Local BDNF Delivery to the Injured Cervical Spinal Cord using an Engineered Hydrogel Enhances Diaphragmatic Respiratory Function.

We developed an innovative biomaterial-based approach to repair the critical neural circuitry that controls diaphragm activation by locally delivering brain-derived neurotrophic factor (BDNF) to injured cervical spinal cord. BDNF can be used to restore respiratory function via a number of potential repair mechanisms; however, widespread BDNF biodistribution resulting from delivery methods such as systemic injection or lumbar puncture can lead to inefficient drug delivery and adverse side effects. As a viable alternative, we developed a novel hydrogel-based system loaded with polysaccharide-BDNF particles self-assembled by electrostatic interactions that can be safely implanted in the intrathecal space for achieving local BDNF delivery with controlled dosing and duration. Implantation of BDNF hydrogel after C4/C5 contusion-type spinal cord injury (SCI) in female rats robustly preserved diaphragm function, as assessed b

Claudin-1 induced sealing of blood-brain barrier tight junctions ameliorates chronic experimental autoimmune encephalomyelitis

In experimental autoimmune encephalomyelitis (EAE), an animal model for multiple sclerosis (MS), loss of the blood-brain barrier (BBB) tight junction (TJ) protein claudin-3 correlates with immune cell infiltration into the CNS and BBB leakiness. Here we show that sealing BBB TJs by ectopic tetracycline-regulated expression of the TJ protein claudin-1 in Tie-2 tTA//TRE-claudin-1 double transgenic C57BL/6 mice had no influence on immune cell trafficking across the BBB during EAE and furthermore did not influence the onset and severity of the first clinical disease episode. However, expression of claudin-1 did significantly reduce BBB leakiness for both blood borne tracers and endogenous plasma proteins specifically around vessels expressing claudin-1. In addition, mice expressing claudin-1 exhibited a reduced disease burden during the chronic phase of EAE as compared to control littermates. Our study identifies BBB TJs as the critical structure regulating BBB permeability but not immune cell trafficking into CNS during EAE, and indicates BBB dysfunction is a potential key event contributing to disease burden in the chronic phase of EAE. Our observations suggest that stabilizing BBB barrier function by therapeutic targeting of TJs may be beneficial in treating MS, especially when anti-inflammatory treatments have faile

Developing a group intervention to manage fatigue in rheumatoid arthritis through modifying physical activity

© 2019 The Author(s). Background: Fatigue is a major symptom of rheumatoid arthritis (RA). There is some evidence that physical activity (PA) may be effective in reducing RA fatigue. However, few PA interventions have been designed to manage fatigue and there is limited evidence of end-user input into intervention development. The aim of this research was to co-design an intervention to support self-management of RA fatigue through modifying PA. Methods: A series of studies used mixed methodological approaches to co-design a fatigue management intervention focused on modifying PA based on UK Medical Research Council guidance, and informed by the Behaviour Change Wheel theoretical framework. Development was based on existing evidence, preferences of RA patients and rheumatology healthcare professionals, and practical issues regarding intervention format, content and implementation. Results: The resulting group-based intervention consists of seven sessions delivered by a physiotherapist over 12 weeks. Each session includes an education and discussion session followed by supervised PA chosen by the participant. The intervention is designed to support modification and maintenance of PA as a means of managing fatigue. This is underpinned by evidence-based behaviour change techniques that might support changes in PA behaviour. Intervention delivery is interactive and aims to enhance capability, opportunity and motivation for PA. Conclusion: This study outlines stages in the systematic development of a theory-based intervention designed through consultation with RA patients and healthcare professionals to reduce the impact of RA fatigue. The feasibility of future evaluation of the intervention should now be determined

Evaluation of Low-Gravity Smoke Particulate for Spacecraft Fire Detection

Tests were conducted on the International Space Station to evaluate the smoke particulate size from materials and conditions that are typical of those expected in spacecraft fires. Five different materials representative of those found in spacecraft (Teflon, Kapton, cotton, silicone rubber and Pyrell) were heated to temperatures below the ignition point with conditions controlled to provide repeatable sample surface temperatures and air flow. The air flow past the sample during the heating period ranged from quiescent to 8 cm/s. The effective transport time to the measurement instruments was varied from 11 to 800 seconds to simulate different smoke transport conditions in spacecraft. The resultant aerosol was evaluated by three instruments which measured different moments of the particle size distribution. These moment diagnostics were used to determine the particle number concentration (zeroth moment), the diameter concentration (first moment), and the mass concentration (third moment). These statistics were combined to determine the diameter of average mass and the count mean diameter and by assuming a log-normal distribution, the geometric mean diameter and the geometric standard deviations were also calculated. Smoke particle samples were collected on TEM grids using a thermal precipitator for post flight analysis. The TEM grids were analyzed to determine the particle morphology and shape parameters. The different materials produced particles with significantly different morphologies. Overall the majority of the average smoke particle sizes were found to be in the 200 to 400 nanometer range with the quiescent cases and the cases with increased transport time typically producing with substantially larger particles. The results varied between materials but the smoke particles produced in low gravity were typically twice the size of particles produced in normal gravity. These results can be used to establish design requirements for future spacecraft smoke detectors

Particle Morphology and Size Results from the Smoke Aerosol Measurement Experiment-2

Results are presented from the Reflight of the Smoke Aerosol Measurement Experiment (SAME-2) which was conducted during Expedition 24 (July-September 2010). The reflight experiment built upon the results of the original flight during Expedition 15 by adding diagnostic measurements and expanding the test matrix. Five different materials representative of those found in spacecraft (Teflon, Kapton, cotton, silicone rubber and Pyrell) were heated to temperatures below the ignition point with conditions controlled to provide repeatable sample surface temperatures and air flow. The air flow past the sample during the heating period ranged from quiescent to 8 cm/s. The smoke was initially collected in an aging chamber to simulate the transport time from the smoke source to the detector. This effective transport time was varied by holding the smoke in the aging chamber for times ranging from 11 to 1800 s. Smoke particle samples were collected on Transmission Electron Microscope (TEM) grids for post-flight analysis. The TEM grids were analyzed to observe the particle morphology and size parameters. The diagnostics included a prototype two-moment smoke detector and three different measures of moments of the particle size distribution. These moment diagnostics were used to determine the particle number concentration (zeroth moment), the diameter concentration (first moment), and the mass concentration (third moment). These statistics were combined to determine the diameter of average mass and the count mean diameter and, by assuming a log-normal distribution, the geometric mean diameter and the geometric standard deviations can also be calculated. Overall the majority of the average smoke particle sizes were found to be in the 200 nm to 400 nm range with the quiescent cases producing some cases with substantially larger particles

A novel acrylic resin palatal device contaminated with Candida albicans biofilm for denture stomatitis induction in Wistar rats

Denture stomatitis is the most frequent oral lesion in removable prosthesis wearers, with high recurrence rates and a complex treatment. Objective: This study describes a protocol to obtain and to contaminate a palatal device with Candida albicans biofilm that could be used for an animal model of denture stomatitis. Methodology: Acrylic resin devices (N=41) were obtained from impressions of the palates of Wistar rats with individual trays and polyether. The efficacy of microwave irradiation (MW), ultraviolet light (UV), or ultrasonic bath (US) was assessed by colony viability and spectrophotometric analyses (n=5) in order to select the most appropriate method for sterilizing the devices. Then, different devices (n=5) were contaminated with C. albicans and evaluated by CFU/mL determination, scanning electron microscopy, and laser confocal microscopy. Device stabilization was assessed with either autopolymerizing acrylic resins or a self-adhesive resin cement (n=2). The spectrophotometric data were analyzed by one-way ANOVA followed by the Tukey’s HSD post-hoc test (α=0.05). Results: MW was the only method capable of sterilizing the devices, and the contamination protocol developed a mature and viable C. albicans biofilm (~1.2 x 106 CFU/mL). The self-adhesive resin cement was the best stabilization material. Conclusions: This acrylic resin palatal device was designed to be similar to the clinical situation of contaminated prostheses, with easy manufacturing and handling, effective stabilization, and satisfactory contamination. Thus, the acrylic device can be a valuable tool in the development of denture stomatitis in rats

Claudin-1 induced sealing of blood-brain barrier tight junctions ameliorates chronic experimental autoimmune encephalomyelitis

In experimental autoimmune encephalomyelitis (EAE), an animal model for multiple sclerosis (MS), loss of the blood-brain barrier (BBB) tight junction (TJ) protein claudin-3 correlates with immune cell infiltration into the CNS and BBB leakiness. Here we show that sealing BBB TJs by ectopic tetracycline-regulated expression of the TJ protein claudin-1 in Tie-2 tTA//TRE-claudin-1 double transgenic C57BL/6 mice had no influence on immune cell trafficking across the BBB during EAE and furthermore did not influence the onset and severity of the first clinical disease episode. However, expression of claudin-1 did significantly reduce BBB leakiness for both blood borne tracers and endogenous plasma proteins specifically around vessels expressing claudin-1. In addition, mice expressing claudin-1 exhibited a reduced disease burden during the chronic phase of EAE as compared to control littermates. Our study identifies BBB TJs as the critical structure regulating BBB permeability but not immune cell trafficking into CNS during EAE, and indicates BBB dysfunction is a potential key event contributing to disease burden in the chronic phase of EAE. Our observations suggest that stabilizing BBB barrier function by therapeutic targeting of TJs may be beneficial in treating MS, especially when anti-inflammatory treatments have failed

The Second-Generation Guide Star Catalog: Description and Properties

The GSC-II is an all-sky database of objects derived from the uncompressed DSS that the STScI has created from the Palomar and UK Schmidt survey plates and made available to the community. Like its predecessor (GSC-I), the GSC-II was primarily created to provide guide star information and observation planning support for HST. This version, however, is already employed at some of the ground-based new-technology telescopes such as GEMINI, VLT, and TNG, and will also be used to provide support for the JWST and Gaia space missions as well as LAMOST, one of the major ongoing scientific projects in China. Two catalogs have already been extracted from the GSC-II database and released to the astronomical community. A magnitude-limited (R=18.0) version, GSC2.2, was distributed soon after its production in 2001, while the GSC2.3 release has been available for general access since 2007. The GSC2.3 catalog described in this paper contains astrometry, photometry, and classification for 945,592,683 objects down to the magnitude limit of the plates. Positions are tied to the ICRS; for stellar sources, the all-sky average absolute error per coordinate ranges from 0.2" to 0.28" depending on magnitude. When dealing with extended objects, astrometric errors are 20% worse in the case of galaxies and approximately a factor of 2 worse for blended images. Stellar photometry is determined to 0.13-0.22 mag as a function of magnitude and photographic passbands (B,R,I). Outside of the galactic plane, stellar classification is reliable to at least 90% confidence for magnitudes brighter than R=19.5, and the catalog is complete to R=20.Comment: 52 pages, 33 figures, to be published in AJ August 200