Combined use of microbubbles of various sizes and single-transducer dual-frequency ultrasound for safe and efficient inner ear drug delivery.

We have previously applied ultrasound (US) with microbubbles (MBs) to enhance inner ear drug delivery, with most experiments conducted using single-frequency, high-power density US, and multiple treatments. In the present study, the treatment efficacy was enhanced and safety concerns were addressed using a combination of low-power-density, single-transducer, dual-frequency US (I SPTA = 213 mW/cm2) and MBs of different sizes coated with insulin-like growth factor 1 (IGF-1). This study is the first to investigate the drug-coating capacity of human serum albumin (HSA) MBs of different particle sizes and their drug delivery efficiency. The concentration of HSA was adjusted to produce different MB sizes. The drug-coating efficiency was significantly higher for large-sized MBs than for smaller MBs. In vitro Franz diffusion experiments showed that the combination of dual-frequency US and large MB size delivered the most IGF-1 (24.3 ± 0.47 ng/cm2) to the receptor side at the second hour of treatment. In an in vivo guinea pig experiment, the efficiency of IGF-1 delivery into the inner ear was 15.9 times greater in animals treated with the combination of dual-frequency US and large MBs (D-USMB) than in control animals treated with round window soaking (RWS). The IGF-1 delivery efficiency was 10.15 times greater with the combination of single-frequency US and large size MBs (S-USMB) than with RWS. Confocal microscopy of the cochlea showed a stronger distribution of IGF-1 in the basal turn in the D-USMB and S-USMB groups than in the RWS group. In the second and third turns, the D-USMB group showed the greatest IGF-1 distribution. Hearing assessments revealed no significant differences among the D-USMB, S-USMB, and RWS groups. In conclusion, the combination of single-transducer dual-frequency US and suitably sized MBs can significantly reduce US power density while enhancing the delivery of large molecular weight drugs, such as IGF-1, to the inner ear.

Caffeine Suppresses Apoptosis of Bladder Cancer RT4 Cells in Response to Ionizing Radiation by Inhibiting Ataxia Telangiectasia Mutated-Chk2-p53 Axis.

BACKGROUND: Caffeine suppresses ataxia telangiectasia and Rad3 related and ataxia telangiectasia mutated (ATM) activities; ATM is the major kinase for DNA damage detection. This study aimed to investigate the effects of caffeine on DNA damage responses in cells from the bladder cancer cell line RT4 those were exposed to ionizing radiation (IR). METHODS: Immunofluorescent staining was performed to investigate changes in the proteins involved in DNA damage responses with or without caffeine. A mouse xenograft model was used to study the effects of caffeine on the DNA damage responses. Western blotting was used to investigate the effects of caffeine pretreatment on the ATM-Chk2-p53-Puma axis, while real-time polymerase chain reaction (RT-PCR) assessed changes in messenger RNA levels of p53 and downstream targets responding to IR. Finally, terminal deoxynucleotidyl transferase-dUTP nick end labeling assay. Western blotting and colony formation assay were used to measure the effects of caffeine on radiation-related apoptosis. All of the data were analyzed with a two-tailed Student's t-test. RESULTS: Immunofluorescent staining showed that caffeine pretreatment profoundly suppressed the formation of γH2AXand p53-binding protein 1 foci in RT4 cells in response to irradiation. Cellular and animal experiments suggested that this suppression was mediated by suppression of the ATM-Chk2-p53-Puma DNA damage-signaling axis. RT-PCR indicated caffeine also attenuated transactivation of p53 and p53-inducible genes. The colony formation assay revealed that caffeine displayed radioprotective effects on RT4 cells in response to low-dose radiation compared to the radiosensitization effects on T24 cells. CONCLUSION: Caffeine may inhibit IR-related apoptosis of bladder cancer RT4 cells by suppressing activation of the ATM-Chk2-p53-Puma axis.

Pod shattering resistance associated with domestication is mediated by a NAC gene in soybean.

Loss of seed dispersal is a key agronomical trait targeted by ancient human selection and has been regarded as a milestone of crop domestication. In this study, in the legume crop soybean Glycine max (L.) Merr. which provides vegetable oils and proteins for humans, we show that the key cellular feature of the shattering-resistant trait lies in the excessively lignified fibre cap cells (FCC) with the abscission layer unchanged in the pod ventral suture. We demonstrate that a NAC (NAM, ATAF1/2 and CUC2) gene shattering1-5 (SHAT1-5) functionally activates secondary wall biosynthesis and promotes the significant thickening of FCC secondary walls by expression at 15-fold the level of the wild allele, which is attributed to functional disruption of the upstream repressor. We show that strong artificial selection of SHAT1-5 has caused a severe selective sweep across ~ 116 kb on chromosome 16. This locus and regulation mechanism could be applicable to legume crop improvement.

A new method to guard inpatient medication safety by the implementation of RFID.

Since life is invaluable, the patient safety is always an important issue. How to reduce the malpractices and advance the patient safety is the primary goal of many countries. The current problem is that the hospitals cannot quickly and precisely identify the name of medicine, the position of patient and staff and the servicing time and dosage taken by patients. The application of Radio Frequency Identification (RFID) is rocketing in popularity as varieties of expanded uses. However, due to the investment consideration, there are few cases that practically implement such a technology in healthcare industries. This paper presents a Wisely Aware RFID Dosage (WARD) system, which based on an integration of barcodes and RFID tags, to demonstrate effective and safe patient care environment, for preventing the risk of medication error. Finally, through an evaluation of users' satisfaction, a reliability of 0.92 and a criterion-related validity of 0.82 show that this system is able to effectively construct the patient-safety-centric environment.

Electrical twitch-obtaining intramuscular stimulation in lower back pain: a pilot study.

OBJECTIVES: To determine if electrical twitch-obtaining intramuscular stimulation (ETOIMS) provides greater myofascial lower back pain relief than muscle stimulation or skin stimulation. DESIGN: In this single-blinded, crossover, pilot trial performed at a university-affiliated outpatient rehabilitation medicine department in Taiwan, 12 acupuncture-naive patients with lower back pain of 3-60 mos duration received one crossover treatment every 2 wks by monopolar needle electrode insertion at bilateral T10-S1 levels to: (1) paraspinal muscles, (2) overlying skin, and (3) paraspinal muscles with ETOIMS applied via the needle electrode at individual treatment sites. A total of 30 manual insertions per side per treatment were performed, with withdrawal after 2 secs. Beginning 1 wk before each trial and continuing until 2 wks after, patients completed a visual analog scale twice daily. In addition, on the day of treatment, patients received a physical examination and completed a visual analog scale both before and after treatment. RESULTS: Significant and immediate reduction in the visual analog scale levels was noted only with ETOIMS. Immediate improvement occurred in one of nine physical tests with muscle stimulation and ETOIMS only. In the 2 wks after treatment, absolute visual analog scale levels for ETOIMS were significantly lower than muscle stimulation and skin stimulation. ETOIMS resulted in a greater percentage of pain relief in the first week after treatment, although it was not statistically significant from muscle stimulation and skin stimulation. CONCLUSIONS: ETOIMS provided significantly greater immediate and sustained myofascial lower back pain relief than muscle stimulation and skin stimulation. Although a greater percentage of pain reduction occurred with ETOIMS, it was not statistically significant.