Intermediate Follow-up of Pediatric Patients With Hemolytic Uremic Syndrome During the 2011 Outbreak Caused by E. coli O104:H4.

BACKGROUND.: In 2011 Escherichia coli O104:H4 caused an outbreak with >800 cases of hemolytic uremic syndrome (HUS) in Germany, including 90 children. Data on the intermediate outcome in children after HUS due to E. coli O104:H4 have been lacking. METHODS.: Follow-up data were gathered retrospectively from the medical records of patients who had been included in the German Pediatric HUS Registry during the 2011 outbreak. RESULTS.: Seventy-two of the 89 (81%) patients were included after a median follow-up of 3.0 (0.9-4.7) years. Hypertension and proteinuria were present in 19% and 28% of these patients, respectively. Of 4 patients with chronic kidney disease (CKD) > stage 2 at short-term follow-up, 1 had a normalized estimated glomerular filtration rate, and 3 (4%) had persistent CKD > stage 2. In 1 of these patients, CKD improved from stage 4 to 3; 1 who had CKD stage 5 at presentation received kidney transplantation; and 1 patient required further hemodialysis during follow-up. One patient (1.4%) still had major neurological symptoms at the latest follow-up. Dialysis during the acute phase (P = .01), dialysis duration (P = .01), and the duration of oligo-/anuria (P = .005) were associated with the development of renal sequelae. Patients treated with eculizumab (n = 11) and/or plasmapheresis (n = 13) during the acute phase of HUS had comparable outcomes. CONCLUSIONS.: The overall outcome of pediatric patients after HUS due to E. coli O104:H4 was equivalent to previous reports on HUS due to other types of Shiga toxin-producing E. coli (STEC). Regular follow-up visits in patients are recommended after STEC-HUS.

Designed 2D protein crystals as dynamic molecular gatekeepers for a solid-state device.

The sensitivity and responsiveness of living cells to environmental changes are enabled by dynamic protein structures, inspiring efforts to construct artificial supramolecular protein assemblies. However, despite their sophisticated structures, designed protein assemblies have yet to be incorporated into macroscale devices for real-life applications. We report a 2D crystalline protein assembly of C98/E57/E66L-rhamnulose-1-phosphate aldolase (CEERhuA) that selectively blocks or passes molecular species when exposed to a chemical trigger. CEERhuA crystals are engineered via cobalt(II) coordination bonds to undergo a coherent conformational change from a closed state (pore dimensions <1 nm) to an ajar state (pore dimensions ~4 nm) when exposed to an HCN(g) trigger. When layered onto a mesoporous silicon (pSi) photonic crystal optical sensor configured to detect HCN(g), the 2D CEERhuA crystal layer effectively blocks interferents that would otherwise result in a false positive signal. The 2D CEERhuA crystal layer opens in selective response to low-ppm levels of HCN(g), allowing analyte penetration into the pSi sensor layer for detection. These findings illustrate that designed protein assemblies can function as dynamic components of solid-state devices in non-aqueous environments.

Remote Detection of HCN, HF, and Nerve Agent Vapors Based on Self-Referencing, Dye-Impregnated Porous Silicon Photonic Crystals.

A one-dimensional photonic crystal is prepared from porous silicon (pSi) and impregnated with a chemically specific colorimetric indicator dye to provide a self-referenced vapor sensor for the selective detection of hydrogen fluoride (HF), hydrogen cyanide (HCN), and the chemical nerve agent diisopropyl fluorophosphate (DFP). The photonic crystal is prepared with two stop bands: one that coincides with the optical absorbance of the relevant activated indicator dye and the other in a spectrally "clear" region, to provide a reference. The inner pore walls of the pSi sample are then modified with octadecylsilane to provide a hydrophobic interior, and the indicator dye of interest is then loaded into the mesoporous matrix. Remote analyte detection is achieved by measurement of the intensity ratio of the two stop bands in the white light reflectance spectrum, which provides a means to reliably detect colorimetric changes in the indicator dye. Indicator dyes were chosen for their specificity for the relevant agents: rhodamine-imidazole (RDI) for HF and DFP, and monocyanocobinamide (MCbi) for HCN. The ratiometric readout allows detection of HF and HCN at concentrations (14 and 5 ppm, respectively) that are below their respective IDLH (immediately dangerous to life and health) concentrations (30 ppm for HF; 50 ppm for HCN); detection of DFP at a concentration of 114 ppb is also demonstrated. The approach is insensitive to potential interferents such as ammonia, hydrogen chloride, octane, and the 43-component mixture of VOCs known as EPA TO-14A, and to variations in relative humidity (20-80% RH). Detection of HF and HCN spiked into the complex mixture EPA TO-14A is demonstrated. The approach provides a general means to construct robust remote detection systems for chemical agents.