Tailoring Electrochemical CO2 Reduction on Copper by Reactive Ionic Liquid and Native Hydrogen Bond Donors.

Electrochemical CO2 reduction (CO2 RR) on copper (Cu) shows promise for higher-value products beyond CO. However, challenges such as the limited CO2 solubility, high overpotentials, and the competing hydrogen evolution reaction (HER) in aqueous electrolytes hinder the practical realization. We propose a functionalized ionic liquid (IL) which generates ion-CO2 adducts and a hydrogen bond donor (HBD) upon CO2 absorption to modulate CO2 RR on Cu in a non-aqueous electrolyte. As revealed by transient voltammetry, electrochemical impedance spectroscopy (EIS), and in situ surface-enhanced Raman spectroscopy (SERS) complemented with image charge augmented quantum-mechanical/molecular mechanics (IC-QM/MM) computations, a unique microenvironment is constructed. In this microenvironment, the catalytic activity is primarily governed by the IL and HBD concentrations; former controlling the double layer thickness and the latter modulating the local proton availability. This translates to ample CO2 availability, reduced overpotential, and suppressed HER where C4 products are obtained. This study deepens the understanding of electrolyte effects in CO2 RR and the role of IL ions towards electrocatalytic microenvironment design.

Optimization of a commercial Histoplasma galactomannan EIA test in a population from an endemic area of histoplasmosis in southern Brazil.

BACKGROUND: Since 2020 the World Health Organization (WHO) recommends Histoplasma antigen detection for the diagnosis of disseminated histoplasmosis (DH) in people living with HIV (PLHIV). OBJECTIVE: Here we aimed to optimise the IMMY's Clarus® Histoplasma GM enzyme immunoassay (EIA), evaluating the best cut-off in the semi-quantitative (SQ-HGM EIA), also known as 'calibrator cut-off procedure'. METHODS: The optimization was done using the quantitative standard procedure (Q-HGM EIA), also known as 'standard curve procedure', as reference test. A retrospective study from an endemic area of DH in southern Brazil was carried out including 264 patients investigated for DH using the test. Receiver Operator Characteristic curve was plotted, and sensitivity and specificity of the SQ-HGM EIA were calculated. RESULTS: The study included 24 positive (values ≥ 0.20 ng/ml) and 240 negative patients by the Q-HGM EIA. According to the manufacturer SQ-HGM EIA protocol, the new SQ-HGM EIA cut-off of 0.8 EIA units was validated, resulting in sensitivity and specificity of 88% and 98.7%, respectively. CONCLUSION: Our study pioneers and brings important data about the optimization of the Histoplasma antigen testing for the diagnosis of DH in a population from Southern Brazil. This optimization also reduced the amount of reagents used, lowering the cost associated with testing.

Comparison between Ab Initio Molecular Dynamics and OPLS-Based Force Fields for Ionic Liquid Solvent Organization.

OPLS-based force fields (FFs) have been shown to provide accurate bulk-phase properties for a wide variety of imidazolium-based ionic liquids (ILs). However, the ability of OPLS to reproduce an IL solvent structure is not as well-validated given the relative lack of high-level theoretical or experimental data available for comparison. In this study, ab initio molecular dynamics (AIMD) simulations were performed for three widely used ILs: the 1-butyl-3-methylimidazolium cation with chloride, tetrafluoroborate, or hexafluorophosphate anions, that is, [BMIM][Cl], [BMIM][BF4], and [BMIM][PF6], respectively, as a basis for further assessment of two unique IL FFs: the ±0.8 charge-scaled OPLS-2009IL FF and the OPLS-VSIL FF. The OPLS-2009IL FF employs a traditional all-atom functional form, whereas the OPLS-VSIL FF was developed using a virtual site that offloads negative charge to inside the plane of the ring with careful attention given to reproducing hydrogen bonding. Detailed comparisons between AIMD and the OPLS FFs were made based on radial distribution functions (RDFs), combined distribution functions (CDFs), and spatial distribution functions (SDFs) to examine cation-anion interactions and π+-π+ stacking between the imidazolium rings. While both FFs were able to correctly capture the general solvent structure of these popular ILs, the OPLS-VSIL FF quantitatively reproduced interaction distances more accurately. In addition, this work provides further insights into the different short- and long-range structure patterns of these popular ILs.

Evolution of microscopic heterogeneity and dynamics in choline chloride-based deep eutectic solvents.

Deep eutectic solvents (DESs) are an emerging class of non-aqueous solvents that are potentially scalable, easy to prepare and functionalize for many applications ranging from biomass processing to energy storage technologies. Predictive understanding of the fundamental correlations between local structure and macroscopic properties is needed to exploit the large design space and tunability of DESs for specific applications. Here, we employ a range of computational and experimental techniques that span length-scales from molecular to macroscopic and timescales from picoseconds to seconds to study the evolution of structure and dynamics in model DESs, namely Glyceline and Ethaline, starting from the parent compounds. We show that systematic addition of choline chloride leads to microscopic heterogeneities that alter the primary structural relaxation in glycerol and ethylene glycol and result in new dynamic modes that are strongly correlated to the macroscopic properties of the DES formed.

Outcomes of a Total Joint Arthroplasty Enhanced Recovery Program in a Community Hospital Setting.

BACKGROUND: Same-day discharge (SDD) total joint arthroplasty (TJA) is increasingly popular, yet there remain concerns regarding patient safety, complication rates, and unforeseen overnight admission (failure to launch; FTL). The aim of this study is to retrospectively examine the outcomes of a large consecutive SDD-TJA series in the community hospital setting. METHODS: We retrospectively reviewed 1200 consecutive SDD-TJA candidates between March 2017 and December 2019 by 5 surgeons at a community hospital. Patient demographics, perioperative data including anesthesia type, and 30-day complications were evaluated, including FTL, infection, intraoperative fracture, postoperative periprosthetic fracture or dislocation, return to operating room, and unplanned postoperative care. RESULTS: We included 1200 SDD patients (582/618 total hip arthroplasty/total knee arthroplasty, mean age 62.1 years, 595 females, 605 males). Spinal anesthesia was more common than general anesthesia (1087 vs 113 patients). There were 85 FTLs (7.1%), of this cohort 58.8% were female, with a mean age of 62.4 years. General anesthesia increased the risk of FTL (odds ratio 2.93). Complications resulting in FTL included block-induced neuropraxia (32.1%), orthostatic hypotension (26.1%), urinary retention (19.0%), and nausea (13.1%). Sixteen patients were readmitted within 30 days (1.3%). Six patients returned to the operating room for periprosthetic fracture (4), wound dehiscence (1), and superficial surgical site infection (1). CONCLUSION: SDD-TJA can be safely performed at community hospitals, but general anesthesia should be avoided to decrease risk of FTL. Inpatient programs may allow young surgeons to gain experience with SDD-TJA while retaining overnight admission as a safety net for their patients. LEVEL OF EVIDENCE: Level III (Prognostic).

The Influence of Hospital Site on Emergency Physician Press Ganey Scores.

Background: The use of physician satisfaction scores to evaluate emergency medicine physicians' performance and compensation is controversial. Prior studies have shown that the clinical environment may influence scores. This study compared satisfaction scores for the same physician at different emergency departments (ED). Differences in their individual score may indicate the ED environment could be as important as the physician's interaction. Methods: Press Ganey satisfaction scores were obtained for physicians at three EDs-Grand Strand, South Strand and North Strand-between July 2018 and June 2019. Included physicians worked at all 3 facilities and had at least 6 patient satisfaction surveys at each site. The Press Ganey scale ranges from 1-5, with 1 as "very poor" and 5 as "very good". Using top-box methodology, the total physician score was generated from the average of 4 questions: courtesy, keeping patients informed, patient comfort and listening. We utilized descriptive statistics to compare scores for all physicians at each of the 3 sites. In addition, each physician's top box scores were averaged by site for analysis (two-way ANOVA) to determine if individual physician scores varied in different EDs. Results: Fourteen physicians met inclusion criteria. Physicians at the main ED had an average total score of 73.37 ± 6.08 (SD) versus 76.5 ± 8.87 and 85.09 ± 7.75 at the 2 free standing EDs. Two-way ANOVA showed that the Press Ganey scores were significantly different for individual physicians between the newer free-standing ED and either the main ED or the other free-standing ED, p<0.001 and p=0.014, respectively. The observed difference between the main ED and the older free-standing ED was not statistically significant, p=0.111. When applying the same analysis to the 4 individual physician questions, the significant differences or trends persisted. Conclusion: Physician satisfaction scores demonstrated a significant variance depending on where they practiced. The highest patient satisfaction scores were received at the newest of the 3 facilities with individual rooms. The findings suggest that Press Ganey scores may not be reliable when comparing patient satisfaction scores for providers who practice in different EDs.

Deep Eutectic Solvents: A Review of Fundamentals and Applications.

Deep eutectic solvents (DESs) are an emerging class of mixtures characterized by significant depressions in melting points compared to those of the neat constituent components. These materials are promising for applications as inexpensive "designer" solvents exhibiting a host of tunable physicochemical properties. A detailed review of the current literature reveals the lack of predictive understanding of the microscopic mechanisms that govern the structure-property relationships in this class of solvents. Complex hydrogen bonding is postulated as the root cause of their melting point depressions and physicochemical properties; to understand these hydrogen bonded networks, it is imperative to study these systems as dynamic entities using both simulations and experiments. This review emphasizes recent research efforts in order to elucidate the next steps needed to develop a fundamental framework needed for a deeper understanding of DESs. It covers recent developments in DES research, frames outstanding scientific questions, and identifies promising research thrusts aligned with the advancement of the field toward predictive models and fundamental understanding of these solvents.

Comparative Study of Newer and Established Methods of Diagnosing Coccidioidal Meningitis.

Meningitis is the most devastating form of coccidioidomycosis. A convenient, rapid diagnostic method could result in early treatment and avoid many meningitis complications. We studied cerebrospinal fluid (CSF) samples in patients with documented coccidioidal meningitis, and controls, with complement fixation (CF), immunodiffusion (ID) (the "classical" assays), lateral flow assays (LFA; one-strip and two-strip), and two enzyme immunoassays (EIA). The two-strip LFA and EIAs not only enabled separate testing for IgG and IgM antibodies separately, but also could aggregate results for each method. CF with ID or the aggregate use of IgG and IgM tests were considered optimal test uses. LFAs and EIAs were evaluated at 1:21 and 1:441 dilutions of specimens. All assays were compared to true patient status. With 49 patient specimens and 40 controls, this is the largest comparative study of CSF coccidioidal diagnostics. Sensitivity of these tests ranged from 71-95% and specificity 90-100%. IgM assays were less sensitive. Assays at 1:441 were similarly specific but less sensitive, suggesting that serial dilutions of samples could result in assays yielding titers. Agreement of positive results on cases was 87-100%. When kits are available, hospital laboratories in endemic areas can perform testing. LFA assays do not require a laboratory, are simple to use, and give rapid results, potentially even at the bedside.

Liquid Structure and Transport Properties of the Deep Eutectic Solvent Ethaline.

A range of techniques including physical property measurements, neutron scattering experiments, ab initio molecular dynamics, and classical molecular dynamics simulations are used to probe the structural, thermodynamic, and transport properties of a deep eutectic solvent comprised of a 1:2 molar ratio of choline chloride and ethylene glycol. This mixture, known as Ethaline, has many desirable properties for use in a range of applications, and therefore, understanding its liquid structure and transport properties is of interest. Simulation results are able to capture experimental densities, diffusivities, viscosities, and structure factors extremely well. The solvation environment is dynamic and dominated by different hydrogen bonding interactions. Dynamic heterogeneities resulting from hydrogen bonding interactions are quantified. Rotational dynamics of molecular dipole moments of choline and ethylene glycol are computed and found to exhibit a fast and slow mode.

Accurate Diels-Alder Energies and Endo Selectivity in Ionic Liquids Using the OPLS-VSIL Force Field.

Our recently developed optimized potentials for liquid simulations-virtual site ionic liquid (OPLS-VSIL) force field has been shown to provide accurate bulk phase properties and local ion-ion interactions for a wide variety of imidazolium-based ionic liquids. The force field features a virtual site that offloads negative charge to inside the plane of the ring with careful attention given to hydrogen bonding interactions. In this study, the Diels-Alder reaction between cyclopentadiene and methyl acrylate was computationally investigated in the ionic liquid 1-butyl-3-methylimidazolium hexafluorophosphate, [BMIM][PF6], as a basis for the validation of the OPLS-VSIL to properly reproduce a reaction medium environment. Mixed ab initio quantum mechanics and molecular mechanics (QM/MM) calculations coupled to free energy perturbation and Monte Carlo sampling (FEP/MC) that utilized M06-2X/6-31G(d) and OPLS-VSIL gave activation free energy barriers of 14.9 and 16.0 kcal/mol for the endo-cis and exo-cis Diels-Alder reaction pathways, respectively (exptl. ΔH‡ of 14.6 kcal/mol). The endo selectivity trend was correctly predicted with a calculated 73% endo preference. The rate and selectivity enhancements present in the endo conformation were found to arise from preferential hydrogen bonding with the exposed C4 ring hydrogen on the BMIM cation. Weaker electronic stabilization of the exo transition state was predicted. For comparison, our earlier ±0.8 charge-scaled OPLS-2009IL force field also yielded a ΔG‡ of 14.9 kcal/mol for the favorable endo reaction pathway but did not adequately capture the highly organized solvent interactions present between the cation and Diels-Alder transition state.

Improvement in health status with once-daily indacaterol/glycopyrronium 110/50 µg in COPD patients: real-world evidence from an observational study in Ireland.

AIMS: Indacaterol/glycopyrronium (IND/GLY) 110/50 µg is a once-daily (o.d.) fixed-dose combination of long-acting ß2-agonist/long-acting muscarinic antagonist approved in over 90 countries, including Ireland, for the management of COPD. The present study was conducted to evaluate health status of COPD patients, initiated on IND/GLY 110/50 µg o.d., using the Clinical COPD Questionnaire (CCQ) tool in a real-world primary care setting in Ireland. METHODS: This was a real-world, prospective, open-label study. COPD patients aged > 40 years and with a smoking history of > 10 pack-years were included and switched to once-daily IND/GLY 110/50 µg. Enrolment of patients into the study occurred only after the decision had been made by the physician to prescribe IND/GLY 110/50 µg. Data were collected at baseline and Week 26. Health status was assessed using the validated CCQ. RESULTS: A total of 200 patients were included in study. The mean CCQ total score decreased from 2.36 at baseline to 1.44 at Week 26 (Δ, 0.92; P < 0.0005). Of the 156 patients who completed study, 113 (72.4%) achieved minimum clinically important difference in CCQ total score with IND/GLY 110/50 µg. CCQ domain scores also decreased during the study. Improvement in health status was observed across all GOLD groups and irrespective of prior COPD treatment. Adverse events were reported by 20% of patients with COPD exacerbation/infected COPD being the most common AE, reported by 11 patients. CONCLUSIONS: In real-life clinical practice in Ireland, IND/GLY 110/50 µg o.d. demonstrated statistically significant and clinically important improvement in health status in patients with COPD.

OPLS Force Field for Choline Chloride-Based Deep Eutectic Solvents.

Deep eutectic solvents (DES) are a class of solvents frequently composed of choline chloride and a neutral hydrogen bond donor (HBD) at ratios of 1:1, 1:2, or 1:3, respectively. As cost-effective and eco-friendly solvents, DESs have gained considerable popularity in multiple fields, including materials, separations, and nanotechnology. In the present work, a comprehensive set of transferable parameters have been fine-tuned to accurately reproduce bulk-phase physical properties and local intermolecular interactions for 8 different choline chloride-based DESs. This nonpolarizable force field, OPLS-DES, gave near quantitative agreement at multiple temperatures for experimental densities, viscosities, heat capacities, and surface tensions yielding overall mean absolute errors (MAEs) of ca. 1.1%, 1.6%, 5.5%, and 1.5%, respectively. Local interactions and solvent structuring between the ions and HBDs, including urea, glycerol, phenol, ethylene glycol, levulinic acid, oxalic acid, and malonic acid, were accurately reproduced when compared to radial distribution functions and coordination numbers derived from experimental liquid-phase neutron diffraction data and from first-principles molecular dynamics simulations. The reproduction of transport properties presented a considerable challenge and behaved more like a supercooled liquid near room temperature; higher-temperature simulations, e.g., 400-500 K, or an alternative polarizable force field is recommended when computing self-diffusion coefficients.

Virtual Site OPLS Force Field for Imidazolium-Based Ionic Liquids.

Molecular simulations of ionic liquids can provide deeper insight into the relationship between intermolecular interactions and macroscopic measurements for the solvents. However, many existing force fields have multiple shortcomings, including poor solvent dynamics, the underestimation of hydrogen-bonding strength, and errors in solvent interactions/organization. A new force field, called optimized potentials for liquid simulation-ionic-liquid virtual site (OPLS-VSIL), has been developed for imidazolium-based ionic liquids featuring a novel topology incorporating a virtual site bisecting the nitrogen atoms that offloads negative charge to inside the plane of the ring. Guided by free energy of hydration calculations, an empirically derived set of partial charges and nonbonded Lennard-Jones terms for both 1-alkyl-3-methylimidazolium and 11 different anions provided accurate bulk-phase ionic-liquid properties and produced radial distribution functions nearly indistinguishable from ab initio molecular dynamics simulations. For example, overall mean absolute errors (MAEs) of 3.1-3.4% were computed for the density, heat of vaporization, and viscosity of approximately 20 different ion pair combinations. Additional physical properties, such as, self-diffusion coefficients, heat capacity, and surface tension also gave significant MAE improvements using OPLS-VSIL compared to the existing fixed-charge ionic-liquid force fields. Local interactions, including cation-anion hydrogen bonding and π-π stacking between the imidazolium rings, were also accurately reproduced.

Revisiting OPLS Force Field Parameters for Ionic Liquid Simulations.

Our OPLS-2009IL force field parameters (J. Chem. Theory Comput. 2009, 5, 1038-1050) were originally developed and tested on 68 unique ionic liquids featuring the 1-alkyl-3-methylimidazolium [RMIM], N-alkylpyridinium [RPyr], and choline cations. Experimental validation was limited to densities and a few, largely conflicting, heat of vaporization (ΔHvap) values reported in the literature at the time. Owing to the use of Monte Carlo as our sampling technique, it was also not possible to investigate the reproduction of dynamics. The [RMIM] OPLS-2009IL parameters have been revisited in this work and adapted for use in molecular dynamics (MD) simulations. In addition, new OPLS-AA parameters have been developed for multiple anions, i.e., AlCl4-, BF4-, Br-, Cl-, NO3-, PF6-, acetate, benzoate bis(pentafluoroethylsulfonyl)amide, bis(trifluoroethylsulfonyl)amide, dicyanamide, formate, methylsulfate, perchlorate, propanoate, thiocyanate, tricyanomethanide, and trifluoromethanesulfonate. The computed solvent densities, heats of vaporization, viscosities, diffusion coefficients, heat capacities, surface tensions, and other relevant solvent data compared favorably with experiment. A charge scaling of ±0.8 e was also investigated as a means to mimic polarization and charge transfer effects. The 0.8-scaling led to significant improvements for ΔHvap, surface tension, and self-diffusivity; however, a concern when scaling charges is the potential degradation of local intermolecular interactions at short ranges. Radial distribution functions (RDFs) were used to examine cation-anion interactions when employing 0.8*OPLS-2009IL and the scaled force field accurately reproduced RDFs from ab initio MD simulations.

Examining Ionic Liquid Effects on Mononuclear Rearrangement of Heterocycles Using QM/MM Simulations.

The mononuclear rearrangement of heterocycles (MRH) reaction of the Z-phenylhydrazone of 3-benzoyl-5-phenyl-1,2,4-oxadiazole into 4-benzoylamino-2,5-diphenyl-1,2,3-triazole derives a sizable rate enhancement in the 1-butyl-3-methylimidazolium tetrafluoroborate [BMIM][BF4] ionic liquid as compared to the hexafluorophosphate-based [BMIM][PF6] and conventional organic solvents. However, the origin of the rate difference between [BMIM][BF4] and [BMIM][PF6] has proven difficult to rationalize as no experimental trend relates the physical properties of the solvents, e.g., polarity and viscosity, to the rates of reaction. QM/MM calculations in combination with free-energy perturbation theory and Monte Carlo sampling have been carried out for the MRH reaction to elucidate the disparities in rates when using ionic liquids, methanol, and acetonitrile. Activation barriers and solute-solvent interactions have been computed for both an uncatalyzed and a specific base-catalyzed mechanism. Energetic and structural analyses determined that favorable π+-π interactions between the BMIM cation, the substrate phenyl rings, and the bicyclic quasi-aromatic 10π oxadiazole/triazole transition state region imposed a preordered geometric arrangement that enhanced the rate of reaction. An ionic liquid clathrate formation enforced a coplanar orientation of the phenyl rings that maximized the electronic effects exerted on the reaction route. In addition, site-specific electrostatic stabilization between the ions and the MRH substrate was more prevalent in [BMIM][BF4] as compared to [BMIM][PF6].

Prevalence, correlates, and outcomes of cryptococcal antigen positivity among patients with AIDS, United States, 1986-2012.

BACKGROUND: Cryptococcal meningitis (CM) is one of the most common causes of AIDS-related mortality worldwide, accounting for 33%-63% of all cases of adult meningitis in sub-Saharan Africa and >500 000 deaths annually. In sub-Saharan Africa, the World Health Organization recommends routinely screening AIDS patients with a CD4 count ≤100 cells/µL for cryptococcal infection. In the United States, there are no recommendations for routine screening. We aimed to determine the prevalence of cryptococcal infection and outcomes of those infected among people living with advanced AIDS in the United States, to inform updates in the prevention and management of CM. METHODS: Using stored sera from participants in the Multicenter AIDS Cohort Study and the Women's Interagency HIV Study from 1986 to 2012, we screened 1872 specimens with CD4 T-cell counts ≤100 cells/µL for cryptococcal antigen (CrAg) using the CrAg lateral flow assay. RESULTS: The overall prevalence of CrAg positivity within the study population was 2.9% (95% confidence interval, .2%-3.8%). Results from multivariable analysis revealed that a previous diagnosis with CM and a CD4 count ≤50 cells/µL were significantly associated with CrAg positivity. Participants who were CrAg positive had significantly shorter survival (2.8 years) than those who were CrAg negative (3.8 years; P = .03). CONCLUSIONS: The prevalence of cryptococcal infection among advanced AIDS patients in the United States was high and above the published cost-effectiveness threshold for routine screening. We recommend routine CrAg screening among human immunodeficiency virus-infected patients with a CD4 count ≤100 cells/µL to detect and treat early infection.

Interfacing a biosurveillance portal and an international network of institutional analysts to detect biological threats.

The Early Alerting and Reporting (EAR) project, launched in 2008, is aimed at improving global early alerting and risk assessment and evaluating the feasibility and opportunity of integrating the analysis of biological, chemical, radionuclear (CBRN), and pandemic influenza threats. At a time when no international collaborations existed in the field of event-based surveillance, EAR's innovative approach involved both epidemic intelligence experts and internet-based biosurveillance system providers in the framework of an international collaboration called the Global Health Security Initiative, which involved the ministries of health of the G7 countries and Mexico, the World Health Organization, and the European Commission. The EAR project pooled data from 7 major internet-based biosurveillance systems onto a common portal that was progressively optimized for biological threat detection under the guidance of epidemic intelligence experts from public health institutions in Canada, the European Centre for Disease Prevention and Control, France, Germany, Italy, Japan, the United Kingdom, and the United States. The group became the first end users of the EAR portal, constituting a network of analysts working with a common standard operating procedure and risk assessment tools on a rotation basis to constantly screen and assess public information on the web for events that could suggest an intentional release of biological agents. Following the first 2-year pilot phase, the EAR project was tested in its capacity to monitor biological threats, proving that its working model was feasible and demonstrating the high commitment of the countries and international institutions involved. During the testing period, analysts using the EAR platform did not miss intentional events of a biological nature and did not issue false alarms. Through the findings of this initial assessment, this article provides insights into how the field of epidemic intelligence can advance through an international network and, more specifically, how it was further developed in the EAR project.