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Background Survivors of community-acquired pneumonia (CAP) are at increased risk of cardiovascular disease, cognitive and functional decline, and death, but the mechanisms remain unknown. Research Question Do CAP survivors have evidence of increased inflammatory activity in their lung parenchyma on 2-deoxy-2-[18F]fluoro- d -glucose (18FDG)-PET/CT imaging after clinical resolution of infection? Study Design and Methods We obtained 18FDG-PET/CT scans from 22 CAP survivors during their hospitalization with pneumonia (acute CAP) and 30 to 45 days after hospital discharge (post-CAP). In each set of scans, we assessed the lungs for foci of increased 18FDG uptake by visual interpretation and by total pulmonary glycolytic activity (tPGA), a background-corrected measure of total metabolic activity (as measured by 18FDG uptake). We also measured, post-CAP, the glycolytic activity of CAP survivor lung areas with volumes similar to the areas in 28 matched historical control subjects without pneumonia. Results Overall, 68% of CAP survivors (95% CI, 45%-85%) had distinct residual areas of increased 18FDG uptake in their post-CAP studies. tPGA decreased from 821.5 (SD, 1,140.2) in the acute CAP period to 80.0 (SD, 81.4) in the post-CAP period (P = .006). The tPGA post-CAP was significantly higher than that in lung areas of similar volume in control subjects (80.0 [SD, 81.4] vs –19.4 [SD, 5.9]; P Interpretation An important proportion of CAP survivors have persistent pulmonary foci of increased inflammatory activity beyond resolution of their infection. As inflammation contributes to cardiovascular disease, cognitive decline, functional waning, and mortality risk in the general population, this finding provides a plausible mechanism for the increased morbidity and mortality that have been observed post-CAP.

Background: Both inherited arrhythmogenic diseases (such as Brugada Syndrome, BrS) and heart failure are associated with reduced voltage-gated Na+ current (lNa) which promotes lethal arrhythmias and sudden deaths. We have shown that WNT/β-catenin signaling, which is active in heart disease, inhibits lNa in rat cardiomyocytes. But whether WNT/β-catenin signaling also regulates lNa in human cardiomyocytes and represents a novel therapeutic target is unknown. Objectives: To investigate if Wnt/β-catenin signaling inhibits lNa in healthy human cardiomyocytes, and to test if inhibition of β-catenin can rescue lNa in BrS patient cardiomyocytes. Methods: Cardiomyocytes were differentiated from human induced pluripotent stem cells (iPSC-CMs) that were derived from healthy volunteers or BrS patients. CHIR-99021 was used to activate Wnt pathway and shRNA was used to knockdown β-catenin. lNa and action potentials were recorded using whole-cell patch-clamp technique. Results: In healthy iPSC-CMs, activation of Wnt/β-catenin signaling reduced peak lNa and action potential upstroke, which were associated with reduced lNa channel protein (nav1.5) and transcript (SCN5A). In BrS iPSC-CMs, peak lNa is only 16% of that in healthy iPSC-CMs. shRNA inhibition of β-catenin in BrS iPSC-CMs led to a 4.4 fold increase in Nav1.5 without affecting cardiac Ca2+ channel. Accordingly, β-catenin inhibition in BrS iPSC-CMs increased peak lNa by 4.9-fold to 78% of the levels in healthy cells, offsetting the fundamental genetic defect. Conclusions: This study demonstrated Wnt/β-catenin-mediated inhibition of human cardiac lNa and, using Brugada Syndrome as an example, demonstrated that β-catenin inhibition is potentially a new therapeutic strategy to rescue lNa in human heart disease.

© 2016 Elsevier B.V. A low-cost, non-hazardous personal-power system based on an aqueous all-iron electrochemical cell is demonstrated. The system is intended to be assembled and operated by developing-world households that lack sufficient access to electricity, thereby enabling LED lighting or mobile phone charging on demand. Lab-scale hardware is used to assess the performance of individual cell components. It is found that coffee filter paper is an effective low-cost separator. Carbon felt is a low-cost electrode material, and its performance and wetting by the electrolyte solution is greatly improved by pre-treatment with sulfuric acid. The carbon felt does not degrade after a week of daily use. By using these components, performance of the system is significantly improved over the previous baseline, with power density more than doubling to 40 mW cm−2, and iron utilization improving from 78% to 88%. The operating cost is estimated to be less than US$0.03 per mobile phone charge. Based on the lab-scale results, a stand-alone prototype consumer product is designed, fabricated, and tested. It successfully provides 2.5 h of LED illumination while consuming 200 mL of electrolyte solution via gravity feed. We anticipate these results will enable deployment of this innovative system to energy-impoverished individuals in the developing world.

Polysaccharide-based vaccines against Neisseria meningitidis (Nm) serogroups A, C, Y and W135 have been available since 1970, but similar vaccine candidates developed for Nm group B (NmB) have not been successful due to both poor immunogenicity and their potential immunological cross-reactivity with human neurological tissue. In previous reports, a protective antigen and vaccine candidate, Ag473, was identified using proteomics and NmB-specific bactericidal monoclonal antibody. To initiate human phase one clinical trials, antigen production and characterization, pre-clinical toxicology and animal studies are required. In the present study, we report the biochemical characterization of Escherichia coli-expressed recombinant Ag473 (rAg473). Using MALDI-TOF mass analysis, chromatographically purified rAg473 was found to have two major isoforms that have molecular masses of 11,306 and 11,544amu, respectively. The isoforms were separated using RP-HPLC and pooled into two fractions. Based on the chromatogram, the ratio of lipoproteins in fractions #1 and #2 was found to be 1-2. GC-MS analysis of lipoproteins was performed, and the acylated fatty acids were identified. The results indicated that the first lipoproteins in fraction #1 contained the lipids palmitic acid (C16:0), cyclopropaneoctanoic acid (C17:1) and, predominately, stearic acid (C18:0). A different lipid composition of cyclopropaneoctanoic acid (C17:1), oleic acid (C18:1) and, predominately, palmitic acid (C16:0) was found in the second lipoprotein fraction. Both lipoprotein isoforms were tested and found to have Toll-like receptor (TLR) agonist activity in stimulating cytokine secretion from THP-1 cells. Circular dichroism (CD) analysis showed the secondary structure of rAg473 to be dominated by α-helices (48%), and the overall protein structure was stable up to 60°C and could refold after having been exposed to a temperature cycle from 20 to 90°C. In addition, the solubility of rAg473 (5mg/mL) was not affected after several freeze-thaw cycles. These biophysical and immunological properties make rAg473 a good vaccine candidate against NmB.