Adherence to institutional stroke alert criteria in an academic adult emergency department population.

Background: Timely recognition of acute ischemic stroke (AIS) is essential to identify patients who may be eligible for acute intervention. Protocols to streamline systems-based care, such as "stroke alerts" in the emergency department (ED) can safely reduce time-to-care while enhancing safety. However, clinician adherence to stroke alert criteria is poorly described.

Switching between Nonisoenergetic Dynamic Covalent Reactions Using Host-Guest Chemistry.

CO reacts with simple amines in the presence of water to generate dynamic combinatorial libraries of majority (i.e., ammonium carbamates) and minority (i.

Tetrameric self-assembling of water-lean solvents enables carbamate anhydride-based CO capture chemistry.

Carbon capture, utilization and storage is a key yet cost-intensive technology for the fight against climate change. Single-component water-lean solvents have emerged as promising materials for post-combustion CO capture, but little is known regarding their mechanism of action. Here we present a combined experimental and modelling study of single-component water-lean solvents, and we find that CO capture is accompanied by the self-assembly of reverse-micelle-like tetrameric clusters in solution.

Self-assembly of achiral building blocks into chiral cyclophanes using non-directional interactions.

The diastereoselective assembly of achiral constituents through a single spontaneous process into complex covalent architectures bearing multiple stereogenic elements still remains a challenge for synthetic chemists. Here, we show that such an extreme level of control can be achieved by implementing stereo-electronic information on synthetic organic building blocks and templates and that non-directional interactions (, electrostatic and steric interactions) can transfer this information to deliver, after self-assembly, high-molecular weight macrocyclic species carrying up to 16 stereogenic elements. Beyond the field of supramolecular chemistry, this proof of concept should stimulate the on-demand production of highly structured polyfunctional architectures.

Efficient Electrochemical Reduction of CO to Formate in Methanol Solutions by Mn-Functionalized Electrodes in the Presence of Amines.

Carbon cloth electrode modified by covalently attaching a manganese organometallic catalyst is used as cathode for the electrochemical reduction of CO in methanol solutions. Six different industrial amines are employed as co-catalyst in millimolar concentrations to deliver a series of new reactive system. While such absorbents were so far believed to provide a CO reservoir and act as sacrificial proton source, we herein demonstrate that this role can be played by methanol, and that the adduct formed between CO and the amine can act as an effector or inhibitor toward the catalyst, thereby enhancing or reducing the production of formate.

The dark side of disulfide-based dynamic combinatorial chemistry.

During the last two decades, disulfide-based dynamic combinatorial chemistry has been extensively used in the field of molecular recognition to deliver artificial receptors for molecules of biological interest. Commonly, the nature of library members and their relative amounts are provided from HPLC-MS analysis of the libraries, allowing the identification of potential binders for a target (bio)molecule. By re-investigating dynamic combinatorial libraries generated from a simple 2,5-dicarboxy-1,4-dithiophenol building block in water, we herein demonstrated that multiple analytical tools were actually necessary in order to comprehensively describe the libraries in terms of size, stereochemistry, affinity, selectivity, and finally to get a true grasp on the different phenomena at work within dynamic combinatorial systems.

Solid organ donor-recipient race-matching: analysis of the United Network for Organ Sharing database.

Donor ethnicity is a prognosticator in organ transplant. However, the impact of donor/recipient race-matching is unclear. We hypothesized that there would be increased survival in donor-recipient race-matched organ recipients because of genetic and physiologic similarities.

Analyzing essays about treating adults with special health care needs and intellectual and developmental disabilities.

Objective: Analyze reflection essays written by one graduating class of students after an initial experience in a clinic for adults with special health care needs (SHCN) and intellectual and developmental disabilities, to draw insights from the patterns of observations expressed.

Methods: Essays were written by students from the University of Colorado School of Dental Medicine during the 2016-2017 academic year after completing a 1-day clinical experience treating this patient population. Readers identified 18 primary themes (PTs) previously identified in essays written during 2012-2013.

Simultaneous CO capture and metal purification from waste streams using triple-level dynamic combinatorial chemistry.

A reduction in CO emissions is required to mitigate global warming. Post-combustion carbon capture is one of the most developed technologies that has the potential to meet this goal, but its cost prevents its widespread use. A different approach would be to use CO directly as it is captured, before it is stored.

Brainstem serotonergic, catecholaminergic, and inflammatory adaptations during chronic hypercapnia in goats.

Despite the prevalence of CO retention in human disease, little is known about the adaptive neurobiological effects of chronic hypercapnia. We have recently shown 30-d exposure to increased inspired CO (InCO) leads to a steady-state ventilation that exceeds the level predicted by the sustained acidosis and the acute CO/H chemoreflex, suggesting plasticity within respiratory control centers. Based on data showing brainstem changes in aminergic and inflammatory signaling during carotid body denervation-induced hypercapnia, we hypothesized chronic hypercapnia will lead to similar changes.

Dendrigraft of Poly-l-lysine as a Promising Candidate To Reverse Heparin-based Anticoagulants in Clinical Settings.

By using a combination of experimental and computational experiments, we demonstrated that a second-generation dendrigraft of poly-l-lysine neutralizes the anticoagulant activity of unfractionated heparin, low-molecular-weight heparin, and fondaparinux more efficiently than protamine does in human plasma, making this synthetic polymer a promising surrogate of this problematic protein in clinical settings.

Wetting the lock and key enthalpically favours polyelectrolyte binding.

By using a combination of readily accessible experimental and computational experiments in water, we explored the factors governing the association between polyanionic dyn[4]arene and a series of α,ω-alkyldiammonium ions of increasing chain length. We found that the lock-and-key concept based on the best match between the apolar and polar regions of the molecular partners failed to explain the observed selectivities. Instead, the dissection of the energetic and structural contributions demonstrated that the binding events were actually guided by two crucial solvent-related phenomena as the chain length of the guest increases: the expected decrease of the enthalpic cost of guest desolvation and the unexpected increase of the favourable enthalpy of complex solvation.

Diastereoselective Synthesis of a Dyn[3]arene with Distinct Binding Behaviors toward Linear Biogenic Polyamines.

The extension of the family of dyn[ n]arenes toward a three-membered macrocycle is reported. Through a templated approach, a single diastereoisomer of a dyn[3]arene that bears six carboxyl groups could be isolated by precipitation in 59-63% yield and excellent purity (≥95%). A combination of experimental and computational experiments in water at physiological pH revealed that the macrocycle could bind parent biogenic polyamines with a unique diversity of surface-binding modes.

Dynamic Covalent Chemistry of Carbon Dioxide: Opportunities to Address Environmental Issues.

Extraction and purification of basic chemicals from complex mixtures has been a persistent issue throughout the development of the chemical sciences. The chemical industry and academic research have grown over the centuries by following a deconstruction-reconstruction approach, reminiscent of the metabolism process. Chemists have designed and optimized extraction, purification, and transformation processes of molecules from natural deposits (fossil fuels, biomass, ores), in order to reassemble them into complex adducts.

Chirality sensing and discrimination of lysine derivatives in water with a dyn[4]arene.

The asymmetric deformation of a dyn[4]arene upon the binding of various lysine derivatives leads to distinct induced circular dichroism outputs in buffered water, which can be exploited not only for the determination of their enantiomeric excesses, but also for their classification by linear discriminant analysis.

Slowing down fat digestion and absorption by an oxadiazolone inhibitor targeting selectively gastric lipolysis.

Based on a previous study and in silico molecular docking experiments, we have designed and synthesized a new series of ten 5-Alkoxy-N-3-(3-PhenoxyPhenyl)-1,3,4-Oxadiazol-2(3H)-one derivatives (RmPPOX). These molecules were further evaluated as selective and potent inhibitors of mammalian digestive lipases: purified dog gastric lipase (DGL) and guinea pig pancreatic lipase related protein 2 (GPLRP2), as well as porcine (PPL) and human (HPL) pancreatic lipases contained in porcine pancreatic extracts (PPE) and human pancreatic juices (HPJ), respectively. These compounds were found to strongly discriminate classical pancreatic lipases (poorly inhibited) from gastric lipase (fully inhibited).

Structure elucidation of a complex CO-based organic framework material by NMR crystallography.

A three-dimensional structural model of a complex CO-based organic framework made from high molecular weight, self-assembled, flexible and multi-functional oligomeric constituents has been determined by solid-state NMR including DNP-enhanced experiments. The complete assignment of the N, C and H resonances was obtained from a series of two-dimensional through space and through bond correlation experiments. MM-QM calculations were used to generate different model structures for the material which were then evaluated by comparing multiple experimental and calculated NMR parameters.

On-Demand Cyclophanes: Substituent-Directed Self-Assembling, Folding, and Binding.

A family of p-cyclophanes based on bis- or tetrafunctionalized 1,4-bisthiophenol units linked by disulfide bridges was obtained by self-assembly on a gram scale and without any chromatographic purification. The nature of the functionalities borne by these so-called dyn[4]arenes plays a crucial role on their structural features as well as their molecular recognition abilities. Tuning these functions on demand yields tailored receptors for cations, anions, or zwitterions in organic or aqueous media.

H-adamantylphosphinates as universal precursors of P-stereogenic compounds.

A new family of H-adamantylphosphinates as universal precursors of P-stereogenic ligands was obtained in one step from commercial chlorophosphines. Both enantiomers of these air- and moisture-stable intermediates can easily be separated by semipreparative chiral HPLC on a gram scale and individually undergo stereoselective transformations to afford each enantiomer of a set of P-stereogenic compounds such as secondary phosphine oxides and boron-protected monophosphines.

Supported inhibitor for fishing lipases in complex biological media and mass spectrometry identification.

A synthetic phosphonate inhibitor designed for lipase inhibition but displaying a broader range of activity was covalently immobilized on a solid support to generate a function-directed tool targeting serine hydrolases. To achieve this goal, straightforward and reliable analytical techniques were developed, allowing the monitoring of the solid support's chemical functionalization, enzyme capture processes and physisorption artifacts. This grafted inhibitor was tested on pure lipases and serine proteases from various origins, and assayed for the selective capture of lipases from several complex biological extracts.

Overexpression of Bcl-3 inhibits the development of marginal zone B cells.

The transcription factor Bcl-3 functions as a proto-oncogene via regulation of cell proliferation and apoptosis. Bcl-3 is an atypical member of the IκB family and plays a central role in the immune response through interactions with the NF-κB subunits p50 and p52. To investigate the impact of Bcl-3 on B-cell maturation and regulation, we generated mice that overexpress Bcl-3 specifically in B cells.

Bare histidine-serine models: implication and impact of hydrogen bonding on nucleophilicity.

A new family of 2-hydroxyalk(en/yn)ylimidazoles has been evaluated as serine-histidine bare dyad models for the ring-opening reaction of L-lacOCA, a cyclic O-carboxyanhydride. These models were selected to unravel the implication of intramolecular hydrogen bonding and to substantiate its influence on the nucleophilicity of the alcohol moiety, as it is suspected to occur in enzyme active sites. Although designed to exclusively facilitate the preliminary step of proton transfer during the studied ring-opening reaction, these minimalistic models depicted a measureable increase in reactivity relative to the isolated fragments.

Analysis of the discriminative inhibition of mammalian digestive lipases by 3-phenyl substituted 1,3,4-oxadiazol-2(3H)-ones.

We report here the reactivity and selectivity of three 5-Methoxy-N-3-Phenyl substituted-1,3,4-Oxadiazol-2(3H)-ones (MPOX, as well as meta and para-PhenoxyPhenyl derivatives, i.e.MmPPOX and MpPPOX) with respect to the inhibition of mammalian digestive lipases: dog gastric lipase (DGL), human (HPL) and porcine (PPL) pancreatic lipases, human (HPLRP2) and guinea pig (GPLRP2) pancreatic lipase-related proteins 2, human pancreatic carboxyl ester hydrolase (hCEH), and porcine pancreatic extracts (PPE).

MmPPOX inhibits Mycobacterium tuberculosis lipolytic enzymes belonging to the hormone-sensitive lipase family and alters mycobacterial growth.

Lipid metabolism plays an important role during the lifetime of Mycobacterium tuberculosis, the causative agent of tuberculosis. Although M. tuberculosis possesses numerous lipolytic enzymes, very few have been characterized yet at a biochemical/pharmacological level.

Proteomic analysis identifies new biomarkers for postmenopausal and dry skin.

A proteomic analysis of stratum corneum (SC) samples of normal healthy skin revealed the presence of more than 70 proteins by 2D electrophoresis. The majority of these proteins to our knowledge have not yet been described in normal SC. We analysed by Western blot the levels of 25 proteins in the SC taken from postmenopausal and dry skin compared with young and normal skin, respectively.