The Impact of Vein Mechanical Compliance on Arteriovenous Fistula Outcomes

© 2016 Elsevier Inc. Background Arteriovenous fistulae (AVFs) are the preferred access for hemodialysis but suffer a high early failure rate. The aim of this study was to determine how venous distensibility, as measured in vitro, relates to early outcomes of AVF formed with the sampled vein. Methods Ethical approval was obtained for all aspects of this study. During AVF formation a circumferential segment of the target vein was sampled. Mechanical stress testing of the venous segments was undertaken using a dynamic mechanical analyzer, with progressive stress loading at 2 N/min to a maximum of 10 N or until sample disruption. Stress-strain curves were obtained for vein samples and Young's modulus (YM) calculated. Duplex assessment of the fistulae was undertaken at 30 days. Results Thirty patients consented to participate with 29 samples obtained for analysis. Statistical comparison of YM demonstrated no relationship with common cardiovascular risk factors or dialysis status. Subject age greater than 65 was the only patient factor which showed a significant difference in YM (P = 0.05). Furthermore, a negative correlation was confirmed between age and YM (Pearson's r = -0.465, P < 0.05). Nine of the 29 subjects suffered an early AVF failure. Mann-Whitney U testing for differences in distribution reported that YM was significantly higher in those fistulas which failed (P < 0.005). Conclusions Reduced venous compliance appears to result in higher failure rates of AVFs. With the advancement of clinical tools such as speckle tracing ultrasound identification of vessel compliance in vivo may produce valuable additional information for clinicians planning AVF surgery

Nascent nanocomputers: DNA self-assembly in O(1) stages

DNA self-assembly offers a potential for nanoscale microcircuits and computers. To make that potential possible requires the development of reliable and efficient tile assembly models. Efficiency is often achieved by minimizing tile complexity, as well as by evaluating the cost and reliability of the specific elements of each tile assembly model. We consider a 2D tile assembly model at temperature 1. The standard 2D tile assembly model at temperature 1 has a tile complexity of O(n) for the construction of exact, complete n x n squares. However, previous research found a staged tile assembly model achieved a tile complexity of O(1) to construct n x n squares, with O(logn) stages. Our staged tile assembly model achieves a tile complexity of O(logn) using only O(1) stages to construct n x n squares

Applying Lessons from the Opioid Abuse Epidemic to Protect Consumers from Gray Market Biologics

lmost 17,000 people die per year of overdoses involving prescription opioids, controlled substances prescribed to treat pain and addiction. As such, the Centers for Disease Control and Prevention (“CDC”) has deemed prescription drug abuse a national epidemic. In addition to opioids, several other classes of prescription medications have become prone to abuse, including stimulants and benzodiazepines. As many as twenty percent of college students have used stimulants at some point in their studies for nonmedical use, and the number of admissions to substance abuse treatment programs for benzodiazepine use nearly tripled between 1998 and 2008. And in 2011, benzodiazepines caused the most prescription drug overdose deaths in Georgia

A bulky glycocalyx fosters metastasis formation by promoting G1 cell cycle progression.

Metastasis depends upon cancer cell growth and survival within the metastatic niche. Tumors which remodel their glycocalyces, by overexpressing bulky glycoproteins like mucins, exhibit a higher predisposition to metastasize, but the role of mucins in oncogenesis remains poorly understood. Here we report that a bulky glycocalyx promotes the expansion of disseminated tumor cells in vivo by fostering integrin adhesion assembly to permit G1 cell cycle progression. We engineered tumor cells to display glycocalyces of various thicknesses by coating them with synthetic mucin-mimetic glycopolymers. Cells adorned with longer glycopolymers showed increased metastatic potential, enhanced cell cycle progression, and greater levels of integrin-FAK mechanosignaling and Akt signaling in a syngeneic mouse model of metastasis. These effects were mirrored by expression of the ectodomain of cancer-associated mucin MUC1. These findings functionally link mucinous proteins with tumor aggression, and offer a new view of the cancer glycocalyx as a major driver of disease progression