Accuracy of handheld blood glucose meters at high altitude

Background

Due to increasing numbers of people with diabetes taking part in extreme sports (e.g., high-altitude trekking), reliable handheld blood glucose meters (BGMs) are necessary. Accurate blood glucose measurement under extreme conditions is paramount for safe recreation at altitude. Prior studies reported bias in blood glucose measurements using different BGMs at high altitude. We hypothesized that glucose-oxidase based BGMs are more influenced by the lower atmospheric oxygen pressure at altitude than glucose dehydrogenase based BGMs.

Methodology/Principal Findings

Glucose measurements at simulated altitude of nine BGMs (six glucose dehydrogenase and three glucose oxidase BGMs) were compared to glucose measurement on a similar BGM at sea level and to a laboratory glucose reference method. Venous blood samples of four different glucose levels were used. Moreover, two glucose oxidase and two glucose dehydrogenase based BGMs were evaluated at different altitudes on Mount Kilimanjaro. Accuracy criteria were set at a bias <15% from reference glucose (when >6.5 mmol/L) and <1 mmol/L from reference glucose (when <6.5 mmol/L). No significant difference was observed between measurements at simulated altitude and sea level for either glucose oxidase based BGMs or glucose dehydrogenase based BGMs as a group phenomenon. Two GDH based BGMs did not meet set performance criteria. Most BGMs are generally overestimating true glucose concentration at high altitude.

Conclusion

At simulated high altitude all tested BGMs, including glucose oxidase based BGMs, did not show influence of low atmospheric oxygen pressure. All BGMs, except for two GDH based BGMs, performed within predefined criteria. At true high altitude one GDH based BGM had best precision and accuracy.     

S-Aryltriazole acyclonucleosides: Synthesis and biological evaluation against hepatitis C virus

Novel S-aryltriazole acyclonucleosides were designed as structural analogs based on the previously identified antiviral aryltriazole acyclonucleosides in our laboratories. These S-aryltriazole nucleosides were synthesized in excellent yields via S_NAr-mediated S-arylation, followed by subsequent ammonolysis. X-ray structural analysis revealed special structural feature brought by the S-linkage, which may represent an unfavorable factor contributing to the lack of anti-HCV activity for this family of triazole nucleosides.     

A novel strategy for the comprehensive analysis of the biomolecular composition of isolated plasma membranes

We manufactured a novel type of lipid‐coated superparamagnetic nanoparticles that allow for a rapid isolation of plasma membranes (PMs), enabling high‐resolution proteomic, glycomic and lipidomic analyses of the cell surface. We used this technology to characterize the effects of presenilin knockout on the PM composition of mouse embryonic fibroblasts. We found that many proteins are selectively downregulated at the cell surface of presenilin knockout cells concomitant with lowered surface levels of cholesterol and certain sphingomyelin species, indicating defects in specific endosomal transport routes to and/or from the cell surface. Snapshots of N‐glycoproteomics and cell surface glycan profiling further underscored the power and versatility of this novel methodology. Since PM proteins provide many pathologically relevant biomarkers representing two‐thirds of the currently used drug targets, this novel technology has great potential for biomedical and pharmaceutical applications.     

Microbial metabolic exchange--the chemotype-to-phenotype link

The function of microbial interactions is to enable microorganisms to survive by establishing a homeostasis between microbial neighbors and local environments. A microorganism can respond to environmental stimuli using metabolic exchange-the transfer of molecular factors, including small molecules and proteins. Microbial interactions not only influence the survival of the microbes but also have roles in morphological and developmental processes of the organisms themselves and their neighbors. This, in turn, shapes the entire habitat of these organisms. Here we highlight our current understanding of metabolic exchange as well as the emergence of new technologies that are allowing us to eavesdrop on microbial conversations comprising dozens to hundreds of secreted metabolites that control the behavior, survival and differentiation of members of the community. The goal of the rapidly advancing field studying multifactorial metabolic exchange is to devise a microbial 'Rosetta stone' in order to understand the language by which microbial interactions are negotiated and, ultimately, to control the outcome of these conversations.     

Comparison of the sensitivity of culture, PCR and quantitative real-time PCR for the detection of Pseudomonas aeruginosa in sputum of cystic fibrosis patients

Background  

Pseudomonas aeruginosa is the major pathogen involved in the decline of lung function in cystic fibrosis (CF) patients. Early aggressive antibiotic therapy has been shown to be effective in preventing chronic colonization. Therefore, early detection is important and sensitive detection methods are warranted. In this study, we used a dilution series of P. aeruginosa positive sputa, diluted in a pool of P. aeruginosa negative sputa, all from CF patients - to mimick as closely as possible the sputa sent to routine laboratories - to compare the sensitivity of three culture techniques versus that of two conventional PCR formats and four real-time PCR formats, each targeting the P. aeruginosa oprL gene. In addition, we compared five DNA-extraction protocols.     

5-imidazolyl-quinolinones, -quinazolinones and -benzo-azepinones as farnesyltransferase inhibitors

The evaluation of structure-activity relationships associated with the modification of the R115777 quinolinone ring moiety displaying potent in vitro inhibiting activity is described.     

Global patterns of intraspecific leaf trait responses to elevation

Elevational gradients are often used to quantify how traits of plant species respond to abiotic and biotic environmental variations. Yet, such analyses are frequently restricted spatially and applied along single slopes or mountain ranges. Since we know little on the response of intraspecific leaf traits to elevation across the globe, we here perform a global meta‐analysis of leaf traits in 109 plant species located in 4 continents and reported in 71 studies published between 1983 and 2018. We quantified the intraspecific change in seven morpho‐ecophysiological leaf traits along global elevational gradients: specific leaf area (SLA), leaf mass per area (LMA), leaf area (LA), nitrogen concentration per unit of area (Narea), nitrogen concentration per unit mass (Nmass), phosphorous concentration per unit mass (Pmass) and carbon isotope composition (δ¹³C). We found LMA, Narea, Nmass and δ¹³C to significantly increase and SLA to decrease with increasing elevation. Conversely, LA and Pmass showed no significant pattern with elevation worldwide. We found significantly larger increase in Narea, Nmass, Pmass and δ¹³C with elevation in warmer regions. Larger responses to increasing elevation were apparent for SLA of herbaceous compared to woody species, but not for the other traits. Finally, we also detected evidences of covariation across morphological and physiological traits within the same elevational gradient. In sum, we demonstrate that there are common cross‐species patterns of intraspecific leaf trait variation across elevational gradients worldwide. Irrespective of whether such variation is genetically determined via local adaptation or attributed to phenotypic plasticity, the leaf trait patterns quantified here suggest that plant species are adapted to live on a range of temperature conditions. Since the distribution of mountain biota is predominantly shifting upslope in response to changes in environmental conditions, our results are important to further our understanding of how plants species of mountain ecosystems adapt to global environmental change.     

Effects of cigarette smoke condensate on proliferation and wound closure of bronchial epithelial cells in vitro: role of glutathione

Background

Increased airway epithelial proliferation is frequently observed in smokers. To elucidate the molecular mechanisms leading to these epithelial changes, we studied the effect of cigarette smoke condensate (CSC) on cell proliferation, wound closure and mitogen activated protein kinase (MAPK) activation. We also studied whether modulation of intracellular glutathione/thiol levels could attenuate CSC-induced cell proliferation.

Methods

Cells of the bronchial epithelial cell line NCI-H292 and subcultures of primary bronchial epithelial cells were used for the present study. The effect of CSC on epithelial proliferation was assessed using 5-bromo-2-deoxyuridine (BrdU) incorporation. Modulation of epithelial wound repair was studied by analysis of closure of 3 mm circular scrape wounds during 72 hours of culture. Wound closure was calculated from digital images obtained at 24 h intervals. Activation of mitogen-activated protein kinases was assessed by Western blotting using phospho-specific antibodies.

Results

At low concentrations CSC increased proliferation of NCI-H292 cells, whereas high concentrations were inhibitory as a result of cytotoxicity. Low concentrations of CSC also increased epithelial wound closure of both NCI-H292 and PBEC, whereas at high concentrations closure was inhibited. At low, mitogenic concentrations, CSC caused persistent activation of ERK1/2, a MAPK involved in cell proliferation. Inhibition of cell proliferation by high concentrations of CSC was associated with activation of the pro-apoptotic MAP kinases p38 and JNK. Modulation of intracellular glutathione (GSH)/thiol levels using N-acetyl-L-cysteine, GSH or buthionine sulphoximine (BSO), demonstrated that both the stimulatory and the inhibitory effects of CSC were regulated in part by intracellular GSH levels.

Conclusion

These results indicate that CSC may increase cell proliferation and wound closure dependent on the local concentration of cigarette smoke and the anti-oxidant status. These findings are consistent with increased epithelial proliferation in smokers, and may provide further insight in the development of lung cancer.