Inhibition of p300 increases cytotoxicity of cisplatin in pancreatic cancer cells.

Pancreatic cancer is a notoriously deadly disease with a five-year survival rate around 10 percent. Since early detection of these tumors is difficult, pancreatic cancers are often diagnosed at advanced stages. At this point, genotoxic chemotherapeutics can be used to manage tumor growth. However, side effects of these drugs are severe, limiting the amount of treatment that can be given and resulting in sub-optimal dosing. Thus, there is an urgent need to identify chemo-sensitizing agents that can lower the effective dose of genotoxic agents and as a result reduce the side effects. Here, we use transformed and non-transformed pancreatic cell lines to evaluate DNA repair inhibitors as chemo-sensitizing agents. We used a novel next generation sequencing approach to demonstrate that pancreatic cancer cells have a reduced ability to faithfully repair DNA damage. We then determine the extent that two DNA repair inhibitors (CCS1477, a small molecule inhibitor of p300, and ART558, a small molecule inhibitor of polymerase theta) can exploit this repair deficiency to make pancreatic cancer cells more sensitive to cisplatin, a commonly used genotoxic chemotherapeutic. Immunofluorescence microscopy and cell viability assays show that CCS1477 delayed repair and significantly sensitized pancreatic cancer cells to cisplatin. The increased toxicity was not seen in a non-transformed pancreatic cell line. We also found that while ART558 sensitizes pancreatic cancer cells to cisplatin, it also sensitized non-transformed pancreatic cancer cells.

Accessibility attributes of blood glucose meter and home blood pressure monitor displays for visually impaired persons.

The vast majority of diabetes-related self-management technology utilizes small visual displays (SVDs) that often produce a low level of contrast and suffer from high levels of reflection (glare). This is a major accessibility issue for the 3.5 million Americans with diabetes who have reduced vision. The purpose of this article is to gather comparative data on the key display attributes of the SVDs used in blood glucose meters (BGMs) and home blood pressure monitors (HBPMs) on the market today and determine which displays offer the best prospect for being accessible to people with reduced vision. Nine BGMs and eight HBPMs were identified for this study on the basis of amount of devices sold, fullfunctionality speech output, and advanced display technologies. An optical instrumentation system obtained contrast, reflection (glare), and font height measurements for all 17 displays. The contrast, reflection, and font-height values for the BGMs and HBPMs varied greatly between models. The Michelson contrast values for the BGMs ranged from 11% to 98% and font heights ranged 0.39-1.00 in. for the measurement results. The HBPMs had Michelson contrast values ranging 55-96% and font height ranging 0.28-0.94 in. for the measurement results. Due largely to the lack of display design standards for the technical requirements of SVDs, there is tremendous variability in the quality and readability of BGM and HBPM displays. There were two BGMs and one HBPM that exhibited high-contrast values and large font heights, but most of the devices exhibited either poor contrast or exceptionally high reflection.

Analysis: including visually impaired participants in validation design studies of diabetes technology.

In an article in this issue of Journal of Diabetes Science and Technology, Sherwyn Schwartz, M.D., presents a study to validate the design of the ClikSTAR® insulin pen from sanofi-aventis and demonstrates that the device can be used correctly by participants with diabetes. Concern with this article lies with the selection of participants, which was meant to reflect the intended audience for the insulin pen device but does not address the inclusion of visually impaired individuals, who comprise over 20% of the adult diabetes population. Visually impaired individuals need to be included as part of the intended audience for insulin administration technology, and manufacturers of these devices need to design their products for safe use by all people, including those who are visually impaired. The study demonstrated successful use of the ClikSTAR insulin pen in a population that did not include subjects with severe visual impairment. We believe that future validation studies for insulin administration technology should also include samples of visually impaired users and that visually impaired patients will embrace the use of insulin pens designed with their needs in mind.

Are current insulin pumps accessible to blind and visually impaired people?

BACKGROUND: In 2004, Uslan and colleagues determined that insulin pumps (IPs) on the market were largely inaccessible to blind and visually impaired persons. The objective of this study is to determine if accessibility status changed in the ensuing 4 years. METHODS: Five IPs on the market in 2008 were acquired and analyzed for key accessibility traits such as speech and other audio output, tactual nature of control buttons, and the quality of visual displays. It was also determined whether or not a blind or visually impaired person could independently complete tasks such as programming the IP for insulin delivery, replacing batteries, and reading manuals and other documentation. RESULTS: It was found that IPs have not improved in accessibility since 2004. None have speech output, and with the exception of the Animas IR 2020, no significantly improved visual display characteristics were found. Documentation is still not completely accessible. CONCLUSION: Insulin pumps are relatively complex devices, with serious health consequences resulting from improper use. For IPs to be used safely and independently by blind and visually impaired patients, they must include voice output to communicate all the information presented on their display screens. Enhancing display contrast and the size of the displayed information would also improve accessibility for visually impaired users. The IPs must also come with accessible user documentation in alternate formats.