In a companion study, the authors describe the development of a new instrument named the Wireless Instantaneous Neurotransmitter Concentration System (WINCS), which couples digital telemetry with ...fast-scan cyclic voltammetry (FSCV) to measure extracellular concentrations of dopamine. In the present study, the authors describe the extended capability of the WINCS to use fixed potential amperometry (FPA) to measure extracellular concentrations of dopamine, as well as glutamate and adenosine. Compared with other electrochemical techniques such as FSCV or high-speed chronoamperometry, FPA offers superior temporal resolution and, in combination with enzyme-linked biosensors, the potential to monitor nonelectroactive analytes in real time.
The WINCS design incorporated a transimpedance amplifier with associated analog circuitry for FPA; a microprocessor; a Bluetooth transceiver; and a single, battery-powered, multilayer, printed circuit board. The WINCS was tested with 3 distinct recording electrodes: 1) a carbon-fiber microelectrode (CFM) to measure dopamine; 2) a glutamate oxidase enzyme-linked electrode to measure glutamate; and 3) a multiple enzyme-linked electrode (adenosine deaminase, nucleoside phosphorylase, and xanthine oxidase) to measure adenosine. Proof-of-principle analyses included noise assessments and in vitro and in vivo measurements that were compared with similar analyses by using a commercial hardwired electrochemical system (EA161 Picostat, eDAQ; Pty Ltd). In urethane-anesthetized rats, dopamine release was monitored in the striatum following deep brain stimulation (DBS) of ascending dopaminergic fibers in the medial forebrain bundle (MFB). In separate rat experiments, DBS-evoked adenosine release was monitored in the ventrolateral thalamus. To test the WINCS in an operating room setting resembling human neurosurgery, cortical glutamate release in response to motor cortex stimulation (MCS) was monitored using a large-mammal animal model, the pig.
The WINCS, which is designed in compliance with FDA-recognized consensus standards for medical electrical device safety, successfully measured dopamine, glutamate, and adenosine, both in vitro and in vivo. The WINCS detected striatal dopamine release at the implanted CFM during DBS of the MFB. The DBS-evoked adenosine release in the rat thalamus and MCS-evoked glutamate release in the pig cortex were also successfully measured. Overall, in vitro and in vivo testing demonstrated signals comparable to a commercial hardwired electrochemical system for FPA.
By incorporating FPA, the chemical repertoire of WINCS-measurable neurotransmitters is expanded to include glutamate and other nonelectroactive species for which the evolving field of enzyme-linked biosensors exists. Because many neurotransmitters are not electrochemically active, FPA in combination with enzyme-linked microelectrodes represents a powerful intraoperative tool for rapid and selective neurochemical sampling in important anatomical targets during functional neurosurgery.
The influence of the reduction process on paired-pulse voltammetry (PPV), which consists of two identical triangle-shaped pulses, was studied in this study by increasing peak potential duration. We ...propose sawhorse waveform as an optimized PPV waveform for enhancing the responses of PPV on dopamine and serotonin (5-HT). To investigate the influence of the scanning parameters on the reduction process and response of PPV, the responses of dopamine were measured by changing the switching potential (from 1.0V to 1.5V), and scan rates (from 400V/s to 1000V/s) based on triangle shaped PPV. As a result, the oxidation and reduction peak ratio in the response of the primary pulse in PPV decreased in a linear fashion with increases to the duration between oxidation and reduction potential, which lead us to obtain more defined features in the subtracted voltammograms (primarysecondary) in PPV. Based on these results, sawhorse waveform PPV with prolonged switching potential duration was suggested to increase the sensitivity of PPV while maintaining its own advantages, and it is also confirmed in an in vivo experiment. In addition to the dopamine experiments, we also conducted an experiment with serotonin utilizing the N-shaped sawhorse waveform PPV. The subtracted voltammogram in the N-shaped PPV with 1.0V peak and 4ms peak potential duration clearly showed the characteristics of serotonin. In conclusion, PPV waveforms could be optimized to improve the sensitivity of PPV responses by the control of the reduction process.
To investigate whether the use of antihypertensive and statin medication in very old adults is associated with the level of motor performance.
Cross-sectional study.
A community-based study recruited ...from over 40 residential facilities across the metropolitan Chicago area.
Community-dwelling very old adults (n = 1520; mean age 80.2; standard deviation 7.7).
Eleven motor performances were summarized using a composite motor score. All prescription and over the counter medications taken by participants were inspected and coded using the Medi-Span Data Base System. Demographic characteristics and medical history were obtained by means of detailed interview and medical examinations.
In multiple linear regression models, antihypertensive medications were associated with global motor score β = -0.075, standard error (SE) 0.011, P < .001. Thus, motor function in an individual with antihypertensive medication, was on average, about 7.5% lower than an age-, sex-, and education-matched individual without antihypertensive medication. The number of antihypertensive medications, which were being used had an additive effect, such that a reduction in the level of motor function was observed with each additional medication, and receiving 3 or more antihypertensive medications was associated with about a 15% reduction in the level of motor function. The association between antihypertensive medications and motor function was robust, and remained unchanged after adjusting for confounding by indication using several potentially confounding variables: smoking, hypertension, diabetes, stroke, congestive heart failure, myocardial infarction, and intermittent claudication (β = -0.05, SE 0.015, P = .001). In contrast, the use of statin medications was not related to motor function (unadjusted: β = 0.003, SE 0.015, P = .826; fully adjusted: β = 0.018, SE 0.014, P = .216).
The use of antihypertensive medications is associated with a lower level of motor function in very old adults. The nature of this association warrants further investigation.
Abstract
Background
Indoleamine-2,3-dioxygenase (IDO) mediated tryptophan (TRP) depletion has antimicrobial and immuno-regulatory effects. Increased kynurenine (KYN)-to-TRP (KT) ratios, reflecting ...increased IDO activity, have been associated with poorer outcomes from several infections.
Methods
We performed a case-control (1:2; age and sex matched) analysis of adults hospitalized with influenza A(H1N1)pdm09 with protocol-defined disease progression (died/transferred to ICU/mechanical ventilation) after enrollment (cases) or survived without progression (controls) over 60 days of follow-up. Conditional logistic regression was used to analyze the relationship between baseline KT ratio and other metabolites and disease progression.
Results
We included 32 cases and 64 controls with a median age of 52 years; 41% were female, and the median durations of influenza symptoms prior to hospitalization were 8 and 6 days for cases and controls, respectively (P = .04). Median baseline KT ratios were 2-fold higher in cases (0.24 mM/M; IQR, 0.13–0.40) than controls (0.12; IQR, 0.09–0.17; P ≤ .001). When divided into tertiles, 59% of cases vs 20% of controls had KT ratios in the highest tertile (0.21–0.84 mM/M). When adjusted for symptom duration, the odds ratio for disease progression for those in the highest vs lowest tertiles of KT ratio was 9.94 (95% CI, 2.25–43.90).
Conclusions
High KT ratio was associated with poor outcome in adults hospitalized with influenza A(H1N1)pdm09. The clinical utility of this biomarker in this setting merits further exploration.
ClinicalTrials.gov Identifier
NCT01056185.
The concept of quasi-particles forms the theoretical basis of our microscopic understanding of emergent phenomena associated with quantum-mechanical many-body interactions. However, the ...quasi-particle theory in disordered materials has proven difficult, resulting in the predominance of mean-field solutions. Here, we report first-principles phonon calculations and inelastic X-ray and neutron-scattering measurements on equiatomic alloys (NiCo, NiFe, AgPd, and NiFeCo) with force-constant dominant disorder—confronting a key 50-year-old assumption in the Hamiltonian of all mean-field quasi-particle solutions for off-diagonal disorder. Our results have revealed the presence of a large, and heretofore unrecognized, impact of local chemical environments on the distribution of the species-pair-resolved force-constant disorder that can dominate phonon scattering. This discovery not only identifies a critical analysis issue that has broad implications for other elementary excitations, such as magnons and skyrmions in magnetic alloys, but also provides an important tool for the design of materials with ultralow thermal conductivities.
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