The experience of a severe hypoglycaemic event from the perspective of people with diabetes and their caregivers: "What am I going to do?"

AIMS: Among people with diabetes using insulin, severe hypoglycaemia (SH) can be a life-threatening complication, if untreated. The personal experiences during an SH event from the perspectives of people with diabetes and their caregivers are not well-characterized. This study assessed the perceptions of the event and the decision making processes of people with diabetes (T1D n = 36; T2D n = 24) and their caregivers during SH events. METHODS: In-depth one-on-one telephone interviews were conducted with dyads of people with diabetes and caregivers in the United States (n = 120). An initial synopsis and inductive codebook schema were used to analyse the data with two independent coders (kappa = 0.87-0.89). Themes were developed from the codes, and codes were re-mapped to the themes. RESULTS: Four themes were formed: (1) Caregivers scramble to do the right thing and support people with diabetes in treating SH; (2) Decision making capacity is impaired during an SH event, often a panicked time; (3) People learn to manage SH events through their own experiences and frequently make lifestyle changes to prevent and treat future events; and (4) Discussion with healthcare providers about SH, and particularly SH treatment, is limited. CONCLUSIONS: SH events are stressful and often evoke emotional reactions that can impair decision making. Thus, advance treatment planning of SH events needs to occur. Much of the knowledge about SH treatment derives from prior experience rather than healthcare provider guidance, suggesting a need for healthcare providers to initiate proactive discussions about SH treatment.

Characterization of fatty amides produced by lipase-catalyzed amidation of multi-hydroxylated fatty acids.

Novel multi-hydroxylated primary fatty amides produced by direct amidation of 7,10-dihydroxy-8(E)-octadecenoic acid and 7,10,12-trihydroxy-8(E)-octadecenoic acid were characterized by GC-MS and NMR. The amidation reactions were catalyzed by immobilized Pseudozyma (Candida) antarctica lipase B (Novozym 435) in organic solvent with ammonium carbamate. The mass spectra of the underivatized products exhibited characteristic primary amide peaks at m/z 59 and m/z 72 that differed in peak intensities. Other peaks present were consistent with cleavage next to the hydroxyl groups. The mass spectra of the silylated amidation products showed the correct molecular weight and the typical fragmentation pattern of silylated hydroxy compounds. The mass spectra, together with proton and 13C NMR data, suggest that the products of lipase-catalyzed direct amidation of 7,10-dihydroxy-8(E)-octadecenoic acid and 7,10,12-trihydroxy-8(E)-octadecenoic acid are, 7,10-dihydroxy-8(E)-octadecenamide and 7,10,12-trihydroxy-8(E)-octadecenamide acid, respectively. Amidation of multi-hydroxylated fatty acids had increased the melting point, but reduced the surface active property of the resulting primary amides.

Growth factor engineering by degenerate homoduplex gene family recombination.

There is great interest in engineering human growth factors as potential therapeutic agonists and antagonists. We approached this goal with a synthetic DNA recombination method. We aligned a pool of "top-strand" oligonucleotides incorporating polymorphisms from mammalian genes encoding epidermal growth factor (EGF) using multiple polymorphic "scaffold" oligonucleotides. Top strands were then linked by gap filling and ligation. This approach avoided heteroduplex annealing in the linkage of highly degenerate oligonucleotides and thus achieved completely random recombination. Cloned genes from a human-mouse chimeric library captured every possible permutation of the parental polymorphisms, creating an apparently complete recombined gene-family library, which has not been previously described. This library yielded a chimeric protein whose agonist activity was enhanced 123-fold. A second library from five mammalian EGF homologs possessed the highest reported recombination density (1 crossover per 12.4 bp). The five-homolog library yielded the strongest-binding hEGF variant yet reported. In addition, it contained strongly binding EGF variants with antagonist properties. Our less biased approach to DNA shuffling should be useful for the engineering of a wide variety of proteins.