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    Insulin adsorption to catheter materials used for intensive insulin therapy in critically ill patients: Polyethylene versus polyurethane - possible cause of variation in glucose control?
    (Sharjah : Bentham Science Publishers B.V., 2014) Ley, S.C.; Ammann, J.; Herder, C.; Dickhaus, T.; Hartmann, M.; Kindgen-Milles, D.
    Introduction: Restoring and maintaining normoglycemia by intensified insulin therapy in critically ill patients is a matter of ongoing debate since the risk of hypoglycemia may outweigh positive effects on morbidity and mortality. In this context, adsorption of insulin to different catheter materials may contribute to instability of glucose control. We studied the adsorption of insulin to different tubing materials in vitro and the effects on glycemic control in vivo. Materials and Methods: In vitro experiments: A syringe pump was filled with 50 IU insulin diluted to 50 ml saline. A flow of 2 ml/h was perfused through polyethylene (PET) or polyurethane (PUR) tubing. Insulin concentrations were measured at the end of the tube for 24 hours using Bradford's protein assay. In vivo study: In a randomized double-blinded cross-over design, 10 intensive care patients received insulin via PET and PUR tubes for 24 hours each, targeting blood glucose levels of 80-150 mg/dl. We measured blood glucose levels, the insulin dose required to maintain target levels, and serum insulin and C-peptide levels. Results: In vitro experiments: After the start of the insulin infusion, only 20% (median, IQR 20-27) (PET) and 22% (IQR 16-27) (PUR) of the prepared insulin concentration were measured at the end of the 2 meter tubing. Using PET, after one hour infusion the concentration increased to 34% (IQR 29-36) and did not increase significantly during the next 24 hours (39% (IQR 39-40)). Using PUR, higher concentrations were detected than for PET at every measurement from 1 hour (82% (IQR 70-86)) to 24 hours (79% (IQR 64-87)). In vivo study: Glycemic control was effective and not different between groups. Significantly higher volumes of insulin solution had to be infused with PET compared to PUR (median PET 70.0 (IQR 56-82) ml vs. PUR 42 (IQR 31-63) ml; p=0.0015). Serum insulin concentrations did not decrease significantly one hour after changing to PET or PUR tubing. Conclusion: Polyurethane tubing systems allow application of insulin with significantly lower adsorption rates than polyethylene tubing systems. As a consequence, less insulin solution has to be infused to patients for effective blood glucose control. Tubing material of the insulin infusion may be crucial for safe and effective glycemic control in critically ill patients.
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    Towards dynamical network biomarkers in neuromodulation of episodic migraine
    (Berlin : De Gruyter, 2013) Dahlem, M.A.; Rode, S.; May, A.; Fujiwara, N.; Hirata, Y.; Aihara, K.; Kurths, J.
    Computational methods have complemented experimental and clinical neurosciences and led to improvements in our understanding of the nervous systems in health and disease. In parallel, neuromodulation in form of electric and magnetic stimulation is gaining increasing acceptance in chronic and intractable diseases. In this paper, we firstly explore the relevant state of the art in fusion of both developments towards translational computational neuroscience. Then, we propose a strategy to employ the new theoretical concept of dynamical network biomarkers (DNB) in episodic manifestations of chronic disorders. In particular, as a first example, we introduce the use of computational models in migraine and illustrate on the basis of this example the potential of DNB as early-warning signals for neuromodulation in episodic migraine.
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    Short term associations of ambient nitrogen dioxide with daily total, cardiovascular, and respiratory mortality: multilocation analysis in 398 cities
    (London : BMJ Publ. Group, 2021) Meng, Xia; Liu, Cong; Chen, Renjie; Sera, Francesco; Vicedo-Cabrera, Ana Maria; Milojevic, Ai; Guo, Yuming; Tong, Shilu; Coelho, Micheline de Sousa Zanotti Stagliorio; Saldiva, Paulo Hilario Nascimento; Lavigne, Eric; Correa, Patricia Matus; Ortega, Nicolas Valdes; Osorio, Samuel; Garcia, null; Kyselý, Jan; Urban, Aleš; Orru, Hans; Maasikmets, Marek; Jaakkola, Jouni J. K.; Ryti, Niilo; Huber, Veronika; Schneider, Alexandra; Katsouyanni, Klea; Analitis, Antonis; Hashizume, Masahiro; Honda, Yasushi; Ng, Chris Fook Sheng; Nunes, Baltazar; Teixeira, João Paulo; Holobaca, Iulian Horia; Fratianni, Simona; Kim, Ho; Tobias, Aurelio; Íñiguez, Carmen; Forsberg, Bertil; Åström, Christofer; Ragettli, Martina S.; Guo, Yue-Liang Leon; Pan, Shih-Chun; Li, Shanshan; Bell, Michelle L.; Zanobetti, Antonella; Schwartz, Joel; Wu, Tangchun; Gasparrini, Antonio; Kan, Haidong
    Objective To evaluate the short term associations between nitrogen dioxide (NO2) and total, cardiovascular, and respiratory mortality across multiple countries/regions worldwide, using a uniform analytical protocol. Design Two stage, time series approach, with overdispersed generalised linear models and multilevel meta-analysis. Setting 398 cities in 22 low to high income countries/regions. Main outcome measures Daily deaths from total (62.8 million), cardiovascular (19.7 million), and respiratory (5.5 million) causes between 1973 and 2018. Results On average, a 10 μg/m3 increase in NO2 concentration on lag 1 day (previous day) was associated with 0.46% (95% confidence interval 0.36% to 0.57%), 0.37% (0.22% to 0.51%), and 0.47% (0.21% to 0.72%) increases in total, cardiovascular, and respiratory mortality, respectively. These associations remained robust after adjusting for co-pollutants (particulate matter with aerodynamic diameter ≤10 μm or ≤2.5 μm (PM10 and PM2.5, respectively), ozone, sulfur dioxide, and carbon monoxide). The pooled concentration-response curves for all three causes were almost linear without discernible thresholds. The proportion of deaths attributable to NO2 concentration above the counterfactual zero level was 1.23% (95% confidence interval 0.96% to 1.51%) across the 398 cities. Conclusions This multilocation study provides key evidence on the independent and linear associations between short term exposure to NO2 and increased risk of total, cardiovascular, and respiratory mortality, suggesting that health benefits would be achieved by tightening the guidelines and regulatory limits of NO2.