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Highly scattering samples, such as polymer droplets or solid-state powders, are difficult to study via coherent two-dimensional infrared (2D IR) spectroscopy. Previously, researchers have employed (quasi-) phase cycling, local-oscillator chopping, and polarization control to reduce scattering, but the latter method poses a limit on polarization-dependent measurements. Here, we present a method for Scattering Elimination Immune from Detector Artifacts (SEIFDA) in pump-probe 2D IR experiments. Our method extends the negative probe delay method of removing scattering from pump-probe spectroscopy to 2D experiments. SEIFDA works well for all polarizations when combined with the optimized noise reduction scheme to remove additive and multiplicative noise. We demonstrate that our method can be employed with any polarization scheme and reliably lowers the scattering at parallel polarization to comparable levels to the conventional 8-frame phase cycling with probe chopping (8FPCPC) at perpendicular polarization. Our system can acquire artifact free spectra in parallel polarization when the signal intensity is as little as 5% of the intensity of the interference between the pump pulses scattered into the detector. It reduces the time required to characterize the scattering term by at least 50% over 8FPCPC. Through detailed analysis of detector nonlinearity, we show that the performance of 8FPCPC can be improved by incorporating nonlinear correction factors, but it is still worse than that of SEIFDA. Application of SEIFDA to study the encapsulation of Nile red in polymer droplets demonstrates that this method will be very useful for probing highly scattering systems.

Inspired by the adaptability of biological materials, a variety of synthetic, chemically driven self-assembly processes have been developed that result in the transient formation of supramolecular structures. These structures form through two simultaneous reactions, forward and backward, which generate and consume a molecule that undergoes self-assembly. The dynamics of these assembly processes have been shown to differ from conventional thermodynamically stable molecular assemblies. However, the evolution of nanoscale morphologies in chemically driven self-assembly and how they compare to conventional assemblies has not been resolved. Here, we use a chemically driven redox system to separately carry out the forward and backward reactions. We analyze the forward and backward reactions both sequentially and synchronously with time-resolved cryogenic transmission electron microscopy (cryoEM). Quantitative image analysis shows that the synchronous process is more complex and heterogeneous than the sequential process. Our key finding is that a thermodynamically unstable stacked nanorod phase, briefly observed in the backward reaction, is sustained for ∼6 hours in the synchronous process. Kinetic Monte Carlo modeling show that the synchronous process is driven by multiple cycles of assembly and disassembly. The collective data suggest that chemically driven self-assembly can create sustained morphologies not seen in thermodynamically stable assemblies by kinetically stabilizing transient intermediates. This finding provides plausible design principles to develop and optimize supramolecular materials with novel properties.

Purpose: To determine the interobserver reliability of perceived displacement (PD) ≥ 1 cm of lateral compression type 1 (LC1) pelvic ring fractures and to determine if PD correlated with published methods of measuring fracture displacement and adverse events. Methods: The injury and follow-up radiographs of 10 patients with nonoperative minimally displaced LC1 injuries were reviewed by 27 orthopaedic trauma surgeons to determine if they perceived an interval fracture displacement ≥ 1 cm. Perceived displacement (PD) was compared to 11 measurements of displacement: the difference in heights of iliac crests (IC), sourcils, and ischial tuberosities on AP/outlet radiographs; the distance from femoral head (FH) to the sacral midline and the distance between the radiographic teardrops (TD) on the AP; the distance from the TD to sacral midline and the difference in distances between the SI joints and the contralateral TD on the inlet. The interobserver reliability and correlation of PD and measured displacement was calculated. The association between PD and adverse events was also evaluated. Results: PD had weak interobserver reliability (kappa = 0.46). Many of the measurements of displacement were poorly sensitive for PD. The magnification-corrected AP TD measurement had the highest sensitivity (100%) for PD and excellent interobserver reliability (Intraclass correlation 0.97), but had a low specificity (57.1%). All three patients with PD had adverse events while patients without PD had uneventful recoveries (p = 0.008). Conclusions: The AP TD measurement detected all cases of PD and had excellent reliability. PD was associated with adverse events, suggesting that accurate and reliable measurements of displacement are warranted. Level of evidence III: Diagnostic. [ABSTRACT FROM AUTHOR]

Polymerization‐induced self‐assembly (PISA) has emerged as a scalable one‐pot technique to prepare block copolymer (BCP) nanoparticles. Recently, a PISA process, that results in poly(l‐lactide)‐b‐poly(ethylene glycol) BCP nanoparticles coined ring‐opening polymerization (ROP)‐induced crystallization‐driven self‐assembly (ROPI‐CDSA), was developed. The resulting nanorods demonstrate a strong propensity for aggregation, resulting in the formation of 2D sheets and 3D networks. This article reports the synthesis of poly(N,N‐dimethyl acrylamide)‐b‐poly(l)‐lactide BCP nanoparticles by ROPI‐CDSA, utilizing a two‐step, one‐pot approach. A dual‐functionalized photoiniferter is first used for controlled radical polymerization of the acrylamido‐based monomer, and the resulting polymer serves as a macroinitiator for organocatalyzed ROP to form the solvophobic polyester block. The resulting nanorods are highly stable and display anisotropy at higher molecular weights (>12k Da) and concentrations (>20% solids) than the previous report. This development expands the chemical scope of ROPI‐CDSA BCPs and provides readily accessible nanorods made with biocompatible materials. [ABSTRACT FROM AUTHOR]

Electron tomography holds great promise as a tool for investigating the 3D morphologies and internal structures of metal‐organic framework‐based protein biocomposites (protein@MOFs). Understanding the 3D spatial arrangement of proteins within protein@MOFs is paramount for developing synthetic methods to control their spatial localization and distribution patterns within the biocomposite crystals. In this study, the naturally occurring iron oxide mineral core of the protein horse spleen ferritin (Fn) is leveraged as a contrast agent to directly observe individual proteins once encapsulated into MOFs by electron microscopy techniques. This methodology couples scanning electron microscopy, transmission electron microscopy, and electron tomography to garner detailed 2D and 3D structural interpretations of where proteins spatially lie in Fn@MOF crystals, addressing the significant gaps in understanding how synthetic conditions relate to overall protein spatial localization and aggregation. These findings collectively reveal that adjusting the ligand‐to‐metal ratios, protein concentration, and the use of denaturing agents alters how proteins are arranged, localized, and aggregated within MOF crystals. [ABSTRACT FROM AUTHOR]

Objectives: To demonstrate fracture displacement, patient tolerance, and in-hospital safety quantifying lateral compression type 1 (LC1) pelvis fracture stability with awake stress radiography using a pelvic binder (PBR)., Design: Prospective clinical trial of PBR diagnostic intervention., Setting: Two centers, Level I trauma center and academic hospital., Patient Selection Criteria: Alert adults with LC1 (OTA/AO B1.1/2.1) pelvic fractures from blunt mechanism presenting within 3 weeks of injury between February and December 2023 without hypotension or injury precluding pelvic binder application., Outcome Measures and Comparisons: The primary outcome was fracture displacement on PBR. Secondary outcomes included feasibility (≥85% patient tolerance) and safety (no major adverse events). Exploratory outcomes included pain during examination, opioid medication consumption within 96 hours, length of hospital stay, discharge destination, and correlation between fracture displacement on PBR and examination under anesthetic., Results: One hundred sixty-nine patients with pelvis fractures were screened, 58 were eligible, and 31 were enrolled. The mean age of enrolled patients was 58.7 ± 23 years, 54.8% were female, 22.6% were White, and 67.7% Hispanic. Fracture displacement was 4.3 ± 4.7 mm on PBR at 5 kg and 8.4 ± 9.0 mm at 10 kg. All patients tolerated PBR. Sixteen patients (52%) reported pain during PBR but completed the test. No patient experienced an adverse event. Patients received 40.4 ± 56.4 mg oral morphine equivalents within 96 hours of PBR. Ten patients (32.2%) received internal fixation. The median hospital stay was 6 days (interquartile range 5.5 days) with no inpatient mortality. Fourteen patients (45.2%) discharged home., Conclusions: PBR is feasible and safe as a point-of-care test for LC1 pelvis fracture instability., Level of Evidence: Level II Diagnostic., Competing Interests: J. T. Patterson reports research support and committee membership with AO North America and Orthopaedic Trauma Association and consulting fees from Stryker and Johnson & Johnson. J. L. Gary reports research support from AO North America, committee membership with AO North America and Orthopaedic Trauma Association, editorial or governing board with Journal of Bone and Joint Surgery, Journal of the American Academy of Orthopaedic Surgeons, Wolters Kluwer Health—Lippincott Williams & Wilkins, consulting fees from Baim Institute for Clinical Research, speaker payments from Curvafix, Smith & Nephew, Stryker, and Synthes, stock or stock options in Summitt Medventures. The remaining authors report no conflicts of interest., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Introduction: The purpose of this study was to determine the degree of disability that geriatric patients with sacral U-type fractures experience., Methods: Patients older than 65 years presenting from 2013 to 2019 with a U-type sacral fracture were included. Patient demographics, treatment type, preinjury domicile, preinjury use of assistive devices, and neurologic deficits were recorded. Outcomes included mortality, return to preinjury domicile, and use of assistive devices for mobility., Results: Among 46 patients in the treatment period, ground-level fall was the most common mechanism of injury (60.8%). Thirty-four patients (74%) were treated surgically, most commonly with closed percutaneous fixation (n = 27). Thirteen percent of patients died during the admission. At the final follow-up, 14 (45%) had not returned to their prior domicile and 18 (58%) required more supportive assistive devices. Seventy-three percent of patients who presented delayed required a new gait aid, compared with 47% presenting acutely. Between those presenting with low-energy versus high-energy mechanisms, similar rates of need were observed for new assistive devices (50% low and 73% high) and lack of return to preinjury domicile (40% low, 50% high)., Discussion: Many geriatric patients were disabled by or died after sustaining a sacral U-type fracture, highlighting the morbidity regardless of high-energy or low-energy trauma., (Copyright © 2024 The Authors. Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Orthopaedic Surgeons.)

Mutations in the GNAO1 gene, which encodes the abundant brain G-protein G α o , result in neurologic disorders characterized by developmental delay, epilepsy, and movement abnormalities. There are over 50 mutant alleles associated with GNAO1 disorders; the R209H mutation results in dystonia, choreoathetosis, and developmental delay without seizures. Mice heterozygous for the human mutant allele ( Gnao1 +/R209H ) exhibit hyperactivity in open field tests but no seizures. We developed self-complementary adeno-associated virus serotype 9 (scAAV9) vectors expressing two splice variants of human GNAO1 G α o isoforms 1 (G o A, GNAO1.1 ) and 2 (G o B, GNAO1.2 ). Bilateral intrastriatal injections of either scAAV9- GNAO1.1 or scAAV9- GNAO1.2 significantly reversed mutation-associated hyperactivity in open field tests. GNAO1 overexpression did not increase seizure susceptibility, a potential side effect of GNAO1 vector treatment. This represents the first report of successful preclinical gene therapy for GNAO1 encephalopathy applied in vivo. Further studies are needed to uncover the molecular mechanism that results in behavior improvements after scAAV9-mediated G α o expression and to refine the vector design. SIGNIFICANCE STATEMENT: GNAO1 mutations cause a spectrum of developmental, epilepsy, and movement disorders. Here we show that intrastriatal delivery of scAAV9- GNAO1 to express the wild-type G α o protein reduces the hyperactivity of the Gnao1 +/R209H mouse model, which carries one of the most common movement disorder-associated mutations. This is the first report of a gene therapy for GNAO1 encephalopathy applied in vivo on a patient-allele model., (Copyright © 2024 by The American Society for Pharmacology and Experimental Therapeutics.)

Background: Studies evaluating surgical-site infection have had conflicting results with respect to the use of alcohol solutions containing iodine povacrylex or chlorhexidine gluconate as skin antisepsis before surgery to repair a fractured limb (i.e., an extremity fracture)., Methods: In a cluster-randomized, crossover trial at 25 hospitals in the United States and Canada, we randomly assigned hospitals to use a solution of 0.7% iodine povacrylex in 74% isopropyl alcohol (iodine group) or 2% chlorhexidine gluconate in 70% isopropyl alcohol (chlorhexidine group) as preoperative antisepsis for surgical procedures to repair extremity fractures. Every 2 months, the hospitals alternated interventions. Separate populations of patients with either open or closed fractures were enrolled and included in the analysis. The primary outcome was surgical-site infection, which included superficial incisional infection within 30 days or deep incisional or organ-space infection within 90 days. The secondary outcome was unplanned reoperation for fracture-healing complications., Results: A total of 6785 patients with a closed fracture and 1700 patients with an open fracture were included in the trial. In the closed-fracture population, surgical-site infection occurred in 77 patients (2.4%) in the iodine group and in 108 patients (3.3%) in the chlorhexidine group (odds ratio, 0.74; 95% confidence interval [CI], 0.55 to 1.00; P = 0.049). In the open-fracture population, surgical-site infection occurred in 54 patients (6.5%) in the iodine group and in 60 patients (7.3%) in the chlorhexidine group (odd ratio, 0.86; 95% CI, 0.58 to 1.27; P = 0.45). The frequencies of unplanned reoperation, 1-year outcomes, and serious adverse events were similar in the two groups., Conclusions: Among patients with closed extremity fractures, skin antisepsis with iodine povacrylex in alcohol resulted in fewer surgical-site infections than antisepsis with chlorhexidine gluconate in alcohol. In patients with open fractures, the results were similar in the two groups. (Funded by the Patient-Centered Outcomes Research Institute and the Canadian Institutes of Health Research; PREPARE ClinicalTrials.gov number, NCT03523962.)., (Copyright © 2024 Massachusetts Medical Society.)