Analysis of prognostic factors and the role of epilepsy in neurosurgical patients with brain metastases.

Background: Brain metastases (BMs) represent the most frequent brain tumors in adults. The identification of key prognostic factors is essential for choosing the therapeutic strategy tailored to each patient. Epilepsy can precede several months of other clinical presentations of BMs. This work aimed to study the impact of epilepsy and other prognostic factors on BMs patients' survival. Methods: This retrospective study included 51 patients diagnosed with BMs and who underwent neurosurgery between 2010 and 2021. The impact of BM features and patient's clinical characteristics on the overall survival (OS) was analyzed through uni- and multivariate analysis. Results: The average OS was 25.98 months and differed according to the histology of the primary tumor. The primary tumor localization and the presence of extracranial metastases had a statistically significant impact on the OS, and patients with single BM showed a superior OS to those with multifocal lesions. The localization of BMs in the temporal lobe correlated with the highest OS. The OS was significantly higher in patients who presented seizures in their clinical onset and in those who had better post-surgical Karnofsky performance status, no post-surgical complications, and who underwent post-surgical treatment. Conclusion: Our study has highlighted prognostically favorable patient and tumor factors. Among those, a clinical onset with epileptic seizures can help identify brain metastasis hitherto silent. This could lead to immediate diagnostic-therapeutic interventions with more aggressive therapies after appropriate multidisciplinary evaluation.

Modeling sea ice albedo and transmittance measurements with a fully-coupled radiative transfer model.

A rigorous treatment of the sea ice medium has been incorporated in the advanced Coupled Ocean-Atmosphere Radiative Transfer (COART) model. The inherent optical properties (IOPs) of brine pockets and air bubbles over the 0.25-4.0 µm spectral region are parameterized as a function of the sea ice physical properties (temperature, salinity and density). We then test the performance of the upgraded COART model using three physically-based modeling approaches to simulate the spectral albedo and transmittance of sea ice, and compare them with measurements collected during the Impacts of Climate on the Ecosystems and Chemistry of the Arctic Pacific Environment (ICESCAPE) and the Surface Heat Budget of the Arctic Ocean (SHEBA) field campaigns. The observations are adequately simulated when at least three layers are used to represent bare ice, including a thin surface scattering layer (SSL), and two layers to represent ponded ice. Treating the SSL as a low-density ice layer yields better model-observation agreement than treating it as a snow-like layer. Sensitivity results indicate that air volume (which determines the ice density) has the largest impact on the simulated fluxes. The vertical profile of density drives the optical properties but available measurements are scarce. The approach where the scattering coefficient for the bubbles is inferred in lieu of density leads to essentially equivalent modeling results. For ponded ice, the albedo and transmittance in the visible are mainly determined by the optical properties of the ice underlying the water layer. Possible contamination from light-absorbing impurities, such as black carbon or ice algae, is also implemented in the model and is able to effectively reduce the albedo and transmittance in the visible spectrum to further improve the model-observation agreement.

Glioblastoma: A Retrospective Analysis of the Role of the Maximal Surgical Resection on Overall Survival and Progression Free Survival.

BACKGROUND: Glioblastoma (GBM) is the most common and aggressive primary brain tumor in adults; despite advances in the understanding of GBM pathogenesis, significant achievements in treating this disease are still lacking. The aim of this study was to evaluate the prognostic significance of the extent of surgical resection (EOR), beyond the neoplastic mass, on the overall survival (OS). METHODS: A retrospective review of a single-institution glioblastoma patient database (January 2012-September 2021) was undertaken. The series is composed of 64 patients who underwent surgery at the University Department of Neurosurgery of Ancona; the series was divided into four groups based on the amount of tumor mass excision with the fluid-attenuated inversion recovery (FLAIR) abnormalities (SUPr-supratotal resection, GTR-gross total resection, STR-subtotal resection, BIOPSY). The hypothesis was that the maximal resection of FLAIR abnormalities may improve the overall survival compared to the resection of the visible T1 contrast-enhanced neoplastic area only. RESULTS: In the univariate analysis, SUPr and GTR are correlated with the overall survival (p = 0.001); the percentage of total neoplastic removal threshold conditioning outcome was 90% (p = 0.027). These results were confirmed by the multivariate analysis. CONCLUSIONS: Maximal surgical resection, when feasible, involving areas of FLAIR abnormalities represents an advantageous approach for the OS in GBM patients.

A fast and accurate learning-based decoding algorithm for the classification of cardiovascular and respiratory challenges using intraneural electrodes in the pig vagus nerve.

Bioelectronic medicine is a new approach for developing closed-loop neuromodulation protocols on the peripheral nervous system (PNS) to treat a wide range of disorders currently treated with pharmacological approaches. Algorithms need to have low computational cost in order to acquire, process and model data for the modulation of the PNS in real time. Here, we present a fast learning-based decoding algorithm for the classification of cardiovascular and respiratory functional alterations (i.e., challenges) by using neural signals recorded from intraneural electrodes implanted in the vagus nerve of 5 pigs. Our algorithm relies on 9 handcrafted features, extracted following signal temporal windowing, and a multi-layer perceptron (MLP) for feature classification. We achieved fast and accurate classification of the challenges, with a computational time for feature extraction and prediction lower than 1.5 ms. The MLP achieved a balanced accuracy higher than 80 % for all recordings. Our algorithm could represent a step towards the development of a closed-loop system based on a single intraneural interface with both the potential of real time classification and selective modulation of the PNS.

Structure and Functions of the Vagus Nerve in Mammals.

We review the structure and function of the vagus nerve, drawing on information obtained in humans and experimental animals. The vagus nerve is the largest and longest cranial nerve, supplying structures in the neck, thorax, and abdomen. It is also the only cranial nerve in which the vast majority of its innervation territory resides outside the head. While belonging to the parasympathetic division of the autonomic nervous system, the nerve is primarily sensory-it is dominated by sensory axons. We discuss the macroscopic and microscopic features of the nerve, including a detailed description of its extensive territory. Histochemical and genetic profiles of afferent and efferent axons are also detailed, as are the central nuclei involved in the processing of sensory information conveyed by the vagus nerve and the generation of motor (including parasympathetic) outflow via the vagus nerve. We provide a comprehensive review of the physiological roles of vagal sensory and motor neurons in control of the cardiovascular, respiratory, and gastrointestinal systems, and finish with a discussion on the interactions between the vagus nerve and the immune system. © 2022 American Physiological Society. Compr Physiol 12: 1-49, 2022.

Effects of nociceptive and mechanosensitive afferents sensitization on central and peripheral hemodynamics following exercise-induced muscle damage.

This study aims to test the separated and combined effects of mechanoreflex activation and nociception through exercise-induced muscle damage (EIMD) on central and peripheral hemodynamics before and during single passive leg movement (sPLM). Eight healthy young males undertook four experimental sessions, in which a sPLM was performed on the dominant limb while in each specific session the contralateral was: 1) in a resting condition (CTRL), 2) stretched (ST), 3) resting after EIMD called delayed onset muscle soreness (DOMS) condition, or 4) stretched after EIMD (DOMS + ST). EIMD was used to induce DOMS in the following 24-48 h. Femoral blood flow (FBF) was assessed using Doppler ultrasound whereas central hemodynamics were assessed via finger photoplethysmography. Leg vascular conductance (LVC) was calculated as FBF/mean arterial pressure (MAP). RR-intervals were analyzed in the time (root mean squared of successive intervals; RMSSD) and frequency domain [low frequency (LF)/high frequency (HF)]. Blood samples were collected before each condition and gene expression analysis showed increased fold changes for P2X4 and IL1ß in DOMS and DOMS + ST compared with baseline. Resting FBF and LVC were decreased only in the DOMS + ST condition (-26 mL/min and -50 mL/mmHg/min respectively) with decreased RMSSD and increased LF/HF ratio. MAP, HR, CO, and SV were increased in ST and DOMS + ST compared with CTRL. Marked decreases of Δpeaks and AUC were observed for FBF (Δ: -146 mL/min and -265 mL respectively) and LVC (Δ: -8.66 mL/mmHg/min and ±1.7 mL/mmHg/min respectively) all P < 0.05. These results suggest that the combination of mechanoreflex and nociception resulted in decreased vagal tone and concomitant rise in sympathetic drive that led to increases in resting central hemodynamics with reduced limb blood flow before and during sPLM.NEW & NOTEWORTHY Exercise-induced muscle damage (EIMD) is a well-known model to study mechanical hyperalgesia and muscle peripheral nerve sensitizations. The combination of static stretching protocol on the damaged limb extensively increases resting central hemodynamics with reduction in resting limb blood flow and passive leg movement-induced hyperemia. The mechanism underlining these results may be linked to reduction of vagal tone with concomitant increase in sympathetic activity following mechano- and nociceptive activation.

A lightweight learning-based decoding algorithm for intraneural vagus nerve activity classification in pigs.

Objective.Bioelectronic medicine is an emerging field that aims at developing closed-loop neuromodulation protocols for the autonomic nervous system (ANS) to treat a wide range of disorders. When designing a closed-loop protocol for real time modulation of the ANS, the computational execution time and the memory and power demands of the decoding step are important factors to consider. In the context of cardiovascular and respiratory diseases, these requirements may partially explain why closed-loop clinical neuromodulation protocols that adapt stimulation parameters on patient's clinical characteristics are currently missing.Approach.Here, we developed a lightweight learning-based decoder for the classification of cardiovascular and respiratory functional challenges from neural signals acquired through intraneural electrodes implanted in the cervical vagus nerve (VN) of five anaesthetized pigs. Our algorithm is based on signal temporal windowing, nine handcrafted features, and random forest (RF) model for classification. Temporal windowing ranging from 50 ms to 1 s, compatible in duration with cardio-respiratory dynamics, was applied to the data in order to mimic a pseudo real-time scenario.Main results.We were able to achieve high balanced accuracy (BA) values over the whole range of temporal windowing duration. We identified 500 ms as the optimal temporal windowing duration for both BA values and computational execution time processing, achieving more than 86% for BA and a computational execution time of only ∼6.8 ms. Our algorithm outperformed in terms of BA and computational execution time a state of the art decoding algorithm tested on the same dataset (Valloneet al2021J. Neural Eng.180460a2). We found that RF outperformed other machine learning models such as support vector machines, K-nearest neighbors, and multi-layer perceptrons.Significance.Our approach could represent an important step towards the implementation of a closed-loop neuromodulation protocol relying on a single intraneural interface able to perform real-time decoding tasks and selective modulation of the VN.

Sympathetic and Vagal Nerve Activity in COPD: Pathophysiology, Presumed Determinants and Underappreciated Therapeutic Potential.

This article explains the comprehensive state of the art assessment of sympathetic (SNA) and vagal nerve activity recordings in humans and highlights the precise mechanisms mediating increased SNA and its corresponding presumed clinical determinants and therapeutic potential in the context of chronic obstructive pulmonary disease (COPD). It is known that patients with COPD exhibit increased muscle sympathetic nerve activity (MSNA), as measured directly using intraneural microelectrodes-the gold standard for evaluation of sympathetic outflow. However, the underlying physiological mechanisms responsible for the sympathoexcitation in COPD and its clinical relevance are less well understood. This may be related to the absence of a systematic approach to measure the increase in sympathetic activity and the lack of a comprehensive approach to assess the underlying mechanisms by which MSNA increases. The nature of sympathoexcitation can be dissected by distinguishing the heart rate increasing properties (heart rate and blood pressure variability) from the vasoconstrictive drive to the peripheral vasculature (measurement of catecholamines and MSNA) (Graphical Abstract Figure 1). Invasive assessment of MSNA to the point of single unit recordings with analysis of single postganglionic sympathetic firing, and hence SNA drive to the peripheral vasculature, is the gold standard for quantification of SNA in humans but is only available in a few centres worldwide because it is costly, time consuming and requires a high level of training. A broad picture of the underlying pathophysiological determinants of the increase in sympathetic outflow in COPD can only be determined if a combination of these tools are used. Various factors potentially determine SNA in COPD (Graphical Abstract Figure 1): Obstructive sleep apnoea (OSA) is highly prevalent in COPD, and leads to repeated bouts of upper airway obstructions with hypoxemia, causing repetitive arousals. This probably produces ongoing sympathoexcitation in the awake state, likely in the "blue bloater" phenotype, resulting in persistent vasoconstriction. Other variables likely describe a subset of COPD patients with increase of sympathetic drive to the heart, clinically likely in the "pink puffer" phenotype. Pharmacological treatment options of increased SNA in COPD could comprise beta blocker therapy. However, as opposed to systolic heart failure a similar beneficial effect of beta blocker therapy in COPD patients has not been shown. The point is made that although MSNA is undoubtedly increased in COPD (probably independently from concomitant cardiovascular disease), studies designed to determine clinical improvements during specific treatment will only be successful if they include adequate patient selection and translational state of the art assessment of SNA. This would ideally include intraneural recordings of MSNA and-as a future perspective-vagal nerve activity all of which should ideally be assessed both in the upright and in the supine position to also determine baroreflex function.

Quantification of cardiac and respiratory modulation of axonal activity in the human vagus nerve.

We recently documented the first microelectrode recordings from the cervical vagus nerve in awake humans. Here we aimed to quantify cardiac and respiratory modulation of vagal activity to assess the feasibility of targeting axons supplying the heart and airways. Multi-unit activity was recorded from 43 sites in 19 healthy participants in the left (n = 10) and right (n = 9) vagus nerves with ECG, continuous non-invasive blood pressure and respiration. Cross-correlation histograms were constructed between axonal spikes and the R-waves or the peaks of inspiration. The latencies for the peak in cardiac modulation showed a bimodal distribution: while the majority of sites (72%) had peak latencies that preceded the R-wave by up to 550 ms (mean ± SD, -300 ± 178 ms), 12 sites had latencies of up to 250 ms following the R-wave (64 ± 87 ms). Interestingly, the majority of sites with negative latencies (68%) were found in the left nerve whereas most of those with positive latencies (75%) were found in the right. Conversely, on average the peak of respiratory modulation straddled the peak of inspiration. Sites showing respiratory modulation were more prevalent and showed stronger modulation than those with cardiac modulation: calculated for sites with modulation indices ≥15%, the median cardiac and respiratory modulation indices were 23.4% (n = 17) and 44.5% (n = 35), respectively. We conclude that, despite the fact that much of the vagus nerve supplies the gut, cardiac and respiratory modulation of vagal nerve activity can be identified through invasive recordings in awake humans. KEY POINTS: Intraneural recordings from the cervical vagus were obtained in awake humans via tungsten microelectrodes inserted into the nerve through ultrasound guidance. Cross-correlation analysis of multi-unit vagal activity revealed cardiac and respiratory modulation, from which the amplitude and latency of the peaks could be computed. The magnitude of the cardiac modulation (23%) was weaker than that of the respiratory modulation (45%). The latencies for the peak in cardiac modulation showed a bimodal distribution: the majority of sites (72%) had peak latencies that preceded the R-wave, while the remainder had latencies that followed the R-wave. The majority of sites with negative latencies (68%) were found in the left nerve whereas most of those with positive latencies (75%) were found in the right. On average the peak of respiratory modulation coincided with the peak of inspiration.

Closed-Loop Vagus Nerve Stimulation for the Treatment of Cardiovascular Diseases: State of the Art and Future Directions.

The autonomic nervous system exerts a fine beat-to-beat regulation of cardiovascular functions and is consequently involved in the onset and progression of many cardiovascular diseases (CVDs). Selective neuromodulation of the brain-heart axis with advanced neurotechnologies is an emerging approach to corroborate CVDs treatment when classical pharmacological agents show limited effectiveness. The vagus nerve is a major component of the cardiac neuroaxis, and vagus nerve stimulation (VNS) is a promising application to restore autonomic function under various pathological conditions. VNS has led to encouraging results in animal models of CVDs, but its translation to clinical practice has not been equally successful, calling for more investigation to optimize this technique. Herein we reviewed the state of the art of VNS for CVDs and discuss avenues for therapeutic optimization. Firstly, we provided a succinct description of cardiac vagal innervation anatomy and physiology and principles of VNS. Then, we examined the main clinical applications of VNS in CVDs and the related open challenges. Finally, we presented preclinical studies that aim at overcoming VNS limitations through optimization of anatomical targets, development of novel neural interface technologies, and design of efficient VNS closed-loop protocols.

The Impact of the SARS-CoV-2 Pandemic on Healthcare Provision in Italy to non-COVID Patients: a Systematic Review.

BACKGROUND: Italy has been one of the countries most affected by the SARS-CoV-2 pandemic, and the regional healthcare system has had to quickly adapt its organization to meet the needs of infected patients. This has led to a drastic change in the routine management of non-communicable diseases with a potential long-term impact on patient health care. Therefore, we investigated the management of non-COVID-19 patients across all medical specialities in Italy. METHODS: A PRISMA guideline-based systematic review of the literature was performed using PubMed, Embase, and Scopus, restricting the search to the main outbreak period in Italy (from February 20 to June 25 2020). We selected articles in English or Italian that detailed changes in the Italian hospital care for non-COVID-19 patients due to the pandemic. Our keywords included all medical specialities combined with our geographical focus (Italy) and COVID-19. RESULTS: Of the 4643 potentially eligible studies identified by the search, 247 were included. A decrease in the management of emergencies in non-COVID patients was found together with an increase in mortality. Similarly, non-deferrable conditions met a tendency toward decreased diagnosis. All specialities have been affected by the re-organization of healthcare provision in the hub-and-spoke system and have benefited from telemedicine. CONCLUSIONS: Our work highlights the changes in the Italian public healthcare system to tackle the developing health crisis due to the COVID-19 pandemic. The findings of our review may be useful to analyse future directions for the healthcare system in the case of new pandemic scenarios.

Simultaneous decoding of cardiovascular and respiratory functional changes from pig intraneural vagus nerve signals.

Objective. Bioelectronic medicine is opening new perspectives for the treatment of some major chronic diseases through the physical modulation of autonomic nervous system activity. Being the main peripheral route for electrical signals between central nervous system and visceral organs, the vagus nerve (VN) is one of the most promising targets. Closed-loop VN stimulation (VNS) would be crucial to increase effectiveness of this approach. Therefore, the extrapolation of useful physiological information from VN electrical activity would represent an invaluable source for single-target applications. Here, we present an advanced decoding algorithm novel to VN studies and properly detecting different functional changes from VN signals.Approach. VN signals were recorded using intraneural electrodes in anaesthetized pigs during cardiovascular and respiratory challenges mimicking increases in arterial blood pressure, tidal volume and respiratory rate. We developed a decoding algorithm that combines discrete wavelet transformation, principal component analysis, and ensemble learning made of classification trees.Main results. The new decoding algorithm robustly achieved high accuracy levels in identifying different functional changes and discriminating among them. Interestingly our findings suggest that electrodes positioning plays an important role on decoding performances. We also introduced a new index for the characterization of recording and decoding performance of neural interfaces. Finally, by combining an anatomically validated hybrid neural model and discrimination analysis, we provided new evidence suggesting a functional topographical organization of VN fascicles.Significance. This study represents an important step towards the comprehension of VN signaling, paving the way for the development of effective closed-loop VNS systems.

Microfluidic Flow Injection Immunoassay System for Algal Toxins Determination: A Case of Study.

A novel flow injection microfluidic immunoassay system for continuous monitoring of saxitoxin, a lethal biotoxin, in seawater samples is presented in this article. The system consists of a preimmobilized G protein immunoaffinity column connected in line with a lab-on-chip setup. The detection of saxitoxin in seawater was carried out in two steps: an offline incubation step (competition reaction) performed between the analyte of interest (saxitoxin or Ag, as standard or seawater sample) and a tracer (an enzyme-conjugated antigen or Ag*) toward a specific polyclonal antibody. Then, the mixture was injected through a "loop" of a few µL using a six-way injection valve into a bioreactor, in line with the valve. The bioreactor consisted of a small glass column, manually filled with resin upon which G protein has been immobilized. When the mixture flowed through the bioreactor, all the antibody-antigen complex, formed during the competition step, is retained by the G protein. The tracer molecules that do not interact with the capture antibody and protein G are eluted out of the column, collected, and mixed with an enzymatic substrate directly within the microfluidic chip, via the use of two peristaltic pumps. When Ag* was present, a color change (absorbance variation, ΔAbs) of the solution is detected at a fixed wavelength (655 nm) by an optical chip docking system and registered by a computer. The amount of saxitoxin, present in the sample (or standard), that generates the variation of the intensity of the color, will be directly proportional to the concentration of the analyte in the analyzed solution. Indeed, the absorbance response increased proportionally to the enzymatic product and to the concentration of saxitoxin in the range of 3.5 × 10-7-2 × 10-5 ng ml-1 with a detection limit of 1 × 10-7 ng ml-1 (RSD% 15, S N-1 equal to 3). The immunoanalytical system has been characterized, optimized, and tested with seawater samples. This analytical approach, combined with the transportable and small-sized instrumentation, allows for easy in situ monitoring of marine water contaminations.

Bioelectronic medicine for the autonomic nervous system: clinical applications and perspectives.

Bioelectronic medicine (BM) is an emerging new approach for developing novel neuromodulation therapies for pathologies that have been previously treated with pharmacological approaches. In this review, we will focus on the neuromodulation of autonomic nervous system (ANS) activity with implantable devices, a field of BM that has already demonstrated the ability to treat a variety of conditions, from inflammation to metabolic and cognitive disorders. Recent discoveries about immune responses to ANS stimulation are the laying foundation for a new field holding great potential for medical advancement and therapies and involving an increasing number of research groups around the world, with funding from international public agencies and private investors. Here, we summarize the current achievements and future perspectives for clinical applications of neural decoding and stimulation of the ANS. First, we present the main clinical results achieved so far by different BM approaches and discuss the challenges encountered in fully exploiting the potential of neuromodulatory strategies. Then, we present current preclinical studies aimed at overcoming the present limitations by looking for optimal anatomical targets, developing novel neural interface technology, and conceiving more efficient signal processing strategies. Finally, we explore the prospects for translating these advancements into clinical practice.

Q-PINE: A quick to implant peripheral intraneural electrode.

Objective. The implantation of intraneural electrodes in amputees has been observed to be effective in providing subjects with sensory feedback. However, this implantation is challenging and time consuming. Surgeons must be especially trained to execute the implantation. Therefore, we aimed at developing a novel peripheral intraneural electrode and insertion mechanism, which could drastically reduce the overall implantation time while achieving a high neural selectivity.Approach.A new insertion method based on hollow microneedles was developed to realize the prompt and effective simultaneous implantation of up to 14 active sites in a transversal manner. Each needle guided two Pt/Ir microwires through the nervous tissue. After the insertion, the microneedles were released, leaving behind the microwires. Each microwire had one active site, which was coated with poly-3,4-ethylenedioxythiophene (PEDOT) to enhance the electrochemical properties. The active sites were characterized by evaluating the impedance, charge storage capacity, and maximum injectable charge. Twelve quick to implant peripheral intraneural electrodes (Q-PINEs) were implanted in four pig sciatic nerves to evaluate the implantation time and neural selectivity. We compared the stimulation of the sciatic nerve with that of its branches.Main results. The average surgical access time was 23 min. The insertion time for 12 electrodes was 6.7 min (std. ±1.6 min). The overall implantation time was reduced by 40.3 min compared to the previously reported values. The Q-PINE system demonstrated a satisfactory performance duringin vitroandin vivocharacterization. The electrochemical results showed that the PEDOT coating successfully increased the electrochemical parameters of the active sites.Significance.With an average impedance of 1.7 kΩ, a maximum charge level of 76.2 nC could be achieved per active site. EMG recruitment curves showed that 46% of the active sites exhibited selective stimulation of four out of six muscles. The histological analysis indicated that the microwires successfully penetrated the nerve and single fascicles.

In vivo recordings from the human vagus nerve using ultrasound-guided microneurography.

KEY POINTS: The vagus nerve is the largest cranial nerve and innervates many structures in the neck, thorax and abdomen. Although single-unit recordings from the vagus nerve have been performed in experimental animals for several decades, no recordings have ever been made from the human vagus nerve. The vagus nerve is routinely stimulated clinically, yet we know little of its physiology in humans. We describe the methodology and provide preliminary results of the first intraneural single-unit recordings from the cervical vagus in awake humans, using tungsten microelectrodes inserted into the nerve through ultrasound guidance. ABSTRACT: Intraneural microelectrodes have been used extensively to record from single somatosensory axons supplying muscle, tendons, joints and skin, as well as to record from postganglionic sympathetic axons supplying muscle and skin, in accessible peripheral nerves in awake humans. However, the vagus nerve has never been targeted, probably because of its close proximity to the carotid artery and jugular vein in the neck. Here, we report the first unitary recordings from the human cervical vagus nerve, obtained using ultrasound-guided insertion of tungsten microelectrodes into fascicles of the nerve. We identified tonically-active neurones in which firing rates were inversely related to heart rate (and directly related to the cardiac interval), which we classified as putative preganglionic parasympathetic axons directed to the sinoatrial node of the heart. We also recorded from tonically-active presumed sensory axons from the airways and presumed motor axons to the larynx. This new methodology opens exciting new opportunities for studying the physiology of the human vagus nerve in health and disease.

Intercomparison of airborne multi-angle polarimeter observations from the Polarimeter Definition Experiment.

In early 2013, three airborne polarimeters were flown on the high altitude NASA ER-2 aircraft in California for the Polarimeter Definition Experiment (PODEX). PODEX supported the pre-formulation NASA Aerosol-Cloud-Ecosystem (ACE) mission, which calls for an imaging polarimeter in polar orbit (among other instruments) for the remote sensing of aerosols, oceans, and clouds. Several polarimeter concepts exist as airborne prototypes, some of which were deployed during PODEX as a capabilities test. Two of those instruments to date have successfully produced Level 1 (georegistered, calibrated radiance and polarization) data from that campaign: the Airborne Multiangle Spectropolarimetric Imager (AirMSPI) and the Research Scanning Polarimeter (RSP). We compared georegistered observations of a variety of scene types by these instruments to test whether Level 1 products agreed within stated uncertainties. Initial comparisons found radiometric agreement, but polarimetric biases beyond measurement uncertainties. After subsequent updates to calibration, georegistration, and the measurement uncertainty models, observations from the instruments now largely agree within stated uncertainties. However, the 470 nm reflectance channels have a roughly +6% bias of AirMSPI relative to RSP, beyond expected measurement uncertainties. We also find that observations of dark (ocean) scenes, where polarimetric uncertainty is expected to be largest, do not agree within stated polarimetric uncertainties. Otherwise, AirMSPI and RSP observations are consistent within measurement uncertainty expectations, providing credibility for the subsequent creation of Level 2 (geophysical product) data from these instruments, and comparison thereof. The techniques used in this work can also form a methodological basis for other intercomparisons, for example, of the data gathered during the recent Aerosol Characterization from Polarimeter and Lidar (ACEPOL) field campaign, carried out in October and November of 2017 with four polarimeters (including AirMSPI and RSP).

p140Cap Regulates GABAergic Synaptogenesis and Development of Hippocampal Inhibitory Circuits.

The neuronal scaffold protein p140Cap was investigated during hippocampal network formation. p140Cap is present in presynaptic GABAergic terminals and its genetic depletion results in a marked alteration of inhibitory synaptic activity. p140Cap-/- cultured neurons display higher frequency of miniature inhibitory postsynaptic currents (mIPSCs) with no changes of their mean amplitude. Consistent with a potential presynaptic alteration of basal GABA release, p140Cap-/- neurons exhibit a larger synaptic vesicle readily releasable pool, without any variation of single GABAA receptor unitary currents and number of postsynaptic channels. Furthermore, p140Cap-/- neurons show a premature and enhanced network synchronization and appear more susceptible to 4-aminopyridine-induced seizures in vitro and to kainate-induced seizures in vivo. The hippocampus of p140Cap-/- mice showed a significant increase in the number of both inhibitory synapses and of parvalbumin- and somatostatin-expressing interneurons. Specific deletion of p140Cap in forebrain interneurons resulted in increased susceptibility to in vitro epileptic events and increased inhibitory synaptogenesis, comparable to those observed in p140Cap-/- mice. Altogether, our data demonstrate that p140Cap finely tunes inhibitory synaptogenesis and GABAergic neurotransmission, thus regulating the establishment and maintenance of the proper hippocampal excitatory/inhibitory balance.

Airborne and shipborne polarimetric measurements over open ocean and coastal waters: intercomparisons and implications for spaceborne observations.

Comprehensive polarimetric closure is demonstrated using observations from two in-situ polarimeters and Vector Radiative Transfer (VRT) modeling. During the Ship-Aircraft Bio-Optical Research (SABOR) campaign, the novel CCNY HyperSAS-POL polarimeter was mounted on the bow of the R/V Endeavor and acquired hyperspectral measurements from just above the surface of the ocean, while the NASA GISS Research Scanning Polarimeter was deployed onboard the NASA LaRC's King Air UC-12B aircraft. State-of-the-art, ancillary measurements were used to characterize the atmospheric and marine contributions in the VRT model, including those of the High Spectral Resolution Lidar (HSRL), the AErosol RObotic NETwork for Ocean Color (AERONET-OC), a profiling WETLabs ac-9 spectrometer and the Multi-spectral Volume Scattering Meter (MVSM). An open-ocean and a coastal scene are analyzed, both affected by complex aerosol conditions. In each of the two cases, it is found that the model is able to accurately reproduce the Stokes components measured simultaneously by each polarimeter at different geometries and viewing altitudes. These results are mostly encouraging, considering the different deployment strategies of RSP and HyperSAS-POL, which imply very different sensitivities to the atmospheric and ocean contributions, and open new opportunities in above-water polarimetric measurements. Furthermore, the signal originating from each scene was propagated to the top of the atmosphere to explore the sensitivity of polarimetric spaceborne observations to changes in the water type. As expected, adding polarization as a measurement capability benefits the detection of such changes, reinforcing the merits of the full-Stokes treatment in modeling the impact of atmospheric and oceanic constituents on remote sensing observations.

Reduced availability of voltage-gated sodium channels by depolarization or blockade by tetrodotoxin boosts burst firing and catecholamine release in mouse chromaffin cells.

KEY POINTS: Mouse chromaffin cells (MCCs) of the adrenal medulla possess fast-inactivating Nav channels whose availability alters spontaneous action potential firing patterns and the Ca(2+)-dependent secretion of catecholamines. Here, we report MCCs expressing large densities of neuronal fast-inactivating Nav1.3 and Nav1.7 channels that carry little or no subthreshold pacemaker currents and can be slowly inactivated by 50% upon slight membrane depolarization. Reducing Nav1.3/Nav1.7 availability by tetrodotoxin or by sustained depolarization near rest leads to a switch from tonic to burst-firing patterns that give rise to elevated Ca(2+)-influx and increased catecholamine release. Spontaneous burst firing is also evident in a small percentage of control MCCs. Our results establish that burst firing comprises an intrinsic firing mode of MCCs that boosts their output. This occurs particularly when Nav channel availability is reduced by sustained splanchnic nerve stimulation or prolonged cell depolarizations induced by acidosis, hyperkalaemia and increased muscarine levels. ABSTRACT: Action potential (AP) firing in mouse chromaffin cells (MCCs) is mainly sustained by Cav1.3 L-type channels that drive BK and SK currents and regulate the pacemaking cycle. As secretory units, CCs optimally recruit Ca(2+) channels when stimulated, a process potentially dependent on the modulation of the AP waveform. Our previous work has shown that a critical determinant of AP shape is voltage-gated sodium channel (Nav) channel availability. Here, we studied the contribution of Nav channels to firing patterns and AP shapes at rest (-50 mV) and upon stimulation (-40 mV). Using quantitative RT-PCR and immunoblotting, we show that MCCs mainly express tetrodotoxin (TTX)-sensitive, fast-inactivating Nav1.3 and Nav1.7 channels that carry little or no Na(+) current during slow ramp depolarizations. Time constants and the percentage of recovery from fast inactivation and slow entry into closed-state inactivation are similar to that of brain Nav1.3 and Nav1.7 channels. The fraction of available Nav channels is reduced by half after 10 mV depolarization from -50 to -40 mV. This leads to low amplitude spikes and a reduction in repolarizing K(+) currents inverting the net current from outward to inward during the after-hyperpolarization. When Nav channel availability is reduced by up to 20% of total, either by TTX block or steady depolarization, a switch from tonic to burst firing is observed. The spontaneous occurrence of high frequency bursts is rare under control conditions (14% of cells) but leads to major Ca(2+)-entry and increased catecholamine release. Thus, Nav1.3/Nav1.7 channel availability sets the AP shape, burst-firing initiation and regulates catecholamine secretion in MCCs. Nav channel inactivation becomes important during periods of high activity, mimicking stress responses.