Neuromechanisms of simulation-based arthroscopic skills assessment: a fNIRS study.

BACKGROUND: The neural mechanisms underlying differences in the performance of simulated arthroscopic skills across various skill levels remain unclear. Our primary objective is to investigate the learning mechanisms of simulated arthroscopic skills using functional near-infrared spectroscopy (fNIRS). METHODS: We recruited 27 participants, divided into three groups: novices (n = 9), intermediates (n = 9), and experts (n = 9). Participants completed seven arthroscopic tasks on a simulator, including diagnostic navigation, triangulation, grasping stars, diagnostic exploration, meniscectomy, synovial membrane cleaning, and loose body removal. All tasks were videotaped and assessed via the simulator system and the Arthroscopic Surgical Skill Evaluation Tool (ASSET), while cortical activation data were collected using fNIRS. Simulator scores and ASSET scores were analyzed to identify different level of performance of all participants. Brain region activation and functional connectivity (FC) of different types of participants were analyzed from fNIRS data. RESULTS: Both the expert and intermediate groups scored significantly higher than the novice group (p < 0.001). There were significant differences in ASSET scores between experts and intermediates, experts and novices, and intermediates and novices (p = 0.0047, p < 0.0001, p < 0.0001), with the trend being experts > intermediates > novices. The intermediate group exhibited significantly greater activation in the left primary motor cortex (LPMC) and left prefrontal cortex (LPFC) compared to the novice group (p = 0.0152, p = 0.0021). Compared to experts, the intermediate group demonstrated significantly increased FC between the presupplementary motor area (preSMA) and the right prefrontal cortex (RPFC; p < 0.001). Additionally, the intermediate group showed significantly increased FC between the preSMA and LPFC, RPFC and LPFC, and LPMC and LPFC compared to novices (p = 0.0077, p = 0.0285, p = 0.0446). CONCLUSION: Cortical activation and functional connectivity reveal varying levels of activation intensity in the PFC, PMC, and preSMA among novices, intermediates, and experts. The intermediate group exhibited the highest activation intensity.

Application of TCM Rehabilitation in Joint Function Recovery After Treatment of Distal Radius Fractures: A Meta-Analysis.

Objective: To evaluate the effect of traditional Chinese medicine (TCM) rehabilitation on the postoperative function of patients with distal radius fractures by Meta-analysis. Methods: PubMed, Embase, CNKI, Wanfang, and other databases were searched for retrospective controlled trials and prospective randomized controlled trials on the effect of traditional Chinese medicine rehabilitation on the function of patients with distal radius fractures after surgery from the establishment of the database to May 2023. Revman version 5.3 software was used to analyze the extracted and screened index data. Results: Eight studies involving 455 patients were included. Meta-analysis results showed Overall analysis showed that there was a significant difference in wrist function between the TCM rehabilitation group and the control group (MD = -12.16, 95%CI:-17.21 to -7.11, P < .00001), low heterogeneity (I2=40%, P = .17), the difference in dorsiflexion function between the TCM rehabilitation group and the control group was statistically significant (MD = -1.16, 95%CI:-2.24 to -0.08, P = .04), with high heterogeneity (I2=79%, P = .003), that there was a significant difference in grip strength between the TCM rehabilitation group and the control group at 6 weeks (MD= 0.48, 95%CI: 0.24 to 0.71, P < .0001) with low heterogeneity (I2=45%, P = .12), there was no significant difference between the TCM rehabilitation group and the control group (OR= -0.00, 95%CI: -0.08 to 0.08, P = .99), and there was no heterogeneity (I2=0%, P = .66). Conclusion: Traditional Chinese medicine rehabilitation treatment of distal radius fractures can increase the range of motion of wrist joints, reduce pain, shorten the rehabilitation time of patients, improve the quality of life, and is conducive to the standardized treatment of patients.

Organic Semiconductor Nanosheets for Sulfite Detecting Based on Activation of Sulfite and a Synergetic Chemiluminescence Resonance Energy Transfer Process in a Mild System of Fe2+-SO32.

Sulfur dioxide (SO2) as one kind of air pollution not only causes extreme environmental pollution but also negatively affects human health. Chemiluminescence (CL) methods applied for sulfite analysis with high selectivity based on activating sulfite with oxidants are always implemented in acid media with a high background rise. In this work, we proposed to develop a mild CL system of Fe2+-SO32- to detect sulfite under neutral conditions and provide in situ CL spectral data for deeply studying the CL mechanism of Fe2+-SO32-. Herein, we first synthesized one type of water-soluble supramolecular nanosheets, APDI NSs, which had a strong oxidation potential (+2.9 V) due to a π-conjugated system for activation of sulfite to enhance the generation of SO3̇- and other active radicals, and strong a CL signal from the APDI NSs-Fe2+-SO32- system was generated. By studying the CL mechanism under acidic and neutral conditions, a new CL reaction pathway (path-1) and a key intermediate, S2O42-, from the reaction of Fe2+ and SO32- were found. The CL signal was emitted by SO2* after oxidation of S2O42- by strong oxidants like SO4•- and further amplified by APDI NSs through the CL resonance energy transfer (CRET) process. Based on the APDI NSs-Fe2+-SO32- system under neutral conditions, a CL method for detecting SO32- was established. The detection limit was 2.7 × 10-8 M (S/N = 3), and the recovery rates in spiked water samples were in the range of 87%-101%. This study strengthens the understanding of the CL reaction process of the Fe2+-SO32- system and provides a mild sulfite sensing platform for environmental samples.

Novel Near-Infrared Iridium(III) Complex for Chemiluminescence Imaging of Hypochlorous Acid.

Chemiluminescence (CL) probes that possess near-infrared (NIR) emission are highly desirable for in vivo imaging due to their deeper tissue penetration ability and intrinsically high sensitivity. Herein, a novel iridium-based CL probe (NIRIr-CL-1) with direct NIR emission was reported as the result of hypochlorous acid (HClO)-initiated oxidative deoximation. To improve its biocompatibility and extend the CL time for in vivo imaging applications, this NIRIr-CL-1 was prepared as a CL nanoparticle probe (NIRIr-CL-1 dots) through encapsulation by an amphiphilic polymer Pluronic F127 (F127). All results demonstrate that the NIRIr-CL-1 dots have good selectivity and sensitivity for visualization of HClO even at the depth of 1.2 cm. Owing to these advantages, the CL imaging of exogenous and endogenous HClO in mice was achieved. This study could provide new insights into the construction of new NIR emission CL probes and expand their applications in biomedical imaging.

"Iridium Signature" Mass Spectrometric Probes: New Tools Integrated in a Liquid Chromatography-Mass Spectrometry Workflow for Routine Profiling of Nitric Oxide and Metabolic Fingerprints in Cells.

Nitric oxide (NO) is a highly reactive signaling molecule involved in diverse biological processes. Simultaneous profiling of NO and associated metabolic fingerprints in a single assay allows more accurate assessments of cell states and offers the possibility to better understand its exact biological roles. Herein, a multiplexing LC-MS workflow was established for simultaneous detection of intracellular NO and various metabolites based on a novel "iridium signature" mass spectrometric probe (Ir-MSP841). This Ir-MSP841 can convert highly liable NO to a stable permanently charged triazole product (Ir-TP852), enabling direct MS detection of NO. This 191/193Ir-signature mass spectrometric probe-based approach is endowed with overwhelming advantages of interference-free, high quantitative accuracy, and great sensitivity (limit of detection down to 0.14 nM). It also reveals good linearity over a wide concentration range 12.5-500 nM and has been successfully employed for exploring the release behaviors of three representative NO donors in cells. Meanwhile, metabolic profiling results reveal that varying the concentrations of NO has distinct effects on various cellular metabolites. This study provides a robust, sensitive, and versatile method for simultaneous detection of NO and numerous metabolites in a single LC-MS run and expands its applications in biomedical research.

Monocarboxylate transporter 4 protects against myocardial ischemia/reperfusion injury by inducing oxidative phosphorylation/glycolysis interconversion and inhibiting oxidative stress.

Myocardial ischemia/reperfusion (I/R) injury is the primary cause of heart damage in the treatment of myocardial infarction, and the imbalance of the energy metabolism in the pathogenesis of myocardial I/R is one of the main triggers of cardiac dysfunction. Monocarboxylate transporter 4 (MCT4) is a key transporter of lactate, which plays a vital role in cellular metabolism. The present study investigated the role and underlying mechanism of MCT4 in myocardial I/R injury. The results of this study showed that MCT4 was upregulated during oxygen-glucose deprivation (OGD) and restored after reoxygenation in cardiomyocytes HL-1. Interestingly, the overexpression of MCT4 increased cell viability and decreased apoptosis of OGD/R-induced HL-1 cells. Furthermore, MCT4 boosted glucose uptake and lactate levels and promoted protein expression of glycolysis regulator LDHA, while also impeding oxidative phosphorylation (OXPHOS) regulators C-MYC and NDUFB8 in OGD/R-induced HL-1 cells. A reduction in reactive oxygen species and oxidative stress markers malonaldehyde and superoxide dismutase was also observed within the OGD/R stimulated HL-1 cells. Additionally, the in vivo exogenous application of MCT4 restored cardiac function, as demonstrated by the reduced infarct size and decreased myocardial apoptosis in I/R rats. OXPHOS and oxidative stress declined, while glycolysis was activated when the I/R mice were injected with AAV-MCT4. Our findings indicate that MCT4 could exert a cardioprotective effect after myocardial I/R injury by inducing OXPHOS/glycolysis interconversion and inhibiting oxidative stress.

A spaced retraining schedule with 2-day interval improves the acquisition and retention of simulation-based basic arthroscopic skills.

PURPOSE: To compare the effect of three differently spaced retraining schedules (1-day, 2-day, and 1-week intervals) on the acquisition of basic arthroscopic skills and skill retention after 3 months. METHODS: Thirty orthopaedic residents without arthroscopic experience were enrolled in a double-blind, randomised, parallel-controlled trial. Spaced retaining schedules were divided into massed training and retraining phases. Participants were required to obtain perfect scores in all tasks on the simulator in the massed training phase, followed by a pretest to evaluate the training effect. During the retraining phase, participants were randomly assigned to Groups A (1-day interval), B (2-day interval) or C (1-week interval). A posttest was used to evaluate the effect of different retraining patterns. Follow-up evaluations were conducted at 1 week, 1 month and 3 months after the completion of spaced retraining schedules to measure skill retention. One-way ANOVA and paired-sample t tests were used for statistical analysis. RESULTS: Significant between-group differences in diagnostic arthroscopy (137.0 ± 24.8 vs. 140.1 ± 21.3 vs. 175.3 ± 27.4 s, P(A-C) = 0.005, P(B-C) = 0.010) and loose body removal (193.1 ± 33.9 vs. 182.0 ± 32.1 vs. 228.7 ± 42.9 s, P(B-C) = 0.025) completion times were observed. No significant differences were found in other posttest metrics. An assessment of skill retention after the 3-month follow-up (Evaluation 3) showed significant differences in diagnostic arthroscopy completion time (202.5 ± 53.3 vs. 172.0 ± 27.2 vs. 225.5 ± 42.1 s, P(B-C) = 0.026). No significant differences were found in other Evaluation 3 metrics. CONCLUSION: The 2-day retraining schedule was the most effective for the acquisition and retention of basic arthroscopic skills and could be integrated into arthroscopic skills curricula. After a 3-month follow-up, residents who followed this schedule showed better skill retention than those who followed the 1-week interval schedule. LEVEL OF EVIDENCE: Level I.

Time-Resolved Persistent Luminescence Encoding for Multiplexed Severe Acute Respiratory Syndrome Coronavirus 2 Detection.

Capable of precise simultaneous multitarget identifications within a minimized sample, optical multiplexing is vital for accurate diagnosis of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) while remaining spectral crowding and background interfering. In merits of an autofluorescence-free background and high-capability throughput, a persistent luminescence (PersL) lifetime/color binary encoding strategy was herein proposed for SARS-CoV-2 diagnosis. Based on luminescence resonance energy transfer processes, the intense lifetimes and representative emissions of PersL nanoplatforms were rationally manipulated to create a temporal coding dimension within a wide seconds-to-minutes range through three individual channels. Particularly, at least four populations of barcoding in a certain channel were successfully decoded by a purpose-built time-resolved PersL technology. As a proof-of-concept, functionalized PersL nanoplatforms were further well developed for the simultaneous quantification of five-plex SARS-CoV-2 biomarkers with limits of detection in the subnanomolar range. Remarkably, PersL nanoplatforms enabled a highly differentiable discrimination of multitargets at various concentrations of ultralow background and high-fidelity resolutions, thereby advancing a powerful tool for optical multiplexing in biomedical applications.

Single Nanoparticle Counting-Based Liquid Biopsy for Cancer Diagnosis.

Liquid biopsy has become a sought-after technique for disease diagnosis because it provides real-time, dynamic, and comprehensive information that can alleviate the dilemmas faced by tissue biopsy. Multiplexed microRNAs (miRNAs) have been demonstrated to be promising biomarkers in liquid biopsy but fall short in providing simple and sensitive analytical methods. In this work, we established a novel nanoparticle counting strategy to accomplish simultaneous analysis of three breast cancer-associated miRNAs for breast cancer diagnosis. The frequency of nanoparticles not involved in the formation of sandwich structures was detected by single-particle inductively coupled plasma mass spectrometry (SP-ICPMS) to quantify the targets. The detection limits for miR-21, miR-155, and miR-16 were 49, 51, and 55 amol, respectively. The strategy was applied to clinical samples and successfully achieved the diagnosis between normal individuals and breast cancer patients. The area under the curve (AUC) for the combination of the relative expression of miR-21 and miR-155 was 0.818. The above results indicate that this strategy has potential and holds great promise for playing an essential role in cancer diagnosis.

Single-Nanoparticle Differential Immunoassay for Multiplexed Gastric Cancer Biomarker Monitoring.

Precision medicine demands the best application of multiple unambiguous biomarkers to bring uniform decisions in disease prognosis. The remarkable development of heterogeneous immunoassay greatly promotes precision medicine when combined with the biomarker combination strategy. Nevertheless, the cumbersome washing steps in heterogeneous immunoassay have inevitably compromised the accuracy because of the sample losses and nature change of the matrix, challenging the further exploration of a more facile and lower limit-of-detection analysis. The new methodologies with high throughputs and specificity are never out of date to provide simultaneous evaluations and uniform decisions on multiple analytes through a simple process. Herein, we propose a new wash-free immunoassay, named differential assay, for multiplexed biomarker monitoring. The method is based on counting the number difference of unbound nanoparticle tags before and after immunoreactions from a solid support (i.e., magnetic microsphere) by single-particle inductively coupled plasma mass spectrometry (sp-ICP-MS), discarding the tedious washing steps. We primarily explore the proof-of-concept proposal within two types (sandwich and competitive assay), demonstrating the good feasibility for further facile clinical practice. To provide efficient multiplexed evaluations, we synthesized PtNPs with four diameters and screened the most suitable size for efficient differential immunoassay. The wash-free strategy was successfully utilized in simultaneous serological biomarker (CA724, CA199, and CEA) evaluation, with results in good accordance with those measured by the clinical routine method. Potentially, the proposed differential bioassay can be regarded as a more facile and valuable tool in malignancy prognosis and cancer recurrence monitoring.

Transient Chemiluminescence Assay for Real-Time Monitoring of the Processes of SO32--Based Advanced Oxidation Reactions.

The hydroxyl radical (·OH) is a strong oxidizing agent in situ generated in advanced oxidation processes (AOPs) and crucial for assessing the performances of AOPs toward organic contaminants' degradation. Herein, we developed a specific luminescent probe, APDI (N' N'-di(propylethylenediamine)-perylene-3,4,9,10-tetracarboxylic diimide), to selectively detect ·OH among diverse reactive oxygen species and other radicals. Based on the transient chemiluminescence (TCL) spectra, the in situ concentration profile of ·OH within 0.01 s interval time in classical Fenton reactions and four kinds of SO32--based AOPs was obtained, which provides insights into the high dynamic processes of the whole ·OH generation and consumption processes. Besides, compared with acidic conditions, reduced degradation efficiencies in Fe2+-SO32- and Fe2+-SO32--H2O2 systems were found under neutral conditions. The complete depletion of active free radicals due to SO2-̇ radicals generated from Fe2+ and SO32- should account most for decreased degradation efficiencies evidenced by a new SO2* TCL signal discovered in the TCL spectra. In addition, similar phenomena have also been found in other M(n-1)+-SO32--related AOPs. As SO32- and HSO3- often exist naturally in wastewater, more efforts are needed to improve the performance of Fe2+-H2O2 systems. This discovery has important significance for organic contaminant degradation in a natural environment.

Ezrin regulates synovial angiogenesis in rheumatoid arthritis through YAP and Akt signalling.

This study aimed to investigate the role and regulatory mechanisms of Ezrin in synovial vessels in rheumatoid arthritis (RA). Synovial tissues were obtained from people with osteoarthritis people and patients with RA patients. We also used an antigen-induced arthritis (AIA) mice model by using Freund's adjuvant injections. Ezrin expression was analysed by immunofluorescence and immunohistochemical staining in synovial vessels of patients with RA and AIA mice. We investigated the role of Ezrin on vascular endothelial cells and its regulatory mechanism in vivo and in vitro by adenoviral transfection technology. Our results suggest a role for the Ezrin protein in proliferation, migration and angiogenesis of vascular endothelial cells in RA. We also demonstrate that Ezrin plays an important role in vascular endothelial cell migration and tube formation through regulation of the Hippo-yes-associated protein 1 (YAP) pathway. YAP, as a key protein, can further regulate the activity of PI3K/Akt signalling pathway in vascular endothelial cells. In AIA mice experiments, we observed that the inhibition of Ezrin or of its downstream YAP pathway can affect synovial angiogenesis and may lead to progression of RA. In conclusion, Ezrin plays an important role in angiogenesis in the RA synovium by regulating YAP nuclear translocation and interacting with the PI3K/Akt signalling pathway.

Low Back Pain Assessment Based on Alpha Oscillation Changes in Spontaneous Electroencephalogram (EEG).

Objectively and accurately assessing pain in clinical settings is challenging. Previous studies showed that alpha oscillations of electroencephalogram data are correlated with subjective perceived pain. Based on this finding, this study is aimed at assessing chronic low back pain based on alpha oscillations. Multichannel electroencephalogram data were recorded from 27 subjects with chronic low back pain under the simple conditions of closing eyes or opening eyes. Spectral analyses were conducted to extract the alpha band responses, and the alpha powers were calculated for the two conditions, respectively. Normalized alpha power was calculated by subtracting the alpha power in the eyes-open condition from that in the eyes-closed condition. The correlation between the alpha power and the subjective pain intensity was evaluated in frontal, central, and posterior regions. The normalized alpha power in the central region was negatively correlated with the subjective pain intensity (R = -0.50, P = 0.01), with the strongest correlation occurring at the Cz electrode (R = -0.59, P = 0.04). The correlation analysis results demonstrated the possibility of using the differences of alpha spectral power between eyes-closed and eyes-open conditions as a measure for assessing chronic low back pain. The findings suggest that the normalized alpha power in the central region may be used as a measurable and quantitative indicator of chronic pain for clinical applications.

Visible-Light-Driven [2 + 2] Photocycloadditions between Benzophenone and C═C Bonds in Unsaturated Lipids.

The [2 + 2] photocycloaddition of alkenes and carbonyls is of fundamental interest and practical importance, as this process is extensively involved in oxetane-ring constructions. Although individual carbonyl group or alkene moiety has been utilized as photoactive species for oxetane formations upon ultraviolet photoexcitation, direct excitation of the entire noncovalent complex involving alkene and carbonyl substrates to achieve [2 + 2] photocycloadditions is rarely addressed. Herein, complexes with noncovalent interactions between benzophenone and C═C bonds in unsaturated lipids have been successfully characterized, and for the first time a [2 + 2] cycloaddition leading to the formation of oxetanes has been identified under visible-light irradiation. The mechanism of this reaction is distinctly different from the well-studied Paternò-Büchi reaction. The entire complexes characterized as dimeric proton-bonded alkene and carbonyl substrates can be excited under visible light, leading to electron transfer from the alkene moiety in fatty acyls to the carbonyl group within the complex. These results provide new insight into utilizing noncovalent complexes for the synthesis of oxetanes in which the excitation wavelength becomes independent of each individual substrate.

Next-Generation Paternò-Büchi Reagents for Lipid Analysis by Mass Spectrometry.

The Paternò-Büchi (PB) reaction is a photochemical reaction involving [2 + 2] cycloaddition between electronically excited carbonyl and carbon-carbon double bond (C═C). It has been established as a lipid derivatization strategy, leading to confident assignment of C═C locations in lipids when coupled with tandem mass spectrometry (MS/MS). Although acetone and several aryl-containing ketones or aldehydes have been explored as PB reagents, the chemical properties critical to achieving efficient conversion and minimum side reactions remain unclear. Herein, we investigated a set of acetophenone (AP) derivatives, aiming to provide insights into the development of new PB reagents with enhanced performance for lipid analysis. For AP derivatives, we found that electron-withdrawing groups (e.g., -F and -CF3) on the benzene ring improved the overall conversion, while a bulky group at the ortho-position decreased the conversion. Norrish Type I cleavage was largely diminished; however, the Norrish Type II side reaction was more competitive, producing products isomeric to the PB reaction products. Among all AP derivatives tested, 2',4',6'-trifluoroacetophenone (triFAP) showed the best performance. It offered a relatively high PB yield (20-30%) for different types of C═C, high sensitivity (sub-nM) for C═C identification, and accurate isomer quantitation. Due to the significantly reduced chemical interferences in shotgun analysis, triFAP provided better performance than that from acetone PB-MS/MS. An offline triFAP PB reaction was implemented in a liquid chromatography analysis workflow, which enabled the large-scale identification of phospholipids including C═C location isomers from a complex lipid extract.

Profiling of Cholesteryl Esters by Coupling Charge-Tagging Paternò-Büchi Reaction and Liquid Chromatography-Mass Spectrometry.

The profile of cholesteryl esters (CEs) is increasingly used in metabolic disease monitoring due to the roles of CE in regulating the cholesterol level. While electrospray ionization-tandem mass spectrometry is routinely applied for the identification and quantitation of CE, it has a limitation of not being able to provide the location of carbon-carbon double bond (C═C) within unsaturated fatty acyls. In this study, we paired offline 2-acetylpyridine (2-AP) Paternò-Büchi (PB) reaction and reversed-phase liquid chromatography-tandem mass spectrometry to achieve highly sensitive and structural informative CE analysis from complex mixtures. The 2-AP PB reactions of CE standards provided 20-30% conversion but resulted in enhanced ion signal relative to that of intact CE detected as ammonium adduct ions. MS/MS of 2-AP derivatized CE via collision-induced dissociation produced two abundant diagnostic ions for each C═C in a fatty acyl, leading to both sensitive identification and quantitation of C═C location isomers. Twelve saturated and twenty-seven unsaturated CEs were profiled in pooled human plasma; of the latter group, relative quantitation of 6 groups of C═C location isomers was achieved. A dehydrocholesteryl ester, DHE 18:2 (Δ9,12), was confidently differentiated from coexisting compositional isomers: CE 18:3 (Δ9,12,15) and CE 18:3 (Δ6,9,12). The above results represented improved CE coverage at the C═C location level over those reported by gas chromatography MS or acetone PB-MS/MS methods.

Simulation-Based Arthroscopic Skills Using a Spaced Retraining Schedule Reduces Short-Term Task Completion Time and Camera Path Length.

PURPOSE: To investigate whether acquiring basic knee arthroscopic skills via a spaced retraining schedule could prevent skills deterioration and achieve further skills improvement. METHODS: In the learning phase, 16 residents with no previous hands-on experience in practicing arthroscopic skills were asked to perform basic arthroscopic tasks on a simulator until they attained perfect scores in each task. Immediately after completing the learning phase, a pretest was performed to assess their performance. Next, they were randomly assigned into 2 groups. The spaced retraining group, which undertook a spaced repetitive training phase with a fixed-time interval, returned on days 2, 4 and 6 to repeat the same tasks for 20 minutes per day, whereas the control group did nothing. On day 7, all participants performed a posttest. A 2 × 2 mixed analysis of variance model was used for statistical analysis. RESULTS: Significant differences between the 2 groups were found in task completion time (P = .003) and camera path length (P = .043) but not cartilage injury (P = .186). Residents in the spaced retraining group decreased their task completion time (163.2 ± 23.9 seconds) whereas the task time in the control group increased (351.3 ± 25.5 seconds). The same pattern was found with the camera path length. CONCLUSIONS: Implementing a spaced retraining schedule in 1 week resulted in a reduced task completion time and camera path length but no significant reduction in cartilage injury. It appears that introducing a spaced retraining schedule to retain arthroscopic skills acquired through massed learning may be advantageous. CLINICAL RELEVANCE: In consideration of the training time available to residents and the trend toward massed learning, this spaced retraining schedule may offer a cost-effective and convenient way for residents to maintain and improve their basic arthroscopic skills with no significant increase in time invested.

Analysis of Conjugated Fatty Acid Isomers by the Paternò-Büchi Reaction and Trapped Ion Mobility Mass Spectrometry.

Fatty acids containing conjugated carbon-carbon double bonds (C═Cs), such as conjugated linoleic acids (CLAs), attract growing research interest due to their bioactivities against diabetes, cancer, and atherosclerosis. Analysis of conjugated fatty acid (CFA) is challenging for existing analytical techniques because it requires determination of geometry (cis ( Z) vs trans ( E)) and location of individual C═C. In this study, we developed a method to achieve confident, fast, and quantitative analysis of CFA isomers from mixtures. This method combines the strength of trapped ion mobility spectrometry (TIMS) for fast isomer separation and the Paternò-Büchi (PB) reaction followed by tandem mass spectrometry (MS/MS) for C═C location determination. Notably, the PB reaction of CFA is regioselective to terminal C═Cs, thus forming diagnostic fragment ions unique to conjugated C═Cs from PB-MS/MS. These fragment ions facilitate identification and quantitation of individual CLA isomers differing in C═C locations, affording limit of identification of 1 nM. Given that PB-MS/MS alone cannot identify the geometry of C═C, TIMS has been employed for characterizing C═C geometry. TIMS is capable to separate various C═C geometric isomers of CLAs, allowing visualization of C═C isomerization during the PB reaction. By coupling the PB-MS/MS with TIMS, two CLA isomers, CLA 18:2(9 Z,11 E) (46.9 ± 1.1%) and CLA 18:2(10 E,12 Z) (53.1 ± 1.1%), are quantified in a commercial CLA supplement.

Electrochemical characteristics of microelectrode designed for electrical stimulation.

BACKGROUND: Microelectrode arrays play an important role in prosthetic implants for neural signal recording or applying electrical pulses stimulation to target nerve system. Safety and long-term reliability are essential requirements for microelectrode arrays applied in electrical stimulation. In design and fabrication of the microelectrode array, soft materials are generally chosen to be the substrate for the aim of achieving better compliance with the surrounding tissue while maintaining minimal damage. By flexing of the array to the surface, the array is capable of keeping a more stable electrical contact resulting in a significantly improved signal detected. METHODS: In this study, we design and fabricate a flexible microelectrode array with gold as the electrode material and parylene-C as the substrate. The fabrication process of the array is presented. The in vitro electrochemical characteristics of the microelectrode are investigated by electrochemical impedance spectroscopy and cyclic voltammetry in a three-electrode electrochemical cell containing phosphate-buffered saline. Charge injection capacity measurements are carried out by multichannel systems and the CSC of the microarray is calculated. RESULTS: Electrochemical results showed that impedance decreased with frequency. The average impedance of the Au electrodes at 1 kHz was 36.54 ± 0.88 kΩ. The average phase angle at 1 kHz was - 73.52 ± 1.3°, and the CIC of the microelectrode was 22.3 µC/cm2. The results demonstrated that the microelectrode array performed as expected for neuronal signal recording or stimulation. CONCLUSIONS: With parylene-C as the substrate, the microarray has good flexibility. The electrochemical characteristics' results show that the array has the ability to resist any corrosion on metal-electrolyte interface and has good biocompatibility. This low-cost, flexible parylene-based, gold microelectrode array shows potential for use in implant neurological signal acquisition or neurostimulation applications.

Shotgun Analysis of Diacylglycerols Enabled by Thiol-ene Click Chemistry.

Diacylglycerols (DAGs) are a subclass of neutral lipids actively involved in cell signaling and metabolism. Alteration in DAG metabolism has been associated with onset and progression of several human-related diseases. The structural diversity of DAGs and their low concentrations in biological samples call for the development of methods that are capable of sensitive identification and quantitation of each DAG species as well as rapid profiling when a biochemical pathway is perturbed. In this work, the thiol-ene click chemistry has been employed to introduce a charge-tag, namely, cysteamine (CA), at a carbon-carbon double bond (C═C) of unsaturated DAGs. This one-pot photochemical derivatization is fast (within 1 min), universal (monotagging) for DAGs varying in fatty acyl chain lengths and the number of C═Cs, and suitable for small sample volume (e.g., 1-50 µL plasma). Because of the presence of the amine group in CA, tagged DAGs showed at least 10 times increase in response to electrospray ionization as compared to conventional ammonium adduct formation. Low-energy collision-induced dissociation of CA tagged DAGs allowed confident assignment of fatty acyl composition. A neutral loss scan based on characteristic 95 Da loss (a combined loss of CA and H2O) of tagged DAGs has been established as a sensitive means for unsaturated DAG detection (limit of detection = 100 pM) and quantitation from mixtures. The analytical utility of CA tagging was demonstrated by shotgun analysis of unsaturated DAGs in human plasma, including samples from type 2 diabetes mellitus patients.