Enabling batch and microfluidic non-thermal plasma chemistry: reactor design and testing.

Non-thermal plasma (NTP) is a promising state of matter for carrying out chemical reactions. NTP offers high densities of reactive species, without the need for a catalyst, while operating at atmospheric pressure and remaining at moderate temperature. Despite its potential, NTP cannot be used comprehensively in reactions until the complex interactions of NTP and liquids are better understood. To achieve this, NTP reactors that can overcome challenges with solvent evaporation, enable inline data collection, and achieve high selectivity, high yield, and high throughput are required. Here, we detail the construction of i) a microfluidic reactor for chemical reactions using NTP in organic solvents and ii) a corresponding batch setup for control studies and scale-up. The use of microfluidics enables controlled generation of NTP and subsequent mixing with reaction media without loss of solvent. The construction of a low-cost custom mount enables inline optical emission spectroscopy using a fibre optic probe at points along the fluidic pathway, which is used to probe species arising from NTP interacting with solvents. We demonstrate the decomposition of methylene blue in both reactors, developing an underpinning framework for applications in NTP chemical synthesis.

Challenges to meeting the HIV care needs of older adults in the rural South.

People living with HIV in rural parts of the Southern United States face poor outcomes along the HIV care continuum. Additionally, over half of people with diagnosed HIV are age 50 and older. Older adults living with HIV in the rural South often have complex health and social needs associated with HIV, aging, and the rural environment. Research is needed to understand what support organizations and clinics need in providing care to this population. This qualitative study examines the challenges health and social service providers face in caring for older patients living with HIV. In 2020-2021, we interviewed 27 key informants who work in organizations that provide care to older adults with HIV in the seven states with high rural HIV burden: Alabama, Arkansas, Kentucky, Mississippi, Missouri, Oklahoma, and South Carolina. Our findings highlight how racism and poverty; culture, politics, and religion; and a lack of healthcare infrastructure collectively shape access to HIV care for older adults in the South. Rural health and social service providers need structural-level changes to improve their care and services.

Directional mass transport in an atmospheric pressure surface barrier discharge.

In an atmospheric pressure surface barrier discharge the inherent physical separation between the plasma generation region and downstream point of application reduces the flux of reactive chemical species reaching the sample, potentially limiting application efficacy. This contribution explores the impact of manipulating the phase angle of the applied voltage to exert a level of control over the electrohydrodynamic forces generated by the plasma. As these forces produce a convective flow which is the primary mechanism of species transport, the technique facilitates the targeted delivery of reactive species to a downstream point without compromising the underpinning species generation mechanisms. Particle Imaging Velocimetry measurements are used to demonstrate that a phase shift between sinusoidal voltages applied to adjacent electrodes in a surface barrier discharge results in a significant deviation in the direction of the plasma induced gas flow. Using a two-dimensional numerical air plasma model, it is shown that the phase shift impacts the spatial distribution of the deposited charge on the dielectric surface between the adjacent electrodes. The modified surface charge distribution reduces the propagation length of the discharge ignited on the lagging electrode, causing an imbalance in the generated forces and consequently a variation in the direction of the resulting gas flow.

High intraoperative inspiratory oxygen fraction and risk of major respiratory complications.

BACKGROUND: High inspiratory oxygen fraction ( FIO2 ) may improve tissue oxygenation but also impair pulmonary function. We aimed to assess whether the use of high intraoperative FIO2 increases the risk of major respiratory complications. METHODS: We studied patients undergoing non-cardiothoracic surgery involving mechanical ventilation in this hospital-based registry study. The cases were divided into five groups based on the median FIO2 between intubation and extubation. The primary outcome was a composite of major respiratory complications (re-intubation, respiratory failure, pulmonary oedema, and pneumonia) developed within 7 days after surgery. Secondary outcomes included 30-day mortality. Several predefined covariates were included in a multivariate logistic regression model. RESULTS: The primary analysis included 73 922 cases, of whom 3035 (4.1%) developed a major respiratory complication within 7 days of surgery. For patients in the high- and low-oxygen groups, the median FIO2 was 0.79 [range 0.64-1.00] and 0.31 [0.16-0.34], respectively. Multivariate logistic regression analysis revealed that the median FIO2 was associated in a dose-dependent manner with increased risk of respiratory complications (adjusted odds ratio for high vs low FIO2 1.99, 95% confidence interval [1.72-2.31], P -value for trend <0.001). This finding was robust in a series of sensitivity analyses including adjustment for intraoperative oxygenation. High median FIO2 was also associated with 30-day mortality (odds ratio for high vs low FIO2 1.97, 95% confidence interval [1.30-2.99], P -value for trend <0.001). CONCLUSIONS: In this analysis of administrative data on file, high intraoperative FIO2 was associated in a dose-dependent manner with major respiratory complications and with 30-day mortality. The effect remained stable in a sensitivity analysis controlled for oxygenation. CLINICAL TRIAL REGISTRATION: NCT02399878.

The effects of atmospheric pressure cold plasma treatment on microbiological, physical-chemical and sensory characteristics of vacuum packaged beef loin.

Effects on vacuum packaged and non-packaged beef longissimus samples exposed to atmospheric cold plasma (ACP) generated at different powers were studied over a 10day period of vacuum-, and a subsequent 3day period of aerobic storage. Exposure of non-covered beef samples under high power ACP conditions resulted in increased a*, b*, Chroma and Hue values, but ACP treatment of packaged loins did not impact colour (L*, a*, b*, Chroma, Hue), lipid peroxidation, sarcoplasmic protein denaturation, nitrate/nitrite uptake, or myoglobin isoform distribution. Colour values measured after 3days of aerobic storage following unpackaging (i.e. 20days post-mortem) were similar and all compliant with consumer acceptability standards. Exposure to ACP of the polyamide-polyethylene packaging film inoculated with Staphylococcus aureus, Listeria monocytogenes and two Escherichia coli strains resulted in >2 log reduction without affecting the integrity of the packaging matrix. Results indicate that ACP can reduce microbial numbers on surfaces of beef packages without affecting characteristics of the packaged beef.

Single best answer question-writing tips for clinicians.

Assessment is essential for progression in medical careers. Thus, an important aspect of developing as a clinical teacher is the ability to produce high-quality assessments for junior colleagues. The single best answer (SBA) question format is becoming ubiquitous in the assessment of the application of knowledge in clinical medicine; writing this style of examination question can be a challenge. This concise guide highlights key SBA question-writing tips, aiming to help aspiring clinical teachers set high-quality knowledge assessments.

Impact of food model (micro)structure on the microbial inactivation efficacy of cold atmospheric plasma.

The large potential of cold atmospheric plasma (CAP) for food decontamination has recently been recognized. Room-temperature gas plasmas can decontaminate foods without causing undesired changes. This innovative technology is a promising alternative for treating fresh produce. However, more fundamental studies are needed before its application in the food industry. The impact of the food structure on CAP decontamination efficacy of Salmonella Typhimurium and Listeria monocytogenes was studied. Cells were grown planktonically or as surface colonies in/on model systems. Both microorganisms were grown in lab culture media in petri dishes at 20°C until cells reached the stationary phase. Before CAP treatment, cells were deposited in a liquid carrier, on a solid(like) surface or on a filter. A dielectric barrier discharge reactor generated helium-oxygen plasma, which was used to treat samples up to 10min. Although L. monocytogenes is more resistant to CAP treatment, similar trends in inactivation behavior as for S. Typhimurium are observed, with log reductions in the range [1.0-2.9] for S. Typhimurium and [0.2-2.2] for L. monocytogenes. For both microorganisms, cells grown planktonically are easily inactivated, as compared to surface colonies. More stressing growth conditions, due to cell immobilization, result in more resistant cells during CAP treatment. The main difference between the inactivation support systems is the absence or presence of a shoulder phase. For experiments in the liquid carrier, which exhibit a long shoulder, the plasma components need to diffuse and penetrate through the medium. This explains the higher efficacies of CAP treatment on cells deposited on a solid(like) surface or on a filter. This research demonstrates that the food structure influences the cell inactivation behavior and efficacy of CAP, and indicates that food intrinsic factors need to be accounted when designing plasma treatment.

Optimizing the electrical excitation of an atmospheric pressure plasma advanced oxidation process.

The impact of pulse-modulated generation of atmospheric pressure plasma on the efficiency of organic dye degradation has been investigated. Aqueous samples of methyl orange were exposed to low temperature air plasma and the degradation efficiency was determined by absorbance spectroscopy. The plasma was driven at a constant frequency of 35kHz with a duty cycle of 25%, 50%, 75% and 100%. Relative concentrations of dissolved nitrogen oxides, pH, conductivity and the time evolution of gas phase ozone were measured to identify key parameters responsible for the changes observed in degradation efficiency. The results indicate that pulse modulation significantly improved dye degradation efficiency, with a plasma pulsed at 25% duty showing a two-fold enhancement. Additionally, pulse modulation led to a reduction in the amount of nitrate contamination added to the solution by the plasma. The results clearly demonstrate that optimization of the electrical excitation of the plasma can enhance both degradation efficiency and the final water quality.

Implementation of a standards-based anaesthesia record compliant with the health level 7 (HL7) clinical document architecture (CDA).

With the increasing use of anaesthesia information management systems (AIMS) there is the opportunity for different institutions to aggregate and share information both nationally and internationally. Potential uses of such aggregated data include outcomes research, benchmarking and improvement in clinical practice and patient safety. However, these goals can only be achieved if data contained in records from different sources are truly comparable and there is semantic inter-operability. This paper describes the development of a standard terminology for anaesthesia and also a Domain Analysis Model and implementation guide to facilitate a standard representation of AIMS records as extensible markup language documents that are compliant with the Health Level 7 Version 3 clinical document architecture. A representation of vital signs that is compliant with the International Standards Organization 11073 standard is also discussed.

Pharmacokinetics and pharmacodynamics of inhaled versus intravenous morphine in healthy volunteers.

BACKGROUND: A new pulmonary drug delivery system produces aerosols from disposable packets of medication. This study compared the pharmacokinetics and pharmacodynamics of morphine delivered by an AERx prototype with intravenous morphine. METHODS: Fifteen healthy volunteers were enrolled. Two subjects were administered four inhalations of 2.2 mg morphine each at 1-min intervals or 4.4 mg over 3 min by intravenous infusion. Thirteen subjects were given twice the above doses, i.e., eight inhalations or 8.8 mg intravenously over 7 min. Arterial blood sampling was performed every minute during administration and at 2, 5, 7, 10, 15, 20, 45, 60, 90, 120, 150, 180, and 240 min after administration. The effect of morphine was assessed by measuring pupil diameter and ventilatory response to a hypercapnic challenge. Pharmacokinetic and pharmacodynamic analyses were performed simultaneously using mixed-effect models. RESULTS: The pharmacokinetic data after intravenous administration were described by a three-exponent decay model preceded by a lag time. The pharmacokinetic model for administration by inhalation consisted of the three-exponent intravenous pharmacokinetic model preceded by a two-exponent absorption model. The authors found that, with administration by inhalation, the total bioavailability was 59%, of which 43% was absorbed almost instantaneously and 57% was absorbed with a half-life of 18 min. The median times to the half-maximal miotic effects of morphine were 10 and 5.5 min after inhalation and intravenous administration, respectively (P < 0.01). The pharmacodynamic parameter ke0 was approximately 0.003 min-1. CONCLUSIONS: The onset and duration of the effects of morphine are similar after intravenous administration or inhalation via this new pulmonary drug delivery system. Morphine bioavailability after such administration is 59% of the dose loaded into the dosage form.

Immunologic localization and kinetic characterization of a Na+/Ca2+ exchanger in neuronal and non-neuronal cells.

The plasma membrane Na+/Ca2+ exchanger is believed to play a role in the regulation of Ca2+ fluxes in neurons, though the lack of specific inhibitors has limited the delineation of its precise contribution. We recently reported the development of antibodies against a 36-kDa brain synaptic membrane protein which immunoprecipitated exchanger activity from solubilized membranes. In the present study we examined the kinetics of the Na+/Ca2+ exchanger in primary neurons in culture, in a neuronal hybrid cell line (NCB-20), and in a fibroblast-like cell line (CV-1) to see whether the level of exchanger activity correlated with the degree of immunostaining produced by our antibodies. The Vmax was determined for each cell type and found to be highest in primary neurons. Exchanger activity increased in primary neurons between days 1 and 6 in culture, but no such time-dependent change occurred in either of the cell lines. Immunoblot analysis of the three cell types probed with the anti-36-kDa protein antibodies revealed significantly greater immunostaining in the primary neurons compared with the other two cell types. Intensity of staining of neurons also increased significantly between days 1 and 6 in culture. Immunocytochemistry showed significant labelling of the primary neurons on the neuritic processes and points of contact between cells. The NCB-20 and CV-1 cells showed considerably lower levels of immunoreactivity. The antibodies immunoextracted approximately 90% of the exchanger activity in the primary neurons and approximately 70 and 50% of the activity in NCB-20 and CV-1 cells respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

A fluorimetric assay for the determination of anthranilic acid in biological materials.

In the brain, anthranilic acid may serve as a bioprecursor of the endogenous excitotoxin quinolinic acid. Using a novel isolation procedure followed by HPLC and fluorimetric detection, we have developed an assay which is sufficiently sensitive to determine anthranilic acid in small (> or = 3 mg) samples of rat brain tissue (sensitivity limit: 50 fmol). Anthranilic acid was identified by its retention time in three chromatographic systems. The assay was applied to the measurement of anthranilic acid in rat serum (131 +/- 7 nM) and urine (9.9 +/- 118 nmol/mg creatinine) and in several organs which contained between 0.5 and 2 pmol anthranilic acid/mg protein. Only small differences in anthranilic acid content were found among 10 regions of the rat brain. Neuronal depletion induced by an intrastriatal excitotoxin injection resulted in an increase in anthranilic acid levels, suggesting a nonneuronal localization of the metabolite in the brain. This assay should provide an improved means for the investigation of the neurobiology of anthranilic acid.

4-Chloro-3-hydroxyanthranilate inhibits quinolinate production in the rat hippocampus in vivo.

Quinolinic acid (QUIN) is a potential pathogen in a variety of excitotoxic and neuroviral brain diseases. In the present study, the ability of the QUIN synthesis inhibitor 4-chloro-3-hydroxyanthranilic acid to attenuate the production of QUIN was assessed in the hippocampus of awake rats. To this end, QUIN's immediate bioprecursor 3-hydroxyanthranilic acid (30 microM) was applied through a microdialysis probe, and QUIN production was monitored hourly in the perfusate. After 3 h, 4-chloro-3-hydroxyanthranilic acid (3 microM-3 mM) was included in the perfusion medium, and dialysis was continued for another 3 h. The drug caused dose-dependent inhibition of QUIN neosynthesis, with an apparent IC50 value of 32 microM. Discontinuation of drug administration, with continued perfusion of 3-hydroxyanthranilic acid, revealed that the drug effect was reversible. Intravenous application of 4-chloro-3-hydroxyanthranilic acid (14 mg/kg) resulted in a significant decrease in extracellular QUIN, reaching a nadir of 67% of saline-treated controls after 3 h. The data indicate that both intracerebral and systemic administration of 4-chloro-3-hydroxyanthranilic acid effectively interferes with QUIN production in the rat brain. The results suggest that QUIN synthesis inhibitors such as 4-chloro-3-hydroxyanthranilic acid may become of value in brain diseases that are caused by hyperphysiological quantities of QUIN.

The morality of induced delivery of the anencephalic fetus prior to viability.

In situations where anencephaly is diagnosed and where the mother's life or health is threatened Roman Catholic hospitals are faced with the dilemma of waiting until viability before inducing the fetus, thus potentially putting the mother at further risk. According to most Roman Catholic ethicists, induced delivery before viability is contrary to the Church's prohibition of direct killing of the innocent. The authors propose for discussion a reconsideration of this position in the case of the anencephalic fetus and conclude that taking the life of such a fetus does not constitute an attack on its personal dignity and therefore is morally permissible.

Evaluation of cross-contamination on automatic viscera removal equipment.

Contamination of poultry carcasses by fecal or ingested material is a major problem in the processing of poultry products. It was determined that the automatic equipment used to process uncontaminated carcasses could be used to clean and reprocess contaminated carcasses and significantly reduce the manual labor required to reprocess these carcasses. The potential for cross-contamination of the automatic viscera removal equipment was tested by microbiological evaluation, and it was determined that cross-contamination by this equipment was not a problem.

Association of glycolytic enzymes with the cytoskeleton.

The diverse physical associations of the glycolytic enzymes with structural components of the cell suggest that the glycolytic enzymes are not entirely soluble in the cell. The relatively low affinities of the associations are likely responsible for the apparently transient interactions. The binding phenomenon is suggested to regulate metabolism through changes in enzymatic activity and facilitates localized enrichment of the enzymes.

4-halo-3-hydroxyanthranilic acids: potent competitive inhibitors of 3-hydroxy-anthranilic acid oxygenase in vitro.

The mechanism of action of three potent inhibitors of 3-hydroxyanthranilic acid oxygenase (3HAO), the enzyme responsible for the production of the endogenous excitotoxin quinolinic acid, was examined in vitro. Using either liver homogenate or purified 3HAO, and following the rapid synthesis of the immediate enzymatic product alpha-amino-beta-carboxymuconic acid omega-semialdehyde spectrophotometrically, 4-halogenated (F, Cl, Br) 3-hydroxyanthranilic acids were found to inhibit enzymatic activity in a reversible fashion. Because of the very tight binding of the drugs to 3HAO, reversibility was detected only after warming the protein-inhibitor complexes at 37 degrees. Further studies showed that enzyme inhibition was competitive in nature (apparent Ki values: 190, 6 and 4 nM for the F-, Cl- and Br-compounds, respectively), and suggested that the drugs are metabolized by the enzyme. Specific, reversible, and tightly binding 3HAO inhibitors can be expected to become valuable tools for the study of quinolinate neurobiology. The drugs could also be of interest for the diagnostics and therapeutics of brain diseases which have been speculatively linked to a pathological overabundance of quinolinic acid.