Comonitoring of adenosine and dopamine using the wireless instantaneous neurotransmitter concentration system : proof of principle : laboratory investigation

Object

The authors of previous studies have demonstrated that local adenosine efflux may contribute to the therapeutic mechanism of action of thalamic deep brain stimulation (DBS) for essential tremor. Real-time monitoring of the neurochemical output of DBS-targeted regions may thus advance functional neurosurgical procedures by identifying candidate neurotransmitters and neuromodulators involved in the physiological effects of DBS. This would in turn permit the development of a method of chemically guided placement of DBS electrodes in vivo. Designed in compliance with FDA-recognized standards for medical electrical device safety, the authors report on the utility of the Wireless Instantaneous Neurotransmitter Concentration System (WINCS) for real-time comonitoring of electrical stimulation–evoked adenosine and dopamine efflux in vivo, utilizing fast-scan cyclic voltammetry (FSCV) at a polyacrylonitrile-based (T-650) carbon fiber microelectrode (CFM).
Methods

The WINCS was used for FSCV, which consisted of a triangle wave scanned between −0.4 and +1.5 V at a rate of 400 V/second and applied at 10 Hz. All voltages applied to the CFM were with respect to an Ag/AgCl reference electrode. The CFM was constructed by aspirating a single T-650 carbon fiber (r = 2.5 μm) into a glass capillary and pulling to a microscopic tip using a pipette puller. The exposed carbon fiber (the sensing region) extended beyond the glass insulation by ~ 50 μm. Proof of principle tests included in vitro measurements of adenosine and dopamine, as well as in vivo measurements in urethane-anesthetized rats by monitoring adenosine and dopamine efflux in the dorsomedial caudate putamen evoked by high-frequency electrical stimulation of the ventral tegmental area and substantia nigra.
Results

The WINCS provided reliable, high-fidelity measurements of adenosine efflux. Peak oxidative currents appeared at +1.5 V and at +1.0 V for adenosine, separate from the peak oxidative current at +0.6 V for dopamine. The WINCS detected subsecond adenosine and dopamine efflux in the caudate putamen at an implanted CFM during high-frequency stimulation of the ventral tegmental area and substantia nigra. Both in vitro and in vivo testing demonstrated that WINCS can detect adenosine in the presence of other easily oxidizable neurochemicals such as dopamine comparable to the detection abilities of a conventional hardwired electrochemical system for FSCV.
Conclusions

Altogether, these results demonstrate that WINCS is well suited for wireless monitoring of high-frequency stimulation-evoked changes in brain extracellular concentrations of adenosine. Clinical applications of selective adenosine measurements may prove important to the future development of DBS technology.

Wireless instantaneous neurotransmitter concentration system-based amperometric detection of dopamine, adenosine, and glutamate for intraoperative neurochemical monitoring - laboratory investigation

Object  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.

Methods  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.

Results   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.

Conclusions  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.

Cane toad or computer mouse? Real and computer-simulated laboratory exercises in physiology classes

Traditional practical classes in many countries are being rationalised to reduce costs. The challenge for university educators is to provide students with the opportunity to reinforce theoretical concepts by running something other than a traditional practical program. One alternative is to replace wet labs with comparable computer simulations. These virtual experiments involve no harm to animals and require little ongoing expenditure. This study documents second-year physiology students' perceptions of and attitudes to simulations by incorporating several computer simulations into the practical program. Computer simulations met the conceptual and, to some extent, the motivational goals of university practical programs. While students enjoyed both wet labs and computer-simulated exercises, overwhelmingly the wet lab provided the more memorable and stimulating learning experience. Based on this study, students suggested that computer simulations could be effectively used to complement rather than replace practical classes where students gain laboratory skills.

Larval development of himri, Barbus luteus (Cyprinidae: Cypriniformes) reared in the laboratory

Larval development of the himri barbel, Barbus luteus Heckel, reared at 19-22 ¡C in natural daylight is described. Morphological and some functional character appearances were similar to the main ontogenetic steps of development in most cyprinids. Small hatched larvae attained both metamorphosis and a length of 10.5 mm after almost 35 days. Relative growth of the selected body proportions demonstrated typical priorities in growth compared to the length. An ontogenetic index was inferred from applying age and length criteria at metamorphosis as a scale for ontogenetic events.

On anomalous depth-dependency of the hardness of NiTi shape memory alloys in spherical nanoindentation

An experimental study on the indentation hardness of NiTi shape memory alloys (SMAs) by using a spherical indenter tip and a finite element investigation to understand the experimental results are presented in this paper. It is shown that the spherical indentation hardness of NiTi SMAs increases with the indentation depth. The finding is contrary to the recent study on the hardness of NiTi SMAs using a sharp Berkovich indenter tip, where the interfacial energy plays a dominant role at small indentation depths. Our numerical investigation indicates that the influence of the interfacial energy is not significant on the spherical indentation hardness of SMAs. Furthermore, the depth dependency of SMA hardness under a spherical indenter is explained by the elastic spherical contact theory incorporating the deformation effect of phase transformation of SMAs. Hertz theory for purely elastic contact shows that the spherical hardness increases with the square root of the indentation depth. The phase transformation beneath the spherical tip weakens the depth effect of a purely elastic spherical hardness. This study enriches our knowledge on the basic concept of hardness for SMAs under spherical indentation at micro- and nanoscales.

Descriptive analysis of landings during international netball competition: enhancing ecological validity of laboratory testing environments

Non-contact landings have been identified as a common activity associated with injury in netball. Investigating injury risk factors during landing via laboratory-based analysis warrants the performance of sportspecific landing tasks with the inclusion of “game- like” factors to enhance ecological validity of testing protocols. Understanding how players perform landing tasks in a competitive environment is, therefore, essential.

The purpose of this study was to perform a descriptive analysis of in-game landings performed by netball players, with regard to the landing techniques used and game events surrounding these landings; with the intent of providing information to enhance the ecological validity of laboratory-based testing environments. Landings were categorised according to landing technique and game events surrounding the landing.

Risk factors for impaired respiratory function during nurse-administered procedural sedation and analgesia in the cardiac catheterisation laboratory: a matched case-control study

Background
Side effects of the medications used for procedural sedation and analgesia in the cardiac catheterisation laboratory are known to cause impaired respiratory function. Impaired respiratory function poses considerable risk to patient safety as it can lead to inadequate oxygenation. Having knowledge about the conditions that predict impaired respiratory function prior to the procedure would enable nurses to identify at-risk patients and selectively implement intensive respiratory monitoring. This would reduce the possibility of inadequate oxygenation occurring.

Aim
To identify pre-procedure risk factors for impaired respiratory function during nurse-administered procedural sedation and analgesia in the cardiac catheterisation laboratory.

Design
Retrospective matched case–control.

Methods
21 cases of impaired respiratory function were identified and matched to 113 controls from a consecutive cohort of patients over 18 years of age. Conditional logistic regression was used to identify risk factors for impaired respiratory function.

Results
With each additional indicator of acute illness, case patients were nearly two times more likely than their controls to experience impaired respiratory function (OR 1.78; 95% CI 1.19–2.67; p = 0.005). Indicators of acute illness included emergency admission, being transferred from a critical care unit for the procedure or requiring respiratory or haemodynamic support in the lead up to the procedure.

Conclusion
Several factors that predict the likelihood of impaired respiratory function were identified. The results from this study could be used to inform prospective studies investigating the effectiveness of interventions for impaired respiratory function during nurse-administered procedural sedation and analgesia in the cardiac catheterisation laboratory.

Issues and challenges associated with nurse-administered procedural sedation and analgesia in the cardiac catheterisation laboratory: a qualitative study

Aims and objectives
To explore issues and challenges associated with nurse-administered procedural sedation and analgesia in the cardiac catheterisation laboratory from the perspectives of senior nurses.

Background
Nurses play an important part in managing sedation because the prescription is usually given verbally directly from the cardiologist who is performing the procedure and typically, an anaesthetist is not present.

Design
A qualitative exploratory design was employed.

Methods
Semi-structured interviews with 23 nurses from 16 cardiac catheterisation laboratories across four states in Australia and also New Zealand were conducted. Data analysis followed the guide developed by Braun and Clark to identify the main themes.

Results
Major themes emerged from analysis regarding the lack of access to anaesthetists, the limitations of sedative medications, the barriers to effective patient monitoring and the impact that the increasing complexity of procedures has on patients' sedation requirements.

Conclusions
The most critical issue identified in this study is that current guidelines, which are meant to apply regardless of the clinical setting, are not practical for the cardiac catheterisation laboratory due to a lack of access to anaesthetists. Furthermore, this study has demonstrated that nurses hold concerns about the legitimacy of their practice in situations when they are required to perform tasks outside of clinical practice guidelines. To address nurses' concerns, it is proposed that new guidelines could be developed, which address the unique circumstances in which sedation is used in the cardiac catheterisation laboratory.

Relevance to clinical practice
Nurses need to possess advanced knowledge and skills in monitoring for the adverse effects of sedation. Several challenges impact on nurses' ability to monitor patients during procedural sedation and analgesia. Preprocedural patient education about what to expect from sedation is essential.