Fabrication and Validation of Sub-Cellular Carbon Fiber Electrodes.

Multielectrode arrays for interfacing with neurons are of great interest for a wide range of medical applications. However, current electrodes cause damage over time. Ultra small carbon fibers help to address issues but controlling the electrode site geometry is difficult. Here we propose a methodology to create small, pointed fiber electrodes (SPFe). We compare the SPFe to previously made blowtorched fibers in characterization. The SPFe result in small site sizes [Formula: see text] with consistently sharp points (20.8 ± 7.64°). Additionally, these electrodes were able to record and/or stimulate neurons multiple animal models including rat cortex, mouse retina, Aplysia ganglia and octopus axial cord. In rat cortex, these electrodes recorded significantly higher peak amplitudes than the traditional blowtorched fibers. These SPFe may be applicable to a wide range of applications requiring a highly specific interface with individual neurons.

A Wireless Neural Stimulator IC for Cortical Visual Prosthesis.

We propose a 0.25 × 0.25 × 0.3 mm (~0.02 mm3) optically powered mote for visual cortex stimulation to restore vision. Up to 1024 implanted motes can be individually addressed. The complete StiMote system was confirmed fully functional when optically powered and cortex stimulation was confirmed in-vivo with a live rat brain.

Full-field, conformal epiretinal electrode array using hydrogel and polymer hybrid technology.

Shape-morphable electrode arrays can form 3D surfaces to conform to complex neural anatomy and provide consistent positioning needed for next-generation neural interfaces. Retinal prostheses need a curved interface to match the spherical eye and a coverage of several cm to restore peripheral vision. We fabricated a full-field array that can (1) cover a visual field of 57° based on electrode position and of 113° based on the substrate size; (2) fold to form a compact shape for implantation; (3) self-deploy into a curvature fitting the eye after implantation. The full-field array consists of multiple polymer layers, specifically, a sandwich structure of elastomer/polyimide-based-electrode/elastomer, coated on one side with hydrogel. Electrodeposition of high-surface-area platinum/iridium alloy significantly improved the electrical properties of the electrodes. Hydrogel over-coating reduced electrode performance, but the electrodes retained better properties than those without platinum/iridium. The full-field array was rolled into a compact shape and, once implanted into ex vivo pig eyes, restored to a 3D curved surface. The full-field retinal array provides significant coverage of the retina while allowing surgical implantation through an incision 33% of the final device diameter. The shape-changing material platform can be used with other neural interfaces that require conformability to complex neuroanatomy.

Post-explant profiling of subcellular-scale carbon fiber intracortical electrodes and surrounding neurons enables modeling of recorded electrophysiology.

Objective.Characterizing the relationship between neuron spiking and the signals that electrodes record is vital to defining the neural circuits driving brain function and informing clinical brain-machine interface design. However, high electrode biocompatibility and precisely localizing neurons around the electrodes are critical to defining this relationship.Approach.Here, we demonstrate consistent localization of the recording site tips of subcellular-scale (6.8µm diameter) carbon fiber electrodes and the positions of surrounding neurons. We implanted male rats with carbon fiber electrode arrays for 6 or 12+ weeks targeting layer V motor cortex. After explanting the arrays, we immunostained the implant site and localized putative recording site tips with subcellular-cellular resolution. We then 3D segmented neuron somata within a 50µm radius from implanted tips to measure neuron positions and health and compare to healthy cortex with symmetric stereotaxic coordinates.Main results.Immunostaining of astrocyte, microglia, and neuron markers confirmed that overall tissue health was indicative of high biocompatibility near the tips. While neurons near implanted carbon fibers were stretched, their number and distribution were similar to hypothetical fibers placed in healthy contralateral brain. Such similar neuron distributions suggest that these minimally invasive electrodes demonstrate the potential to sample naturalistic neural populations. This motivated the prediction of spikes produced by nearby neurons using a simple point source model fit using recorded electrophysiology and the mean positions of the nearest neurons observed in histology. Comparing spike amplitudes suggests that the radius at which single units can be distinguished from others is near the fourth closest neuron (30.7 ± 4.6µm,X-± S) in layer V motor cortex.Significance.Collectively, these data and simulations provide the first direct evidence that neuron placement in the immediate vicinity of the recording site influences how many spike clusters can be reliably identified by spike sorting.

Sarcoma de Ewing extraesquelético en cavidad nasal y senos paranasales, reporte de caso / Extra-skeletal Ewing sarcoma in the nasal cavity and paranasal sinus, case report

El sarcoma de ewing es un tumor maligno de rápido crecimiento, con prevalencia de 1-5 casos por cada 1.000.000 habitantes, su forma extraesquelética en la cavidad sinonasal o senos paranasales es inusual. Objetivo: describir la localización atípica de esta neoplasia y la importancia de lograr un diagnóstico oportuno. Paciente femenina, con una masa en la cavidad nasal derecha de dos meses de evolución, cefalea y epistaxis. Con asimetría en región orbitaria derecha y deformidad del tabique nasal, senos paranasales con sintomas de obstrucción. La tomografía reveló una masa que invade senos paranasales. La biopsia mostró un sarcoma de Ewing. Se confirmó con CD99. La paciente recibió quimioterapia y plan de resección quirúrgica, pero falleció. El diagnóstico y tratamiento oportuno del sarcoma de ewing en cavidad sinonasal debe apoyarse con examenes tomográficos, histopatológicos, inmunohistoquímicos y de ser posible citogenéticos para llegar al diagnóstico definitivo en etapas tempranas del tumor

Ewing's sarcoma is a rapidly growing malignant tumor, with a prevalence of 1-5 cases per 1,000,000 inhabitants, its extraskeletal shape in the sinonasal cavity or paranasal sinuses is unusual. Objective: to describe the atypical location of this neoplasm and the importance of achieving a timely diagnosis. Female patient, with a mass in the right nasal cavity of two months of evolution, headache and epistaxis. With asymmetry in the right orbital region and deformity of the nasal septum, paranasal sinuses with symptoms of obstruction. Tomography revealed a mass that invades the paranasal sinuses. The biopsy showed Ewing's sarcoma. It was confirmed with CD99. The patient received chemotherapy and a surgical resection plan, however she died. The timely diagnosis and treatment of Ewing's sarcoma in the sinonasal cavity should not be based solely on clinical evaluation, it requires a tomographic, histopathological, immunohistochemical and, if possible, cytogenetic examination to reach a definitive diagnosis in the early stages of the tumor.

Recycling of Waste Toner Powder as Adsorbent to Remove Aqueous Heavy Metals.

The removal of Cd2+, Zn2+ and Ni2+ from metal solutions onto waste toner power (WTP) was investigated. The influence of parameters such as pH, contact time, initial metal concentration and adsorbent dosage was studied in batch adsorption experiments. Batch equilibrium experiments showed that the highest removal efficiency for Zn2+ and Cd2+ occurs at pH 7, while pH 5 is the most suitable for Ni2+ removal. The amount of metal removed (mg/g) improved when increasing the initial concentration, and sorption of heavy metals reached equilibrium in 24 h. Metals' uptake increased with increasing adsorbent dosage. The adsorption isotherms of Zn2+, Cd2+ and Ni2+ onto WTP fit the Langmuir better than the Freundlich model with correlation coefficient R2 values ranging from 0.998 to 0.968 and 0.989 to 0.881, respectively. The data showed that the maximum adsorption capacity of heavy metals, amax, ranged from 2.42 to 1.61 mg/g, from 6.22 to 2.01 mg/g and from 3.49 to 2.56 mg/g for Ni2+, Zn2+ and Cd2+, respectively, with the three WTPs used in this study. This adsorbent can potentially be used to remove metal ions from wastewater.

Stimulated Generation of Indistinguishable Single Photons from a Quantum Ladder System.

We propose a scheme for the generation of highly indistinguishable single photons using semiconductor quantum dots and demonstrate its performance and potential. The scheme is based on the resonant two-photon excitation of the biexciton followed by stimulation of the biexciton to selectively prepare an exciton. Quantum-optical simulations and experiments are in good agreement and show that the scheme provides significant advantages over previously demonstrated excitation methods. The two-photon excitation of the biexciton suppresses re-excitation and enables ultralow multiphoton errors, while the precisely timed stimulation pulse results in very low timing jitter of the photons, and consequently, high indistinguishability. In addition, the polarization of the stimulation pulse allows us to deterministically program the polarization of the emitted photon (H or V). This ensures that all emission of interest occurs in the polarization of the detection channel, resulting in higher brightness than cross-polarized resonant excitation.

Carbon fiber electrodes for intracellular recording and stimulation.

Objective.To understand neural circuit dynamics, it is critical to manipulate and record many individual neurons. Traditional recording methods, such as glass microelectrodes, can only control a small number of neurons. More recently, devices with high electrode density have been developed, but few of them can be used for intracellular recording or stimulation in intact nervous systems. Carbon fiber electrodes (CFEs) are 8µm-diameter electrodes that can be assembled into dense arrays (pitches ⩾ 80µm). They have good signal-to-noise ratios (SNRs) and provide stable extracellular recordings both acutely and chronically in neural tissuein vivo(e.g. rat motor cortex). The small fiber size suggests that arrays could be used for intracellular stimulation.Approach.We tested CFEs for intracellular stimulation using the large identified and electrically compact neurons of the marine molluskAplysia californica. Neuron cell bodies inAplysiarange from 30µm to over 250µm. We compared the efficacy of CFEs to glass microelectrodes by impaling the same neuron's cell body with both electrodes and connecting them to a DC coupled amplifier.Main results.We observed that intracellular waveforms were essentially identical, but the amplitude and SNR in the CFE were lower than in the glass microelectrode. CFE arrays could record from 3 to 8 neurons simultaneously for many hours, and many of these recordings were intracellular, as shown by simultaneous glass microelectrode recordings. CFEs coated with platinum-iridium could stimulate and had stable impedances over many hours. CFEs not within neurons could record local extracellular activity. Despite the lower SNR, the CFEs could record synaptic potentials. CFEs were less sensitive to mechanical perturbations than glass microelectrodes.Significance.The ability to do stable multi-channel recording while stimulating and recording intracellularly make CFEs a powerful new technology for studying neural circuit dynamics.

Compositional and morphological properties of platinum-iridium electrodeposited on carbon fiber microelectrodes.

Objective. Neural interfaces based on carbon fiber (CF) electrodes have demonstrated key positive attributes such as minimal foreign body response and mechanical strength to self-insert in brain tissue. However, carbon does not form a low impedance electrode interface with neural tissue. Electrodeposited platinum iridium (PtIr) has been used to improve electrode interface properties for metallic bioelectrodes.Approach. In this study, a PtIr electrodeposition process has been performed on CF microelectrode arrays to improve the interfacial properties of these arrays. We study the film morphology and composition as well as electrode durability and impedance.Results. A PtIr coating with a composition of 70% Pt, 30% Ir and a thickness of ∼400 nm was observed. Pt and Ir were evenly distributed within the film. Impedance was decreased by 89% @ 1 kHz. Accelerated soak testing in a heated (T= 50∘C) saline solution showed impedance increase (@ 1 kHz) of ∼12% after 36 days (89 equivalent) of soaking.

Origin of Antibunching in Resonance Fluorescence.

Resonance fluorescence has played a major role in quantum optics with predictions and later experimental confirmation of nonclassical features of its emitted light such as antibunching or squeezing. In the Rayleigh regime where most of the light originates from the scattering of photons with subnatural linewidth, antibunching would appear to coexist with sharp spectral lines. Here, we demonstrate that this simultaneous observation of subnatural linewidth and antibunching is not possible with simple resonant excitation. Using an epitaxial quantum dot for the two-level system, we independently confirm the single-photon character and subnatural linewidth by demonstrating antibunching in a Hanbury Brown and Twiss type setup and using high-resolution spectroscopy, respectively. However, when filtering the coherently scattered photons with filter bandwidths on the order of the homogeneous linewidth of the excited state of the two-level system, the antibunching dip vanishes in the correlation measurement. Our observation is explained by antibunching originating from photon-interferences between the coherent scattering and a weak incoherent signal in a skewed squeezed state. This prefigures schemes to achieve simultaneous subnatural linewidth and antibunched emission.

Ultra-small carbon fiber electrode recording site optimization and improved in vivo chronic recording yield.

OBJECTIVE: Carbon fiber electrodes may enable better long-term brain implants, minimizing the tissue response commonly seen with silicon-based electrodes. The small diameter fiber may enable high-channel count brain-machine interfaces capable of reproducing dexterous movements. Past carbon fiber electrodes exhibited both high fidelity single unit recordings and a healthy neuronal population immediately adjacent to the recording site. However, the recording yield of our carbon fiber arrays chronically implanted in the brain typically hovered around 30%, for previously unknown reasons. In this paper we investigated fabrication process modifications aimed at increasing recording yield and longevity. APPROACH: We tested a new cutting method using a 532nm laser against traditional scissor methods for the creation of the electrode recording site. We verified the efficacy of improved recording sites with impedance measurements and in vivo array recording yield. Additionally, we tested potentially longer-lasting coating alternatives to PEDOT:pTS, including PtIr and oxygen plasma etching. New coatings were evaluated with accelerated soak testing and acute recording. MAIN RESULTS: We found that the laser created a consistent, sustainable 257 ± 13.8 µm2 electrode with low 1 kHz impedance (19 ± 4 kΩ with PEDOT:pTS) and low fiber-to-fiber variability. The PEDOT:pTS coated laser cut fibers were found to have high recording yield in acute (97% > 100 µV pp , N = 34 fibers) and chronic (84% > 100 µV pp , day 7; 71% > 100 µV pp , day 63, N = 45 fibers) settings. The laser cut recording sites were good platforms for the PtIr coating and oxygen plasma etching, slowing the increase in 1 kHz impedance compared to PEDOT:pTS in an accelerated soak test. SIGNIFICANCE: We have found that laser cut carbon fibers have a high recording yield that can be maintained for over two months in vivo and that alternative coatings perform better than PEDOT:pTS in accelerated aging tests. This work provides evidence to support carbon fiber arrays as a viable approach to high-density, clinically-feasible brain-machine interfaces.

Acceptability of Sexual Violence Against Women In Spain: Demographic, Behavioral, and Attitudinal Correlates.

Most research on the social perception of sexual violence is based on samples of university students, while it is rare to find studies with representative samples, despite the vital importance of this information in planning prevention strategies. Furthermore, in Europe, the social perception of sexual violence has been explored very marginally. Our main objective with this study was to explore, by means of a representative sample of the general population (N = 2,465), the relationship between the acceptability of sexual violence and demographic, behavioral, and attitudinal factors in Spain. The variable with the highest impact on the outcome was sexism, followed by knowledge of the most common type of victim-perpetrator relationship, age, perceived frequency of false complaints, and educational background. Other variables such as sex, country of birth, attitudes toward the consumption of prostitution, or opinions regarding prevention of sexual violence were also significant. A better understanding of the factors influencing public attitudes toward sexual violence would be useful to guide prevention efforts.

Nanosecond pulsed electric signals can affect electrostatic environment of proteins below the threshold of conformational effects: The case study of SOD1 with a molecular simulation study.

Electric fields can be a powerful tool to interact with enzymes or proteins, with an intriguing perspective to allow protein manipulation. Recently, researchers have focused the interest on intracellular enzyme modifications triggered by the application of nanosecond pulsed electric fields. These findings were also supported by theoretical predictions from molecular dynamics simulations focussing on significant variations in protein secondary structures. In this work, a theoretical study utilizing molecular dynamics simulations is proposed to explore effects of electric fields of high intensity and very short nanosecond duration applied to the superoxide dismutase (Cu/Zn-SOD or SOD-1), an important enzyme involved in the cellular antioxidant defence mechanism. The effects of 100-nanosecond pulsed electric fields, with intensities ranging from 108 to 7x108 V/m, on a single SOD1 enzyme are presented. We demonstrated that the lowest intensity of 108 V/m, although not inducing structural changes, can produce electrostatic modifications on the reaction centre of the enzyme, as apparent from the dipolar response and the electric field distribution of the protein active site. Electric pulses above 5x108 V/m produced a fast transition between the folded and a partially denatured state, as inferred by the secondary structures analysis. Finally, for the highest field intensity used (7x108 V/m), a not reversible transition toward an unfolded state was observed.

Feasibility of Drug Delivery Mediated by Ultra-Short and Intense Pulsed Electric Fields.

The increasing interest towards biocompatible nanotechnologies in medicine, combined with electric fields stimulation, is leading to the development of electro-sensitive smart systems for drug delivery applications. Common examples of electro-sensitive materials include phospholipids that can be used to design nano-sized vesicles suitable for external electric actuation. To this regard, recently the use of pulsed electric fields to trigger release across phospholipid membranes has been numerically studied, for a deeper understanding of the phenomena at the molecular scale. Aim of this work is to give an experimental validation of the feasibility of controlling drug release from liposomes mediated by nanosecond pulsed electric fields.

Influence of Intimate Partner Violence Severity on the Help-Seeking Strategies of Female Victims and the Influence of Social Reactions to Violence Disclosure on the Process of Leaving a Violent Relationship.

This article uses data from the 2015 Spanish Survey on Violence Against Women, a nationally representative survey of 10,171 women aged 16 or above, to analyze the relationship between the severity of intimate partner violence and formal and informal help-seeking strategies, the link between the severity of abuse and the reasons for not seeking formal help, and the influence of social reactions to violence disclosure on the process of leaving a violent relationship. The results show that in Spain, many abused women disclose violence and seek help. However, the severity of the violence strongly determines their help-seeking strategies, especially the search for formal help. Women who experienced less severe incidents tended to minimize their importance and did not seek formal help. For informal help, the differences were smaller, and a high proportion of women talked about the abuse with someone within their social environment, regardless of the severity of the suffered violence. A supportive reaction to violence disclosure had a strong and positive influence on the process of leaving the abusive relationship. The implications of these findings for the design of public policies, education, and awareness-raising campaigns are discussed.

Frequency-resolved Monte Carlo.

We adapt the Quantum Monte Carlo method to the cascaded formalism of quantum optics, allowing us to simulate the emission of photons of known energy. Statistical processing of the photon clicks thus collected agrees with the theory of frequency-resolved photon correlations, extending the range of applications based on correlations of photons of prescribed energy, in particular those of a photon-counting character. We apply the technique to autocorrelations of photon streams from a two-level system under coherent and incoherent pumping, including the Mollow triplet regime where we demonstrate the direct manifestation of leapfrog processes in producing an increased rate of two-photon emission events.

First observation of the quantized exciton-polariton field and effect of interactions on a single polariton.

Polaritons are quasi-particles that originate from the coupling of light with matter and that demonstrate quantum phenomena at the many-particle mesoscopic level, such as Bose-Einstein condensation and superfluidity. A highly sought and long-time missing feature of polaritons is a genuine quantum manifestation of their dynamics at the single-particle level. Although they are conceptually perceived as entangled states and theoretical proposals abound for an explicit manifestation of their single-particle properties, so far their behavior has remained fully accounted for by classical and mean-field theories. We report the first experimental demonstration of a genuinely quantum state of the microcavity polariton field, by swapping a photon for a polariton in a two-photon entangled state generated by parametric downconversion. When bringing this single-polariton quantum state in contact with a polariton condensate, we observe a disentangling with the external photon. This manifestation of a polariton quantum state involving a single quantum unlocks new possibilities for quantum information processing with interacting bosons.

Can Pulsed Electromagnetic Fields Trigger On-Demand Drug Release from High-Tm Magnetoliposomes?

Recently, magnetic nanoparticles (MNPs) have been used to trigger drug release from magnetoliposomes through a magneto-nanomechanical approach, where the mechanical actuation of the MNPs is used to enhance the membrane permeability. This result can be effectively achieved with low intensity non-thermal alternating magnetic field (AMF), which, however, found rare clinic application. Therefore, a different modality of generating non-thermal magnetic fields has now been investigated. Specifically, the ability of the intermittent signals generated by non-thermal pulsed electromagnetic fields (PEMFS) were used to verify if, once applied to high-transition temperature magnetoliposomes (high-Tm MLs), they could be able to efficiently trigger the release of a hydrophilic model drug. To this end, hydrophilic MNPs were combined with hydrogenated soybean phosphatidylcholine and cholesterol to design high-Tm MLs. The release of a dye was evaluated under the effect of PEMFs for different times. The MNPs motions produced by PEMF could effectively increase the bilayer permeability, without affecting the liposomes integrity and resulted in nearly 20% of release after 3 h exposure. Therefore, the current contribution provides an exciting proof-of-concept for the ability of PEMFS to trigger drug release, considering that PEMFS find already application in therapy due to their anti-inflammatory effects.

Technological and Theoretical Aspects for Testing Electroporation on Liposomes.

Recently, the use of nanometer liposomes as nanocarriers in drug delivery systems mediated by nanoelectroporation has been proposed. This technique takes advantage of the possibility of simultaneously electroporating liposomes and cell membrane with 10-nanosecond pulsed electric fields (nsPEF) facilitating the release of the drug from the liposomes and at the same time its uptake by the cells. In this paper the design and characterization of a 10 nsPEF exposure system is presented, for liposomes electroporation purposes. The design and the characterization of the applicator have been carried out choosing an electroporation cuvette with 1 mm gap between the electrodes. The structure efficiency has been evaluated at different experimental conditions by changing the solution conductivity from 0.25 to 1.6 S/m. With the aim to analyze the influence of device performances on the liposomes electroporation, microdosimetric simulations have been performed considering liposomes of 200 and 400 nm of dimension with different inner and outer conductivity (from 0.05 to 1.6 S/m) in order to identify the voltage needed for their poration.

Cardiovascular autonomic and hemodynamic responses to vagus nerve stimulation in drug-resistant epilepsy.

PURPOSE: Vagus nerve stimulation (VNS) is used as an adjunctive therapy for treating patients with drug-resistant epilepsy. The impact of VNS on cardiovascular autonomic function remains to be fully understood. We determined changes in cardiovascular sympathetic and parasympathetic, and hemodynamic function in association with VNS in patients with drug-resistant focal epilepsy. METHOD: Longitudinal (n=15) evaluation of beat-to-beat blood pressure (BP) and heart rate variability (HRV), baroreflex sensibility, and hemodynamic function performed before VNS implantation, 6-months after implantation, and a mean of 12-months after implantation; and cross-sectional study (n=14) of BP and HR variability and baroreflex sensitivity during VNS on and VNS off. RESULTS: In the longitudinal study, no differences were observed between the baseline, the 6-month visit, and the final visit in markers of parasympathetic cardiovagal tone or baroreflex sensitivity. Systolic and diastolic BP upon 5-min of head-up tilt increased significantly after VNS implantation (Systolic BP: -16.69±5.65mmHg at baseline, 2.86±16.54mmHg at 6-month, 12.25±12.95mmHg at final visit, p=0.01; diastolic BP: -14.84±24.72mmHg at baseline, 0.86±16.97mmHg at 6-month, and 17±12.76mmHg at final visit, p=0.001). CONCLUSION: VNS does not seem to produce alterations in parasympathetic cardiovagal tone, regardless of the laterality of the stimulus. We observed a slight increase in sympathetic cardiovascular modulations. These changes had no significant hemodynamic implications. These findings contribute to the understanding of potential mechanisms of action of VNS.