Softening by charging: how collective modes of ionic association in concentrated redoxmer/electrolyte solutions define the structural and dynamic properties in different states of charge.

Understanding the physical and chemical processes occurring in concentrated electrolyte solutions is required to achieve redox flow batteries with high energy density. Highly concentrated electrolyte solutions are often studied in which collective crowded interactions between molecules and ions become predominant. Herein, experimental and computational methods were used to examine non-aqueous electrolyte solutions in two different states of charge as a function of redoxmer concentration. As the latter increases and the ionic association strengthens, the electric conductivity passes through a maximum and the solution increasingly gels, which is seen through a rapid non-linear increase in viscosity. We establish that the structural rigidity of ionic networks is closely connected with this loss of fluidity and show that charging generally yields softer ionic assemblies with weaker attractive forces and improved dynamical properties.

Aspirin Use Is Associated With Decreased Mechanical Ventilation, Intensive Care Unit Admission, and In-Hospital Mortality in Hospitalized Patients With Coronavirus Disease 2019.

BACKGROUND: Coronavirus disease-2019 (COVID-19) is associated with hypercoagulability and increased thrombotic risk in critically ill patients. To our knowledge, no studies have evaluated whether aspirin use is associated with reduced risk of mechanical ventilation, intensive care unit (ICU) admission, and in-hospital mortality. METHODS: A retrospective, observational cohort study of adult patients admitted with COVID-19 to multiple hospitals in the United States between March 2020 and July 2020 was performed. The primary outcome was the need for mechanical ventilation. Secondary outcomes were ICU admission and in-hospital mortality. Adjusted hazard ratios (HRs) for study outcomes were calculated using Cox-proportional hazards models after adjustment for the effects of demographics and comorbid conditions. RESULTS: Four hundred twelve patients were included in the study. Three hundred fourteen patients (76.3%) did not receive aspirin, while 98 patients (23.7%) received aspirin within 24 hours of admission or 7 days before admission. Aspirin use had a crude association with less mechanical ventilation (35.7% aspirin versus 48.4% nonaspirin, P = .03) and ICU admission (38.8% aspirin versus 51.0% nonaspirin, P = .04), but no crude association with in-hospital mortality (26.5% aspirin versus 23.2% nonaspirin, P = .51). After adjusting for 8 confounding variables, aspirin use was independently associated with decreased risk of mechanical ventilation (adjusted HR, 0.56, 95% confidence interval [CI], 0.37-0.85, P = .007), ICU admission (adjusted HR, 0.57, 95% CI, 0.38-0.85, P = .005), and in-hospital mortality (adjusted HR, 0.53, 95% CI, 0.31-0.90, P = .02). There were no differences in major bleeding (P = .69) or overt thrombosis (P = .82) between aspirin users and nonaspirin users. CONCLUSIONS: Aspirin use may be associated with improved outcomes in hospitalized COVID-19 patients. However, a sufficiently powered randomized controlled trial is needed to assess whether a causal relationship exists between aspirin use and reduced lung injury and mortality in COVID-19 patients.

Development of an MFL Coil Sensor for Testing Pipes in Extreme Temperature Conditions.

This paper aims to design a coil sensor for corrosion monitoring of industrial pipes that could detect variations in thickness using the MFL (Magnetic Flux Leakage) technique. An MFL coil sensor is designed and tested with pipe sample thicknesses of 2, 4, 6, and 8 mm based on the magnetic field effect of ferrite cores. Moreover, a measurement setup for analysing pipe samples up to a temperature of 200° Celsius is suggested. Experimental results reveal that the MFL coil sensor can fulfil the requirements for MFL testing of pipes in high temperature conditions, and that the precision of MFL monitoring of pipes to detect corrosion at high temperatures can be improved significantly.

Stereoselective Catalysis Achieved through in Situ Desymmetrization of an Achiral Iron Catalyst Precursor.

Stereoselective catalysis is described that proceeds with catalyst control but without the need to synthesize preformed chiral catalysts or ligands. Iron-based catalysts were discovered to effect the stereoselective polymerization of lactides starting from a single achiral precursor and the proper choice of an achiral silanol additive. Spectroscopic analysis of the polymer revealed that the stereoselectivity originates from an enantiomorphic site rather than a chain end stereocontrol mechanism. Iron intermediates that are stereogenic at iron are proposed to form in situ as a result of desymmetrization that occurs from a change in the metal coordination number. The proposed mechanism is supported by a combination of spectroscopic measurements, model complexes, kinetic measurements, and DFT calculations.

Electron-Poor Thiophene 1,1-Dioxides: Synthesis, Characterization, and Application as Electron Relays in Photocatalytic Hydrogen Generation.

The synthesis and characterization of electron-poor thiophene 1,1-dioxides bearing cyanated phenyl groups are reported. The electron-accepting nature of these compounds was evaluated by cyclic voltammetry, and highly reversible and facile reductions were observed for several derivatives. Moreover, some of the reduced thiophene dioxides form colorful anions, which were investigated spectroelectrochemically. Photoluminescence spectra of the electron-deficient sulfones were measured in CH2 Cl2, and they emit in the blue-green region with significant variation in the quantum yield depending on the aryl substituents. By expanding the degree of substitution on the phenyl rings, quantum yields up to 34 % were obtained. X-ray diffraction data are reported for two of the thiophene 1,1-dioxides, and the electronic structure was probed for all synthesized derivatives through DFT calculations. The dioxides were also examined as electron relays in a photocatalytic water reduction reaction, and they showed potential to boost the efficiency.

Properties and ATRP activity of copper complexes with substituted tris(2-pyridylmethyl)amine-based ligands.

Synthesis, characterization, electrochemical studies, and ATRP activity of a series of novel copper(I and II) complexes with TPMA-based ligands containing 4-methoxy-3,5-dimethyl-substituted pyridine arms were reported. In the solid state, Cu(I)(TPMA*(1))Br, Cu(I)(TPMA*(2))Br, and Cu(I)(TPMA*(3))Br complexes were found to be distorted tetrahedral in geometry and contained coordinated bromide anions. Pseudo-coordination of the aliphatic nitrogen atom to the copper(I) center was observed in Cu(I)(TPMA*(2))Br and Cu(I)(TPMA*(3))Br complexes, whereas pyridine arm dissociation occurred in Cu(I)(TPMA*(1))Br. All copper(I) complexes with substituted TPMA ligands exhibited a high degree of fluxionality in solution. At low temperature, Cu(I)(TPMA*(1))Br was found to be symmetrical and monomeric, while dissociation of either unsubstituted pyridine and/or 4-methoxy-3,5-dimethyl-substituted pyridine arms was observed in Cu(I)(TPMA*(2))Br and Cu(I)(TPMA*(3))Br. On the other hand, the geometry of the copper(II) complexes in the solid state deviated from ideal trigonal bipyramidal, as confirmed by a decrease in τ values ([Cu(II)(TPMA*(1))Br][Br] (τ = 0.92) > [Cu(II)(TPMA*(3))Br][Br] (τ = 0.77) > [Cu(II)(TPMA*(2))Br][Br] (τ = 0.72)). Furthermore, cyclic voltammetry studies indicated a nearly stepwise decrease (ΔE ≈ 60 mV) of E1/2 values relative to SCE (TPMA (-240 mV) > TPMA*(1) (-310 mV) > TPMA*(2) (-360 mV) > TPMA*(3) (-420 mV)) on going from [Cu(II)(TPMA)Br][Br] to [Cu(II)(TPMA*(3))Br][Br], confirming that the presence of electron-donating groups in the 4 (-OMe) and 3,5 (-Me) positions of the pyridine rings in TPMA increases the reducing ability of the corresponding copper(I) complexes. This increase was mostly the result of a stronger influence of substituted TPMA ligands toward stabilization of the copper(II) oxidation state (log ß(I) = 13.4 ± 0.2, log ß(II) = 19.3 (TPMA*(1)), 20.5 (TPMA*(2)), and 21.5 (TPMA*(3))). Lastly, ARGET ATRP kinetic studies show that with more reducing catalysts an induction period is observed. This was attributed to slow regeneration of Cu(I) species from the corresponding Cu(II).

The fate of phenothiazine-based redox shuttles in lithium-ion batteries.

The stability and reactivity of the multiple oxidation states of aromatic compounds are critical to the performance of these species as additives and electrolytes in energy-storage applications. Both for the overcharge mitigation in ion-intercalation batteries and as electroactive species in redox flow batteries, neutral, radical-cation, and radical-anion species may be present during charging and discharging processes. Despite the wide range of compounds evaluated for both applications, the progress identifying stable materials has been slow, limited perhaps by the overall lack of analysis of the failure mechanism when a material is utilized in an energy-storage device. In this study, we examined the reactivity of phenothiazine derivatives, which have found interest as redox shuttles in lithium-ion battery applications. We explored the products of the reactions of neutral compounds in battery electrolytes and the products of radical cation formation using bulk electrolysis and coin cell cycling. Following the failure of each cell, the electrolytes were characterized to identify redox shuttle decomposition products. Based on these results, a set of decomposition mechanisms is proposed and further explored using experimental and theoretical approaches. The results highlight the necessity to fully characterize and understand the chemical degradation mechanisms of the redox species in order to develop new generations of electroactive materials.

Tuning thiophene with phosphorus: synthesis and electronic properties of benzobisthiaphospholes.

1,4-Dimercapto-2,5-diphosphinobenzene and 3,6-bis(hexyloxy)-1,4-dimercapto-2,5-diphosphinobenzene were synthesized and combined with various acid chlorides to obtain a series of benzobisthiaphospholes. Electrochemical and photophysical properties of the substituted benzobisthiaphospholes have been evaluated, and the observed reductions are more facile than the related benzothiaphospholes and 2,6-diphenylbenzobisthiazole. A benzobisthiaphosphole with C6H4-p-CN substituents was reduced at E(1/2)=-1.08 V (vs. saturated calomel electrode (SCE)). X-ray diffraction data for several of these phosphorus heterocycles has been obtained, and DFT calculations at the B3LYP level have been performed.

[Ir(N

The relatively unexplored luminophore architecture [Ir(N^N^N)(C^N)L](+) (N^N^N = tridentate polypyridyl ligand, C^N = 2-phenylpyridine derivative, and L = monodentate anionic ligand) offers the stability of tridentate polypyridyl coordination along with the tunability of three independently variable ligands. Here, a new family of these luminophores has been prepared based on the previously reported compound [Ir(tpy)(ppy)Cl](+) (tpy = 2,2':6',2″-terpyridine and ppy = 2-phenylpyridine). Complexes are obtained as single stereoisomers, and ligand geometry is unambiguously assigned via X-ray crystallography. Electrochemical analysis of the materials reveals facile HOMO modulation through ppy functionalization and alteration of the monodentate ligand's field strength. Emission reflects similar modulation shifting from orange to greenish-blue upon replacement of chloride with cyanide. Many of the new compounds exhibit impressive room temperature phosphorescence with lifetimes near 3 µs and quantum yields reaching 28.6%. Application of the new luminophores as photosensitizers for photocatalytic hydrogen generation reveals that their photostability in coordinating solvent is enhanced as compared to popular [Ir(ppy)2(bpy)](+) (bpy = 2,2'-bipyridine) photosensitizers. Yet, the binding of their monodentate ligand emerges as a source of instability during the redox processes of cyclic voltammetry and mass spectrometry. DFT modeling of electronic structure is provided for all compounds to elucidate experimental properties.

Cytotoxic constituents from Lobaria scrobiculata and a comparison of two bioassays for their evaluation.

Lichens are resilient organisms, known for their unique profiles of secondary metabolites and for exhibiting antioxidative, antibacterial, and cytotoxic effects. Analyzing the cytotoxic potential of Lobaria scrobiculata, a bioassay-guided fractionation strategy yielded seven known metabolites, with two of these compounds, 2 and 3, exhibiting cytotoxicity against HL-60 cells. In order to verify the potential impact of degradation on observed bioactivity, a purity and stability evaluation was conducted. The consistency of results obtained by the water-soluble tetrazolium salt-1 assay and trypan blue cytotoxicity assay was evaluated for selected compounds.

Concentration-dependent Cycling of Phenothiazine-based Electrolytes in Nonaqueous Redox Flow Cells.

Increasing redox-active species concentrations can improve viability for organic redox flow batteries by enabling higher energy densities, but the required concentrated solutions can become viscous and less conductive, leading to inefficient electrochemical cycling and low material utilization at higher current densities. To better understand these tradeoffs in a model system, we study a highly soluble and stable redox-active couple, N-(2-(2-methoxyethoxy)ethyl)phenothiazine (MEEPT), and its bis(trifluoromethanesulfonyl)imide radical cation salt (MEEPT-TFSI). We measure the physicochemical properties of electrolytes containing 0.2-1 M active species and connect these to symmetric cell cycling behavior, achieving robust cycling performance. Specifically, for a 1 M electrolyte concentration, we demonstrate 94% materials utilization, 89% capacity retention, and 99.8% average coulombic efficiency over 435 h (100 full cycles). This demonstration helps to establish potential for high-performing, concentrated nonaqueous electrolytes and highlights possible failure modes in such systems.

Liberal Intravenous Fluid Administration in a Rare Case of Severe Rhabdomyolysis Secondary to SARS-CoV-2.

SARS-CoV-2 entered the world by storm when it made its appearance at the end of 2019 in Wuhan, China. The severity can range from asymptomatic infection, which occurs in approximately 33% of infected patients, to death. Worldwide deaths due to SARS-CoV-2 are currently approximated at 3.8 million people with close to 600,000 deaths in the United States alone, reiterating the significant impact this virus has on the population. SARS-CoV-2 can affect systems of the body such as respiratory, gastrointestinal tract, neurological, cardiac, renal, and even skeletal muscle tissue. A few cases of rhabdomyolysis are reported in SARS-CoV-2 infection, but the significant level of creatinine kinase in the hundreds of thousands is rare. Our case demonstrates the rarity of SARS-CoV-2 manifestation in a 33-year-old African American male with severe rhabdomyolysis with a creatinine kinase on the admission of 362,445 IU/L. The patient was treated aggressively with intravenous fluids, monitoring electrolytes, renal function, and respiratory status closely. His management includes liberal administration of fluid to treat his rhabdomyolysis, without compromising his respiratory status. He was subsequently discharged home after seven days of hospitalization. We strive to share this information in hopes to share our management for future similar cases.

Cell Death Persists in Rapid Extrusion of Lysis-Resistant Coated Cardiac Myoblasts.

As the demand for organ transplants continues to grow faster than the supply of available donor organs, a new source of functional organs is needed. High resolution high throughput 3D bioprinting is one approach towards generating functional organs for transplantation. For high throughput printing, the need for increased print resolutions (by decreasing printing nozzle diameter) has a consequence: it increases the forces that cause cell damage during the printing process. Here, a novel cell encapsulation method provides mechanical protection from complete lysis of individual living cells during extrusion-based bioprinting. Cells coated in polymers possessing the mechanical properties finely-tuned to maintain size and shape following extrusion, and these encapsulated cells are protected from mechanical lysis. However, the shear forces imposed on the cells during extrusion still cause sufficient damage to compromise the cell membrane integrity and adversely impact normal cellular function. Cellular damage occurred during the extrusion process independent of the rapid depressurization.

High-performance thin layer chromatography method for estimation of conessine in herbal extract and pharmaceutical dosage formulations.

A new, simple, sensitive, precise and robust high-performance thin layer chromatographic (HPTLC) method was developed for the estimation of conessine in herbal extracts and pharmaceutical dosage forms. Analysis of conessine was performed on TLC aluminium plates pre-coated with silica gel 60F-254 as stationary phase. Linear ascending development was carried out in twin trough glass chamber saturated with mobile phase consisting of toluene-ethylacetate-diethyl amine (6.5:2.5:1, v/v/v) at room temperature (25+/-2 degrees C). After derivatized the plate with modified Dragendroff's reagent, Camag TLC scanner III was used for spectrodensitometric scanning and analysis of the plate in absorbance mode at 520 nm. The system was found to give compact spots for conessine (Rf value of 0.82). The data for calibration plots showed good linear relationship with r2=0.9998 in the concentration range of 1-10 microg with respect to peak area. The present method was validated for precision and recovery. The limits of detection and quantification were determined. Statistical analysis of the data showed that the method is reproducible and selective for estimation of conessine.

Opioid drug utilization and cost outcomes associated with the use of buprenorphine-naloxone in patients with a history of prescription opioid use.

BACKGROUND: Management of opioid dependence is associated with many challenges such as the misuse of prescribed treatment and lack of medication adherence that can affect the clinical outcome of the patient. Buprenorphine-naloxone was approved by the U.S. Food and Drug Administration in October 2002 as the first outpatient treatment indicated for opioid dependence. There is only 1 report in the literature on the effectiveness of buprenorphine-naloxone in a real-world setting and no reports on persistence and cost obtained from administrative claims data. OBJECTIVES: To determine (1) the length and cost of therapy with oral buprenorphine-naloxone, and (2) the cost avoidance for opioid dependence as measured by opioid utilization and opioid drug cost obtained from pharmacy claim records. METHODS: The patients for this drug use evaluation (DUE) were identified from a New Jersey managed care organization (MCO) with approximately 1.8 million members with pharmacy benefits who (a) were continuously enrolled from October 1, 2004, through September 30, 2006; (b) had their first buprenorphine-naloxone pharmacy claim during the fixed 6-month initiation period (April 1, 2005, through September 30, 2005); and (c) had at least 1 opioid pharmacy claim in the 6-month pre period preceding the 6-month initiation period. The outcome measures included the number of opioid pharmacy claims, daily dose, days supply, and cost defined as opioid ingredient cost. Member cost share and net plan cost (after subtraction of member cost share) were also measured. The measurement periods for opioid use and cost were the fixed calendar periods for 6 months from October 1, 2004, through March 31, 2005, and for 12 months from October 1, 2005, through September 30, 2006. Persistence in the 12-month follow-up period was defined as a gap of 30 days or less between depletion of the days supply for the preceding pharmacy claim for buprenorphinenaloxone and the date of service (refill date) for the succeeding pharmacy claim for buprenorphine-naloxone. RESULTS: Of the 160 new buprenorphine-naloxone users with continuous pharmacy enrollment for the 2-year period ending September 30, 2006, 84 patients (52.5%) had at least 1 opioid pharmacy claim in the 6-month pre period from October 1, 2004, through March 31, 2005, and were included in this DUE. In the 12-month post period from October 1, 2005, through September 2006, the median length of therapy with buprenorphinenaloxone was 1 month, and the mean length of therapy was 3.5 months. Only 40 patients (47.6%) had a pharmacy claim for buprenorphine-naloxone at month 1 in the 12-month post period. Persistence was 27.4% (n = 23) at 6 months (March 2006) and 20.2% (n = 17) at 12 months (September 2006) in the post period. A total of 24 study patients (28.6%) had no opioid pharmacy claims other than buprenorphine-naloxone in the 12-month post period. Utilization of opioids decreased by 18.8%, from 1.49 opioid pharmacy claims per patient per month (PPPM) in the pre period to 1.21 claims PPPM in the post period (P = 0.031). Excluding the 0.42 buprenorphine-naloxone claims PPPM, opioid utilization decreased by 47.0%, from 1.49 claims PPPM to 0.79 claims PPPM (P < 0.001) in the 12-month post period. Before subtraction of member cost share, the actual drug cost of opioids including buprenorphine-naloxone appeared to be 26.9% lower ($156.24 PPPM) in the post period compared with $213.74 PPPM in the pre period, but the difference was not statistically significant (P = 0.254). Excluding the cost of the buprenorphine-naloxone, actual opioid drug cost decreased 66.5% from $213.74 PPPM pre period to $71.65 PPPM post period (P = 0.047). CONCLUSIONS: Approximately one half of the patients who had a new claim for buprenorphine-naloxone were excluded from this study because there was no utilization of prescription opioids in the 6 months prior to initiation. For patients with documented use of prescription opioids prior to initiation, treatment with buprenorphine-naloxone was associated with a reduction in opioid utilization and cost in the first year of follow-up. Persistence was only 27% at 6 months and 20% at 12 months, and there were no drug cost savings in the follow-up period when the actual cost of the buprenorphine-naloxone therapy was included.

Overcharge performance of 3,7-disubstituted N-ethylphenothiazine derivatives in lithium-ion batteries.

3,7-Disubstituted N-ethylphenothiazine derivatives were synthesized as redox shuttle candidates for lithium-ion batteries. Battery cycling results show that three derivatives prevent overcharge.

Early human prostate adenocarcinomas harbor androgen-independent cancer cells.

Although blockade of androgen receptor (AR) signaling represents the main treatment for advanced prostate cancer (PrCa), many patients progress to a lethal phenotype of "Castration-Resistant" prostate cancer (CR-PrCa). With the hypothesis that early PrCa may harbor a population of androgen-unresponsive cancer cells as precursors to CR-recurrent disease, we undertook the propagation of androgen-independent cells from PrCa-prostatectomy samples of early, localized (Stage-I) cases. A collection of 120 surgical specimens from prostatectomy cases was established, among which 54 were adenocarcinomas. Hormone-free cell culture conditions were developed allowing routine propagation of cells expressing prostate basal cell markers and stem/progenitor cell markers, and which proliferated as spheres/spheroids in suspension cultures. Colonies of androgen-independent epithelial cells grew out from 30/43 (70%) of the adenocarcinoma cases studied in detail. Fluorescence microscopy and flow cytometry showed that CR-PrCa cells were positive for CD44, CD133, CK5/14, c-kit, integrin α2ß1, SSEA4, E-Cadherin and Aldehyde Dehydrogenase (ALDH). All 30 CR-PrCa cell cultures were also TERT-positive, but negative for TMPRSS2-ERG. Additionally, a subset of 22 of these CR-PrCa cell cultures was examined by orthotopic xenografting in intact and castrated SCID mice, generating histologically typical locally-invasive human PrCa or undifferentiated cancers, respectively, in 6-8 weeks. Cultured PrCa cells and orthotopically-induced in vivo cancers lacked PSA expression. We report here the propagation of Cancer Initiating Cells (CIC) directly from Stage I human PrCa tissue without selection or genetic manipulation. The propagation of stem/progenitor-like CR-PrCa cells derived from early human prostate carcinomas suggests the existence of a subpopulation of cells resistant to androgen-deprivation therapy and which may drive the subsequent emergence of disseminated CR-PrCa.

Conjugated polymer nanoparticles for small interfering RNA delivery.

Loosely aggregated conjugated polymer nanoparticles (CPNs) were used as nontoxic and efficient small interfering RNA (siRNA) delivery vehicles with delivery visualization. A significant down regulation (94%) of a target gene was achieved by transfection of HeLa cells with the CPNs/siRNA complexes, supporting CPN as a promising siRNA delivery carrier.

Linear and spiral forms of longitudinal cuts in graphitized N-doped multiwalled carbon nanotubes (g-N-MWCNTs).

Nitrogen-containing multiwalled nanotubes (N-MWCNTs), formed by CVD from a nitrogen-containing feedstock have a 'bamboo' structure in which the axes of the graphene planes are not parallel to the axis of the nanotube and the core is periodically bridged. We find that thermal and chemical treatment of these materials can produce nanotubes that have been cut longitudinally in either a linear or in a spiral manner. In addition, these longitudinally cut nanotubes can be partially or fully unrolled by sonication in an aqueous surfactant, producing graphite platelets as well as narrow structures that could be thin graphite ribbons or very narrow, intact N-MWCNTs. These different morphologies of graphite, available from one source, suggest that there are multiple structures of N-MWCNTs present, few as simple as stacked cups or nested scrolls.