Electrochemical noise and impedance of Au electrode/electrolyte interfaces enabling extracellular detection of glioma cell populations

Microelectrode arrays (MEA) record extracellular local field potentials of cells adhered to the electrodes. A disadvantage is the limited signal-to-noise ratio. The state-of-the-art background noise level is about 10 mu Vpp. Furthermore, in MEAs low frequency events are filtered out. Here, we quantitatively analyze Au electrode/electrolyte interfaces with impedance spectroscopy and noise measurements. The equivalent circuit is the charge transfer resistance in parallel with a constant phase element that describes the double layer capacitance, in series with a spreading resistance. This equivalent circuit leads to a Maxwell-Wagner relaxation frequency, the value of which is determined as a function of electrode area and molarity of an aqueous KCl electrolyte solution. The electrochemical voltage and current noise is measured as a function of electrode area and frequency and follow unambiguously from the measured impedance. By using large area electrodes the noise floor can be as low as 0.3 mu Vpp. The resulting high sensitivity is demonstrated by the extracellular detection of C6 glioma cell populations. Their minute electrical activity can be clearly detected at a frequency below about 10 Hz, which shows that the methodology can be used to monitor slow cooperative biological signals in cell populations

Hot embossing for fabrication of a microfluidic 3D cell culture

Clinically relevant studies of cell function in vitro require a physiologically-representative microenvironment possessing aspects such as a 3D extracellular matrix (ECM) and controlled biochemical and biophysical parameters. A polydimethylsiloxane (PDMS) microfluidic system with a 3D collagen gel has previously served for analysis of factors inducing different responses of cells in a 3D microenvironment under controlled biochemical and biophysical parameters. In the present study, applying the known commercially-viable manufacturing methods to a cyclic olefin copolymer (COC) material resulted in a microfluidic device with enhanced 3D gel capabilities, controlled surface properties, and improved potential to serve high-volume applications. Hot embossing and roller lamination molded and sealed the microfluidic device. A combination of oxygen plasma and thermal treatments enhanced the sealing, ensured proper placement of the 3D gel, and created controlled and stable surface properties within the device. Culture of cells in the new device indicated no adverse effects of the COC material or processing as compared to previous PDMS devices. The results demonstrate a methodology to transition microfludic devices for 3D cell culture from scientific research to high-volume applications with broad clinical impact.National Cancer Institute (U.S.) (award R21CA140096)Charles Stark Draper Laboratory (IR&D Grant

Microfluidics with fluid walls

Microfluidics has great potential, but the complexity of fabricating and operating devices has limited its use. Here we describe a method - Freestyle Fluidics - that overcomes many key limitations. In this method, liquids are confined by fluid (not solid) walls. Aqueous circuits with any 2D shape are printed in seconds on plastic or glass Petri dishes; then, interfacial forces pin liquids to substrates, and overlaying an immiscible liquid prevents evaporation. Confining fluid walls are pliant and resilient; they self-heal when liquids are pipetted through them. We drive flow through a wide range of circuits passively by manipulating surface tension and hydrostatic pressure, and actively using external pumps. Finally, we validate the technology with two challenging applications - triggering an inflammatory response in human cells and chemotaxis in bacterial biofilms. This approach provides a powerful and versatile alternative to traditional microfluidics.The complexity of fabricating and operating microfluidic devices limits their use. Walsh et al. describe a method in which circuits are printed as quickly and simply as writing with a pen, and liquids in them are confined by fluid instead of solid walls

From 2D to 3D: novel nanostructured scaffolds to investigate signalling in reconstructed neuronal networks

To recreate in vitro 3D neuronal circuits will ultimately increase the relevance of results from cultured to whole-brain networks and will promote enabling technologies for neuro-engineering applications. Here we fabricate novel elastomeric scaffolds able to instruct 3D growth of living primary neurons. Such systems allow investigating the emerging activity, in terms of calcium signals, of small clusters of neurons as a function of the interplay between the 2D or 3D architectures and network dynamics. We report the ability of 3D geometry to improve functional organization and synchronization in small neuronal assemblies. We propose a mathematical modelling of network dynamics that supports such a result. Entrapping carbon nanotubes in the scaffolds remarkably boosted synaptic activity, thus allowing for the first time to exploit nanomaterial/cell interfacing in 3D growth support. Our 3D system represents a simple and reliable construct, able to improve the complexity of current tissue culture models

Proposed Standards for Medical Education Submissions to the Journal of General Internal Medicine

To help authors design rigorous studies and prepare clear and informative manuscripts, improve the transparency of editorial decisions, and raise the bar on educational scholarship, the Deputy Editors of the Journal of General Internal Medicine articulate standards for medical education submissions to the Journal. General standards include: (1) quality questions, (2) quality methods to match the questions, (3) insightful interpretation of findings, (4) transparent, unbiased reporting, and (5) attention to human subjects’ protection and ethical research conduct. Additional standards for specific study types are described. We hope these proposed standards will generate discussion that will foster their continued evolution

Attribution-based motivation treatment efficacy in an online learning environment for students who differ in cognitive elaboration

Attribution-based motivation treatments can boost performance in competitive achievement settings (Perry and Hamm 2017), yet their efficacy relative to mediating processes and affect-based treatments remains largely unexamined. In a two-semester, pre-post, randomized treatment study (n = 806), attributional retraining (AR) and stress-reduction (SR) treatments were administered in an online learning environment to first-year college students who differed in cognitive elaboration (low, high). Low elaborators who received AR outperformed their SR peers by nearly a letter grade on a class test assessed 5 months post-treatment. Path analysis revealed this AR-performance linkage was mediated by causal attributions, perceived control, and positive and negative achievement emotions in a hypothesized causal sequence. Results advance the literature by showing AR (vs. SR) improved performance indirectly via cognitive and affective process variables specified by Weiner’s (1985a, 2012) attribution theory of motivation and emotion

Defining the effect and mediators of two knowledge translation strategies designed to alter knowledge, intent and clinical utilization of rehabilitation outcome measures: a study protocol [NCT00298727]

BACKGROUND: A substantial number of valid outcome measures have been developed to measure health in adult musculoskeletal and childhood disability. Regrettably, national initiatives have merely resulted in changes in attitude, while utilization remains unacceptably low. This study will compare the effectiveness and mediators of two different knowledge transfer (KT) interventions in terms of their impact on changing knowledge and behavior (utilization and clinical reasoning) related to health outcome measures. METHOD/DESIGN: Physical and occupational therapists (n = 144) will be recruited in partnership with the national professional associations to evaluate two different KT interventions with the same curriculum: 1) Stakeholder-Hosted Interactive Problem-Based Seminar (SHIPS), and 2) Online Problem-Based course (e-PBL). SHIPS will consist of face-to-face problem-based learning (PBL) for 2 1/2 days with outcome measure developers as facilitators, using six problems generated in consultation with participants. The e-PBL will consist of a 6-week web-based course with six generic problems developed by content experts. SHIPS will be conducted in three urban centers in Canada. Participants will be block-allocated by a minimization procedure to either of the two interventions to minimize any prognostic differences. Trained evaluators at each site will conduct chart audits and chart-stimulated recall. Trained interviewers will conduct semi-structured interviews focused on identifying critical elements in KT and implementing practice changes. Interviews will be transcribed verbatim. Baseline predictors including demographics, knowledge, attitudes/barriers regarding outcome measures, and Readiness to Change will be assessed by self-report. Immediately post-intervention and 6 months later, these will be re-administered. Primary qualitative and quantitative evaluations will be conducted 6-months post-intervention to assess the relative effectiveness of KT interventions and to identify elements that contribute to changing clinical behavior. Chart audits will determine the utilization of outcome measures (counts). Incorporation of outcome measures into clinical reasoning will be assessed using an innovative technique: chart-stimulated recall. DISCUSSION: A strategy for optimal transfer of health outcome measures into practice will be developed and shared with multiple disciplines involved in primary and specialty management of musculoskeletal and childhood disability

A framework for the first‑person internal sensation of visual perception in mammals and a comparable circuitry for olfactory perception in Drosophila

Perception is a first-person internal sensation induced within the nervous system at the time of arrival of sensory stimuli from objects in the environment. Lack of access to the first-person properties has limited viewing perception as an emergent property and it is currently being studied using third-person observed findings from various levels. One feasible approach to understand its mechanism is to build a hypothesis for the specific conditions and required circuit features of the nodal points where the mechanistic operation of perception take place for one type of sensation in one species and to verify it for the presence of comparable circuit properties for perceiving a different sensation in a different species. The present work explains visual perception in mammalian nervous system from a first-person frame of reference and provides explanations for the homogeneity of perception of visual stimuli above flicker fusion frequency, the perception of objects at locations different from their actual position, the smooth pursuit and saccadic eye movements, the perception of object borders, and perception of pressure phosphenes. Using results from temporal resolution studies and the known details of visual cortical circuitry, explanations are provided for (a) the perception of rapidly changing visual stimuli, (b) how the perception of objects occurs in the correct orientation even though, according to the third-person view, activity from the visual stimulus reaches the cortices in an inverted manner and (c) the functional significance of well-conserved columnar organization of the visual cortex. A comparable circuitry detected in a different nervous system in a remote species-the olfactory circuitry of the fruit fly Drosophila melanogaster-provides an opportunity to explore circuit functions using genetic manipulations, which, along with high-resolution microscopic techniques and lipid membrane interaction studies, will be able to verify the structure-function details of the presented mechanism of perception

The cognitive neuroscience of prehension: recent developments

Prehension, the capacity to reach and grasp, is the key behavior that allows humans to change their environment. It continues to serve as a remarkable experimental test case for probing the cognitive architecture of goal-oriented action. This review focuses on recent experimental evidence that enhances or modifies how we might conceptualize the neural substrates of prehension. Emphasis is placed on studies that consider how precision grasps are selected and transformed into motor commands. Then, the mechanisms that extract action relevant information from vision and touch are considered. These include consideration of how parallel perceptual networks within parietal cortex, along with the ventral stream, are connected and share information to achieve common motor goals. On-line control of grasping action is discussed within a state estimation framework. The review ends with a consideration about how prehension fits within larger action repertoires that solve more complex goals and the possible cortical architectures needed to organize these actions