Surface Energy and Wetting Behavior of Dolomite in the Presence of Carboxylic Acid-Based Deep Eutectic Solvents.

This study endeavors to apply experimental and theoretical analyses to assess the viability of wettability alteration for two carboxylic acid-based deep eutectic solvents (DESs). To prepare these chemicals, oxalic acid and citric acid were used as hydrogen bond donors mixed with choline chloride as the hydrogen bond acceptor in an equimolar ratio. In the theoretical part, dolomite and crude oil were characterized using a three-phase setup. Then, the adhesion propensity of brines/crude oil toward dolomite was evaluated by calculating the work of adhesion. Contact angle and interfacial tension measurements were conducted in the experimental part to investigate the impact of chemicals on brine-crude oil and brine-rock interactions. Results revealed that the oxalic acid-based DES outperformed the citric acid-based DES in terms of interfacial tension reduction. In addition, choline chloride/oxalic acid (1:1) could effectively restore the wettability of the dolomite sample to its original state with a wettability alteration index of 82%. Theoretical calculations also confirmed the wettability alteration potential of DESs. Finally, a correlation was proposed to predict the contact angle of brine on the dolomite surface in the presence of crude oil using surface-energy components of brine, crude oil, and dolomite.

1H, 13C, and 15N backbone chemical shift assignments of coronavirus-2 non-structural protein Nsp10.

The international Covid19-NMR consortium aims at the comprehensive spectroscopic characterization of SARS-CoV-2 RNA elements and proteins and will provide NMR chemical shift assignments of the molecular components of this virus. The SARS-CoV-2 genome encodes approximately 30 different proteins. Four of these proteins are involved in forming the viral envelope or in the packaging of the RNA genome and are therefore called structural proteins. The other proteins fulfill a variety of functions during the viral life cycle and comprise the so-called non-structural proteins (nsps). Here, we report the near-complete NMR resonance assignment for the backbone chemical shifts of the non-structural protein 10 (nsp10). Nsp10 is part of the viral replication-transcription complex (RTC). It aids in synthesizing and modifying the genomic and subgenomic RNAs. Via its interaction with nsp14, it ensures transcriptional fidelity of the RNA-dependent RNA polymerase, and through its stimulation of the methyltransferase activity of nsp16, it aids in synthesizing the RNA cap structures which protect the viral RNAs from being recognized by the innate immune system. Both of these functions can be potentially targeted by drugs. Our data will aid in performing additional NMR-based characterizations, and provide a basis for the identification of possible small molecule ligands interfering with nsp10 exerting its essential role in viral replication.

1H, 13C, and 15N backbone chemical shift assignments of the apo and the ADP-ribose bound forms of the macrodomain of SARS-CoV-2 non-structural protein 3b.

The SARS-CoV-2 genome encodes for approximately 30 proteins. Within the international project COVID19-NMR, we distribute the spectroscopic analysis of the viral proteins and RNA. Here, we report NMR chemical shift assignments for the protein Nsp3b, a domain of Nsp3. The 217-kDa large Nsp3 protein contains multiple structurally independent, yet functionally related domains including the viral papain-like protease and Nsp3b, a macrodomain (MD). In general, the MDs of SARS-CoV and MERS-CoV were suggested to play a key role in viral replication by modulating the immune response of the host. The MDs are structurally conserved. They most likely remove ADP-ribose, a common posttranslational modification, from protein side chains. This de-ADP ribosylating function has potentially evolved to protect the virus from the anti-viral ADP-ribosylation catalyzed by poly-ADP-ribose polymerases (PARPs), which in turn are triggered by pathogen-associated sensing of the host immune system. This renders the SARS-CoV-2 Nsp3b a highly relevant drug target in the viral replication process. We here report the near-complete NMR backbone resonance assignment (1H, 13C, 15N) of the putative Nsp3b MD in its apo form and in complex with ADP-ribose. Furthermore, we derive the secondary structure of Nsp3b in solution. In addition, 15N-relaxation data suggest an ordered, rigid core of the MD structure. These data will provide a basis for NMR investigations targeted at obtaining small-molecule inhibitors interfering with the catalytic activity of Nsp3b.

Donor-acceptor interactions in tri(phosphonio)methanide dications [(Ph3P)2CP(X)Ph2]2+ (X = H, Me, CN, NCS, OH, Cl, OTf, F).

The impact of the strongly electron donating carbodiphosphorane moiety in the series of tri(phosphonio)methanide dications as triflate salts [(Ph3P)2CP(X)Ph2][OTf]2 (X = H, Me, CN, NCS, OH, Cl, OTf, F) deriving from [(Ph3P)2CPPh2][OTf] (19[OTf]) is presented. The influence of the introduced substituents X on the electronic structures of these dications is investigated by means of detailed NBO analysis, NMR spectroscopy and X-ray analysis.

Carbodiphosphorane mediated synthesis of a triflyloxyphosphonium dication and its reactivity towards nucleophiles.

A carbodiphosphorane ((Ph3P)2C) mediated synthesis of the first triflyloxyphosphonium dication (12+) bearing two electrophilic sites is presented. Depending on the nucleophile, 12+ reacts selectively either at the sulfur atom of the triflyloxy moiety or at the directly attached phosphorus atom. In substitution reactions at the phosphorus atom the triflyloxy moiety serves as a leaving group and enables the synthesis of rare examples of pseudo-halophosphonium dications.

Formation of the spirocyclic, Si-centered cage cations [ClP(NSiMe3)2Si(NSiMe3)2P5](+) and [P5(NSiMe3)2Si(NSiMe3)2P5](2).

On account of our interest in P4 activation by phosphenium ion insertion into P-P bonds we have developed synthetic routes to bicyclic N-P-Si-heterocycle 7 and probed its reactivity towards GaCl3 and P4. A GaCl3-induced rearrangement of 7 leads to the in situ formation of spirocyclic, Si-centered phosphenium ions. Their insertion into P-P bonds of one or two P4 tetrahedra yields polyphosphorus cages [ClP(NSiMe3)2Si(NSiMe3)2P5](+) (19(+)) and [P5(NSiMe3)2Si(NSiMe3)2P5](2+) (13(2+)).

Synthesis of Selected Cationic Pnictanes [LnPnX3-n](n+) (L = Imidazolium-2-yl; Pn = P, As; n = 1-3) and Replacement Reactions with Pseudohalogens.

Herein we report on reactions of "imidazoliumyl-transfer" reagents [L((R/R'))SiMe3][OTf] (4((R/R'))[OTf]); L = imidazolium-2-yl, R/R': Me/Me, (i)Pr/Me, Dipp/H, Dipp/Cl) with pnictogen trichlorides PnCl3 (Pn = P, As, Sb) in various stoichiometries. In the case of the 1:1 reaction of [L((R/R'))SiMe3][OTf] with PCl3 the corresponding cationic imidazoliumyl-substituted dichlorophosphanes [L((R/R'))PCl2](+) (1P((R/R')))(+) are obtained as triflate salts on a multigram scale. We found that the reactions using various stoichiometries of [L((R/R'))SiMe3][OTf] and PnCl3 are less selective in the case of the heavier congeners or by decreasing steric demand of the R-group attached to the N atoms of the heterocycle. An equilibrium between the monocation [L((Me/Me))PCl2](+) (1P((Me/Me)+)), the dication [L((Me/Me))2PCl](2+) (2P((Me/Me)2+)), and the trication [L((Me/Me))3P](3+) (5P((Me/Me)3+)) is observed in solution. Reactions of the monocationic derivatives [L((R/R'))PnCl2][OTf] (Pn = P, As) with Me3SiX (X = CN, N3) resulted in the exchange of the chloro groups for the respective pseudohalogen and yielded the dicyano [L((R/R'))Pn(CN)2][OTf] (6Pn((R/R'))[OTf]) and diazido-substituted pnictanes [L((R/R'))Pn(N3)2][OTf] (7Pn((R/R'))[OTf]), respectively. All new compounds are thoroughly characterized by multinuclear NMR, IR, and Raman spectroscopy. For most cases the molecular structure was confirmed by X-ray crystal structure analysis.

In vitro activities of fluoroquinolones against the spirochete Borrelia burgdorferi.

Little is known to date about the in vitro activity of fluoroquinolones against Borrelia species. Our study aimed at determining the in vitro activities of 15 quinolones against nine isolates of the Borrelia burgdorferi sensu lato complex in addition to one Borrelia valaisiana and one Borrelia bissettii tick isolate. For the determination of MICs, a standardized colorimetric microdilution method was applied. Determination of minimal borreliacidal concentrations providing 100% killing of the final inoculum (MBCs) after 72 h and time-kill experiments were performed by conventional culture in Barbour-Stoenner-Kelly medium in combination with dark-field microscopy. The rank order of potency on a microgram-per-milliliter basis for the substances with in vitro activity against B. burgdorferi was gemifloxacin (MIC at which 90% of the isolates tested are inhibited [MIC(90)], 0.12 microg/ml) > sitafloxacin (MIC(90), 0.5 microg/ml), grepafloxacin (MIC(90), 0.5 microg/ml) > gatifloxacin (MIC(90), 1 microg/ml), sparfloxacin (MIC(90), 1 microg/ml), trovafloxacin (MIC(90), 1 microg/ml) > moxifloxacin (MIC(90), 2 microg/ml), ciprofloxacin (MIC(90), 2 microg/ml) > levofloxacin (MIC(90), 4 microg/ml) > ofloxacin (MIC(90), 8 microg/ml), norfloxacin (MIC(90), 8 microg/ml) > fleroxacin (MIC(90), >16 microg/ml), and pefloxacin (MIC(90), 32 microg/ml) > nalidixic acid (MIC(90), 256 microg/ml). After 72 h of exposure, gemifloxacin was borreliacidal (100% killing) against the isolates investigated at a median MBC of 4 microg/ml. In the other compounds tested, median MBCs were higher (> or =8 microg/ml). Results of electron microscopy and time-kill studies clearly support an in vitro activity of some fluoroquinolones against borreliae. Our study demonstrates for the first time the enhanced in vitro effectiveness of some of the recently introduced 4-quinolones against B. burgdorferi.

Preventive care in the emergency department: should emergency departments institute a falls prevention program for elder patients? A systematic review.

OBJECTIVE: To perform a systematic review of the emergency medicine literature to assess the appropriateness of an intervention to identify, counsel, and refer emergency department (ED) patients >64 years old who are at high risk for falls. METHODS: The systematic review was facilitated through the use of a structured template, a companion explanatory piece, and a grading and methodological scoring system based on published criteria for critical appraisal. A reference librarian did two PubMed searches using the following: ED visits, patients >64 years old, falls, high risk, and effectiveness of intervention. Emergency Medical Abstracts, Science Citation Index, and the Cochrane Collaboration database were searched. Two team members reviewed the abstracts and selected pertinent articles. References were screened for additional pertinent articles. RESULTS: Twenty-six articles were reviewed. None were ED-based primary or secondary falls prevention in older patients. One randomized controlled trial of an intervention to decrease subsequent falls in elder community-dwelling patients who presented with a fall showed a structured interdisciplinary approach significantly reducing the number of falls. Two ED-based studies showed it was possible to identify ED patients at risk for falls. CONCLUSIONS: Based on one randomized controlled trial demonstrating a significant reduction in the risk of further falls, the burden of suffering caused by falls, and other studies demonstrating the value of interventions to reduce the risk of falling, the authors recommend that EDs conduct research to evaluate the effectiveness of clinical interventions to identify, counsel, and refer ED patients >64 years old who are at high risk for an unintentional fall.

In vitro activity of mezlocillin, meropenem, aztreonam, vancomycin, teicoplanin, ribostamycin and fusidic acid against Borrelia burgdorferi.

The in vitro susceptibility profile of Borrelia burgdorferi is not yet well defined for several antibiotics. Our study explored the in vitro susceptibility of B. burgdorferi to mezlocillin, meropenem, aztreonam, vancomycin, teicoplanin, ribostamycin and fusidic acid. Minimal inhibitory concentrations (MICs) and minimal borreliacidal concentrations (MBCs) were measured using a standardised colorimetric microdilution method and conventional subculture experiments. MIC values were lowest for mezlocillin (MIC(90), < or =0.06 mg/l) and meropenem (MIC(90), 0.33 mg/l). Vancomycin (MIC(90), 0.83 mg/l) was less effective in vitro. Borreliae proved to be resistant to aztreonam (MIC(90), >32 mg/l), teicoplanin (MIC(90), 6.6 mg/l), ribostamycin (MIC(90), 32 mg/l), and fusidic acid (MIC(90), >4 mg/l). The mean MBCs resulting in 100% killing of the final inoculum after 72 h of incubation were lowest for mezlocillin (MBC, 0.83 mg/l). This study gathered further data on the in vitro susceptibility patterns of the B. burgdorferi complex. The excellent in vitro effectiveness of acylamino-penicillin derivatives and their suitability for the therapy of Lyme disease is emphasised.

Intranasal lidocaine for the treatment of migraine headache: a randomized, controlled trial.

OBJECTIVE: To evaluate the effect of intranasal lidocaine for immediate relief (5 minutes) of migraine headache pain. METHODS: A randomized, double-blind, placebo-controlled clinical trial at two university-affiliated community teaching hospitals enrolled patients 18-50 years old with migraine headache as defined by the International Headache Society. Patients who were pregnant, lactating, known to abuse alcohol or drugs, or allergic to one of the study drugs, those who used analgesics within two hours, or those with a first headache were excluded. Statistical significance was assessed by using chi-square or Fisher's exact test for categorical variables and Student's t-test for continuous variables. Patients rated their pain on a 10-centimeter visual analog scale (VAS) prior to drug administration and at 5, 10, 15, 20, and 30 minutes after the initial dose. Medication was either 1 mL of 4% lidocaine or normal saline (placebo) intranasally in split doses 2 minutes apart and intravenous prochlorperazine. Medications were packaged so physicians and patients were unaware of the contents. Successful pain relief was achieved if there was a 50% reduction in pain score or a score below 2.5 cm on the VAS. RESULTS: Twenty-seven patients received lidocaine and 22 placebo. No significant difference was observed between groups in initial pain scores, 8.4 (95% CI = 7.8 to 9.0) lidocaine and 8.6 (95% CI = 8.0 to 9.2) placebo (p = 0.75). Two of 27 patients (7.4%, 95% CI = 0.8, 24.3) in the lidocaine group and three of 22 patients (13.6%, 95% CI = 2.8 to 34.9) in the placebo group had immediate successful pain relief (p = 0.47), with average pain scores of 6.9 (95% CI = 5.9 to 7.8) and 7.0 (95% CI = 5.8 to 8.2), respectively. No difference in pain relief was detected at subsequent measurements. CONCLUSION: There was no evidence that intranasal lidocaine provided rapid relief for migraine headache pain in the emergency department setting.

The effects of mannitol, albumin, and cardioplegia enhancers on 24-h rat heart preservation.

During 24 h in vitro heart preservation and reperfusion, tissue damage occurs that seriously reduces cardiac function. Prevention of free radical production during preservation and reperfusion of ischemic tissue using free radical scavengers is of primary importance in maintaining optimal heart function in long-term preservation protocols. We examined whether mannitol (68 mM) and albumin (1.4 microM) in combination with other cardioplegia enhancers decreased free radical formation and edema and increased cardiac function during 24-h cold (5 degrees C) heart preservation and warm (37 degrees C) reperfusion in the Langendorff-isolated rat heart. The performance of mannitol-treated hearts was significantly decreased compared with that of hearts without mannitol treatment after 24 h of preservation with regard to recovery of diastolic pressure, contractility (+dP/dt), relaxation (-dP/dt), myocardial creatine kinase release, coronary flow, and lipid peroxidation. Albumin-treated hearts demonstrated higher cardiac function (contractility and coronary flow especially) than hearts not treated with albumin or hearts treated with mannitol, and this appears to be due to the positive effects of increased cellular metabolism and the enhancement of membrane stability.

Teenagers: mental health and psychological issues.

Adolescence is a developmental period marked by multiple challenges and demands which create a heightened vulnerability to the development of emotional disorders. Primary care physicians are in an ideal position to intervene in the early stages and prevent the tragic consequences which can occur with an untreated mental health disorder. This article reviews the assessment and treatment of adolescent mental health in the primary care medical setting. Knowledge of these disorders and their manifestations in the primary care environment will enable clinicians to provide higher quality medical care and will reduce the potential for continual life disruptions into the adult years.

Directing an emergency medicine residency: the problems and their potential solutions.

OBJECTIVE: To characterize the problems facing emergency medicine residency directors (EMRDs), to describe potential solutions, and to associate perceptions with anticipated duration in the position of EMRD. METHODS: A confidential questionnaire was mailed to the EMRDs at all Accreditation Council for Graduate Medical Education-approved programs. The survey included a problem and solution list constructed by a panel of EMRDs. The respondents were asked to rate problems using a Likert-like scale and were asked to indicate which of the listed solutions they had used and had found useful, or thought would be useful. Associations of these features and demographic variables with the intention to leave the position of EMRD within 5 years were sought. RESULTS: Eighty-seven of 93 EMRDs (93.5%) completed the survey. Their mean age was 40 years; 50% had been EMRDs for < 3 years. Most of the EMRDs (62%) had an associate EMRD, and 77% had at least one secretary. The EMRDs worked a median of 220 hours per month. Major problems included: insufficient time for the job (57%), career interfering with family needs (44%), and lack of adequate faculty help (38%). The most frequently cited and useful solutions included: attending education courses, self-reading on education and management techniques, and discussing problems with and seeking advice from others. Most (68%) of the EMRDs anticipated continuing as program director for < or = 5 years. Neither age, gender, previous amount of time in the position, number of hours worked, nor nature of the problems faced on the job was a significant predictor of which of the EMRDs anticipated leaving. CONCLUSIONS: Half the responding EMRDs were < 40 years of age, half had been EMRDs for < or = 3 years, and 68% anticipated continuing in their position for < or = 5 years. Major frustrations included lack of knowledge and time. Family and career conflicts were frequent. These problems are similar to those of program directors in other specialties. Some recommendations are made to assist EMRDs.

Quality assurance in emergency medical service systems.

EMS quality assurance programs can help guarantee that the provision of prehospital care is medically accountable. The establishment and management of such a program, although time consuming, are critically important. It is essential that the medical director or a designee responsible for quality assurance activities be allotted the necessary time to carry them out properly. Incident reports, critique sessions, audits, education (training) sessions, observation or debriefing in the emergency department, as well as on-line medical control all play a role in inputting data into the system. The quality assurance program forms a continuous action loop starting and ending with protocols and education. Documentation of variance or compliance with protocols forms the basis for analysis of the quality of care delivered. Any intervention must be based on carefully documented information and should include praise for good work, as well as education when needed, and restriction of function when necessary.

Determination of melengestrol acetate in feedstuffs with liquid chromatographic preparatory column cleanup and quantitative analysis.

Melengestrol acetate (MGA) is determined by liquid chromatography using a fraction from preparatory LC as a means of sample cleanup for feedstuffs, both dry and liquid. Dry ground feed is Soxhlet extracted with hexane and passed through a 2% deactivated alumina column for initial cleanup. The eluate is evaporated, redissolved in methanol, filtered, and injected onto a preparatory LC column. The fraction containing MGA is separated from the remaining matrix, evaporated to dryness, dissolved in methanol, and quantitated by LC analysis. Liquid supplements are extracted in methanol, and the extract is evaporated to near dryness. The residue is diluted with water, extracted with chloroform, passed through sodium sulfate, and evaporated to dryness. The remaining sample is dissolved in methanol prior to preparative LC and quantitative LC. Recoveries for 2 laboratory-fortified commercial feeds, one dry and one liquid, containing 0.39 and 0.40 mg/lb, were 98.3% +/- 4.4 and 95.8% +/- 4.3, respectively. Results compare favorably with existing methods. Up to a 4-fold time savings was realized by this method without automation.

[Results of the complex evaluation of scintigraphy of the intracardiac space in patients with coronary disease]. / Ergebnisse der komplexen Auswertung der Herzbinnenraumszintigraphie bei Patienten mit koronarer Herzkrankheit.

With the help of the comparison of the results of 95 patients with coronary heart disease who were examined by means of the intracardiac space scintigraphy for the purpose of the subjective subdivision according to the NYHA-classification there is no close correlation between the nuclear-medically obtained functional sizes (EF, maximum ejection and filling rate) and the clinical degree of severity of the disease. Only at the degree of severity 3 and 4 a discrimination is possible. In 64 patients laevocardiographic and coronarographic, respectively, findings were present. The trend to the deterioration of the functional parameters and to the increase of the nuclear-medically recognizable disturbances of the kinetics, respectively, with a more intensive expression of the vascular stenoses is distinctly readable. From the examination in rest in the individual case no statement is possible concerning the findings which are to be expected in the invasive diagnostics. When there are discrepancies between the result of the intracardiac space scintigraphy and the clinical and electrocardiographic preliminary investigations in many cases a clarification becomes possible by the immediately following study under submaximal exercise. On the assumption of a close cooperation with experienced cardiologists the relatively little expensive intracardiac space scintigraphy which does not stress the patient provides an essential evidence for the prognosis and estimation of the functional capacity of the patients with coronary heart disease.

Sodium appetite and 24-hour variations in fluid balance, mean arterial pressure and heart rate in SHR and WKY on various sodium diets.

Young spontaneously hypertensive rats (SHR) and Wistar-Kyoto rats (WKY) were compared with respect to firstly, sodium (Na) appetite during 'rest', mild social stress and adrenocorticotrophic hormone (ACTH) injections and secondly, diurnal patterns of water intake, urine output, mean arterial pressure (MAP) and heart rate (HR) while on various Na diets: 0.5 mmol Na (LNa), 5 or 12-13 mmol Na (CNa), 50 (HNa) or 120 mmol Na (vHNa) per 100 g food. Sodium appetite and water intake, being 50% higher in SHR than in WKY (4-4.5 versus 2.5-3 mmol Na/100 g body weight per day), was modestly increased by both social stress and ACTH, more so in WKY. With regard to influences of the various Na diets, daytime resting MAP was modestly lowered in LNaSHR and slightly increased in vHNaSHR compared with CNaSHR, but about equal in all WKY groups. Food and water consumption was concentrated to the active night period, but even high Na water intakes caused no signs of sustained hypervolaemia, as intake bouts were eliminated by urine within 30-40 min in both SHR and WKY. However, the vHNa diet in particular in SHR increased drinking frequency; each drinking bout induced such rapid, 5-10 min long neurogenic MAP and HR increases that they could not be ascribed to blood volume expansion per se. The diurnal MAP-HR patterns in SHR therefore varied markedly with the Na diets, with a considerably raised average MAP in the vHNa group, even though resting daytime MAP was nearly the same as in CNaSHR.(ABSTRACT TRUNCATED AT 250 WORDS)