Comparative Accuracy of 17 Point-of-Care Glucose Meters.

BACKGROUND: The accuracy of point-of-care blood glucose (BG) meters is important for the detection of dysglycemia, calculation of insulin doses, and the calibration of continuous glucose monitors. The objective of this study was to compare the accuracy of commercially available glucose meters in a challenging laboratory study using samples with a wide range of reference BG and hemoglobin values. METHODS: Fresh, discarded blood samples from a hospital STAT laboratory were either used without modification, spiked with a glucose solution, or incubated at 37°C to produce 347 samples with an even distribution across reference BG levels from 20 to 440 mg/dl and hemoglobin values from 9 to 16 g/dl. We measured the BG of each sample with 17 different commercially available glucose meters and the reference method (YSI 2300) at the same time. We determined the mean absolute relative difference (MARD) for each glucose meter, overall and stratified by reference BG and by hemoglobin level. RESULTS: The accuracy of different meters widely, exhibiting a range of MARDs from 5.6% to 20.8%. Accuracy was lower in the hypoglycemic range, but was not consistently lower in samples with anemic blood hemoglobin levels. CONCLUSIONS: The accuracy of commercially available glucose meters varies widely. Although the sample mix in this study was much more challenging than those that would be collected under most use conditions, some meters were robust to these challenges and exhibited high accuracy in this setting. These data on relative accuracy and robustness to challenging samples may be useful in informing the choice of a glucose meter.

TANK-binding kinase 1 (TBK1) controls cell survival through PAI-2/serpinB2 and transglutaminase 2.

The decision between survival and death in cells exposed to TNF relies on a highly regulated equilibrium between proapoptotic and antiapoptotic factors. The TNF-activated antiapoptotic response depends on several transcription factors, including NF-κB and its RelA/p65 subunit, that are activated through phosphorylation-mediated degradation of IκB inhibitors, a process controlled by the IκB kinase complex. Genetic studies in mice have identified the IκB kinase-related kinase TANK-binding kinase 1 (TBK1; also called NAK or T2K) as an additional regulatory molecule that promotes survival downstream of TNF, but the mechanism through which TBK1 exerts its survival function has remained elusive. Here we show that TBK1 triggers an antiapoptotic response by controlling a specific RelA/p65 phosphorylation event. TBK1-induced RelA phosphorylation results in inducible expression of plasminogen activator inhibitor-2 (PAI-2), a member of the serpin family with known antiapoptotic activity. PAI-2 limits caspase-3 activation through stabilization of transglutaminase 2 (TG2), which cross-links and inactivates procaspase-3. Importantly, Tg2(-/-) mice were found to be more susceptible to apoptotic cell death in two models of TNF-dependent acute liver injury. Our results establish PAI-2 and TG2 as downstream mediators in the antiapoptotic response triggered upon TBK1 activation.

Helminth infection suppresses T-cell immune response to HIV-DNA-based vaccine in mice.

A number of HIV-1 vaccines are in various phases of clinical trials and many more are in the developmental pipeline. Vaccines are especially needed for developing countries where morbidity and mortality due to HIV/AIDS is most severe, the prevalence of HIV infection is highest, and its incidence is often still rising dramatically. Individuals living in these regions are often infected with one or more helminth parasites which systemically bias the immune system towards Th2-type as well as drive immune anergy. The goal of this study was to develop a multi-T-cell epitope DNA-based vaccine for HIV-1 subtype C and to determine the impact of helminth infection on the immune response to this vaccine. We found that vaccination of naïve mice with the multi-epitope vaccine, designated TD158, induced a strong HIV-1C-specific T-cell immune response, and that the addition of the Igkappa leader sequence to the TD158 vaccine construct significantly increased the frequencies of IFN-gamma secreting CD8+ T cells. However, the TD158 vaccine specific response of mice infected with the human helminth Schistosoma mansoni was significantly suppressed. The impact of schistosome infection on suppressing the virus-specific immune response was the same whether mice were vaccinated with the TD158 vaccine or with the Igkappa enhanced TD158. The results of this study suggest that helminth infection may pose a serious problem for vaccination with the DNA-based HIV-1 vaccine in developing country populations, and that the prevalence of helminth infections in the vaccine cohorts should be taken into account for HIV-1 vaccine trial design.