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To examine the hypothesis that longer distance from home-to-hospital is associated with worse outcomes among hospitalizations for community-acquired sepsis.A secondary analysis of data from the REasons for Geographic and Racial Differences in Stroke (REGARDS) prospective cohort of 30,239 white and Black US adults greater than or equal to 45 years old was conducted. Self-reported hospitalizations for serious infection between 2003 and 2012 fulfilling 2/4 systemic inflammatory response syndrome criteria were included. Estimated driving distance was derived from geocoded data and evaluated continuously and as quartiles of very close, close, far, very far (3.1, 3.1-5.8, 5.9-11.5, and11.5 miles respectively). The primary outcome was 30-day mortality while the secondary outcome was sequential organ failure assessment (SOFA) score on arrival.Of the 912 hospitalizations for community-acquired sepsis had adequate data for analysis. The median (interquartile range) estimated driving distance was 5.8 miles (3.1,11.7), and 54 (5.9%) experienced the primary outcome. Compared to living very close, participants living very far had a mortality odds ratio of 1.30 (95% CI 0.64,2.62) and presenting SOFA score difference of 0.33 (95% CI -0.03,0.68).Among a national sample of community-acquired sepsis hospitalizations, there was no significant association between home-to-hospital distance and either 30-day mortality or SOFA score on hospital presentation.

Critical care patients who experience acute respiratory distress syndrome are commonly placed on mechanical ventilators to improve oxygen delivery and overall gas exchange of the pulmonary system. With the pulmonary inflammation accompanying acute respiratory distress syndrome (ARDS), patients experience significant alterations in ventilation–perfusion (V/Q) ratios resulting in lower blood oxygenation. In severe cases, patients are typically rotated into a prone position to facilitate improved blood flow to portions of the lung that were not previously participating in the gas exchange process. However, proning a patient increases the risk of complications, requires up to seven hospital staff members to carry out, and does not guarantee an improvement in the patient's condition. The low-cost V/Q vest presented here was designed to reproduce the effects of proning while also requiring less hospital staff than the proning process. Additionally, the V/Q Vest helps hospital staff predict whether patients would respond well to a proning treatment. A pilot study was conducted on nine patients with ARDS from coronavirus disease 2019 (COVID-19). The average increase in oxygenation with the V/Q Vest treatment for all patients was 19.7±38.1%. Six of the nine patients responded positively to the V/Q Vest treatment, exhibiting increased oxygenation. The V/Q Vest also helped hospital staff predict that three of the five patients that were proned would experience an increase in oxygenation. An increase in oxygenation resulting from V/Q Vest treatment exceeded that of the proning treatment in two of these five proned patients.

PKS biocatalysis: The terminal module of erythromycin synthase was used for the in vitro production of chiral triketide lactones. Combining cofactor regeneration, substrate truncation, and enzymatic promiscuity afforded a scalable strategy to generate these molecules from abundant racemic and achiral precursors. The described biocatalytic platform thus facilitates the application and study of enzymes within PKS modules.

SummaryChiral building blocks are valuable intermediates in the syntheses of natural products and pharmaceuticals. A scalable chemoenzymatic route to chiral diketides has been developed that includes the general synthesis of α-substituted, β-ketoacyl N-acetylcysteamine thioesters followed by a biocatalytic cycle in which a glucose-fueled NADPH-regeneration system drives reductions catalyzed by isolated modular polyketide synthase (PKS) ketoreductases (KRs). To identify KRs that operate as active, stereospecific biocatalysts, 11 isolated KRs were incubated with 5 diketides and their products were analyzed by chiral chromatography. KRs that naturally reduce small polyketide intermediates were the most active and stereospecific toward the panel of diketides. Several biocatalytic reactions were scaled up to yield more than 100 mg of product. These syntheses demonstrate the ability of PKS enzymes to economically and greenly generate diverse chiral building blocks on a preparative scale.

To demonstrate the potential of polyketide synthase (PKS) modules as biocatalysts that can synthesize polyketides in vitro, the terminal module and thioesterase (TE) from the erythromycin PKS were employed in the multimilligram, chemoenzymatic syntheses of diverse triketide pyrones. Methylmalonyl-S-NAC extender units were generated by the promiscuous malonyl-CoA ligase Streptomyces coelicolor MatB. Initiating the reaction with β-ketoacyl-S-NAC diketides yielded the anticipated triketide pyrones through chain extension and cyclization. TE-mediated hydrolysis of the substrates prevented quantitative yields; however, a reaction with 200 mg of diketide substrate generated 20 mg of pyrone product. Trace quantities of a particular pyrone were observed in all reactions and was hypothesized to result from extender unit decarboxylation and subsequent “stuttering”. To harness this polymerase-like activity, reactions were initiated with diverse acyl-S-NACs to yield the anticipated triketide pyrones, one harboring a terminal alkyne chemical handle. This biocatalytic system enables more informative analysis of in vitro PKS reactions by HPLC, NMR, and crystallography and sets the stage for the preparative generation of polyketides such as chiral building blocks valuable in the synthesis of natural products and pharmaceuticals.