Serum myostatin as a candidate disease severity and progression biomarker of spinal muscular atrophy.

The identification of biomarkers for spinal muscular atrophy is crucial for predicting disease progression, severity, and response to new disease-modifying therapies. This study aimed to investigate the role of serum levels of myostatin and follistatin as biomarkers for spinal muscular atrophy, considering muscle atrophy secondary to denervation as the main clinical manifestation of the disease. The study evaluated the differential gene expression of myostatin and follistatin in a lesional model of gastrocnemius denervation in mice, as well as in a meta-analysis of three datasets in transgenic mice models of spinal muscular atrophy, and in two studies involving humans with spinal muscular atrophy. Subsequently, a case-control study involving 27 spinal muscular atrophy patients and 27 controls was conducted, followed by a 12-month cohort study with 25 spinal muscular atrophy cases. Serum levels of myostatin and follistatin were analysed using enzyme-linked immunosorbent assay at a single centre in southern Brazil. Skeletal muscle gene expression of myostatin decreased and of follistatin increased following lesional muscle denervation in mice, consistent with findings in the spinal muscular atrophy transgenic mice meta-analysis and in the iliopsoas muscle of five patients with spinal muscular atrophy type 1. Median serum myostatin levels were significantly lower in spinal muscular atrophy patients (98 pg/mL; 5-157) compared to controls (412 pg/mL; 299-730) (P < 0.001). Lower myostatin levels were associated with greater disease severity based on clinician-rated outcomes (Rho = 0.493-0.812; P < 0.05). After 12 months, there was a further reduction in myostatin levels among spinal muscular atrophy cases (P = 0.021). Follistatin levels did not differ between cases and controls, and no significant changes were observed over time. The follistatin:myostatin ratio was significantly increased in spinal muscular atrophy subjects and inversely correlated with motor severity. Serum myostatin levels show promise as a novel biomarker for evaluating the severity and progression of spinal muscular atrophy. The decrease in myostatin levels and the subsequent favourable environment for muscle growth may be attributed to denervation caused by motor neuron dysfunction.

Aqueous angiography in pre-glaucomatous and glaucomatous ADAMTS10-mutant canine eyes: A pilot study.

OBJECTIVE: To evaluate intravenous scleral and intracameral aqueous angiography in normotensive (n = 4) and hypertensive glaucomatous (n = 6) ADAMTS10-mutant canine eyes. ANIMALS STUDIED: Ten ADAMTS10-mutant dogs were used in this study. PROCEDURES: Dogs were sedated and one eye from each dog underwent scleral angiography following intravenous injection of 0.25% indocyanine green (ICG). After a 24-h recovery period, the same eye underwent aqueous angiography via intracameral administration of ICG. Imaging of identical scleral sectors from the same eye was performed using a Heidelberg Spectralis® Confocal Scanning Laser Ophthalmoscope. Intrascleral vessel depth and lumen diameters were measured using Heidelberg Spectralis® optical coherence tomography and computer software. RESULTS: Scleral angiography permitted visualization of vascular components associated with conventional aqueous humor outflow pathways with an average time from injection to fluorescence of 35.8 ± 10.6 s (mean ± SD). Two normotensive eyes (2/10;20%) demonstrated turbulent dye movement, while 4 hypertensive eyes (4/10;40%) exhibited laminar flow. Aqueous angiography demonstrated dye fluorescence within the post-trabecular conventional aqueous humor outflow pathways in all 10 eyes at 34.3 ± 11.0 s post-injection. Sectoral and dynamic outflow patterns were observed primarily within the superotemporal sector in nine eyes (9/10; 90%). Seven eyes (7/10; 70%) demonstrated pulsatile dye movement and five eyes (5/10; 50%) exhibited laminar flow. The degree of laminar movement of dye was greatest in hypertensive eyes. Vessel lumen diameters measured 133.85 ± 28.36 µm and 161.18 ± 6.02 µm in hypertensive and normotensive eyes, respectively. CONCLUSIONS: Aqueous angiography allowed for visualization of fluorescent dye in the superotemporal sclera. Laminar flow and smaller lumen vessels were observed mainly in hypertensive eyes.

A fully transparent, flexible PEDOT:PSS-ITO-Ag-ITO based microelectrode array for ECoG recording.

Integrative neural interfaces combining neurophysiology and optogenetics with neural imaging provide numerous opportunities for neuroscientists to study the structure and function of neural circuits in the brain. Such a comprehensive interface demands miniature electrode arrays with high transparency, mechanical flexibility, electrical conductivity, and biocompatibility. Conventional transparent microelectrodes made of a single material, such as indium tin oxide (ITO), ultrathin metals, graphene and poly-(3,4-ethylenedioxythiophene)/poly(styrenesulfonate) (PEDOT:PSS), hardly possess the desired combination of those properties. Herein, ultra-flexible, highly conductive and fully transparent microscale electrocorticogram (µECoG) electrode arrays made of a PEDOT:PSS-ITO-Ag-ITO assembly are constructed on thin parylene C films. The PEDOT:PSS-ITO-Ag-ITO assembly achieves a maximum ∼14% enhancement in light transmission over a broad spectrum (350-650 nm), a significant reduction in electrochemical impedance by 91.25%, and an increase in charge storage capacitance by 1229.78 µC cm-2. Peeling, bending, and Young's modulus tests verify the enhanced mechanical flexibility and robustness of the multilayer assembly. The µECoG electrodes enable electrical recordings with high signal-to-noise ratios (SNRs) (∼35-36 dB) under different color photostimulations, suggesting that the electrodes are resilient to photon-induced artifacts. In vivo animal experiments confirm that our array can successfully record light-evoked ECoG oscillations from the primary visual cortex (V1) of an anesthetized rat.

A Trimodal Wireless Implantable Neural Interface System-on-Chip.

A wireless and battery-less trimodal neural interface system-on-chip (SoC), capable of 16-ch neural recording, 8-ch electrical stimulation, and 16-ch optical stimulation, all integrated on a 5 ×  3 mm2 chip fabricated in 0.35-µm standard CMOS process. The trimodal SoC is designed to be inductively powered and communicated. The downlink data telemetry utilizes on-off keying pulse-position modulation (OOK-PPM) of the power carrier to deliver configuration and control commands at 50 kbps. The analog front-end (AFE) provides adjustable mid-band gain of 55-70 dB, low/high cut-off frequencies of 1-100 Hz/10 kHz, and input-referred noise of 3.46 µVrms within 1 Hz-50 kHz band. AFE outputs of every two-channel are digitized by a 50 kS/s 10-bit SAR-ADC, and multiplexed together to form a 6.78 Mbps data stream to be sent out by OOK modulating a 434 MHz RF carrier through a power amplifier (PA) and 6 cm monopole antenna, which form the uplink data telemetry. Optical stimulation has a switched-capacitor based stimulation (SCS) architecture, which can sequentially charge four storage capacitor banks up to 4 V and discharge them in selected µLEDs at instantaneous current levels of up to 24.8 mA on demand. Electrical stimulation is supported by four independently driven stimulating sites at 5-bit controllable current levels in ±(25-775) µA range, while active/passive charge balancing circuits ensure safety. In vivo testing was conducted on four anesthetized rats to verify the functionality of the trimodal SoC.

Aqueous Angiography in Normal Canine Eyes.

Purpose: To conduct aqueous angiography (AA) using a clinically applicable technique in normal dogs and to compare findings to intravenous scleral angiography (SA). Methods: We examined 10 canine cadaver eyes and 12 eyes from live normal dogs. A gravity-fed trocar system delivered 2% sodium fluorescein and 0.25% indocyanine green (ICG) intracamerally (IC) in cadaver eyes. In vivo AA was subsequently performed in one eye of each of the 12 dogs via IC bolus of ICG under sedation. The same 12 dogs received SA via intravenous ICG (mean ± SD) 10.7 ± 3.3 days later. Identical scleral sectors were imaged using a Spectralis confocal scanning laser ophthalmoscope. Results: The gravity-fed trocar system permitted visualization of the conventional aqueous humor outflow (CAHO) pathways in cadaver eyes, but not in vivo. Fluorescence was observed superonasally in four of the 10 cadaver eyes within 24.0 ± 3.6 seconds. A single IC bolus of ICG showed CAHO pathways in vivo, demonstrating sectoral outflow patterns in the superotemporal sclera in 10 of the 12 eyes within 35.0 ± 4.3 seconds; four of the 12 eyes exhibited pulsatile aqueous movement. SA exhibited fluorescence patterns comparable to AA with weak pulsatile aqueous humor outflow. Conclusions: Angiography (AA or SA) in dogs permits visualization of the CAHO pathway and its vascular components in vivo. AA may be a more useful modality to assess aqueous humor outflow. Translational Relevance: Intracameral AA has potential utility for evaluating CAHO in vivo in dogs, an important animal model species.

Flexible, diamond-based microelectrodes fabricated using the diamond growth side for neural sensing.

Diamond possesses many favorable properties for biochemical sensors, including biocompatibility, chemical inertness, resistance to biofouling, an extremely wide potential window, and low double-layer capacitance. The hardness of diamond, however, has hindered its applications in neural implants due to the mechanical property mismatch between diamond and soft nervous tissues. Here, we present a flexible, diamond-based microelectrode probe consisting of multichannel boron-doped polycrystalline diamond (BDD) microelectrodes on a soft Parylene C substrate. We developed and optimized a wafer-scale fabrication approach that allows the use of the growth side of the BDD thin film as the sensing surface. Compared to the nucleation surface, the BDD growth side exhibited a rougher morphology, a higher sp 3 content, a wider water potential window, and a lower background current. The dopamine (DA) sensing capability of the BDD growth surface electrodes was validated in a 1.0 mM DA solution, which shows better sensitivity and stability than the BDD nucleation surface electrodes. The results of these comparative studies suggest that using the BDD growth surface for making implantable microelectrodes has significant advantages in terms of the sensitivity, selectivity, and stability of a neural implant. Furthermore, we validated the functionality of the BDD growth side electrodes for neural recordings both in vitro and in vivo. The biocompatibility of the microcrystalline diamond film was also assessed in vitro using rat cortical neuron cultures.

A mm-Sized Free-Floating Wireless Implantable Opto-Electro Stimulation Device.

Towards a distributed neural interface, consisting of multiple miniaturized implants, for interfacing with large-scale neuronal ensembles over large brain areas, this paper presents a mm-sized free-floating wirelessly-powered implantable opto-electro stimulation (FF-WIOS2) device equipped with 16-ch optical and 4-ch electrical stimulation for reconfigurable neuromodulation. The FF-WIOS2 is wirelessly powered and controlled through a 3-coil inductive link at 60 MHz. The FF-WIOS2 receives stimulation parameters via on-off keying (OOK) while sending its rectified voltage information to an external headstage for closed-loop power control (CLPC) via load-shift-keying (LSK). The FF-WIOS2 system-on-chip (SoC), fabricated in a 0.35-µm standard CMOS process, employs switched-capacitor-based stimulation (SCS) architecture to provide large instantaneous current needed for surpassing the optical stimulation threshold. The SCS charger charges an off-chip capacitor up to 5 V at 37% efficiency. At the onset of stimulation, the capacitor delivers charge with peak current in 1.7-12 mA range to a micro-LED (µLED) array for optical stimulation or 100-700 µA range to a micro-electrode array (MEA) for biphasic electrical stimulation. Active and passive charge balancing circuits are activated in electrical stimulation mode to ensure stimulation safety. In vivo experiments conducted on three anesthetized rats verified the efficacy of the two stimulation mechanisms. The proposed FF-WIOS2 is potentially a reconfigurable tool for performing untethered neuromodulation.

Synthesis and base-pairing properties of pyrazine nucleic acids.

The diversity of backbone modifications in the study of primitive informational polymers is partly limited by the plausible formation of their prebiotic starting components. In this paper, we synthesize pyrazine nucleic acid, an acyclic polymer, with the nucleoside derivable from a prebiotic one-pot synthesis containing alanine amide and D-ribose. Pyrazine nucleic acid (PzNA) which has a backbone structurally similar to glycerol nucleic acid (GNA), contain pyrazine derived nucleosides as informational elements that may exhibit base pairing properties similar to the pyrimidines present in RNA.[1] We found that insertion of pyrazinone nucleotides into DNA oligonucleotide sequences is not well-tolerated, and that homogenous sequences of PzNA are unable to form duplexes with RNA or DNA. Reasons for our results may be attributed to the pyrazine-2-one moiety, which is purposed to be a thymine analog, but has a lower pKa (pKa ∼ 8.5) than thymine and uracil. Additionally, we discovered an "apparent" regioselective protection of pyrazine-2-one derivatives in the presence of a secondary hydroxyl group that proved crucial in the preparation of the pyrazine-2-one phosphoramidite. The regioselectivity observed is proposed to be of general interest in the context of heterocyclic chemistry. In the larger context of origins of life studies, it points to the importance of keto-enol preferences of the canonical nucleobases versus pyrazine heterocycles in functioning as recognition elements.

Acute Effects of Sport-Related Concussion on Serum Glial Fibrillary Acidic Protein, Ubiquitin C-Terminal Hydrolase L1, Total Tau, and Neurofilament Light Measured by a Multiplex Assay.

We prospectively evaluated serum concentrations of glial fibrillary acidic protein (GFAP), ubiquitin c-terminal hydrolase L1 (UCH-L1), total tau (T-Tau), and neurofilament light (NF-L) from collegiate athletes at baseline and acutely after sport-related concussion (SRC) using the Quanterix Neurology 4Plex "B" (N4PB) multiplex assay. Uninjured controls were matched on age, sex, race, sport, and concussion history. Clinical outcomes included acute symptom severity, balance, rapid automated naming, computerized cognitive testing, and recovery duration. Baseline (n = 110; median [interquartile range] age = 19 [18-20] years, 54% male, 61% white/Caucasian) and post-SRC (n = 36; median [interquartile range] age = 19 [18-20] years, 50% male, 61% white/Caucasian) blood samples were analyzed. We observed post-SRC elevations from baseline for GFAP (p = 0.001, d = 1.7), T-Tau (p = 0.004, d = 1.3), and NF-L (p = 0.010, d = 1.1). GFAP (area under the curve [AUC] = 0.958, 95% confidence interval [CI] 0.927-0.989, p < 0.001) and NF-L (AUC = 0.904, 95% CI 0.851-0.957, p < 0.001) accurately discriminated SRC from control cases. There were no associations between biomarker concentrations and clinical measurements post-SRC or recovery duration. These findings suggest that, using the multiplex assay, GFAP, T-Tau, and NF-L elevate from baseline acutely after SRC, and both GFAP and NF-L excellently distinguished concussed from control cases. Serum biomarker changes do not necessarily correspond with clinical measurements or recovery duration.

Wireless, passive strain sensor in a doughnut-shaped contact lens for continuous non-invasive self-monitoring of intraocular pressure.

After cataract, glaucoma is the second leading cause of blindness worldwide and real-time monitoring of intraocular pressure (IOP) is of great demand. We present a wireless, passive sensor sitting inside a customized, planar and circular doughnut-shaped contact lens capable of continuous monitoring of the change in the curvature of cornea caused by IOP fluctuations. The sensor consists of a constant capacitor and a variable inductor in the form of a stretchable, closed-loop, serpentine wire that serves as both the sensor and the antenna. Results show a pressure responsivity of 523 kHz per 1% axial strain on a pressurized polydimethylsiloxane membrane and 35.1 kHz per 1 mmHg change in the IOP of a canine eye. The sensor is tested for stability and shows unvaried characteristics after repeated cycles and parasitic movements. Predictable influences of temperature and humidity on the sensor response are also verified experimentally, which can be canceled out using real-time calibration with temperature and humidity sensors to integrate with a reader device. The design reported here has numerous advantages, such as design simplicity, component reliability, high responsivity, and low cost, thereby opening up potential opportunities for the translation of this non-invasive, continuous IOP monitoring technique into clinical applications.

Imidazolium-Catalyzed Synthesis of an Imidazolium Catalyst.

The chemistry of imidazolium-catalyzed imidazolium synthesis was studied as part of an effort to develop a plausible prebiotic synthesis of a small catalytic molecule capable of catalyzing its own synthesis. Specifically, we investigated the one-pot 1-ethyl-3-methylimidazolium acetate (EMIM-Ac) catalyzed synthesis of 1,3-dibutyl-4,5-difuryl-imidazolium acetate (DBDFIM-Ac) from furfural, n-butylamine, formaldehyde, and acetic acid at 80 °C. Liu et al. (2012) had previously demonstrated the first reaction of the synthetic process, the EMIM-Ac catalyzed benzoin condensation of furfural that yields furoin. Our early studies established the second reaction of the synthetic process, the multicomponent reaction of furoin, n-butylamine, formaldehyde, and acetic acid that yields the imidazolium salt, DBDFIM-Ac. Studies of the complete two-reaction process that uses furfural for the synthesis of DBDFIM-Ac showed that the highest yield of DBDFIM-Ac was obtained when the mole ratio of n-butylamine, formaldehyde, and acetic acid relative to furfural was respectively (0.5:0.25:0.25:1.0-furfural), or one-half of the stoichiometric ratio (1.0:0.5:0.5:1.0-furfural). A time course study of the process showed transient formation of furoin, the obligatory reaction intermediate. DBDFIM-Ac and the imidazolium side product, 1,3-dibutyl-4,5-trifuryl-imidazolium acetate (DBTFIM-Ac), were stable under the reaction conditions. Imidazolium products (DBDFIM and DBTFIM) and the furoin intermediate were not formed in control reactions (80 °C, 24 h) in which EMIM catalyst was either absent or replaced with an equal volume of acetonitrile or DMF. The imidazolium product, DBDFIM-Ac, was shown to catalyze the synthesis of structurally similar 1,3-dipentyl-4,5-difuryl-imidazolium acetate (DPDFIM-Ac) from furfural, n-pentylamine, formaldehyde, and acetic acid at 80 °C.

Inductively coupled, mm-sized, single channel optical neuro-stimulator with intensity enhancer.

We introduce a single channel neuro-stimulator consisting of a reflector-coupled microscale light emitting diode (µLED) with an integrated mm-sized wireless receiver (Rx) coil for free-floating, battery-free, untethered optogenetics neuromodulation. The system utilizes a two-coil inductive link to deliver instantaneous power at a low operating frequency (<100 MHz) for continuous optical stimulation with minimized invasiveness and tissue exposure to electromagnetic radiation. Coupling a microscale reflector to the µLED provides significant light intensity enhancement compared to a bare µLED. Our activated stimulators have an operational temperature increase of <1 °C, well below the safety limit of biomedical implants. In vivo experiment and histological analysis verify the efficacy of wireless optical stimulation in the primary visual cortex of rats, using c-Fos biomarker as a reporter of light-evoked neuronal activity.

A mm-Sized Free-Floating Wirelessly Powered Implantable Optical Stimulation Device.

This paper presents a mm-sized, free-floating, wirelessly powered, implantable optical stimulation (FF-WIOS) device for untethered optogenetic neuromodulation. A resonator-based three-coil inductive link creates a homogeneous magnetic field that continuously delivers sufficient power (>2.7 mW) at an optimal carrier frequency of 60 MHz to the FF-WIOS in the near field without surpassing the specific absorption rate limit, regardless of the position of the FF-WIOS in a large brain area. Forward data telemetry carries stimulation parameters by on-off-keying the power carrier at a data rate of 50 kb/s to selectively activate a 4 × 4 µLED array. Load-shift-keying back telemetry controls the wireless power transmission by reporting the FF-WIOS received power level in a closed-loop power control mechanism. LEDs typically require high instantaneous power to emit sufficient light for optical stimulation. Thus, a switched-capacitor-based stimulation architecture is used as an energy storage buffer with one off-chip capacitor to receive charge directly from the inductive link and deliver it to the selected µLED at the onset of stimulation. The FF-WIOS system-on-a-chip prototype, fabricated in a 0.35-µm standard CMOS process, charges a 10-µF capacitor up to 5 V with 37% efficiency and passes instantaneous current spikes up to 10 mA in the selected µLED, creating a bright exponentially decaying flash with minimal wasted power. An in vivo experiment was conducted to verify the efficacy of the FF-WIOS by observing light-evoked local field potentials and immunostained tissue response from the primary visual cortex (V1) of two anesthetized rats.

Dual Immunostaining With SOX10 and AE1/AE3 to Confirm Perineural Invasion on Mohs Sections

Perineural invasion (PNI) is associated with high risk keratinocyte carcinomas. Identification of PNI during Mohs surgery is important for staging and post-adjuvant treatment decisions but can be challenging. To confirm or exclude PNI suspected on hematoxylin and eosin sections, we performed immunohistochemical double staining on Mohs frozen sections. Neural marker SOX10 and pan-cytokeratin marker AE1/AE3 were combined in a simultaneous assay using species-specific (mouse and rabbit) antibodies and horseradish peroxidase and alkaline phosphatase detection systems. Of 23 Mohs cases with suspected PNI, 18 were confirmed to have definitive nerve involvement by tumor using double staining. Double staining frozen tissue is feasible and can be beneficial for real time confirmation of PNI during Mohs. J Drugs Dermatol. 2019;18(3):262-264.

A wireless, smartphone controlled, battery powered, head mounted light delivery system for optogenetic stimulation.

This paper reports the design, fabrication and characterization of a head-mounted, flexible, and ultralight optogenetic system that enables wireless delivery of light into the brains of awake and freely behaving animals. The project is focused on miniaturized design, light weight (2.7g), small volume, low cost (< 25 USD) and simple fabrication. The chip, the substrate material, the battery, and the micro light emitting diode (µLED) are commercially available. The device implementation consists of one step photolithography, soldering, and packaging along with Arduino programming. In vivo study is carried out where the battery-powered µLED stimulates the visual cortex of a rat with parameters that can be controlled wirelessly via a smart-phone user interface application. The efficacy of optical stimulation is validated using c-Fos as a report of light-evoked neuronal activity.

Concussion BASICS II: Baseline serum biomarkers, head impact exposure, and clinical measures.

OBJECTIVE: To examine the effect of concussion history and cumulative exposure to collision sports on baseline serum biomarker concentrations, as well as associations between biomarker concentrations and clinical assessments. METHODS: In this observational cohort study, ß-amyloid peptide 42 (Aß42), total tau, S100 calcium binding protein B (S100B), ubiquitin carboxy-terminal hydrolyzing enzyme L1 (UCH-L1), glial fibrillary acidic protein, microtubule associated protein 2, and 2',3'-cyclic-nucleotide 3'-phosphodiesterase serum concentrations were measured in 415 (61% male, 40% white, aged 19.0 ± 1.2 years) nonconcussed collegiate athletes without recent exposure to head impacts. Regression analyses were used to evaluate the relationship between self-reported history of concussion(s), cumulative years playing collision sports, clinical assessments, and baseline biomarker concentrations. Football-specific analyses were performed using a modified Cumulative Head Impact Index. Clinical assessments included symptom, cognitive, balance, and oculomotor tests. RESULTS: Athletes with a greater number of concussions had a higher baseline Aß42 concentration only (ρ = 0.140, p = 0.005, small effect size). No biomarker concentrations correlated with cumulative exposure to collision sports. Race status fully mediated the correlations of S100B, UCH-L1, and Aß42 with cognitive scores. Football exposure, specifically, was not associated with serum biomarker concentrations or clinical assessment scores based on the modified Cumulative Head Impact Index. CONCLUSION: Concussion-related serum biomarkers showed no consistent association with concussion history, cumulative exposure to collision sports, or clinical assessments in a sample of healthy collegiate athletes. Serum Aß42 concentrations could increase following multiple previous concussions. Considering race status is essential when investigating links between biomarkers and cognition. The biomarkers studied may not detect residual effects of concussion or repetitive head impact exposure in otherwise asymptomatic collegiate athletes without recent exposure to head impacts. Much more research is needed for identifying reliable and valid blood biomarkers of brain trauma history.

Concussion Biomarkers Assessed in Collegiate Student-Athletes (BASICS) I: Normative study.

OBJECTIVE: To describe variability in concussion biomarker concentrations collected from serum in a sample of healthy collegiate athletes, as well as report reliability metrics in a subsample of female athletes. METHODS: In this observational cohort study, ß-amyloid peptide 42 (Aß42), total tau, S100 calcium binding protein B (S100B), ubiquitin carboxy-terminal hydrolyzing enzyme L1 (UCH-L1), glial fibrillary acidic protein, microtubule associated protein 2, and 2',3'-cyclic-nucleotide 3'-phosphodiesterase (CNPase) serum concentrations were measured in 415 (61% male, 40% white, aged 19.0 ± 1.2 years) nonconcussed collegiate athletes without recent exposure to head impacts. Standardized normative distributions are reported for each biomarker. We evaluated main effects (analyses of variance) of sex and race, reporting demographic-specific normative metrics when appropriate. In a subset of 31 female participants, test-retest reliability (Pearson r) and reliable change indices (80%, 90%, and 95% confidence intervals) across a 6- to 12-month interval are reported for Aß42, total tau, S100B, and UCH-L1. RESULTS: Males exhibited higher UCH-L1 (p < 0.001, Cohen d = 0.75) and S100B (p < 0.001, d = 0.56) than females, while females had higher CNPase (p < 0.001, d = 0.43). Regarding race, black participants had higher baseline levels of UCH-L1 (p < 0.001, d = 0.61) and S100B (p < 0.001, d = 1.1) than white participants. Conversely, white participants had higher baseline levels of Aß42 (p = 0.005, d = 0.28) and CNPase (p < 0.001, d = 0.46). Test-retest reliability was generally poor, ranging from -0.02 to 0.40, and Aß42 significantly increased from time 1 to time 2. CONCLUSION: Healthy collegiate athletes express concussion-related serum biomarkers in variable concentrations. Accounting for demographic factors such as sex and race is essential. Evidence suggested poor reliability for serum biomarkers; however, understanding how other factors influence biomarker expression, as well as knowledge of reliable change metrics, may improve clinical interpretation and future study designs.

Wireless opto-electro neural interface for experiments with small freely behaving animals.

OBJECTIVE: We have developed a wireless opto-electro interface (WOENI) device, which combines electrocorticogram (ECoG) recording and optical stimulation for bi-directional neuromodulation on small, freely behaving animals, such as rodents. APPROACH: The device is comprised of two components, a detachable headstage and an implantable polyimide-based substrate. The headstage establishes a bluetooth low energy (BLE) bi-directional data communication with an external custom-designed USB dongle for receiving user commands and optogenetic stimulation patterns, and sending digitalized ECoG data. MAIN RESULTS: The functionality and stability of the device were evaluated in vivo on freely behaving rats. When the animal received optical stimulation on the primary visual cortex (V1) and visual stimulation via eyes, spontaneous changes in ECoG signals were recorded from both left and right V1 during four consecutive experiments with 7 d intervals over a time span of 21 d following device implantation. Immunostained tissue analyses showed results consistent with ECoG analyses, validating the efficacy of optical stimulation to upregulate the activity of cortical neurons expressing ChR2. SIGNIFICANCE: The proposed WOENI device is potentially a versatile tool in the studies that involve long-term optogenetic neuromodulation.

Synthesis of ß-Peptide Standards for Use in Model Prebiotic Reactions.

A one-pot method was developed for the preparation of a series of ß-alanine standards of moderate size (2 to ≥12 residues) for studies concerning the prebiotic origins of peptides. The one-pot synthesis involved two sequential reactions: (1) dry-down self-condensation of ß-alanine methyl ester, yielding ß-alanine peptide methyl ester oligomers, and (2) subsequent hydrolysis of ß-alanine peptide methyl ester oligomers, producing a series of ß-alanine peptide standards. These standards were then spiked into a model prebiotic product mixture to confirm by HPLC the formation of ß-alanine peptides under plausible reaction conditions. The simplicity of this approach suggests it can be used to prepare a variety of ß-peptide standards for investigating differences between α- and ß-peptides in the context of prebiotic chemistry.

Multimodal Vacuum-Assisted Plasma Ion (VaPI) Source with Transmission Mode and Laser Ablation Sampling Capabilities.

We have developed a multimodal ion source design that can be configured on the fly for various analysis modes, designed for more efficient and reproducible sampling at the mass spectrometer atmospheric pressure (AP) interface in a number of different applications. This vacuum-assisted plasma ionization (VaPI) source features interchangeable transmission mode and laser ablation sampling geometries. Operating in both AC and DC power regimes with similar results, the ion source was optimized for parameters including helium flow rate and gas temperature using transmission mode to analyze volatile standards and drug tablets. Using laser ablation, matrix effects were studied, and the source was used to monitor the products of model prebiotic synthetic reactions.