Noninvasive and targeted interruption of the blood brain barrier for drug delivery using focused ultrasound in the treatment of CNS disorders

Despite the prevalence of CNS disorders, treatment options for CNS disorders fall woefully behind treatment options for other systemic disorders. This is due to the presence of the blood brain barrier (BBB) acting as an obstacle, preventing foreign substances from entering the brain. A newly developed and innovative biomedical procedure attempts to bypass the BBB in the delivery of therapeutics by using focused ultrasound (FUS) to disrupt and temporarily open the BBB. The use of FUS-facilitated BBB opening is able to target specific tissue for noninvasive, localized BBB penetration. As the technique is experimental and in it's nascent stage of development, there are only a few studies that investigate its abilities in delivering treatments directly to the brain. The studies involve delivery of large, hydrophilic molecules that traditionally would not be able to bypass the BBB and enter the brain, and analysis of CNS concentrations of the molecules after FUS treatment, as well as the therapeutic successes. Results of FUS the studies are promising and the results demonstrate that the procedure is able to significantly increase drug concentrations in the brain, increase survival rates in animal models, decrease tumor growth, and decrease tumor margins and volume. The potential and power of FUS should be further explored as the future of CNS disorder treatments

Nanoscale Texture and Microstructure in a NdFeAs(O,F)/IBAD-MgO Superconducting Thin Film with Superior Critical Current Properties

This paper reports the nanoscale texture and microstructure of a high-performance NdFeAs(O,F) superconducting thin film grown by molecular beam epitaxy on a textured MgO/Y2O3/Hastelloy substrate. The NdFeAs(O,F) film forms a highly textured columnar grain structure by epitaxial growth on the MgO template. Although the film contains stacking faults along the ab-plane as well as grain boundaries perpendicular to the ab-plane, good superconducting properties are measured: a critical temperature, T-c, of 46 K and a self-field critical current density, J(c), of 2 x 10(6) A/cm(2) at 4.2 K. Automated crystal orientation mapping by scanning precession electron diffraction in transmission electron microscope is employed to analyze the misorientation angles between adjacent grains in a large ensemble (247 grains), and 99% of the grain boundaries show in-plane misorientation angles (Delta gamma) less than the critical angle theta(c), which satisfies one of the necessary conditions for the high J(c). Comparing the columnar grain size distribution with the mean distance of the flux line lattice, the triple junctions of low-angle grain boundaries are found to be effective pinning centers, even at high temperatures (>= 35 K) and/or low magnetic fields

A Systematic Review of Reproductive Counseling in Cases of Parental Constitutional Reciprocal Translocation (9;22) Mimicking BCR-ABL1

We aim to determine the spectrum of cytogenetic abnormalities and outcomes in unbalanced offspring of asymptomatic constitutional balanced t(9;22) carriers through a systematic literature review. We also include a case of a constitutional balanced t(9;22) carrier from our institution. Among the 16 balanced t(9;22) carriers in our review, 13 were maternal and 3 were paternal. Of the 15 unbalanced translocation cases identified, 13 were live births, one was a missed abortion, and one resulted in pregnancy termination. The spectrum of established syndromes reported among the live births was the following: trisomy 9p syndrome (6/13), dual trisomy 9p and DiGeorge syndrome (3/13), dual 9q subtelomere deletion syndrome and DiGeorge syndrome (1/13), 9q subtelomere deletion syndrome (1/13), and DiGeorge syndrome (1/13). One unbalanced case did not have a reported syndrome. The phenotype of the unbalanced cases included cardiac abnormalities (5/13), neurological findings (7/13), intellectual disability (6/10), urogenital anomalies (3/13), respiratory or immune dysfunction (3/13), and facial or skeletal dysmorphias (13/13). Any constitutional balanced reciprocal t(9;22) carrier should be counseled regarding the increased risk of having a child with an unbalanced translocation, the spectrum of possible cytogenetic abnormalities, and predicted clinical phenotype for the unbalanced derivative

Study of the Fire Behavior of Multilayer Cables in a Mine Tunnel

Fires caused by cables occur frequently in mines, which endanger the safety of workers. To explore the characteristics of a multilayer cable fire in a mine tunnel, multilayer cable fire simulations were carried out using the Fire Dynamics Simulator (FDS). The influence of cable tray spacing, ignition position, and tunnel ventilation speed on the characteristics of the fire were studied. The results showed that these factors change the amount of contact between the cable and air, the heat accumulation, and the heat transfer by the flame interaction between the cables. It was also noted that increasing the spacing or wind speed both made the peak of heat release rate (PHRR) initially increase and then decrease. The influence of wind speed on the cable burnout rate in the upstream and downstream sides of the fire source was not consistent, and the wind speed had a sensitive effect on the cable burn out rate in the upstream side of the fire source. The higher the ignition position was, the longer the arrival time of PHRR was and the slower the fire developed. There was a higher burn velocity close to the ceiling. The cable hooks obstructed the cable fire. This study provides a theoretical basis for cable fire prevention and control in mine tunnels

Study of the Fire Behavior of Multilayer Cables in a Mine Tunnel

Fires caused by cables occur frequently in mines, which endanger the safety of workers. To explore the characteristics of a multilayer cable fire in a mine tunnel, multilayer cable fire simulations were carried out using the Fire Dynamics Simulator (FDS). The influence of cable tray spacing, ignition position, and tunnel ventilation speed on the characteristics of the fire were studied. The results showed that these factors change the amount of contact between the cable and air, the heat accumulation, and the heat transfer by the flame interaction between the cables. It was also noted that increasing the spacing or wind speed both made the peak of heat release rate (PHRR) initially increase and then decrease. The influence of wind speed on the cable burnout rate in the upstream and downstream sides of the fire source was not consistent, and the wind speed had a sensitive effect on the cable burn out rate in the upstream side of the fire source. The higher the ignition position was, the longer the arrival time of PHRR was and the slower the fire developed. There was a higher burn velocity close to the ceiling. The cable hooks obstructed the cable fire. This study provides a theoretical basis for cable fire prevention and control in mine tunnels

Impact of Inoculating with Indigenous <i>Bacillus marcorestinctum</i> YC-1 on Quality and Microbial Communities of Yibin Yacai (Fermented Mustard) during the Fermentation Process

Bacillus species play an important role in improving the quality of some fermented foods and are also one of the dominant bacteria in Yibin Yacai (fermented mustard). However, little is known about their effects on the quality of Yibin Yacai. Here, the effect of Bacillus marcorestinctum YC-1 on the quality and microbial communities of Yibin Yacai during the fermentation process was investigated. Results indicated that the inoculation of Bacillus marcorestinctum YC-1 promoted the growth of Weissella spp. and Lactobacillus spp. and inhibited the growth of pathogens, accelerating the synthesis of free amino acids and organic acids and the degradation of nitrite. Furthermore, inoculating Yibin Yacai with YC-1 could effectively enhance the synthesis of alcohols and terpenoids in yeasts, thus producing more linalool, terpinen-4-ol, and α-muurolen in Yibin Yacai, and endowing it with pleasant floral, fruity, woody, and spicy aromas. These findings reveal that the inoculation of B. marcorestinctum YC-1 can improve the quality and safety of Yibin Yacai by changing microbial communities as fermentation proceeds

Noninvasive and localized blood–brain barrier disruption using focused ultrasound can be achieved at short pulse lengths and low pulse repetition frequencies

Ultrasound methods in conjunction with microbubbles have been used for brain drug delivery, treatment of stroke, and imaging of cerebral blood flow. Despite advances in these areas, questions remain regarding the range of ultrasound parameters that disrupt the blood–brain barrier (BBB). In this study, several conditions were investigated to either enhance or reduce the likelihood of BBB disruption. Pulsed focused ultrasound (frequency: 1.5 MHz, pressure: 0.46 MPa, pulse repetition frequency (PRF): 0.1 to 25 Hz, pulse length (PL): 0.03 to 30 milliseconds) was noninvasively and locally administered to a predetermined region in the left hemisphere in the presence of circulating preformed microbubbles (Definity, Lantheus Medical Imaging, N. Billerica, MA, USA; 0.01, 0.05, 0.25 μL/g). Trans-BBB delivery of 3-kDa dextran was observed at PRFs as low as 1 Hz, whereas consistent delivery was observed at 5 Hz and above. Delivery was demonstrated at a PL as low as 33 microseconds. Although the delivered dextran concentration increased with the PL, this also increased the heterogeneity of the resulting distribution. In conclusion, key parameters that disrupt the BBB were identified out of a wide range of conditions. Reducing the total number of emitted acoustic cycles by shortening the PL, or decreasing the PRF, was also found to facilitate a more spatially uniform distribution of delivered dextran

Study on Flame Spread Characteristics of Flame-Retardant Cables in Mine

Polymer combustion is an important factor in mine fires. Based on the actual environment in a mine tunnel, a cable combustion experiment platform was established to study the regularities of the cable fire spread speed and smoke temperature under different conditions, including various fire loads and ventilation speeds. The flame change and molten dripping behaviour during the fire spread process were also analyzed. The experimental results show that the flame-retardant cable can be ignited and continuously burnt at a certain wind speed, but the combustion can be restrained at high wind speed. The combustion speed of the flame-retardant cable is affected by the fire load and ventilation speed. The combustion droplets can change the shape of the flame, which can consequently ignite other combustible materials. The analysis of the experimental results provides an important basis for the prevention of tunnel fires