After each targeting attempt, a confirmation scan was acquired to analyze the needle placement accuracy. During the volunteer studies, a more comfortable and ergonomic shoulder brace was used, and the complete clinical workflow was followed to measure the total procedure time. In the cadaver study, the needle was successfully placed in the shoulder joint space in all the targeting attempts with translational and rotational accuracy of 2.07 ± 1.22 mm and 1.46 ± 1.06 degrees, respectively. The total time for the entire procedure was 94 min and the average time for each targeting attempt was 20 min in the cadaver study, while the average time for the entire workflow for the volunteer studies was 36 min. No image quality degradation due to the presence of the robot was detected. This Thiel-embalmed cadaver study along with the clinical workflow studies on human volunteers demonstrated the feasibility of using an MR-conditional, patient-mounted robotic system for MRI-guided shoulder arthrography procedure. Future work will be focused on moving the technology to clinical practice.

Graphite intercalation compound (GIC) crystal monochromators for cold neutron instruments: Characterization of KC24 by time-of-flight neutron diffraction.

Graphite intercalation compounds (GICs) are a group of layered materials that are suitable as monochromators for cold neutrons. KC24 is a particularly interesting compound in this regard as it features a large c-axis lattice spacing of 8.74 Å, high reflectivity, and the possibility to produce large crystals with mosaicity that matches the beam divergence of cold neutron guides. GICs can be synthesized with different levels of intercalation, known as the stage of the compounds. Each stage displays a specific d-spacing. Impure GIC-monochromators containing multiple stages produce mixing of neutron wavelengths, which complicates data analysis on neutron reflectometers. We discuss the implications of GIC crystal purity and stage contamination for neutron reflectometry and show how GIC crystals can be characterized by time-of-flight neutron diffraction providing an efficient and quantifiable measure of the reflected wavelength spectrum. This allows taking into account multiple wavelength contaminations and ascertains the robustness of reflectometry measurements.

MR-guided focused ultrasound application for moving target tumor ablation in abdominal area: coil selection.

BACKGROUND: Magnetic Resonance Imaging (MRI)-guided Focused Ultrasound Surgery (MRgFUS) is a non-invasive thermal ablation method utilizing high-intensity focused ultrasound (HI-FU) energy for tissue ablation under MRI with real-time thermal mapping. Ablating to a dynamic target as in the liver is very challenging, requiring approval. A novel quality-assured liver tumor ablation system has been proposed for clinics. The paper reports the evaluation of conventional and new MR-receiving coils. PURPOSE: To evaluate the suitability of MR coils as part of the MRgFUS treatment system for liver, while simulating breathing motion in pre-clinical settings. MATERIAL AND METHODS: The novel software communicates with the MR scanner and the transducer. To monitor the temperature via proton resonance frequency (PRF) methodology echo planar imaging (EPI) sequence was used while the algorithms of static, static and dynamic tracking were tested with sonications of 100 W for 30 s on tissue-mimicking phantoms. Different coil sets were used to assess the performance of the system for fitness for dynamic thermometry. Finally, in vivo experiments were performed over a porcine model. RESULTS: Single-loop four-channel Duoflex and Gem coils provided adequate signal-to-noise ratio and contrast with consistent thermal readings. Body array coils showed severe loss of signal in dynamic cases since the integration of tracking algorithm causes low efficiency. CONCLUSION: Body array coils are unsuitable for MRgFUS of the liver due to signal loss. The dedicated coil set with a single loop around the FUS transducer combined with four-channel arrays might be the best option for liver treatment using dynamic MRgFUS applications.

X-ray nano-tomography of complete scales from the ultra-white beetles Lepidiota stigma and Cyphochilus.

High resolution X-ray nano-tomography experiments are often limited to a few tens of micrometer size volumes due to detector size. It is possible, through the use of multiple overlapping tomography scans, to produce a large area scan which can encompass a sample in its entirety. Mounting and positioning regions to be scanned is highly challenging and normally requires focused ion beam approaches. In this work we have imaged intact beetle scale cells mounted on the tip of a needle using a micromanipulator stage. Here we show X-ray holotomography data for single ultra-white scales from the beetles Lepidiota stigma (L. stigma) and Cyphochilus which exhibit the most effective scattering of white light in the literature. The final thresholded matrices represent a scan area of 25 × 70 × 362.5 µm and 25 × 67.5 × 235µm while maintaining a pixel resolution of 25 nm. This tomographic approach allowed the internal structure of the scales to be captured completely intact and undistorted by the sectioning required for traditional microscopy techniques.

Facile Control over the Supramolecular Ordering of Self-assembled Peptide Scaffolds by Simultaneous Assembly with a Polysacharride.

Enabling control over macromolecular ordering and the spatial distribution of structures formed via the mechanisms of molecular self-assembly is a challenge that could yield a range of new functional materials. In particular, using the self-assembly of minimalist peptides, to drive the incorporation of large complex molecules will allow a functionalization strategy for the next generation of biomaterial engineering. Here, for the first time, we show that co-assembly with increasing concentrations of a highly charged polysaccharide, fucoidan, the microscale ordering of Fmoc-FRGDF peptide fibrils and subsequent mechanical properties of the resultant hydrogel can be easily and effectively manipulated without disruption to the nanofibrillar structure of the assembly.

The Search for Nanobubbles by Using Specular and Off-Specular Neutron Reflectometry.

We apply specular and off-specular neutron reflection at the hydrophobic silicon/water interface to check for evidence of nanoscopic air bubbles whose presence is claimed after an ad hoc procedure of solvent exchange. Nanobubbles and/or a depletion layer at the hydrophobic/water interface have long been discussed and generated a plethora of controversial scientific results. By combining neutron reflectometry (NR), off-specular reflectometry (OSS), and grazing incidence small angle neutron scattering (GISANS), we studied the interface between hydrophobized silicon and heavy water before and after saturation with nitrogen gas. Our specular reflectometry results can be interpreted by assuming a submolecular sized depletion layer and the off-specular measurements show no change with nitrogen super saturated water. This picture is consistent with the assumption that, following the solvent exchange, no additional nanobubbles are introduced at significant concentrations (if present at all). Furthermore, we discuss the results in terms of the maximum surface coverage of nanobubbles that could be present on the hydrophobic surface compatibly with the sensitivity limit of these techniques.

Coassembled nanostructured bioscaffold reduces the expression of proinflammatory cytokines to induce apoptosis in epithelial cancer cells.

The local inflammatory environment of the cell promotes the growth of epithelial cancers. Therefore, controlling inflammation locally using a material in a sustained, non-steroidal fashion can effectively kill malignant cells without significant damage to surrounding healthy cells. A promising class of materials for such applications is the nanostructured scaffolds formed by epitope presenting minimalist self-assembled peptides; these are bioactive on a cellular length scale, while presenting as an easily handled hydrogel. Here, we show that the assembly process can distribute an anti-inflammatory polysaccharide, fucoidan, localized to the nanofibers within the scaffold to create a biomaterial for cancer therapy. We show that it supports healthy cells, while inducing apoptosis in cancerous epithelial cells, as demonstrated by the significant down-regulation of gene and protein expression pathways associated with epithelial cancer progression. Our findings highlight an innovative material approach with potential applications in local epithelial cancer immunotherapy and drug delivery.

A Case Series: The Identification of Buried Bumper Syndrome With Abdominal Computed Tomography Scan in Two Severely Brain Injured Rehabilitation Patients.

Buried bumper syndrome is a potentially dangerous complication related to percutaneous endoscopic gastrostomy tube placement. Early diagnosis of this condition is important to avoid further complications related to subcutaneous or intraperitoneal administration of tube feedings. However, diagnosis in persons with altered mental status due to brain injury is challenging because of the patient's lack of ability to communicate and report symptoms. We present 2 case studies that demonstrate both the importance of early diagnosis and management and the lack of adequate sensitivity of a Gastrografin-aided kidney, ureter, and bladder (KUB) study.

Spatially modulated structural colour in bird feathers.

Eurasian Jay (Garrulus glandarius) feathers display periodic variations in the reflected colour from white through light blue, dark blue and black. We find the structures responsible for the colour are continuous in their size and spatially controlled by the degree of spinodal phase separation in the corresponding region of the feather barb. Blue structures have a well-defined broadband ultra-violet (UV) to blue wavelength distribution; the corresponding nanostructure has characteristic spinodal morphology with a lengthscale of order 150 nm. White regions have a larger 200 nm nanostructure, consistent with a spinodal process that has coarsened further, yielding broader wavelength white reflectance. Our analysis shows that nanostructure in single bird feather barbs can be varied continuously by controlling the time the keratin network is allowed to phase separate before mobility in the system is arrested. Dynamic scaling analysis of the single barb scattering data implies that the phase separation arrest mechanism is rapid and also distinct from the spinodal phase separation mechanism i.e. it is not gelation or intermolecular re-association. Any growing lengthscale using this spinodal phase separation approach must first traverse the UV and blue wavelength regions, growing the structure by coarsening, resulting in a broad distribution of domain sizes.

Graphene oxide hydration and solvation: an in situ neutron reflectivity study.

Graphene oxide membranes were recently suggested for applications in separation of ethanol from water using a vapor permeation method. Using isotope contrast, neutron reflectivity was applied to evaluate the amounts of solvents intercalated into a membrane from pure and binary vapors and to evaluate the selectivity of the membrane permeation. Particularly, the effect of D2O, ethanol and D2O-ethanol vapours on graphene oxide (GO) thin films (∼25 nm) was studied. The interlayer spacing of GO and the amount of intercalated solvents were evaluated simultaneously as a function of vapour exposure duration. The significant difference in neutron scattering length density between D2O and ethanol allows distinguishing insertion of each component of the binary mixture into the GO structure. The amount of intercalated solvent at saturation corresponds to 1.4 molecules per formula unit for pure D2O (∼1.4 monolayers) and 0.45 molecules per formula unit (one monolayer) for pure ethanol. This amount is in addition to H2O absorbed at ambient humidity. Exposure of the GO film to ethanol-D2O vapours results in intercalation of GO with both solvents even for high ethanol concentration. A mixed D2O-ethanol layer inserted into the GO structure is water enriched compared to the composition of vapours due to slower ethanol diffusion into GO interlayers.

Carbohydrate conformation and lipid condensation in monolayers containing glycosphingolipid Gb3: influence of acyl chain structure.

Globotriaosylceramide (Gb3), a glycosphingolipid found in the plasma membrane of animal cells, is the endocytic receptor of the bacterial Shiga toxin. Using x-ray reflectivity (XR) and grazing incidence x-ray diffraction (GIXD), lipid monolayers containing Gb3 were investigated at the air-water interface. XR probed Gb3 carbohydrate conformation normal to the interface, whereas GIXD precisely characterized Gb3's influence on acyl chain in-plane packing and area per molecule (APM). Two phospholipids, 1,2-distearoyl-sn-glycero-3-phosphocholine (DSPC) and 1,2-dipalmitoyl-sn-glycero-3-phosphoethanolamine (DPPE), were used to study Gb3 packing in different lipid environments. Furthermore, the impact on monolayer structure of a naturally extracted Gb3 mixture was compared to synthetic Gb3 species with uniquely defined acyl chain structures. XR results showed that lipid environment and Gb3 acyl chain structure impact carbohydrate conformation with greater solvent accessibility observed for smaller phospholipid headgroups and long Gb3 acyl chains. In general, GIXD showed that Gb3 condensed phospholipid packing resulting in smaller APM than predicted by ideal mixing. Gb3's capacity to condense APM was larger for DSPC monolayers and exhibited different dependencies on acyl chain structure depending on the lipid environment. The interplay between Gb3-induced changes in lipid packing and the lipid environment's impact on carbohydrate conformation has broad implications for glycosphingolipid macromolecule recognition and ligand binding.

Specialized early treatment for persons with disorders of consciousness: program components and outcomes.

OBJECTIVES: To describe a specialized early treatment program for persons with disorders of consciousness (DOC) that includes family education; to identify rates of secondary conditions, imaging used, and selected interventions; and to evaluate outcomes. DESIGN: A single-center, retrospective, pre-post design using electronic medical record data. SETTING: A Commission on Accreditation of Rehabilitation Facilities-accredited, long-term acute care hospital that provides acute medical and inpatient rehabilitation levels of care for people with catastrophic injuries. PARTICIPANTS: Persons (N=210) aged 14 to 69 years with DOC of primarily traumatic etiology admitted at a mean ± SD of 41.0 ± 27.2 days postinjury; 2% were in coma, 41% were in the vegetative state, and 57% were in the minimally conscious state. INTERVENTIONS: An acute medical level of care with ≥90 minutes of daily interdisciplinary rehabilitation and didactic and hands-on caretaking education for families. MAIN OUTCOME MEASURES: Coma Recovery Scale-Revised, Modified Ashworth Scale, and discharge disposition. RESULTS: Program admission medical acuity included dysautonomia (15%), airway modifications (79%), infections (eg, pneumonia, 16%; urinary tract infection, 14%; blood, 11%), deep vein thrombosis (17%), pressure ulcers (14%), and marked hypertonia (30% in each limb). There were 168 program interruptions (ie, 139 surgeries, 29 nonsurgical intensive care unit transfers). Mean length of stay ± SD was 39.1 ± 29.4 days (range, 6-204d). Patients showed improved consciousness and respiratory function and reduced presence or severity of pressure ulcers and upper extremity hypertonia. At discharge, 54% showed sufficient emergence from a minimally conscious state to transition to mainstream inpatient rehabilitation, and 29% did not emerge but were discharged home to family with ongoing programmatic support; only 13% did not emerge and were institutionalized. CONCLUSIONS: Persons with DOC resulting primarily from a traumatic etiology who receive specialized early treatment that includes acute medical care and ≥90 minutes of daily rehabilitation are likely to show improved consciousness and body function; more than half may transition to mainstream inpatient rehabilitation. Families who receive comprehensive education and hands-on training with ongoing follow-up support may be twice as likely to provide care for medically stable persons with DOC in their homes versus nursing facility placement.

Ageing and traumatic brain injury: age, decline in function and level of assistance over the first 10 years post-injury.

OBJECTIVES: To understand the course of changes in function and need for assistance in the chronic stages of TBI; and to identify factors associated with these changes. DESIGN: Longitudinal review of participants in the TBI Model Systems Database, who have been prospectively followed for at least 10 years. PARTICIPANTS: Four hundred and seventy-eight individuals with TBI that occurred between 25 October 1988 and 31 December 1998, enrolled in the TBI Model Systems National Database, eligible for 10-year follow-up when data was extracted, with completed data collection at either year 1 or 2 and year 10. RESULTS: Significant between age group differences were found for FIM toileting, bladder, bowel, toilet transfers, locomotion, problem-solving and memory; SRS; DRS level of functioning, employability and total; and GOS. With regard to functional independence, there were significant differences by age category for all FIM components except memory. Significant differences were noted for age category and level of dependence as measured by the DRS (LOF 1.5-5) and GOS (GOS 2-4). Supervision needs significantly increased as a function of age. Significant differences were found for diminished function over time. Significant differences were noted for residence at 10 years post-injury. CONCLUSIONS: For those individuals that survive to 10 years post-TBI, age is a major factor in requiring assistance of another person for supervision as well as assistance in basic self-care, continence and mobility.

Pharmacotherapy to enhance arousal: what is known and what is not.

Severe brain injury results in a disturbance among a wide range of critical neurotransmitter systems. Each neurotransmitter system places its own functional role while being interconnected to a multitude of other systems and functions. This chapter seeks to review the major neurotransmitter systems involved after severe acquired brain injury. While limited in their construct, animal models of brain injury have demonstrated agents that may assist in the recovery process and those that may further slow recovery. We review further the issue of laboratory evidence and what is transferable to the clinic. Lastly, this chapter reviews published clinical pharmacotherapy studies or trials in the arena of arousal for those with clinical severe brain injury. We discuss limitations as well as findings and present the available evidence in a table-based format. While no clear evidence exists to suggest a defined and rigid pharmacotherapeutic approach, interesting data does suggest that several medications have been associated with enhanced arousal. Several studies are underway or about to begin that will shed more light on the utility of such agents in improving function after severe brain injury. For now, clinicians must employ their own judgment and what has been learned from the limited literature to the care of a challenging group of persons.

Falling in Parkinson disease: identifying and prioritizing risk factors in recurrent fallers.

OBJECTIVES: To identify falling risk factors in a study population of recurrent fallers compared with nonfallers who have Parkinson disease, and to prioritize falling risk factors in this patient population to target them for modification. DESIGN: Twenty-three recurrent fallers and 25 nonfallers who have Parkinson disease were recruited, and they participated in a comprehensive assessment probing for the presence of falling risk factors. To identify falling risk factors, a group comparative design was used to compare recurrent fallers and nonfallers across an array of variables. To prioritize those risk factors, modeling using recursive partitioning was performed, entering into the model falling, risk factors identified in this and other studies that were considered potentially modifiable. RESULTS: A specific profile of variables distinguished recurrent fallers who have Parkinson disease in our study population: higher disease severity, higher level of motor impairment, higher level of disability, impaired leg agility or lower-limb coordination, impaired ability to arise from a chair or compromised proximal lower-limb motor control, impaired ambulation, impaired motor planning of the hands and feet, impaired dynamic balance as measured by ability to walk in tandem, and fear of falling. Recursive partitioning prioritized three risk factors: impaired ambulation, impaired lower-limb motor planning, and orthostasis. CONCLUSIONS: In this study, an idiosyncratic falling risk factor profile was demonstrated among our subjects who have Parkinson disease. Three variables were prioritized for potential modification: impaired ambulation, impaired lower-limb motor planning, and orthostasis.