RESUMEN
The natural product hinokitiol mobilizes iron across lipid bilayers at low concentrations and restores hemoglobinization in iron transporter protein-deficient systems. But hinokitiol fails to similarly mobilize iron at higher concentrations, limiting its uses in chemical biology and medicine. Here we show that at higher concentrations, hinokitiol3:Fe(III) complexes form large, higher-order aggregates, leading to loss of transmembrane iron mobilization. Guided by this understanding and systematic structure-function studies enabled by modular synthesis, we identified FeM-1269, which minimally aggregates and dose-dependently mobilizes iron across lipid bilayers even at very high concentrations. In contrast to hinokitiol, FeM-1269 is also well-tolerated in animals at high doses for extended periods of time. In a mouse model of anemia of inflammation, FeM-1269 increases serum iron, transferrin saturation, hemoglobin and hematocrit. This rationally developed iron-mobilizing small molecule has enhanced potential as a molecular prosthetic for understanding and potentially treating iron transporter deficiencies.
RESUMEN
OBJECTIVE: To determine the utility of Autologous Skin Cell Suspension (ASCS) in closing full-thickness (FT) defects from injury and infection. SUMMARY BACKGROUND DATA: Although ASCS has documented success in closing partial-thickness burns, far less is known about the efficacy of ASCS in FT defects. METHODS: Fifty consecutive patients with FT defects (burn 17, necrotizing infection 13, crush 7, degloving 5, other 8) underwent closure with the bilayer technique of 3:1 widely-meshed, thin, split-thickness skin graft and 80:1 expanded ASCS. End points were limb salvage rate, donor site reduction, operative and hospital throughput, incidence of complications, and re-epithelialization by 4, 8, and 12 weeks. RESULTS: Definitive wound closure was achieved in 76%, 94%, and 98% of patients, at 4, 8, and 12 weeks, respectively. Limb salvage occurred in 42/43 patients (10 upper, 33 lower extremities). Mean area grafted was 435 cm2; donor site size was 212 cm2, representing a potential reduction of 50%. Mean surgical time was 71 minutes; total OR time was 124 minutes. Mean length-of-stay was 26.4 days; time from grafting to discharge was 11.2 days. 4/50 patients (8%) required 6 reoperations for bleeding (1), breakdown (4), and amputation (1). 4/50 patients (8%) developed hypertrophic scarring, which responded to silicone sheeting (2) and laser resurfacing (2). Mean follow-up was 92.7 days. CONCLUSION: When used for closure of FT wounds, point-of-care ASCS is effective and safe. Benefits include rapid re-epithelialization, high rate of limb salvage, reduction of donor site size and morbidity, and low incidence of hypertrophic scarring.
RESUMEN
Gold shops in artisanal and small-scale gold mining communities represent major point sources of airborne mercury pollution. Concentrations of elemental mercury (Hg0) emitted by these shops can be determined using a portable atomic absorbance spectrometer (AAS) with Zeeman correction. These measured Hg0 concentrations can then be correlated to position as determined by a hand-held GPS unit, and the resulting data mapped using a Geographic Information System (GIS). A detailed method for obtaining and analyzing data collected near gold shops in Mazuko, Peru is provided. Maps generated using this method were employed to identify point sources of Hg0 contamination originating from gold shops in ASGM communities and were shared with local city managers to assist in urban planning.â¢A detailed method is provided to collect and process data, ultimately generating a map that allows for the screening of a community to identify point sources of Hg0 contamination.â¢Raw data is provided, as well as a video detailing data processing and mapping using a common spreadsheet program and an open-source GIS.â¢The generated map can be used for determining areas where people may be exposed to elevated Hg0 concentrations and/or occupational mercury vapor exposure, targeted enforcement, or outreach to limit Hg0 pollution.