Steerable Microinvasive Probes for Localized Drug Delivery to Deep Tissue

Enhanced understanding of neuropathologies has created a need for more advanced tools. Current neural implants result in extensive glial scarring and are not able to highly localize drug delivery due to their size. Smaller implants reduce surgical trauma and improve spatial resolution, but such a reduction requires improvements in device design to enable accurate and chronic implantation in subcortical structures. Flexible needle steering techniques offer improved control over implant placement, but often require complex closed‐loop control for accurate implantation. This study reports the development of steerable microinvasive neural implants (S‐MINIs) constructed from borosilicate capillaries (OD = 60 µm, ID = 20 µm) that do not require closed‐loop guidance or guide tubes. S‐MINIs reduce glial scarring 3.5‐fold compared to prior implants. Bevel steered needles are utilized for open‐loop targeting of deep‐brain structures. This study demonstrates a sinusoidal relationship between implant bevel angle and the trajectory radius of curvature both in vitro and ex vivo. This relationship allows for bevel‐tipped capillaries to be steered to a target with an average error of 0.23 mm ± 0.19 without closed‐loop control. Polished microcapillaries present a new microinvasive tool for chronic, predictable targeting of pathophysiological structures without the need for closed‐loop feedback and complex imaging.     

Neonatal hind-paw injury disrupts acquisition of an instrumental response in adult spinal rats.

The present study was designed to evaluate the impact of neonatal injury on adult spinal plasticity in rats. Subjects were randomly assigned to 1 of 4 experimental conditions: (a) hind-paw injury at Postnatal Day (PD) 2, (b) hind-paw injury at PD 5, (c) anesthesia exposure only on PD 2, or (d) anesthesia exposure only on PD 5. Subjects receiving a unilateral neonatal hind-paw injury showed decreased mechanical threshold (hyperalgesia) on the previously injured hind paw throughout development. This decrease in threshold survived spinal transection (at T2) at 12 weeks of age. Injured subjects also showed significant impairment in a spinal instrumental learning task performed by the previously injured hind paw. This disruption of learning indicates a disruption of spinal plasticity that may be due to induction of long-term changes in nociceptive processing within the spinal cord. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Anoxic Versus Traumatic Brain Injury: Amount of Tissue Loss, Not Etiology, Alters Cognitive and Emotional Function.

Research in neuropsychology suggests that the etiology of a neurologic injury determines the neuropathological and neuropsychological changes. This study compared neuropsychological outcome in subjects who had traumatic brain injury (TBI) with subjects who had anoxic brain injury (ABI), who were matched for age, gender, and ventricle-to-brain ratio. There were no group differences for morphologic or neuropsychological measures. Both groups exhibited impaired memory, attention, and executive function, as well as slowed mental processing speed. Intelligence correlated with whole brain volume, and measures of memory correlated with hippocampal atrophy. There was no unique contribution of hippocampal atrophy on neuropsychological outcome between the groups. In the absence of localized lesions, the amount of neural tissue loss, rather than etiology, may be the critical factor in neuropsychological outcome. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Mortality from ship emissions: a global assessment

Epidemiological studies consistently link ambient concentrations of particulate matter (PM) to negative health impacts, including asthma, heart attacks, hospital admissions, and premature mortality. We model ambient PM concentrations from oceangoing ships using two geospatial emissions inventories and two global aerosol models. We estimate global and regional mortalities by applying ambient PM increases due to ships to cardiopulmonary and lung cancer concentration-risk functions and population models. Our results indicate that shipping-related PM emissions are responsible for approximately 60,000 cardiopulmonary and lung cancer deaths annually, with most deaths occurring near coastlines in Europe, East Asia, and South Asia. Under current regulation and with the expected growth in shipping activity, we estimate that annual mortalities could increase by 40% by 2012.     

Extrusion of highly filled flexible polymer sheet

Highly-filled polymer systems include color masterbatches, feedstocks for powder injection molding, and rigid sheets with high levels of flame retardants, but they have not been explored for flexible sheet. This work investigated the (a) selecting a polymer matrix with enough melt strength and flexibility to form a stable sheet with high filler loading, (b) the maximum achievable filler loading for the sheet, and (c) optimizing the process of extruding a highly-filled flexible polymer system. Extrusion grade low-density polyethylene (LDPE) provided sufficient flexibility and permitted a maximum filler loading of 36 vol% (~78 wt%). Good dispersion of the nanoparticle filler, however, required two passes through multiple screw extruders and a small reduction in the viscosity of the LDPE. Sheet with thickness of 415 μm, surface roughness of <1 μm, and sufficient flexibility was extruded continuously at a rate of 10 m/min., but it required a more traditional coat hanger manifold to prevent filler hang up in the sheet die. The filler particles were distributed uniformly through the core and skin of the sheet, giving the sheet good mechanical properties.     

An in situ intercalative polymerization method for preparing UV curable clay–polymer nanocomposites

A novel in situ intercalative polymerization technique was used to disperse clay mineral in a precursor resin for use in UV curing by performing an in situ ion exchange reaction during polyesterification. Unmodified montmorillonite (MMT) was added to a reaction mixture composed of monomers and methyl, tallow, bis‐2‐hydroxyethyl ammonium (MTEtOH) during the synthesis of unsaturated polyesters to create resins containing highly dispersed, organically modified MMT. UV‐curable clay–polymer nanocomposite (CPN) films were then prepared utilizing donor–acceptor chemistry through reactions of the unsaturated polyester resin with triethylene glycol divinyl ether. Functional group conversion improved up to 15% by the incorporation of clay mineral into the polymer matrix through the in situ polymerization method. The CPNs also had improved barrier, mechanical, and thermal properties over a control film containing no clay mineral. © 2015 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2015 , 132, 42601.     

2-Aminobenzothiazoles Inhibit Virulence Gene Expression and Block Polymyxin Resistance in Salmonella enterica

One promising strategy to combat antibiotic-resistant bacteria is to develop compounds that block bacterial defenses against antibacterial conditions produced by the innate immune system. Salmonella enterica, which causes food-borne gastroenteritis and typhoid fever, requires histidine kinases (HKs) to resist innate immune defenses such as cationic antimicrobial peptides (CAMPs). Herein, we report that 2-aminobenzothiazoles block histidine kinase-dependent phenotypes in Salmonella enterica serotype Typhimurium. We found that 2-aminobenzothiazoles inhibited growth under low Mg²⁺, a stressful condition that requires histidine kinase-mediated responses, and decreased expression of the virulence genes pagC and pagK. Furthermore, we discovered that 2-aminobenzothiazoles weaken Salmonella’s resistance to polymyxin B and polymyxin E, which are last-line antibiotics and models for host defense CAMPs. These findings raise the possibilities that 2-aminobenzothiazoles can block HK-mediated bacterial defenses and can be used in combination with polymyxins to treat infections caused by Salmonella.     

Organoiron Polyelectrolytes: Synthesis and Characterization of Cationic Cyclopentadienyliron Complexes of Polyarylether-Imines

The synthesis of an aromatic ether complex of cyclopentadienyliron containing two terminal aldehyde groups was achieved via metal-mediated nucleophilic aromatic substitution reactions. This dialdehyde monomer was subsequently reacted with a variety of aliphatic and aromatic diamines to produce the corresponding soluble cationic organoiron polyether-imines. These cationic organometallic polymers were characterized using IR, ¹H, and ¹³C NMR, viscosity and thermogravimetric analysis. Viscosity measurements showed that these polymers exhibited polyelectrolyte effects in DMSO solutions. Thermogravimetric analysis showed that decoordination of the iron moieties occurred at about 300°C for polymers with aliphatic spacers in their backbones, while the cyclopentadienyliron moieties were cleaved from the polymers with aromatic spacers in their backbones at about 200°C. Photolytic demetallation of the organoiron polymers resulted in the removal of the pendent cyclopentadienyliron moieties and allowed for the isolation of their organic analogs. While the organoiron polymers were soluble in polar organic solvents, the corresponding organic polymers exhibited very limited solubilities or were insoluble. The organic polymers had glass transition temperatures between 101 and 120°C     

A Water Cyclone to Preserve Insoluble Aerosols in Liquid Flow—An Interface to Flow Cytometry to Detect Airborne Nucleic Acid

A miniature cyclone was designed to gently capture fine aerosols into a continuous liquid flow. The geometry of the cyclone was designed so that the friction of the turning air swirls a 100 μl volume of water at the base of the cone, creating a standing liquid vortex which coats the inside deposition surface. The collection efficiency of the cyclone was characterized as a function of insoluble particle size, both in stand-alone operation and preceded by aerosol growth by water vapor condensation. The aerosol growth lowered the smallest collected particle size and created synonymous sample-into-substrate material conditions at the point of impact. The cyclone collection efficiencies were higher than 88% for the fluorescent polystyrene latex bead diameter sizes 50–3000 nm. The cyclone was further interfaced to a flow cytometer to detect airborne nucleic acid (as a virus test aerosol) in the cyclone sample flow. The flow cytometer, which is commonly used for single cell identification via fluorescence, was modified to accept a continuous sample flow (nominal 60 μl min^?1) from the cyclone for real-time detection. A rod-shaped plant virus (Tobamovirus) and a protein-enveloped insect virus (Baculovirus) were aerosolized, collected by the cyclone, and stained inline using the nucleic acid dyes SYBR Green I, SYTO-9, and SYTO-24 (Molecular Probes, Inc.). In addition, an Environmental Scanning Electron Microscope (ESEM) was used to confirm the collection of single virus particles and qualitatively evaluate the degree to which the aerosolization and collection process affected the integrity of the virus.