Mutagenicity of acrylamide and glycidamide in human TP53 knock-in (Hupki) mouse embryo fibroblasts.

Acrylamide is a suspected human carcinogen formed during high-temperature cooking of starch-rich foods. It is metabolised by cytochrome P450 2E1 to its reactive metabolite glycidamide, which forms pre-mutagenic DNA adducts. Using the human TP53 knock-in (Hupki) mouse embryo fibroblasts (HUFs) immortalisation assay (HIMA), acrylamide- and glycidamide-induced mutagenesis was studied in the tumour suppressor gene TP53. Selected immortalised HUF clones were also subjected to next-generation sequencing to determine mutations across the whole genome. The TP53-mutant frequency after glycidamide exposure (1.1 mM for 24 h, n = 198) was 9% compared with 0% in cultures treated with acrylamide [1.5 (n = 24) or 3 mM (n = 6) for 48 h] and untreated vehicle (water) controls (n = 36). Most glycidamide-induced mutations occurred at adenines with A > T/T > A and A > G/T > C mutations being the most common types. Mutations induced by glycidamide occurred at specific TP53 codons that have also been found to be mutated in human tumours (i.e., breast, ovary, colorectal, and lung) previously associated with acrylamide exposure. The spectrum of TP53 mutations was further reflected by the mutations detected by whole-genome sequencing (WGS) and a distinct WGS mutational signature was found in HUF clones treated with glycidamide that was again characterised by A > G/T > C and A > T/T > A mutations. The WGS mutational signature showed similarities with COSMIC mutational signatures SBS3 and 25 previously found in human tumours (e.g., breast and ovary), while the adenine component was similar to COSMIC SBS4 found mostly in smokers' lung cancer. In contrast, in acrylamide-treated HUF clones, only culture-related background WGS mutational signatures were observed. In summary, the results of the present study suggest that glycidamide may be involved in the development of breast, ovarian, and lung cancer.

Sustaining and Expanding Telehealth: A Survey of Business Models from Selected Prominent U.S. Telehealth Centers.

INTRODUCTION: Telehealth centers across the country, including our own center, are addressing sustainability and best practice business models. We undertook this survey to explore the business models being used at other established telehealth centers. In the literature on telehealth and sustainability, there is a paucity of comparative studies as to how successful telehealth centers function. METHODS: In this study, we compared the business models of 10 successful telehealth centers. We conducted the study by interviewing key individuals at the centers, either through teleconference or telephone. RESULTS: We found that there are five general approaches to sustaining a telehealth center: grants, telehealth network membership fees, income from providing clinical services, per encounter charges, and operating as a cost center. We also found that most centers use more than one approach. CONCLUSION: We concluded that, although the first four approaches can contribute to the success of a center, telehealth centers are and should remain cost centers for their respective institutions.

Aldehyde dehydrogenase 3A1 protects airway epithelial cells from cigarette smoke-induced DNA damage and cytotoxicity.

Aldehyde dehydrogenase 3A1 (ALDH3A1), an ALDH superfamily member, catalyzes the oxidation of reactive aldehydes, highly toxic components of cigarette smoke (CS). Even so, the role of ALDH3A1 in CS-induced cytotoxicity and DNA damage has not been examined. Among all of the ALDH superfamily members, ALDH3A1 mRNA levels showed the greatest induction in response to CS extract (CSE) exposure of primary human bronchial epithelial cells (HBECs). ALDH3A1 protein accumulation was accompanied by increased ALDH enzymatic activity in CSE-exposed immortalized HBECs. The effects of overexpression or suppression of ALDH3A1 on CSE-induced cytotoxicity and DNA damage (γH2AX) were evaluated in cultured immortalized HBECs. Enforced expression of ALDH3A1 attenuated cytotoxicity and downregulated γH2AX. SiRNA-mediated suppression of ALDH3A1 blocked ALDH enzymatic activity and augmented cytotoxicity in CSE-exposed cells. Our results suggest that the availability of ALDH3A1 is important for cell survival against CSE in HBECs.

Center forTelehealth and Cybermedicine Research, University of New Mexico Health Sciences Center: a model of a telehealth program within an academic medical center.

An overview of the Center for Telehealth and Cybermedicine Research at the University of New Mexico Health Sciences Center was presented along with several other national and international programs as part of the of a symposium-workshop on telehealth, "Sustaining and Realizing the Promise of Telemedicine," held at the University of Michigan Health System in Ann Arbor, MI, May 18-19, 2012 and hosted by the University of Michigan Telemedicine Resource Center and its Director, Rashid Bashshur. This article describes our Center, its business plan, and a view to the future.