Polymeric rapid prototyping for inexpensive and portable medical diagnostics

Tianchi Ma, Victoria Northrup, Andrew O. Fung, D. Moira Glerum, Christopher J. Backhouse, "Polymeric rapid prototyping for inexpensive and portable medical diagnostics", Proc. SPIE 8412, Photonics North 2012, 84120B (24 October 2012); doi: 10.1117/12.2001470. Copyright 2012, Society of Photo Optical Instrumentation Engineers. One print or electronic copy may be made for personal use only. Systematic reproduction and distribution, duplication of any material in this paper for a fee or for commercial purposes, or modification of the content of the paper are prohibited. https://doi.org/10.1117/12.2001470The advent of inexpensive CO2 laser systems has led to a wide range of demonstrations of microfabricated lab on chip systems built of acrylic. However, there has been little application of these systems to building microfluidics for DNA analysis. In this work we explore the use of CO2 laser systems for building microfluidics for DNA analysis and relate the artifacts of the fabrication technology to the performance of the system. We show that surface roughness that leads to significant constrictions in the separation channel provides an upper limit of the size of DNA that can be analysed. Below that upper limit, the resolution of the chip is strongly affected by the degree to which the separation channel is exposed to redeposited by-products of the ablation process. We show that by controlling these effects we are reliably able to discern two types of PCR product as a test representative of a real application. By being able to do this is in microfluidic devices the size of a postage stamp we have shown that we can now use CO2 laser systems for the development of extremely inexpensive diagnostic systems using a rapid prototyping approach.Natural Sciences and Engineering Research Council of CanadaTeledyne-DALS

Racial Similarities in Response to Standardized Offer of Influenza Vaccination

Despite known benefits of influenza vaccination and coverage by Medicare Part B, elderly minority patients are less likely to receive influenza vaccination than whites. OBJECTIVES : To test whether a nonphysician-initiated standardized offer of influenza vaccination to all elderly primary care patients would result in similar proportions of African-American and white patients accepting vaccine. DESIGN : In 7 metropolitan Detroit primary care practices during the 2003 influenza vaccination season, medical assistants assessed influenza immunization status of all patients 65 years and older and collected limited demographic data. Eligible patients were offered vaccination. MEASUREMENTS : Proportion of patients accepting influenza vaccination by race and predictors of vaccine acceptance. RESULTS : Four hundred and fifty-four eligible patients with complete racial information were enrolled: 40% African American, 52% white, 8% other race/ethnicity. Similar proportions of African Americans and whites had already received the 2003 vaccine (11.6% and 11.0%, respectively) or stated vaccination as the reason for visit (23.8% and 30.5%, respectively). Among the remainder, there also were similar proportions who accepted vaccination: 68.9% white and 62.1% African-American patients. History of previous vaccination was the only statistically significant predictor of vaccine acceptance (odds ratio [OR] 8.64, 95% confidence interval [CI] 4.17, 17.91, P <.001). After adjusting for history of previous vaccination, age, gender, and education, the odds of vaccine acceptance were no different for whites and African Americans (OR 1.20, 95% CI 0.63, 2.29, P =.57). CONCLUSIONS : Vaccination acceptance differed little between African-American and white elderly patients. Using nonphysician personnel to identify and offer influenza vaccine to eligible patients is easily accomplished in primary care offices and has the potential to eliminate racial disparities in influenza vaccination.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/74908/1/j.1525-1497.2006.00401.x.pd

Rate of malignancy for thyroid nodules with AUS/FLUS cytopathology in a tertiary care center – a retrospective cohort study

Abstract Background Thyroid nodules are stratified through fine-needle aspiration (FNA) and are often categorized using The Bethesda System for Reporting Thyroid Cytopathology, which estimates the risk of malignancy for six cytopathological categories. The atypia of undetermined significance (AUS) and follicular lesion of undetermined significance (FLUS) categories have varying malignancy rates reported in the literature which can range from 6 to 72.9%. Due to this heterogeneity, we assessed the malignancy rate and effectiveness of repeat FNA (rFNA) for AUS/FLUS thyroid cytopathology at our institution. Methods Electronic health records of patients with AUS/FLUS thyroid cytopathology on FNA at our center since the implementation of the Bethesda System on May 1, 2014–December 31, 2019 were retrospectively reviewed. Patient demographics, treatment pathway, and pathology results were collected. The treatment pathway of the nodules, the rFNA results, and the malignant histopathology results were reported. Malignancy rates were calculated as an upper and lower limit estimate. Results This study described 182 AUS/FLUS thyroid nodules from 177 patients. In total, 24 thyroid nodules were deemed malignant upon histopathology, yielding a final malignancy rate of 13.2–25.3%. All of the malignancies were variants of papillary thyroid carcinoma. The malignancy rate of the nodules which underwent resection without rFNA (21.5%) was lower than the malignancy rate of the nodules which underwent resection after rFNA (43.8%). 45.5% of the rFNA results were re-classified into more definitive categories. Conclusion The malignancy rate of AUS/FLUS thyroid cytopathology at our center is in line with the risk of malignancy stated by the 2017 Bethesda System. However, our malignancy rate is lower than some other Canadian centers and approximately half of our rFNAs were re-classified, highlighting the importance of establishing center-specific malignancy and rFNA re-classification rates to guide treatment decisions

Genetic and Pharmacological Inhibition of PDK1 in Cancer Cells: CHARACTERIZATION OF A SELECTIVE ALLOSTERIC KINASE INHIBITOR

Phosphoinositide-dependent kinase 1 (PDK1) is a critical activator of multiple prosurvival and oncogenic protein kinases and has garnered considerable interest as an oncology drug target. Despite progress characterizing PDK1 as a therapeutic target, pharmacological support is lacking due to the prevalence of nonspecific inhibitors. Here, we benchmark literature and newly developed inhibitors and conduct parallel genetic and pharmacological queries into PDK1 function in cancer cells. Through kinase selectivity profiling and x-ray crystallographic studies, we identify an exquisitely selective PDK1 inhibitor (compound 7) that uniquely binds to the inactive kinase conformation (DFG-out). In contrast to compounds 1–5, which are classical ATP-competitive kinase inhibitors (DFG-in), compound 7 specifically inhibits cellular PDK1 T-loop phosphorylation (Ser-241), supporting its unique binding mode. Interfering with PDK1 activity has minimal antiproliferative effect on cells growing as plastic-attached monolayer cultures (i.e. standard tissue culture conditions) despite reduced phosphorylation of AKT, RSK, and S6RP. However, selective PDK1 inhibition impairs anchorage-independent growth, invasion, and cancer cell migration. Compound 7 inhibits colony formation in a subset of cancer cell lines (four of 10) and primary xenograft tumor lines (nine of 57). RNAi-mediated knockdown corroborates the PDK1 dependence in cell lines and identifies candidate biomarkers of drug response. In summary, our profiling studies define a uniquely selective and cell-potent PDK1 inhibitor, and the convergence of genetic and pharmacological phenotypes supports a role of PDK1 in tumorigenesis in the context of three-dimensional in vitro culture systems