Structural, Functional, and Genetic Changes Surrounding Electrodes Implanted in the Brain.

Implantable neurotechnology enables monitoring and stimulating of the brain signals responsible for performing cognitive, motor, and sensory tasks. Electrode arrays implanted in the brain are increasingly used in the clinic to treat a variety of sources of neurological diseases and injuries. However, the implantation of a foreign body typically initiates a tissue response characterized by physical disruption of vasculature and the neuropil as well as the initiation of inflammation and the induction of reactive glial states. Likewise, electrical stimulation can induce damage to the surrounding tissue depending on the intensity and waveform parameters of the applied stimulus. These phenomena, in turn, are likely influenced by the surface chemistry and characteristics of the materials employed, but further information is needed to effectively link the biological responses observed to specific aspects of device design. In order to inform improved design of implantable neurotechnology, we are investigating the basic science principles governing device-tissue integration. We are employing multiple techniques to characterize the structural, functional, and genetic changes that occur in the cells surrounding implanted electrodes. First, we have developed a new "device-in-slice" technique to capture chronically implanted electrodes within thick slices of live rat brain tissue for interrogation with single-cell electrophysiology and two-photon imaging techniques. Our data revealed several new observations of tissue remodeling surrounding devices: (a) there was significant disruption of dendritic arbors in neurons near implants, where losses were driven asymmetrically on the implant-facing side. (b) There was a significant loss of dendritic spine densities in neurons near implants, with a shift toward more immature (nonfunctional) morphologies. (c) There was a reduction in excitatory neurotransmission surrounding implants, as evidenced by a reduction in the frequency of excitatory postsynaptic currents (EPSCs). Lastly, (d) there were changes in the electrophysiological underpinnings of neuronal spiking regularity. In parallel, we initiated new studies to explore changes in gene expression surrounding devices through spatial transcriptomics, which we applied to both recording and stimulating arrays. We found that (a) device implantation is associated with the induction of hundreds of genes associated with neuroinflammation, glial reactivity, oligodendrocyte function, and cellular metabolism and (b) electrical stimulation induces gene expression associated with damage or plasticity in a manner dependent upon the intensity of the applied stimulus. We are currently developing computational analysis tools to distill biomarkers of device-tissue interactions from large transcriptomics data sets. These results improve the current understanding of the biological response to electrodes implanted in the brain while producing new biomarkers for benchmarking the effects of novel electrode designs on responses. As the next generation of neurotechnology is developed, it will be increasingly important to understand the influence of novel materials, surface chemistries, and implant architectures on device performance as well as the relationship with the induction of specific cellular signaling pathways.

Advancing Molecular Weight Determination of Lignin by Multi-Angle Light Scattering.

Due to the complexity and recalcitrance of lignin, its chemical characterization is a key factor preventing the valorization of this abundant material. Multi-angle light scattering (MALS) is becoming a sought-after technique for absolute molecular weight (MW) determination of polymers and proteins. Lignin is a suitable candidate for MW determination via MALS, yet further investigation is required to confirm its absolute MW values and molecular size. Studies aiming to break down lignin into a variety of renewable products will benefit greatly from a simple and reliable determination method like MALS. Recent pioneering studies, discussed in this review, addressed several key challenges in lignin's MW characterization. Nevertheless, some lignin-specific issues still need to be considered for in-depth characterization. This study explores how MALS instrumentation manages the complexities of determining lignin's MW, e.g., with simultaneous fractionation and fluorescence interference mitigation. Additionally, we rationalize the importance of a more detailed light scattering analysis for lignin characterization, including aspects like the second virial coefficient and radius of gyration.

Acute biomechanical responses to wearing a controlled ankle motion (CAM) Walker boot during walking.

BACKGROUND: Controlled ankle motion (CAM) boots are often prescribed during the rehabilitation of lower limb injuries and pathologies to reduce foot and ankle movement and loading whilst allowing the patient to maintain normal daily function. RESEARCH QUESTION: The aim of this study was to quantify the compensatory biomechanical mechanisms undergone by the ipsilateral hip and knee joints during walking. In addition, the compensatory mechanisms displayed by the contralateral limb were also considered. METHODS: Twelve healthy participants walked on an instrumented treadmill at their preferred walking speed. They underwent kinematic and kinetic analysis during four footwear conditions: normal shoes (NORM), a Malleo Immobil Air Walker on the right leg (OTTO), a Rebound® Air Walker on the right leg with (EVEN) and without (OSS) an Evenup Shoelift™ on the contralateral leg. RESULTS: CAM boot wear increased the relative joint contribution to total mechanical work from the ipsilateral hip and knee joints (p < 0.05), which was characterised by increased hip and knee abduction during the swing phase of the gait cycle. EVEN increased the absolute work done and relative contribution of the contralateral limb. CAM boot wear reduced walking speed (p < 0.05), which was partially compensated for during EVEN. SIGNIFICANCE: The increased hip abduction in the ipsilateral leg was likely caused by the increase in effective leg length and limb mass, which could lead to secondary site complications following prolonged CAM boot wear. Although prescribing an even-up walker partially mitigates these compensatory mechanisms, adverse effects to contralateral limb kinematics and kinetics (e.g., elevated knee joint work) should be considered.

Saltwater-Induced Rapid Gelation of Photoredox-Responsive Mucomimetic Hydrogels.

Shear-thinning hydrogels represent an important class of injectable soft materials that are often used in a wide range of biomedical applications. Creation of new shear-thinning materials often requires that factors such as viscosity, injection rate/force, and needle gauge be evaluated to achieve efficient delivery, while simultaneously protecting potentially sensitive cargo. Here, a new approach to establishing shear-thinning hydrogels is reported where a host-guest cross-linked network initially remains soluble in deionized water but is kinetically trapped as a viscous hydrogel once exposed to saltwater. The shear-thinning properties of the hydrogel is then "switched on" in response to heating or exposure to visible light. These hydrogels consist of polynorbornene-based bottlebrush copolymers with porphyrin- and oligoviologen-containing side chains that are cross-linked through the reversible formation of ß-cyclodextrin-adamantane inclusion complexes. The resultant viscous hydrogels display broad adhesive properties across polar and nonpolar substrates, mimicking that of natural mucous and thus making it easier to distribute onto a wide range of surfaces. Additional control over the hydrogel's mechanical properties (storage/loss moduli) and performance (adhesion) is achieved post-injection using a low-energy (blue light) photoinduced electron-transfer process. This work envisions these injectable copolymers and multimodal hydrogels can serve as versatile next-generation biomaterials capable of light-based mechanical manipulation post-injection.

Scale-up of Sodium Persulfate Mediated, Nitroxide Catalyzed Oxidative Functionalization Reactions.

BACKGROUND: Oxidation is a valuable tool in preparative organic chemistry. Oxoammonium salts and nitroxides have proven valuable as reagents and catalysts in this endeavor. OBJECTIVE: The objective of this study is to scale up the oxidative amidation, ester formation, and nitrile formation using nitroxide as an organocatalyst. METHODS: Oxidative functionalization reactions were scaled from the 1 mmol to the 1-mole level. Sodium persulfate was used as the primary oxidant, and a nitroxide was employed as a catalyst. The products of the reactions were isolated in analytically pure form by extraction with no need for column chromatography. RESULTS: The oxidative amidation and esterification of aldehydes can be scaled up from 1 mmol to 1 mole effectively, with comparable product yields being obtained at each increment. This work shows that conditions developed on a small scale can be transferred to a larger scale without reoptimization. The oxidative functionalization of aldehydes to prepare nitriles is not amenable to direct scale-up due to the concomitant formation of significant quantities of the corresponding carboxylic acid, thereby compromising the product yield. CONCLUSION: Two of the three oxidative transformations studied here can be scaled up successfully from the 1 mmol to the 1-mole level.

Understanding Pedophilia: A Theoretical Framework on the Development of Sexual Penchants.

Pedophilia is a significant public health problem. Despite its cost to society, little effort has been directed toward understanding idiographic differences in the development and maintenance of pedophilia. Extant literature emphasizes biological underpinnings and predictors of re-offense. In this article, we posit that pedophilic penchants in males originate due to language, cognition, emotions, and emotion regulation. Adverse childhood experiences, such as emotional and sexual abuse, are posited as a major contributor to the etiology of pedophilia. However, not all individuals attracted to minors present with similar childhood adversities. The development of pedophilia, in the absence of such direct training (childhood adversities), is difficult to comprehend. Relational frame theory, a comprehensive account of human language and cognition, aids in deciphering the idiographic underpinnings of pedophilia. The role of maladaptive emotion regulation in maintaining pedophilia is also described. This article presents examples of how relational frames are established and activated in distressing contexts. Finally, implications for future research are discussed.

In Vitro Biofouling Performance of Boron-Doped Diamond Microelectrodes for Serotonin Detection Using Fast-Scan Cyclic Voltammetry.

Neurotransmitter release is important to study in order to better understand neurological diseases and treatment approaches. Serotonin is a neurotransmitter known to play key roles in the etiology of neuropsychiatric disorders. Fast-scan cyclic voltammetry (FSCV) has enabled the detection of neurochemicals, including serotonin, on a sub-second timescale via the well-established carbon fiber microelectrode (CFME). However, poor chronic stability and biofouling, i.e., the adsorption of interferent proteins to the electrode surface upon implantation, pose challenges in the natural physiological environment. We have recently developed a uniquely designed, freestanding, all-diamond boron-doped diamond microelectrode (BDDME) for electrochemical measurements. Key potential advantages of the device include customizable electrode site layouts, a wider working potential window, improved stability, and resistance to biofouling. Here, we present a first report on the electrochemical behavior of the BDDME in comparison with CFME by investigating in vitro serotonin (5-HT) responses with varying FSCV waveform parameters and biofouling conditions. While the CFME delivered lower limits of detection, we also found that BDDMEs showed more sustained 5-HT responses to increasing or changing FSCV waveform-switching potential and frequency, as well as to higher analyte concentrations. Biofouling-induced current reductions were significantly less pronounced at the BDDME when using a "Jackson" waveform compared to CFMEs. These findings are important steps towards the development and optimization of the BDDME as a chronically implanted biosensor for in vivo neurotransmitter detection.

Ultrafast Water H-Bond Rearrangement in a Metal-Organic Framework Probed by Femtosecond Time-Resolved Infrared Spectroscopy.

We investigated the water H-bond network and its dynamics in Ni2Cl2BTDD, a prototypical MOF for atmospheric water harvesting, using linear and ultrafast IR spectroscopy. Utilizing isotopic labeling and infrared spectroscopy, we found that water forms an extensive H-bonding network in Ni2Cl2BTDD. Further investigation with ultrafast spectroscopy revealed that water can reorient in a confined cone up to ∼50° within 1.3 ps. This large angle reorientation indicates H-bond rearrangement, similar to bulk water. Thus, although the water H-bond network is confined in Ni2Cl2BTDD, different from other confined systems, H-bond rearrangement is not hindered. The picosecond H-bond rearrangement in Ni2Cl2BTDD corroborates its reversibility with minimal hysteresis in water sorption.

An Evaluation of Maximum Determination Methods for Center Line Slope Analysis.

Ultrafast molecular dynamics are frequently extracted from two-dimensional (2D) spectra via the center line slope (CLS) method. The CLS method depends on the accurate determination of frequencies where the 2D signal is at a maximum, and multiple approaches exist for the determination of that maximum. Various versions of peak fitting for CLS analyses have been utilized; however, the impact of peak fitting on the accuracy and precision of the CLS method has not been reported in detail. Here, we evaluate several versions of CLS analyses using both simulated and experimental 2D spectra. The CLS method was found to be significantly more robust when fits were used to extract the maxima, particularly fitting methods that utilize pairs of opposite-sign peaks. However, we also observed that pairs of opposite-signed peaks required more assumptions than single peaks, which are important to check when interpreting experimental spectra using peak pairs.

Structure and thermodynamics of water adsorption in NU-1500-Cr.

Metal-organic frameworks (MOFs) are a class of materials with diverse chemical and structural properties, and have been shown to effectively adsorb various types of guest molecules. The mechanism of water adsorption in NU-1500-Cr, a high-performance atmospheric water harvesting MOF, is investigated using a combination of molecular dynamics simulations and infrared spectroscopy. Calculations of thermodynamic and dynamical properties of water as a function of relative humidity allow for following the adsorption process from the initial hydration stage to complete filling of the MOF pores. Initial hydration begins at the water molecules that saturate the open Cr3+ sites of the framework, which is then followed by the formation of water chains that extend along the channels connecting the hexagonal pores of the framework. Water present in these channels gradually coalesces and fills the hexagonal pores sequentially after the channels are completely hydrated. The development of hydrogen-bond networks inside the MOF pores as a function of relative humidity is characterized at the molecular level using experimental and computational infrared spectroscopy. A detailed analysis of the OH-stretch vibrational band indicates that the low-frequency tail stems from strongly polarized hydrogen-bonded water molecules, suggesting the presence of some structural disorder in the experimental samples. Strategies for designing efficient water harvesting MOFs are also proposed based on the mechanism of water adsorption in NU-1500-Cr.

The effects of sex, nation, ethnicity, age and self-reported pubertal development on participant-measured right-left 2D:4D (Dr-l) in the BBC internet study.

Digit ratio (2D:4D) - a proxy for prenatal sex steroids - shows sex, nationality and ethnic differences and is linked to pubertal onset. It is unclear whether right-left 2D:4D (Dr-l) also correlates with prenatal sex steroids, as evidence of these differences has been less conclusive. The present study examined the effects of sex, nation, ethnicity, age and self-reported pubertal development (i.e. the rate of physical development and age at menarche [females] or first shave [males]) on Dr-l in a large online study (the BBC internet study). Digit lengths were self-measured in 201,865 adults (110,955 males) and the sample of nations included 41 countries. Participants reported the self-perceived rate of physical pubertal development on a five-point scale (from very slow to very fast) and provided information on the age at menarche or first shave. Adult (>17 years) males had lower Dr-l than females with weak effect size across 41 nations (males-females; d = -.065, p < .0001). There were sex and ethnicity effects on Dr-l across seven ethnic groups with males < females and lower Dr-l in Whites and Middle/Near Eastern participants compared to Asian, Black and Chinese respondents. Considering age effects, the authors focused on participants >12 years; there were stable sex differences and a weak positive effect of age on Dr-l. Dr-l showed a positive relationship with the rate of physical development and a negative relationship with age at menarche or first shave. Relationships were present in males and females with stronger effects in the latter. It is concluded that Dr-l shows a weak sex difference (males < females) independent of nation, ethnicity and age, and suggest that Dr-l is a proxy for prenatal sex steroids.

The amphiphilic nanostructure of ionic liquids affects the dehydration of alcohols.

The effect of the amphiphilic nanostructure of ionic liquids on the dehydration of secondary alcohols to alkenes has been investigated. The influence of these nanostructures was inverted when an acid catalyst was added to the reaction. This phenomenon was ascribed to a balance between ion-solute interactions and the formation of solute-catalyst hydrogen bonds, highlighting the complex interplay between interactions and reaction outcomes in these nanostructured solvent systems.

Associations of experiential avoidance with burnout, wellbeing, and productivity loss among police officers: The mediating role of negative and positive affect.

OBJECTIVES: The current study aims to investigate the indirect associations between experiential avoidance (EA) and burnout, wellbeing, and productivity loss (PL) via the mediating role of positive and negative emotions among police officers. METHODS: Data were collected on 187 officers (84% male) aged 21-64 years between 2019 and 2020. Participants completed online self-report measures. RESULTS: EA was indirectly associated with burnout via positive and negative affect. EA was indirectly associated with wellbeing through positive affect, positive affect and burnout, and negative affect and burnout. Finally, EA was indirectly associated with PL via positive affect and burnout, and negative affect and burnout. CONCLUSION: Results provide support for the role of EA in officers' wellbeing and job performance via increasing negative affect and decreasing positive affect. This highlights the importance of interventions, such as acceptance and commitment therapy that target acceptance and psychological flexibility.

Preparation of nitriles from aldehydes using ammonium persulfate by means of a nitroxide-catalysed oxidative functionalisation reaction.

A methodology for the preparation of nitriles from aldehydes by means of an oxidative functionalisation reaction is reported. It employs ammonium persulfate as both the primary oxidant and the nitrogen source, and a catalytic amount of a nitroxide. It is applicable to a range of structurally diverse (hetero)aromatic aldehydes furnishing the nitrile products in 30-97% isolated yield. Given the ready accessibility of aldehydes and that ammonium persulfate is cheap and less toxic than many other reagents for generating nitriles, this methodology offers a simple and easy to use approach to this valuable class of compounds.

Parental income inequality and children's digit ratio (2D:4D): a 'Trivers-Willard' effect on prenatal androgenization?

Income inequality is associated positively with disease prevalence and mortality. Digit ratio (2D:4D) - a negative proxy for prenatal testosterone and a positive correlate of prenatal oestrogen - is related to several diseases. This study examined the association of income inequality (operationalized as relative parental income) and children's 2D:4D. Participants self-measured finger lengths (2D=index finger, and 4D=ring finger) in a large online survey conducted in July 2005 (the BBC Internet Study) and reported their parents' income. Children of parents of above-average income had low 2D:4D (high prenatal testosterone, low prenatal oestrogen) while the children of parents of below-average income had high 2D:4D (low prenatal testosterone, high prenatal oestrogen). The effects were significant in the total sample, present among Whites (the largest group in the sample), in the two largest national samples (UK and USA) and were greater for males than females. The findings suggest a Trivers-Willard effect, such that high-income women may prenatally masculinize their sons at the expense of the fitness of their daughters. Women with low income may prenatally feminize their daughters at the fitness expense of their sons. The effect could, in part, explain associations between low income, high 2D:4D (low prenatal testosterone) and some major causes of mortality such as cardiovascular disease.

Digit ratio (2D:4D) and body mass index in the BBC Internet Study: prenatal sex steroids and a Trivers-Willard effect on body composition.

Digit ratio - a putative measure of prenatal sex steroids - may be related to body mass index (BMI). However, reports of correlations between 2D:4D and BMI have yielded mixed results with some studies showing no relationship while others have reported positive associations in men or women only. This study considers associations between self-reported 2D:4D and BMI in a large online survey (i.e. the BBC Internet Study). At the individual level, there was a weak positive association between 2D:4D and BMI in both sexes with greater effect sizes in women. Body mass index was positively related to age and negatively related to parental income; however, the relationship between 2D:4D and BMI was independent of both variables. At the national level, mean 2D:4D per country showed positive associations with mean national BMI but those correlations were restricted to females. It is concluded that BMI is positively related to low prenatal testosterone and high prenatal oestrogen. Parental income inequality may influence both prenatal sex steroids (through a 'Trivers-Willard' effect) and BMI such that increases in inequality result in reductions in prenatal testosterone and increases in BMI at the individual and national level.

Preference for biological motion is reduced in ASD: implications for clinical trials and the search for biomarkers.

BACKGROUND: The neurocognitive mechanisms underlying autism spectrum disorder (ASD) remain unclear. Progress has been largely hampered by small sample sizes, variable age ranges and resulting inconsistent findings. There is a pressing need for large definitive studies to delineate the nature and extent of key case/control differences to direct research towards fruitful areas for future investigation. Here we focus on perception of biological motion, a promising index of social brain function which may be altered in ASD. In a large sample ranging from childhood to adulthood, we assess whether biological motion preference differs in ASD compared to neurotypical participants (NT), how differences are modulated by age and sex and whether they are associated with dimensional variation in concurrent or later symptomatology. METHODS: Eye-tracking data were collected from 486 6-to-30-year-old autistic (N = 282) and non-autistic control (N = 204) participants whilst they viewed 28 trials pairing biological (BM) and control (non-biological, CTRL) motion. Preference for the biological motion stimulus was calculated as (1) proportion looking time difference (BM-CTRL) and (2) peak look duration difference (BM-CTRL). RESULTS: The ASD group showed a present but weaker preference for biological motion than the NT group. The nature of the control stimulus modulated preference for biological motion in both groups. Biological motion preference did not vary with age, gender, or concurrent or prospective social communicative skill within the ASD group, although a lack of clear preference for either stimulus was associated with higher social-communicative symptoms at baseline. LIMITATIONS: The paired visual preference we used may underestimate preference for a stimulus in younger and lower IQ individuals. Our ASD group had a lower average IQ by approximately seven points. 18% of our sample was not analysed for various technical and behavioural reasons. CONCLUSIONS: Biological motion preference elicits small-to-medium-sized case-control effects, but individual differences do not strongly relate to core social autism associated symptomatology. We interpret this as an autistic difference (as opposed to a deficit) likely manifest in social brain regions. The extent to which this is an innate difference present from birth and central to the autistic phenotype, or the consequence of a life lived with ASD, is unclear.

Pump Slice Amplitudes: A Simple and Robust Method for Connecting Two-Dimensional Infrared and Fourier Transform Infrared Spectra.

Ultrafast two-dimensional infrared (2D IR) spectroscopy and Fourier transform infrared (FTIR) spectroscopy are often performed in tandem, with FTIR typically used to interpret and provide hypotheses for 2D IR experiments. Comparisons between 2D IR and FTIR spectra can also be used to examine the structure and orientation in systems of coupled vibrational chromophores. The most common method for comparing 2D IR and FTIR lineshapes, the diagonal slice method, contains significant artifacts when applied to oscillators with low anharmonicities. Here, we introduce a new technique, the pump slice amplitude (PSA) method, for relating 2D IR lineshapes to FTIR lineshapes and compare PSAs against diagonal slices using theoretical and experimental spectra. We find that PSAs are significantly more similar to FTIR lineshapes than diagonal slices in systems with low anharmonicity.

Effect of Pre-Exercise Music on Bench Press Power, Velocity, and Repetition Volume.

The purpose of this study was to examine the effects of listening to pre-exercise music on bench press performance. We recruited 10 resistance trained males (M age= 22.8, SD = 5.8 years; M height= 173.7, SD = 8.3 cm; M body mass = 81.0, SD = 18.2 kg) for this crossover counterbalanced research design. Participants completed two bench press exercise trials of (a) No music (NM), and (b) Pre-exercise music (PreExM) separated by at least 48 hours. For each trial, following a warm-up, participants listened to music or no music for three minutes. After this 3-minute period, they completed one set of bench press repetitions with maximum explosive intent at 75% one repetition maximum (1 RPM). We used a rotary encoder to measure power and velocity of barbell movement. After a 3-minute rest during which they again listened to music or no music, participants completed another set of repetitions to failure (RTF) at 75% of 1RM. Immediately following this second set of repetitions, we measured exercise motivation with a visual analog scale (VAS). We found that the PreExM condition increased mean power output (p = 0.005; d = 0.792) and barbell velocity (p = 0.015; d = 0.722). RTF were significantly higher during the PreExM versus NM trial (p = 0.002; d = 0.985), and motivation was significantly higher in the PreExM trial versus NM (p = 0.001; d = 0.932). These findings suggest improved muscle power explosiveness and strength-endurance when listening to music before a bench press exercise. From a practical standpoint, athletes who have the option of listening to music immediately prior to resistance exercise may benefit from its use.