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Uterine fibroid embolization (UFE) cases performed from 2013 to 2019 were reviewed. 72 patients were treated with a standard protocol consisting of sedation, ketorolac, ondansetron, and overnight parenteral analgesics and antiemetics. 96 were treated with a new protocol, which added transdermal scopolamine, lorazepam, and IV acetaminophen. Outpatient UFE (OP-UFE) was successful with 81.4% and 2.7% of patients treated with the new and old protocols, respectively (p.0001, OR 141.4). Procedural fentanyl doses were lower with the new protocol than the old one (mean 148 vs. 186 mcg, p=.0016). In the new protocol subset, patients were 1.01 times more likely to fail OP-UFE for every microgram increase in procedural fentanyl (OR 0.99, p = 0.009), and those presenting with pain were less likely to succeed with OP-UFE than those with bleeding or bulk symptoms (OR 0.31, p=0.04). Conclusion: Decreasing opioids while increasing anti-emetics and non-opioid analgesics improves chances of OP-UFE.

Purpose To determine the reproducibility of MRI aortic hemodynamic markers and to assess their relationship to aortic growth in a cohort of patients with bicuspid aortic valves (BAV).

Quantitative aortic magnetic resonance (MR) blood flow imaging is a rapidly advancing technique that is likely to impact clinical medicine in the near future. The acquisition of comprehensive 4D velocity datasets is now possible in a clinically acceptable time frame. Unique and intuitive visualization methods are available. A number of important hemodynamic biomarkers can be derived from the data, and exploited to help understand how abnormal flow is inter-related with aortic pathology. Initial data suggest that some of the derived biomarkers can refine the clinical assessment of aortic disease and predict disease progression. We provide an overview of aortic imaging with emphasis on how flow imaging is currently used, discuss the fundamental technical aspects of multidimensional MR flow imaging, introduce key hemodynamic markers, and show how this type of imaging may soon be used for the early identification of patients at risk for the development of potentially devastating aortic complications.

In modern academic and industrial laboratories, evolutionary strategies are used routinely to identify biopolymers with novel activities. Large libraries of nucleic acids (∼1015) or peptides and proteins (∼1013) can be subjected to multiple rounds of selective pressure, amplification, and diversification, yielding individual sequences with desirable properties. Although the evolutionary approach is a powerful search tool, the chemical nature of biopolymers is not suited for all purposes. Application of evolutionary strategies to libraries of arbitrary chemical composition would overcome this problem, and radically change traditional small-molecule discovery. The chemical make-up of in vitro evolution libraries has necessarily been limited, because library synthesis relies on enzymes. A great deal of current research focuses on expanding the chemical repertoire of in vitro evolution by (a) broadening enzyme substrate specificities to include unnatural building blocks, or (b) developing methods to translate DNA sequences into multistep organic syntheses. We discuss the strengths and weaknesses of the approaches, review the successes, and consider the future of chemical evolution as a tool.

This paper reports crossed laser-molecular beam scattering experiments measuring the photofragment velocities and product branching in the photodissociation of trimethylamine (N(CH3)3) at 193 nm. We have observed two primary N–CH3 bond fission channels that ultimately produce different nitrogen-containing species, CH3+N(CH3)2 (X 2B1); CH3+N(CH3)2*→CH3+CH2NCH3+H. The data also indicate that a third minor channel may contribute to the dissociation dynamics, CH3+N(CH3)2†→CH3+NC2H4+H2. The experiments show that ground state N(CH3)2 radicals are formed in the photodissociation, in sharp contrast to the exclusive production of NH2 (A 2A1) in a similar molecule, methylamine. We discuss how this results from the differing dynamics through the S1–S0 conical intersection in the exit channel in these two dissociating amines. We also use the photodissociation results to calibrate the mass spectrometric sensitivity at the m/e=15 daughter ion for methyl radicals vs N(CH3)2 and CH2NCH3 products. This provides the only ...

To determine the reproducibility of MRI aortic hemodynamic markers and to assess their relationship to aortic growth in a cohort of patients with bicuspid aortic valves (BAV).Twenty-five patients previously studied with four-dimensional (4D) Flow imaging who had at least two separate cross-sectional imaging studies to assess for aortic growth were included: tricuspid aortic valve (TAV) controls without valvular disease (n = 12) and patients with BAV (n = 13). Flow data from the ascending aorta was used for calculation of peak velocity, normalized flow displacement, maximum wall shear stress (WSS), mean WSS, and minimal WSS. Pearson's correlation was used to evaluate interobserver agreement, and linear regression to evaluate the correlation between the different hemodynamic markers and growth. Patient informed consent was waived by the institutional review board that approved the study.Peak velocity and flow displacement were very reproducible (r = 0.90-1.0 and r = 0.91-0.98, respectively). The range of WSS parameters was largely reproducible (0.47r0.96) with the greatest variability at the data extraction stage of analysis (0.47r0.85). Flow displacement best correlated with interval aortic growth (r = 0.65), peak velocity was moderately correlated (r = 0.35), but the WSS parameters did not correlate well with growth (r0.17).Flow displacement is a simple and reproducible hemodynamic marker that shows good correlation with aortic growth in patients with bicuspid aortic valves.

A large body of in vitro evolution work establishes the utility of biopolymer libraries comprising 1010 to 1015 distinct molecules for the discovery of nanomolar-affinity ligands to proteins.[1], [2], [3], [4], [5] Small-molecule libraries of comparable complexity will likely provide nanomolar-affinity small-molecule ligands.[6], [7] Unlike biopolymers, small molecules can offer the advantages of cell permeability, low immunogenicity, metabolic stability, rapid diffusion and inexpensive mass production. It is thought that such desirable in vivo behavior is correlated with the physical properties of small molecules, specifically a limited number of hydrogen bond donors and acceptors, a defined range of hydrophobicity, and most importantly, molecular weights less than 500 Daltons.[8] Creating a collection of 1010 to 1015 small molecules that meet these criteria requires the use of hundreds to thousands of diversity elements per step in a combinatorial synthesis of three to five steps. With this goal in mind, we have reported a set of mesofluidic devices that enable DNA-programmed combinatorial chemistry in a highly parallel 384-well plate format. Here, we demonstrate that these devices can translate DNA genes encoding 384 diversity elements per coding position into corresponding small-molecule gene products. This robust and efficient procedure yields small molecule-DNA conjugates suitable for in vitro evolution experiments.

Hybrid combinatorial chemistry strategies that use DNA as an information-carrying medium are proving to be powerful tools for molecular discovery. In order to extend these efforts, we present a highly parallel format for DNA-programmed chemical library synthesis. The new format uses a standard microwell plate footprint and is compatible with commercially available automation technology. It can accommodate a wide variety of combinatorial synthetic schemes with up to 384 different building blocks per chemical step. We demonstrate that fluidic routing of DNA populations in the highly parallel format occurs with excellent specificity, and that chemistry on DNA arrayed into 384 well plates proceeds robustly, two requirements for the high-fidelity translation and efficient in vitro evolution of small molecules.

The recognition and catalytic properties of biopolymers derive from an elegant evolutionary mechanism, whereby the genetic material encoding molecules with superior functional attributes survives a selective pressure and is propagated to subsequent generations. This process is routinely mimicked in vitro to generate nucleic-acid or peptide ligands and catalysts. Recent advances in DNA-programmed organic synthesis have raised the possibility that evolutionary strategies could also be used for small-molecule discovery, but the idea remains unproven. Here, using DNA-programmed combinatorial chemistry, a collection of 100 million distinct compounds is synthesized and subjected to selection for binding to the N-terminal SH3 domain of the proto-oncogene Crk. Over six generations, the molecular population converges to a small number of novel SH3 domain ligands. Remarkably, the hits bind with affinities similar to those of peptide SH3 ligands isolated from phage libraries of comparable complexity. The evolutionary approach has the potential to drastically simplify and accelerate small-molecule discovery.