Defining the Spatial Resolution of Analyte Recovery during Microperfusion-Based Sampling of Brain Parenchyma.

The unique architecture of the brain and the blood-brain barrier imposes challenges for the measurement of parenchyma-derived biomarkers that prevent sufficient understanding of transient neuropathogenic processes. One solution to this challenge is direct sampling of brain interstitial fluid via implanted microperfusion probes. Seeking to understand spatial limitations to microperfusion in the brain, we employed computational fluid dynamics modeling and empirical recovery of fluorescently labeled dextrans in an animal model. We found that dextrans were successfully recovered via microperfusion over a 6 h sampling period, especially at probes implanted 2 mm from the dextran infusion point relative to probes implanted 5 mm from the injection site. Experimental recovery was consistently around 1% of simulated, suggesting that this parameter can be used to set practical limits on the maximal tissue concentration of proteins measured in microperfusates and on the spatial domain sampled by our multimodal microperfusion probe.

Anti-manic effect of deep brain stimulation of the ventral tegmental area in an animal model of mania induced by methamphetamine.

BACKGROUND: Treatment of refractory bipolar disorder (BD) is extremely challenging. Deep brain stimulation (DBS) holds promise as an effective treatment intervention. However, we still understand very little about the mechanisms of DBS and its application on BD. AIM: The present study aimed to investigate the behavioural and neurochemical effects of ventral tegmental area (VTA) DBS in an animal model of mania induced by methamphetamine (m-amph). METHODS: Wistar rats were given 14 days of m-amph injections, and on the last day, animals were submitted to 20 min of VTA DBS in two different patterns: intermittent low-frequency stimulation (LFS) or continuous high-frequency stimulation (HFS). Immediately after DBS, manic-like behaviour and nucleus accumbens (NAc) phasic dopamine (DA) release were evaluated in different groups of animals through open-field tests and fast-scan cyclic voltammetry. Levels of NAc dopaminergic markers were evaluated by immunohistochemistry. RESULTS: M-amph induced hyperlocomotion in the animals and both DBS parameters reversed this alteration. M-amph increased DA reuptake time post-sham compared to baseline levels, and both LFS and HFS were able to block this alteration. LFS was also able to reduce phasic DA release when compared to baseline. LFS was able to increase dopamine transporter (DAT) expression in the NAc. CONCLUSION: These results demonstrate that both VTA LFS and HFS DBS exert anti-manic effects and modulation of DA dynamics in the NAc. More specifically the increase in DA reuptake driven by increased DAT expression may serve as a potential mechanism by which VTA DBS exerts its anti-manic effects.

SmartFSCV: An Artificial Intelligence Enabled Miniaturised FSCV Device Targeting Serotonin.

Goal: Dynamically monitoring serotonin in real-time within target brain regions would significantly improve the diagnostic and therapeutic approaches to a variety of neurological and psychiatric disorders. Current systems for measuring serotonin lack immediacy and portability and are bulky and expensive. Methods: We present a new miniaturised device, named SmartFSCV, designed to monitor dynamic changes of serotonin using fast-scan cyclic voltammetry (FSCV). This device outputs a precision voltage potential between -3 to +3 V, and measures current between -1.5 to +1.5 µA with nano-ampere accuracy. The device can output modifiable arbitrary waveforms for various measurements and uses an N-shaped waveform at a scan-rate of 1000 V/s for sensing serotonin. Results: Four experiments were conducted to validate SmartFSCV: static bench test, dynamic serotonin test and two artificial intelligence (AI) algorithm tests. Conclusions: These tests confirmed the ability of SmartFSCV to accurately sense and make informed decisions about the presence of serotonin using AI.

A self-stiffening compliant intracortical microprobe.

Utilising a flexible intracortical microprobe to record/stimulate neurons minimises the incompatibility between the implanted microprobe and the brain, reducing tissue damage due to the brain micromotion. Applying bio-dissolvable coating materials temporarily makes a flexible microprobe stiff to tolerate the penetration force during insertion. However, the inability to adjust the dissolving time after the microprobe contact with the cerebrospinal fluid may lead to inaccuracy in the microprobe positioning. Furthermore, since the dissolving process is irreversible, any subsequent positioning error cannot be corrected by re-stiffening the microprobe. The purpose of this study is to propose an intracortical microprobe that incorporates two compressible structures to make the microprobe both adaptive to the brain during operation and stiff during insertion. Applying a compressive force by an inserter compresses the two compressible structures completely, resulting in increasing the equivalent elastic modulus. Thus, instant switching between stiff and soft modes can be accomplished as many times as necessary to ensure high-accuracy positioning while causing minimal tissue damage. The equivalent elastic modulus of the microprobe during operation is ≈ 23 kPa, which is ≈ 42% less than the existing counterpart, resulting in ≈ 46% less maximum strain generated on the surrounding tissue under brain longitudinal motion. The self-stiffening microprobe and surrounding neural tissue are simulated during insertion and operation to confirm the efficiency of the design. Two-photon polymerisation technology is utilised to 3D print the proposed microprobe, which is experimentally validated and inserted into a lamb's brain without buckling.

A Bluetooth-Enabled Device for Real-Time Detection of Sitting, Standing, and Walking: Cross-Sectional Validation Study.

BACKGROUND: This study assesses the accuracy of a Bluetooth-enabled prototype activity tracker called the Sedentary behaviOR Detector (SORD) device in identifying sedentary, standing, and walking behaviors in a group of adult participants. OBJECTIVE: The primary objective of this study was to determine the criterion and convergent validity of SORD against direct observation and activPAL. METHODS: A total of 15 healthy adults wore SORD and activPAL devices on their thighs while engaging in activities (lying, reclining, sitting, standing, and walking). Direct observation was facilitated with cameras. Algorithms were developed using the Python programming language. The Bland-Altman method was used to assess the level of agreement. RESULTS: Overall, 1 model generated a low level of bias and high precision for SORD. In this model, accuracy, sensitivity, and specificity were all above 0.95 for detecting sitting, reclining, standing, and walking. Bland-Altman results showed that mean biases between SORD and direct observation were 0.3% for sitting and reclining (limits of agreement [LoA]=-0.3% to 0.9%), 1.19% for standing (LoA=-1.5% to 3.42%), and -4.71% for walking (LoA=-9.26% to -0.16%). The mean biases between SORD and activPAL were -3.45% for sitting and reclining (LoA=-11.59% to 4.68%), 7.45% for standing (LoA=-5.04% to 19.95%), and -5.40% for walking (LoA=-11.44% to 0.64%). CONCLUSIONS: Results suggest that SORD is a valid device for detecting sitting, standing, and walking, which was demonstrated by excellent accuracy compared to direct observation. SORD offers promise for future inclusion in theory-based, real-time, and adaptive interventions to encourage physical activity and reduce sedentary behavior.

ViTab Transformer Framework for Predicting Induced Electric Field and Focality in Transcranial Magnetic Stimulation.

Transcranial magnetic stimulation is an electromagnetic induction-based non-invasive therapeutic technique for neurological diseases. For finding new clinical applications and enhancing the efficacy of TMS in existing neurological disorders, the current study focuses on a deep learning-based prediction model as an alternative to time-consuming electromagnetic (EM) simulation software. The main bottleneck of the existing prediction models is to consider very few input parameters of a standard coil such as coil type and coil position for predicting an output of electric field value. To overcome this limitation, a transformer-based prediction model titled as ViTab transformer is developed in this work to predict electric field (E-max), focality or area of stmulation (S-half), and volume of stimulation (V-half) by considering several input parameters such as sources of MRI images, types of coils, coil position, rate of change of current, brain tissues conductivity, and coil distance from the scalp. The proposed framework consists of a vision and a tab transformer to handle both image and tabular-type data. The prediction performance of the offered model is evaluated in terms of coefficient determination, R2 score, for E-max, V-half, and S-half in the testing phase. The obtained result in terms of R2 score for E-max, V-half, and S-half are found 0.97, 0.87, and 0.90 respectively. The results indicate that the suggested ViTab transformer model can predict electric field as well as focality more accurately than the current state-of-the-art methods. The reduced computational time, as well as efficient prediction accuracy, resembles that ViTab transformer can assist the neuroscientist and neurosurgeon prior to providing superior TMS treatment in near future.

Dual core photonic crystal fiber based plasmonic refractive index sensor with ultra-wide detection range.

In this study, an ultra-wide range plasmonic refractive index sensor based on dual core photonic crystal fiber is suggested and analyzed numerically. The proposed design achieves fabrication feasibility by employing external sensing mechanism in which silver is deposited onto the flat outer surface of the fiber as plasmonic material. A thin layer of titanium oxide (TiO2) is considered on top of the silver layer for preventing its oxidation problem. The sensor attains identification of a vast array of analytes consisting a wide range of refractive indices of 1.10 - 1.45. It achieves a maximum spectral sensitivity of 24300 nm/RIU along with its corresponding resolution of 4.12 × 10-6 RIU. The maximum figure of merit of the sensor is 120 RIU-1. The sensor also supports amplitude interrogation approach and exhibits a maximum amplitude sensitivity of 172 RIU-1. The impact of the design parameters such as radius of air holes, polishing distance, thickness of silver and titanium oxide layers are investigated thoroughly. An ultra-wide detection range with high sensitivity, fabrication feasibility, and easy application make the sensor a potential candidate for detection of a wide array of bio-originated materials, chemicals, and other analytes.

Oxycodone-induced dopaminergic and respiratory effects are modulated by deep brain stimulation.

Introduction: Opioids are the leading cause of overdose death in the United States, accounting for almost 70,000 deaths in 2020. Deep brain stimulation (DBS) is a promising new treatment for substance use disorders. Here, we hypothesized that VTA DBS would modulate both the dopaminergic and respiratory effect of oxycodone. Methods: Multiple-cyclic square wave voltammetry (M-CSWV) was used to investigate how deep brain stimulation (130 Hz, 0.2 ms, and 0.2 mA) of the rodent ventral segmental area (VTA), which contains abundant dopaminergic neurons, modulates the acute effects of oxycodone administration (2.5 mg/kg, i.v.) on nucleus accumbens core (NAcc) tonic extracellular dopamine levels and respiratory rate in urethane-anesthetized rats (1.5 g/kg, i.p.). Results: I.V. administration of oxycodone resulted in an increase in NAcc tonic dopamine levels (296.9 ± 37.0 nM) compared to baseline (150.7 ± 15.5 nM) and saline administration (152.0 ± 16.1 nM) (296.9 ± 37.0 vs. 150.7 ± 15.5 vs. 152.0 ± 16.1, respectively, p = 0.022, n = 5). This robust oxycodone-induced increase in NAcc dopamine concentration was associated with a sharp reduction in respiratory rate (111.7 ± 2.6 min-1 vs. 67.9 ± 8.3 min-1; pre- vs. post-oxycodone; p < 0.001). Continuous DBS targeted at the VTA (n = 5) reduced baseline dopamine levels, attenuated the oxycodone-induced increase in dopamine levels to (+39.0% vs. +95%), and respiratory depression (121.5 ± 6.7 min-1 vs. 105.2 ± 4.1 min-1; pre- vs. post-oxycodone; p = 0.072). Discussion: Here we demonstrated VTA DBS alleviates oxycodone-induced increases in NAcc dopamine levels and reverses respiratory suppression. These results support the possibility of using neuromodulation technology for treatment of drug addiction.

A self-healing nanocomposite double network bacterial nanocellulose/gelatin hydrogel for three dimensional printing.

Extrusion-based three-dimensional (3D) printing of gelatin is important for additive manufactured tissue engineering scaffolds, but gelatin's thermal instability has remained an ongoing challenge. The gelatin tends to suddenly collapse at mild temperatures, which is a significant limitation for using it at physiological temperature of 37 °C. Hence, fabrication of a thermo-processable gelatin hydrogel adapted for extrusion-based additive manufacturing is still a challenge. To achieve this, a self-healing nanocomposite double-network (ncDN) gelatin hydrogel was fabricated with high thermo-processability, shear-thinning, mechanical strength, self-healing, self-recovery, and biocompatibility. To do this, amino group-rich gelatin was first created by combining gelatin with carboxyl methyl chitosan. Afterwards, a self-healing ncDN gelatin hydrogel was formed via an in-situ formation of imine bonds between the blend of gelatin/carboxyl methyl chitosan (Gel/CMCh) and dialdehyde-functionalized bacterial nanocellulose (dBNC). dBNC plays as nanofiber cross-linkers capable of simultaneously crosslinking and reinforcing the double networks of Gel/CMCh through formation of dynamic 3D imine bonds. Based on our findings, our self-healing ncDA gelatin hydrogel displayed great potential as a promising ink for additive manufactured tissue engineering scaffolds.

Evaluation of machine learning-based models for prediction of clinical deterioration: A systematic literature review.

BACKGROUND AND OBJECTIVE: Early identification of patients at risk of deterioration can prevent life-threatening adverse events and shorten length of stay. Although there are numerous models applied to predict patient clinical deterioration, most are based on vital signs and have methodological shortcomings that are not able to provide accurate estimates of deterioration risk. The aim of this systematic review is to examine the effectiveness, challenges, and limitations of using machine learning (ML) techniques to predict patient clinical deterioration in hospital settings. METHODS: A systematic review was performed in accordance with the Preferred Reporting Items for Systematic Reviews and meta-Analyses (PRISMA) guidelines using EMBASE, MEDLINE Complete, CINAHL Complete, and IEEExplore databases. Citation searching was carried out for studies that met inclusion criteria. Two reviewers used the inclusion/exclusion criteria to independently screen studies and extract data. To address any discrepancies in the screening process, the two reviewers discussed their findings and a third reviewer was consulted as needed to reach a consensus. Studies focusing on use of ML in predicting patient clinical deterioration that were published from inception to July 2022 were included. RESULTS: A total of 29 primary studies that evaluated ML models to predict patient clinical deterioration were identified. After reviewing these studies, we found that 15 types of ML techniques have been employed to predict patient clinical deterioration. While six studies used a single technique exclusively, several others utilised a combination of classical techniques, unsupervised and supervised learning, as well as other novel techniques. Depending on which ML model was applied and the type of input features, ML models predicted outcomes with an area under the curve from 0.55 to 0.99. CONCLUSIONS: Numerous ML methods have been employed to automate the identification of patient deterioration. Despite these advancements, there is still a need for further investigation to examine the application and effectiveness of these methods in real-world situations.