No abstract

Site-specific PEGylation is an important strategy for enhancing the pharmacokinetic properties of protein drugs, and has been enabled by the recent development of many chemoselective reactions for protein side-chain modification. However, the impact of these different conjugation strategies on the properties of PEG-protein conjugates is poorly understood. Here we show that the ability of PEG to enhance protein conformational stability depends strongly on the identity of the PEG-protein linker, with the most stabilizing linkers involving conjugation of PEG to planar polar groups near the peptide backbone. We also find that branched PEGs provide superior stabilization relative to their linear counterparts, suggesting additional applications for branched PEGs in protein stabilization.

Background: It remains unclear whether volar locked plating (VLP) yields a better functional outcome than closed reduction and casting (CRC) for elderly patients with an acute, displaced distal radial fracture. Our purpose was to conduct a systematic review and meta-analysis of randomized controlled trials comparing outcomes of VLP and CRC for elderly patients (age, ≥60 years). Methods: Multiple databases, including MEDLINE, were searched for randomized controlled trials evaluating outcomes following distal radial fracture treatment. Raw data were obtained for studies that included patients of all ages, and the elderly subgroup was included for analysis. The primary outcome was the Disabilities of the Arm, Shoulder and Hand (DASH) score at ≥1 year of follow-up. Secondary outcomes included the 3-month DASH score, range of motion, final radiographic alignment, and complications. Effect sizes for the comparison of each outcome between groups were pooled across studies using random-effects models with the inverse variance weighting method. Changes in DASH score were compared with a minimal clinically important difference (MCID) estimate of 10 to assess clinical relevance. Results: Of 2,152 screened articles, 6 were included. Demographics were similar for the 274 VLP and 287 CRC patients. DASH scores were significantly better following VLP than CRC at the time of final follow-up (12 to 24 months postoperatively; score difference, −5.9; 95% confidence interval [CI], −8.7 to −3.1) and at 3 months (−8.9; 95% CI, −13.0 to −4.8). VLP yielded significantly better palmar tilt, radial inclination, and supination, with no differences in ulnar variance, flexion-extension, pronation, or total complication rates. Conclusions: Functional outcome was significantly better following VLP than CRC 3 months into the treatment of acute, displaced distal radial fractures in an elderly population and up to 2 years after injury. However, the observed differences in the final DASH score did not exceed published estimates of the MCID, suggesting that clinical outcomes are similar for both treatment options. Level of Evidence: Therapeutic Level I. See Instructions for Authors for a complete description of levels of evidence.

The complete electro-oxidation of glycerol to CO2 is performed through an oxidation cascade using a hybrid catalytic system combining a recombinant enzyme, oxalate decarboxylase from Bacillus subtilis, and an organic oxidation catalyst, 4-amino-TEMPO. This system is capable of electrochemically oxidizing glycerol at a carbon electrode collecting all 14 electrons per molecule.