Positive predictive values of selected hospital discharge diagnoses to identify infections responsible for hospitalization in the French national hospital database.

PURPOSE: The identification of infections in electronic health databases is a key issue for pharmacoepidemiology research. The aim of this study was to assess the positive predictive values (PPVs) of hospitalizations for infection in the Système National d'Information Inter-régimes de l'Assurance Maladie, that is the electronic database recording in-and-out hospital data for the entire French population (66 million inhabitants). METHODS: The source of data was the database of hospitalizations (Programme de Médicalisation des Systèmes d'Informations) of Toulouse University hospital, South of France (2880 beds). Among all hospital stays between September and December 2014, we randomly selected 100 stays with an International Classification of Diseases, 10th revision code of infection as primary diagnosis and 100 as related diagnosis. Medical charts were reviewed to assess the PPV of infection codes, as well as the PPV of correct coding of infection type among the true positive cases. RESULTS: The PPVs of codes of infection as reason for hospitalization were 0.97, 95% confidence interval (CI) [0.93-1.00] for primary diagnosis codes and 0.70, 95% CI [0.61-0.71] for related diagnosis codes. Among the true positive cases, the PPVs of correct coding of the type of infection were, respectively, 0.98, 95% CI [0.95-1.00] and 0.93, 95% CI [0.88-0.98]. CONCLUSIONS: Hospitalizations for infection codes have very good PPVs in the Programme de Médicalisation des Systèmes d'Informations. Copyright © 2016 John Wiley & Sons, Ltd.

New exploration of the γ-gliadin structure through its partial hydrolysis.

The partial enzymatic hydrolysis of wheat gliadins constitutes an interesting tool to unravel their structural specificity. In this work, the structure and conformation of γ-gliadin were investigated through its limited chymotrypsic digestion. Using a combination of computational, biochemical and biophysical tools, we studied each of its N and C terminal domains. Our results reveal that γ-gliadin is a partially disordered protein with an unfolded N-terminal domain surprisingly resistant to chymotrypsin and a folded C-terminal domain. Using spectroscopic tools, we showed that structural transitions occured over the disordered N-terminal domain for decreasing ethanol/water ratios. Using SAXS measurements, low-resolution 3D structures of γ-gliadin were proposed. To relate the repeated motifs of the N-terminal domain of γ-gliadin to its structure, engineered peptide models PQQPY/F were also studied. Overall results demonstrated similarities between the N-terminal domain and its derived model peptides. Our findings support the use of these peptides as general templates for understanding the wheat protein assembly and dynamics.

Role of protein conformation and weak interactions on γ-gliadin liquid-liquid phase separation.

Wheat storage proteins, gliadins, were found to form in vitro condensates in 55% ethanol/water mixture by decreasing temperature. The possible role of this liquid-liquid phase separation (LLPS) process on the in vivo gliadins storage is elusive and remains to be explored. Here we use γ-gliadin as a model of wheat proteins to probe gliadins behavior in conditions near physiological conditions. Bioinformatic analyses suggest that γ-gliadin is a hybrid protein with N-terminal domain predicted to be disordered and C-terminal domain predicted to be ordered. Spectroscopic data highlight the disordered nature of γ-gliadin. We developed an in vitro approach consisting to first solubilize γ-gliadin in 55% ethanol (v/v) and to progressively decrease ethanol ratio in favor of increased aqueous solution. Our results show the ability of γ-gliadin to self-assemble into dynamic droplets through LLPS, with saturation concentrations ranging from 25.9 µM ± 0.85 µM (35% ethanol (v/v)) to 3.8 µM ± 0.1 µM (0% ethanol (v/v)). We demonstrate the importance of the predicted ordered C-terminal domain of γ-gliadin in the LLPS by highlighting the protein condensates transition from a liquid to a solid state under reducing conditions. We demonstrate by increasing ionic strength the role displayed by electrostatic interactions in the phase separation. We also show the importance of hydrogen bonds in this process. Finally, we discuss the importance of gliadins condensates in their accumulation and storage in the wheat seed.