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With 42,000 cases reported annually in the United States and an approximate 10% mortality rate, [1] pediatric septic shock is a major health problem that is often difficult to treat effectively. Several studies have shown that children experiencing pediatric septic shock often have critically low levels of serum zinc (Zn), suggesting supplementation of Zn to be an effective therapeutic strategy. However, to protect the safety and well-being of the patient, it is extremely important to monitor blood serum concentration of Zn during supplementation in order to ensure that levels remain at or near the physiological norm and thus minimize the risk of heavy metal toxicity from over supplementation. Current methods for quantifying Zn in serum typically require sending serum samples to external laboratory facilities resulting in turnaround times ranging from hours to a few days. Therefore, timely monitoring of Zn levels in serum is often not possible in the clinical setting which ultimately limits the ability to use Zn supplementation as a therapeutic intervention. This paper reports on the development of a Point-of-Care device for rapid electrochemical measurement of Zn in serum. The device is centered on a three electrode sensor which uses Anodic stripping voltammetry (ASV) for sensing Zn levels. The Cu based sensor is read using a reader that has been developed using commercially available embedded system parts in combination with custom analog circuitry that is able to produce quantification results in approximately 6 minutes.

To test the role of nucleotide-binding fold (NBF) 2 and its interaction with the regulatory (R) domain in the function of the cystic fibrosis transmembrane conductance regulator (CFTR) channel, we used three deletion mutants of CFTR: DeltaR(708-835), DeltaNBF2(1185-1349) and DeltaR-DeltaNBF2. In lipid bilayers, DeltaNBF2 channel activity is ATP- and cAMP-dependent protein kinase (PKA)-dependent, but unlike wild-type (wt) CFTR, it displays a reduced activity and insensitivity to 5'-adenylylimidodiphosphate (AMP-PNP). Both DeltaR and DeltaR-DeltaNBF2 channels are PKA-independent, but DeltaR activity is reduced whereas DeltaR-DeltaNBF2 activity is increased. Deletion of NBF2 from CFTR affects protein trafficking and channel gating kinetics. The data suggest that NBF2 could have inhibitory and stimulatory roles in CFTR activity by interaction with NBF1 directly or indirectly via the R domain.