Comparison of colorimetric analyses to determine cortisol in human sweat

Colorimetric analysis, which relies on a chemical reaction to facilitate a change in visible color, is a great strategy for detecting cortisol, which is necessary to diagnose and manage the wide variety of diseases related to the hormone, because it is simple in design, inexpensive, and reliable as a standard cortisol analysis technique. In this study, four different colorimetric cortisol analyses that use various chromogens, which include sulfuric acid, Porter−Silber reagent, Prussian blue, and blue tetrazolium, are studied. Modifications to the classic Porter−Silber method are made by increasing the carbon content of the alcohol and adding gold nanoparticles, which result in a twofold increase in reaction rate and a slight decrease in the limit of detection (LoD). After a comparison of the reaction rate, LoD, dynamic range, characteristic peaks, and color stability of all methods, blue tetrazolium demonstrates a low LoD (97 ng/mL), broad dynamic range (0.05−2 μg/mL), and quick reaction rate (color development as fast as 10 min), which are well within the requirements for human biofluids. Cortisol in artificial saliva and sweat and in human sweat was determined while confirming that no excipients or other biomarkers interfered with the reactions. Twenty-one human sweat samples were tested using blue tetrazolium and revealed a significant difference between male and female apocrine cortisol concentrations and showed a highly significant difference between apocrine and eccrine cortisol concentrations. Colorimetric methods of cortisol can compete with existing electrochemical sensors because of their similar accuracy and detection range in certain wearable biosensor applications. The simplicity of colorimetric methods advances potential applications in skin-interfaced bio-electronics and point-of-care devices

A Slow Axon Antidromic Blockade Hypothesis for Tremor Reduction via Deep Brain Stimulation

Parkinsonian and essential tremor can often be effectively treated by deep brain stimulation. We propose a novel explanation for the mechanism by which this technique ameliorates tremor: a reduction of the delay in the relevant motor control loops via preferential antidromic blockade of slow axons. The antidromic blockade is preferential because the pulses more rapidly clear fast axons, and the distribution of axonal diameters, and therefore velocities, in the involved tracts, is sufficiently long-tailed to make this effect quite significant. The preferential blockade of slow axons, combined with gain adaptation, results in a reduction of the mean delay in the motor control loop, which serves to stabilize the feedback system, thus ameliorating tremor. This theory, without any tuning, accounts for several previously perplexing phenomena, and makes a variety of novel predictions

Sweat and saliva cortisol response to stress and nutrition factors

Cortisol is a biomarker for stress monitoring; however, the biomedical and clinical relevance is still controversial due to the complexity of cortisol secretion mechanisms and their circadian cycles as well as environmental factors that afect physiological cortisol level, which include individual mood and dietary intake. To further investigate this multifaceted relationship, a human pilot study examined cortisol concentration in sweat and saliva samples collected from 48 college-aged participants during aerobic exercise sessions along with mental distress and nutrition surveys. Enzyme-linked immunosorbent assays determined highly signifcant diferences between apocrine-dominant sweat (AP), saliva before exercise (SBE), and saliva after exercise (SAE) cortisol concentration (AP-SBE: p = 0.0017, AP-SAE: p = 0.0102). A signifcantly greater AP cortisol concentration was detected in males compared to females (p = 0.0559), and signifcant SAE cortisol concentration diferences were also recorded between recreational athletes and non-athletes (p= 0.044). However, Kessler 10 Psychological Distress Scale (K10) scores, an examination administered to deduce overall wellness, provided no signifcant diferences between males and females or athletes and non-athletes in distress levels, which statistically signifes a direct relationship to cortisol was not present. For further analysis, dietary intake from all participants was considered to investigate whether a multiplexed association was prevalent between nutrition, mood, and cortisol release. Signifcant positive correlations between AP cortisol, SAE cortisol, K10 scores, and fat intake among female participants and athletes were discovered. The various machine learning algorithms utilized the extensive connections between dietary intake, overall well-being, sex factors, athletic activity, and cortisol concentrations in various biofuids to predict K10 scores. Indeed, the understanding of physiochemical stress response and the associations between studied factors can advance algorithm developments for cortisol biosensing systems to mitigate stress-based illnesses and improve an individual’s quality of life

Sensor Verification and Analytical Validation of Algorithms to Measure Gait and Balance and Pronation/Supination in Healthy Volunteers

Numerous studies have sought to demonstrate the utility of digital measures of motor function in Parkinson’s disease. Frameworks, such as V3, document digital measure development: technical verification, analytical and clinical validation. We present the results of a study to (1) technically verify accelerometers in an Apple iPhone 8 Plus and ActiGraph GT9X versus an oscillating table and (2) analytically validate software tasks for walking and pronation/supination on the iPhone plus passively detect walking measures with the ActiGraph in healthy volunteers versus human raters. In technical verification, 99.4% of iPhone and 91% of ActiGraph tests show good or excellent agreement versus the oscillating table as the gold standard. For the iPhone software task and algorithms, intraclass correlation coefficients (ICCs) > 0.75 are achieved versus the human raters for measures when walking distance is >10 s and pronation/supination when the arm is rotated more than two times. Passively detected walking start and end time was accurate to approx. 1 s and walking measures were accurate to one unit, e.g., one step. The results suggest that the Apple iPhone and ActiGraph GT9X accelerometers are fit for purpose and that task and passively collected measures are sufficiently analytically valid to assess usability and clinical validity in Parkinson’s patients

Deep brain stimulation may reduce tremor by preferential blockade of slower axons via antidromic activation

Deep brain stimulation (DBS) has been used to ameliorate essential and Parkinsonian tremor, however the detailed mechanism by which tremor reduction is achieved remains unclear. We hypothesize that DBS works by reducing time delays in the feedback paths of the motor control loops. In particular, we suggest that antidromic activation of axonal pathways induced by stimulation will preferentially block axons with longer propagation times, reducing time delays in neuronal motor circuits in a stabilising manner. We demonstrate the plausibility of this hypothesis using two simple computational models which account for a variety of experimental results, and allow us to makes a number of testable predictions

Assumed delay distribution.

<p>The delay distribution is calculated by assuming a mode of 2<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0073456#pone.0073456-Barazany1" target="_blank">[30]</a>.</p

Closed-loop control is used to regulate wrist angle at the horizontal position with control gains selected to reproduce the mean measured amplitude and frequency [2].

<p>Panel (a) shows how the frequency of the oscillation increases and the amplitude decreases when reducing the delay. Panels (b)–(c) show different PD tremor at different conditions: (b) no DBS, (c) a non-optimal DBS, and (d) optimal DBS. (Normal physiological tremor usually ranges between 6–15Hz <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0073456#pone.0073456-Raethjen1" target="_blank">[36]</a>.)</p

Transmission probability of a random orthodromic spike as a function of axonal delay, at different antidromic blocking frequencies.

<p>Computations here were based on <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0073456#pone.0073456.e011" target="_blank">equation (2</a>). If we negglet the refractory period, the blockade is complete when the axonal delay exceeds one-half of the interval between antidromic spikes.</p