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In genetic and refractory epileptic patients, seizure activity exhibits sleep-related modulation/regulation and sleep and seizure are intermingled. In this study, by using one het Gabrg2 Q390X KI mice as a genetic epilepsy model and optogenetic method in vivo , we found that subcortical POA neurons were active within epileptic network from the het Gabrg2 Q390X KI mice and the POA activity preceded epileptic (poly)spike-wave discharges(SWD/PSDs) in the het Gabrg2 Q390X KI mice. Meanwhile, as expected, the manipulating of the POA activity relatively altered NREM sleep and wake periods in both wt and the het Gabrg2 Q390X KI mice. Most importantly, the short activation of epileptic cortical neurons alone did not effectively trigger seizure activity in the het Gabrg2 Q390X KI mice. In contrast, compared to the wt mice, combined the POA nucleus activation and short activation of the epileptic cortical neurons effectively triggered or suppressed epileptic activity in the het Gabrg2 Q390X KI mice, indicating that the POA activity can control the brain state to trigger seizure incidence in the het Gabrg2 Q390X KI mice in vivo. In addition, the suppression of POA nucleus activity decreased myoclonic jerks in the Gabrg2 Q390X KI mice. Overall, this study discloses an operational mechanism for sleep-dependent seizure incidence in the genetic epilepsy model with the implications for refractory epilepsy. This operational mechanism also underlies myoclonic jerk generation, further with translational implications in seizure treatment for genetic/refractory epileptic patients and with contribution to memory/cognitive deficits in epileptic patients., Competing Interests: All authors report no competing interests in relation to the work described.

Successful surgical treatment of drug-resistant epilepsy traditionally relies on the identification of seizure onset zones (SOZs). Connectome-based analyses of electrographic data from stereo electroencephalography (SEEG) may empower improved detection of SOZs. Specifically, connectome-based analyses based on the interictal suppression hypothesis posit that when the patient is not having a seizure, SOZs are inhibited by non-SOZs through high inward connectivity and low outward connectivity. However, it is not clear whether there are other motifs that can better identify potential SOZs. Thus, we sought to use unsupervised machine learning to identify network motifs that elucidate SOZs and investigate if there is another motif that outperforms the ISH. Resting-state SEEG data from 81 patients with drug-resistant epilepsy undergoing a pre-surgical evaluation at Vanderbilt University Medical Center were collected. Directed connectivity matrices were computed using the alpha band (8-13 Hz). Principal component analysis (PCA) was performed on each patient's connectivity matrix. Each patient's components were analysed qualitatively to identify common patterns across patients. A quantitative definition was then used to identify the component that most closely matched the observed pattern in each patient. A motif characteristic of the interictal suppression hypothesis (high-inward and low-outward connectivity) was present in all individuals and found to be the most robust motif for identification of SOZs in 64/81 (79%) patients. This principal component demonstrated significant differences in SOZs compared to non-SOZs. While other motifs for identifying SOZs were present in other patients, they differed for each patient, suggesting that seizure networks are patient specific, but the ISH is present in nearly all networks. We discovered that a potentially suppressive motif based on the interictal suppression hypothesis was present in all patients, and it was the most robust motif for SOZs in 79% of patients. Each patient had additional motifs that further characterized SOZs, but these motifs were not common across all patients. This work has the potential to augment clinical identification of SOZs to improve epilepsy treatment., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Guarantors of Brain.)

Premise: Intraspecific variation may play a key role in shaping the relationships between plants and their interactions with soil microbial communities. The soil microbes of individual plants can generate intraspecific variation in the responsiveness of the plant offspring, yet have been much less studied. To address this need, we explored how the relatedness of seedlings from established clones of Solidago altissima altered the plant-soil interactions of the seedlings., Methods: Seedlings of known parentage were generated from a series of 24 clones grown in a common garden. Seedlings from these crosses were inoculated with soils from maternal, paternal, or unrelated clones and their performance compared to sterilized control inocula., Results: We found that soil inocula influenced by S. altissima clones had an overall negative effect on seedling biomass. Furthermore, seedlings inoculated with maternal or paternal soils tended to experience larger negative effects than seedlings inoculated with unrelated soils. However, there was much variation among individual crosses, with not all responding to relatedness., Conclusions: Our data argue that genetic relatedness to the plant from which the soil microbial inoculum was obtained may cause differential impacts on establishing seedlings, encouraging the regeneration of non-kin adjacent to established clones. Such intraspecific variation represents a potentially important source of heterogeneity in plant-soil microbe interactions with implications for maintaining population genetic diversity., (© 2024 Botanical Society of America.)

Electroencephalography (EEG) is an indispensable tool in epilepsy, sleep, and behavioral research. In rodents, EEG recordings are typically performed with metal electrodes that traverse the skull into the epidural space. In addition to requiring major surgery, intracranial EEG is difficult to perform for more than a few electrodes, is time-intensive, and confounds experiments studying traumatic brain injury. Here, we describe an open-source cost-effective refinement of this technique for chronic mouse EEG recording. Our alternative two-channel (EEG2) and sixteen-channel high-density EEG (HdEEG) arrays use electrodes made of the novel, flexible 2D nanomaterial titanium carbide (Ti 3 C 2 T x ) MXene. The MXene electrodes are placed on the surface of the intact skull and establish an electrical connection without conductive gel or paste. Fabrication and implantation times of MXene EEG electrodes are significantly shorter than the standard approach, and recorded resting baseline and epileptiform EEG waveforms are similar to those obtained with traditional epidural electrodes. Applying HdEEG to a mild traumatic brain injury (mTBI) model in mice of both sexes revealed that mTBI significantly increased spike-wave discharge (SWD) preictal network connectivity with frequencies of interest in the β-spectral band (12-30 Hz). These findings indicate that the fabrication of MXene electrode arrays is a cost-effective, efficient technology for multichannel EEG recording in mice that obviates the need for skull-penetrating surgery. Moreover, increased preictal β-frequency network connectivity may contribute to the development of early post-mTBI SWDs., (Copyright © 2024 Ding et al.)

Background: Transsulcal tubular retractor-assisted minimally invasive parafascicular surgery changes the surgical strategy for deep-seated lesions by promoting a deficit-sparing approach. When integrated with preoperative brain mapping and intraoperative neuromonitoring (IONM), this approach may potentially improve patient outcomes. In this study, we assessed the impact of preoperative brain mapping and IONM in tubular retractor-assisted neuro-oncological surgery., Methods: This retrospective single-center cohort study included patients who underwent transsulcal tubular retractor-assisted minimally invasive parafascicular surgery for resection of deep-seated brain tumors from 2016 to 2022. The cohort was divided into 3 groups: group 1, no preoperative mapping or IONM (17 patients); group 2, IONM only (25 patients); group 3, both preoperative mapping and IONM (38 patients)., Results: We analyzed 80 patients (33 males and 47 females) with a median age of 46.5 years (range: 1-81 years). There was no significant difference in mean tumor volume (26.2 cm 3 [range 1.07-97.4 cm 3 ]; P = 0.740) and mean preoperative depth of the tumor (31 mm [range 3-65 mm], P = 0.449) between the groups. A higher proportion of high-grade gliomas and metastases was present within group 3 (P = 0.003). IONM was related to fewer motor (P = 0.041) and language (P = 0.032) deficits at hospital discharge. Preoperative mapping and IONM were also related to shorter length of stay (P = 0.008)., Conclusions: Preoperative and intraoperative brain mapping and monitoring enhance transsulcal tubular retractor-assisted minimally invasive parafascicular surgery in neuro-oncology. Patients had a reduced length of stay and prolonged overall survival. IONM alone reduces postoperative neurological deficit., (Crown Copyright © 2023. Published by Elsevier Inc. All rights reserved.)

Background: Cervical traumatic spinal cord injury is a devastating condition. Current management (bony decompression) may be inadequate as after acute severe TSCI, the swollen spinal cord may become compressed against the surrounding tough membrane, the dura. DISCUS will test the hypothesis that, after acute, severe traumatic cervical spinal cord injury, the addition of dural decompression to bony decompression improves muscle strength in the limbs at 6 months, compared with bony decompression alone., Methods: This is a prospective, phase III, multicenter, randomized controlled superiority trial. We aim to recruit 222 adults with acute, severe, traumatic cervical spinal cord injury with an American Spinal Injury Association Impairment Scale grade A, B, or C who will be randomized 1:1 to undergo bony decompression alone or bony decompression with duroplasty. Patients and outcome assessors are blinded to study arm. The primary outcome is change in the motor score at 6 months vs. admission; secondary outcomes assess function (grasp, walking, urinary + anal sphincters), quality of life, complications, need for further surgery, and mortality, at 6 months and 12 months from randomization. A subgroup of at least 50 patients (25/arm) also has observational monitoring from the injury site using a pressure probe (intraspinal pressure, spinal cord perfusion pressure) and/or microdialysis catheter (cord metabolism: tissue glucose, lactate, pyruvate, lactate to pyruvate ratio, glutamate, glycerol; cord inflammation: tissue chemokines/cytokines). Patients are recruited from the UK and internationally, with UK recruitment supported by an integrated QuinteT recruitment intervention to optimize recruitment and informed consent processes. Estimated study duration is 72 months (6 months set-up, 48 months recruitment, 12 months to complete follow-up, 6 months data analysis and reporting results)., Discussion: We anticipate that the addition of duroplasty to standard of care will improve muscle strength; this has benefits for patients and carers, as well as substantial gains for health services and society including economic implications. If the addition of duroplasty to standard treatment is beneficial, it is anticipated that duroplasty will become standard of care., Trial Registration: IRAS: 292031 (England, Wales, Northern Ireland) - Registration date: 24 May 2021, 296518 (Scotland), ISRCTN: 25573423 (Registration date: 2 June 2021); ClinicalTrials.gov number : NCT04936620 (Registration date: 21 June 2021); NIHR CRN 48627 (Registration date: 24 May 2021)., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Competing Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Sleep is the preferential period when epileptic spike-wave discharges appear in human epileptic patients, including genetic epileptic seizures such as Dravet syndrome with multiple mutations including SCN1A mutation and GABA A receptor γ2 subunit Gabrg2 Q390X mutation in patients, which presents more severe epileptic symptoms in female patients than male patients. However, the seizure onset mechanism during sleep still remains unknown. Our previous work has shown that the sleep-like state-dependent homeostatic synaptic potentiation can trigger epileptic spike-wave discharges in one transgenic heterozygous Gabrg2 +/Q390X knock-in mouse model. 1 Here, using this heterozygous knock-in mouse model, we hypothesized that slow-wave oscillations themselves in vivo could trigger epileptic seizures. We found that epileptic spike-wave discharges in heterozygous Gabrg2 +/Q390X knock-in mice exhibited preferential incidence during non-rapid eye movement sleep period, accompanied by motor immobility/facial myoclonus/vibrissal twitching and more frequent spike-wave discharge incidence appeared in female heterozygous knock-in mice than male heterozygous knock-in mice. Optogenetically induced slow-wave oscillations in vivo significantly increased epileptic spike-wave discharge incidence in heterozygous Gabrg2 +/Q390X knock-in mice with longer duration of non-rapid eye movement sleep or quiet-wakeful states. Furthermore, suppression of slow-wave oscillation-related homeostatic synaptic potentiation by 4-(diethylamino)-benzaldehyde injection ( i.p. ) greatly attenuated spike-wave discharge incidence in heterozygous knock-in mice, suggesting that slow-wave oscillations in vivo did trigger seizure activity in heterozygous knock-in mice. Meanwhile, sleep spindle generation in wild-type littermates and heterozygous Gabrg2 +/Q390X knock-in mice involved the slow-wave oscillation-related homeostatic synaptic potentiation that also contributed to epileptic spike-wave discharge generation in heterozygous Gabrg2 +/Q390X knock-in mice. In addition, EEG spectral power of delta frequency (0.1-4 Hz) during non-rapid eye movement sleep was significantly larger in female heterozygous Gabrg2 +/Q390X knock-in mice than that in male heterozygous Gabrg2 +/Q390X knock-in mice, which likely contributes to the gender difference in seizure incidence during non-rapid eye movement sleep/quiet-wake states of human patients. Overall, all these results indicate that slow-wave oscillations in vivo trigger the seizure onset in heterozygous Gabrg2 +/Q390X knock-in mice, preferentially during non-rapid eye movement sleep period and likely generate the sex difference in seizure incidence between male and female heterozygous Gabrg2 +/Q390X knock-in mice., (© The Author(s) 2022. Published by Oxford University Press on behalf of the Guarantors of Brain.)

Competing Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

During non-rapid eye movement (NREM) sleep, cortical neuron activity alternates between a depolarized (firing, up-state) and a hyperpolarized state (down-state) coinciding with delta electroencephalogram (EEG) slow-wave oscillation (SWO, 0. 5-4 Hz) in vivo . Recently, we have found that artificial sleep-like up/down-states can potentiate synaptic strength in layer V cortical neurons ex vivo . Using mouse coronal brain slices, whole cell voltage-clamp recordings were made from layer V cortical pyramidal neurons to record spontaneous excitatory synaptic currents (sEPSCs) and inhibitory synaptic currents (sIPSCs). Artificial sleep-like up/down-states (as SWOs, 0.5 Hz, 10 min, current clamp mode) were induced by injecting sinusoidal currents into layer V cortical neurons. Baseline pre-SWO recordings were recorded for 5 min and post-SWO recordings for at least 25-30 min. Compared to pre-SWO sEPSCs or sIPSCs, post-SWO sEPSCs or sIPSCs in layer V cortical neurons exhibited significantly larger amplitudes and a higher frequency for 30 min. This finding suggests that both sEPSCs and sIPSCs could be potentiated in layer V cortical neurons by the low-level activity of SWOs, and sEPSCs and sIPSCs maintained a balance in layer V cortical neurons during pre- and post-SWO periods. Overall, this study presents an ex vivo method to show SWO's ability to induce synaptic plasticity in layer V cortical neurons, which may underlie sleep-related synaptic potentiation for sleep-related memory consolidation in vivo ., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Besing, St. John, Potesta, Gallagher and Zhou.)

Objective: We describe the chronological trends in cerebral revascularization surgery through a single-surgeon experience; and we review whether in the context of giant and fusiform cerebral aneurysms, flow-diverting stents have impacted on the use of cerebral revascularization surgery., Methods: We review our single institution prospectively collected database of cerebral revascularization procedures between 2006 and 2018. Comparing this to our database of flow-diverting endovascular stent procedures, we compare the treatment of fusiform and giant aneurysms. We describe patient demographics, procedural incidence, complications, and outcomes., Results: Between 2006 and 2018, 50 cerebral revascularization procedures were performed. The incidence of cerebral revascularization surgery is declining. In the context of giant/fusiform aneurysm treatment, the decline in cerebral revascularization is accompanied by a rise in the use of flow-diverting endovascular stents. Thirty cerebral revascularizations were performed for moyamoya disease and 11 for giant/fusiform aneurysm. Four (14%) direct bypass grafts occluded without neurological sequela. Other morbidity included hydrocephalus (2%), transient ischemic attacks (2%), and ischemic stroke (2%). There was one procedure-related mortality (2%). Flow-diverting stents were inserted for seven fusiform and seven giant aneurysms. Comparing the treatment of giant/fusiform aneurysms, there was no significant difference in morbidity and mortality between cerebral revascularization and flow-diverting endovascular stents., Conclusion: We conclude that with the decline in the incidence of cerebral revascularization surgery, there is a need for centralization of services to allow high standards and outcomes to be maintained., Competing Interests: Speakers Bureau for Medtronic United Kingdom: TB; Core laboratory for Microvention: TB; Wellcome/Engineering and Physical Sciences Research Council Center for Medical Engineering (WT 203148/Z/16/Z): TB. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Gallagher, Frantzias, Kailaya-Vasan, Booth and Tolias.)

Background: Transsulcal minimally invasive parafasicular (TsMIP) approaches to brain tumor resection use tubular retractors to minimize iatrogenic brain injury. Dynamic cortical and subcortical continuous neurophysiological mapping facilitates safer resection of motor-eloquent tumors., Objective: To describe a new technique to address the challenge of combining TsMIP with tubular retractors and dynamic subcortical mapping using a single electrified stimulating microdebrider instrument., Methods: We adapted the NICO Myriad microdebrider with continuous monopolar stimulation electrification using high-frequency stimulation with the train-of-5 technique. We performed continuous subcortical mapping using this device and compared it with standard dynamic monopolar subcortical mapping using a suction stimulation device. We found no significant difference in recorded stimulation response., Results: Using a single operating instrument that provides synchronous tumor resection and monopolar subcortical mapping with the NICO Brainpath tubular retractor, we observed increased degrees of movement, faster surgical resection times with an enlarged working channel down the retractor, and improved safety because the stimulating probe sits 2 mm deep to the resection window., Conclusion: We show that the adapted device is reliable and provides similar stimulation response as conventional subcortical mapping. We advocate the use of our adapted microdebrider in TsMIP tubular retractor approaches., (Copyright © Congress of Neurological Surgeons 2022. All rights reserved.)

Objective: To determine EEG spatiospectral activation and connectivity in the generalized tonic-clonic seizure (GTCS) semiological subtypes., Methods: 39 patients with genetic generalized epilepsy (GGE) who had GTCS (n = 58) during video-EEG monitoring were identified in the Vanderbilt Epilepsy database. GTCSs were classified as absence tonic-clonic, myoclonic tonic-clonic, or tonic-clonic. Patient characteristics and semiological features were compared. Spectral power and node degree, a network measure of connectivity, were calculated at two seizure epochs, electrographic and tonic-start., Results: Different GTCS subtypes occurred within individual patients. At electrographic-onset, all subtypes activated midline frontal cortex at delta/theta and beta frequencies but differed in network connectivity. In all subtypes, GTCS evolution from electrographic to tonic-start associated with preserved beta frequency spectral power, but reduced connectivity and delta/theta power., Conclusions: Our findings suggest that at GTCS onset, the subtypes activate similar cortical regions and their different initial semiologies relate to their distinct onset long-range connectivity. Upon transition to the tonic-start epoch, the ictal activity is predominantly conveyed by β frequency activity and connectivity., Significance: Future neurostimulation therapies for medically intractable GTCSs may target the same brain regions for all GTCS subtypes and may be most effective prior to the tonic-start epoch., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Published by Elsevier B.V.)

Objectives: To determine the feasibility of monitoring tissue oxygen tension from the injury site (pscto2) in patients with acute, severe traumatic spinal cord injuries., Design: We inserted at the injury site a pressure probe, a microdialysis catheter, and an oxygen electrode to monitor for up to a week intraspinal pressure (ISP), spinal cord perfusion pressure (SCPP), tissue glucose, lactate/pyruvate ratio (LPR), and pscto2. We analyzed 2,213 hours of such data. Follow-up was 6-28 months postinjury., Setting: Single-center neurosurgical and neurocritical care units., Subjects: Twenty-six patients with traumatic spinal cord injuries, American spinal injury association Impairment Scale A-C. Probes were inserted within 72 hours of injury., Interventions: Insertion of subarachnoid oxygen electrode (Licox; Integra LifeSciences, Sophia-Antipolis, France), pressure probe, and microdialysis catheter., Measurements and Main Results: pscto2 was significantly influenced by ISP (pscto2 26.7 ± 0.3 mm Hg at ISP > 10 mmHg vs pscto2 22.7 ± 0.8 mm Hg at ISP ≤ 10 mm Hg), SCPP (pscto2 26.8 ± 0.3 mm Hg at SCPP < 90 mm Hg vs pscto2 32.1 ± 0.7 mm Hg at SCPP ≥ 90 mm Hg), tissue glucose (pscto2 26.8 ± 0.4 mm Hg at glucose < 6 mM vs 32.9 ± 0.5 mm Hg at glucose ≥ 6 mM), tissue LPR (pscto2 25.3 ± 0.4 mm Hg at LPR > 30 vs pscto2 31.3 ± 0.3 mm Hg at LPR ≤ 30), and fever (pscto2 28.8 ± 0.5 mm Hg at cord temperature 37-38°C vs pscto2 28.7 ± 0.8 mm Hg at cord temperature ≥ 39°C). Tissue hypoxia also occurred independent of these factors. Increasing the Fio2 by 0.48 increases pscto2 by 71.8% above baseline within 8.4 minutes. In patients with motor-incomplete injuries, fluctuations in pscto2 correlated with fluctuations in limb motor score. The injured cord spent 11% (39%) hours at pscto2 less than 5 mm Hg (< 20 mm Hg) in patients with motor-complete outcomes, compared with 1% (30%) hours at pscto2 less than 5 mm Hg (< 20 mm Hg) in patients with motor-incomplete outcomes. Complications were cerebrospinal fluid leak (5/26) and wound infection (1/26)., Conclusions: This study lays the foundation for measuring and altering spinal cord oxygen at the injury site. Future studies are required to investigate whether this is an effective new therapy., Competing Interests: Drs. Papadopoulos’s and Saadoun’s institutions received funding from the Wings for Life and the Neurosciences Research Foundation. The remaining authors have disclosed that they do not have any potential conflicts of interest., (Copyright © 2022 by the Society of Critical Care Medicine and Wolters Kluwer Health, Inc. All Rights Reserved.)

Background: Acute, severe traumatic spinal cord injury often causes fecal incontinence. Currently, there are no treatments to improve anal function after traumatic spinal cord injury. Our study aims to determine whether, after traumatic spinal cord injury, anal function can be improved by interventions in the neuro-intensive care unit to alter the spinal cord perfusion pressure at the injury site., Methods: We recruited a cohort of patients with acute, severe traumatic spinal cord injuries (American Spinal Injury Association Impairment Scale grades A-C). They underwent surgical fixation within 72 h of the injury and insertion of an intrathecal pressure probe at the injury site to monitor intraspinal pressure and compute spinal cord perfusion pressure as mean arterial pressure minus intraspinal pressure. Injury-site monitoring was performed at the neuro-intensive care unit for up to a week after injury. During monitoring, anorectal manometry was also conducted over a range of spinal cord perfusion pressures., Results: Data were collected from 14 patients with consecutive traumatic spinal cord injury aged 22-67 years. The mean resting anal pressure was 44 cmH 2 O, which is considerably lower than the average for healthy patients, previously reported at 99 cmH 2 O. Mean resting anal pressure versus spinal cord perfusion pressure had an inverted U-shaped relation (Ȓ 2  = 0.82), with the highest resting anal pressures being at a spinal cord perfusion pressure of approximately 100 mmHg. The recto-anal inhibitory reflex (transient relaxation of the internal anal sphincter during rectal distension), which is important for maintaining fecal continence, was present in 90% of attempts at high (90 mmHg) spinal cord perfusion pressure versus 70% of attempts at low (60 mmHg) spinal cord perfusion pressure (P < 0.05). During cough, the rise in anal pressure from baseline was 51 cmH 2 O at high (86 mmHg) spinal cord perfusion pressure versus 37 cmH 2 O at low (62 mmHg) spinal cord perfusion pressure (P < 0.0001). During anal squeeze, higher spinal cord perfusion pressure was associated with longer endurance time and spinal cord perfusion pressure of 70-90 mmHg was associated with stronger squeeze. There were no complications associated with anorectal manometry., Conclusions: Our data indicate that spinal cord injury causes severe disruption of anal sphincter function. Several key components of anal continence (resting anal pressure, recto-anal inhibitory reflex, and anal pressure during cough and squeeze) markedly improve at higher spinal cord perfusion pressure. Maintaining too high of spinal cord perfusion pressure may worsen anal continence., (© 2021. The Author(s).)

Objective: The authors sought to investigate the effect of acute, severe traumatic spinal cord injury on the urinary bladder and the hypothesis that increasing the spinal cord perfusion pressure improves bladder function., Methods: In 13 adults with traumatic spinal cord injury (American Spinal Injury Association Impairment Scale grades A-C), a pressure probe and a microdialysis catheter were placed intradurally at the injury site. We varied the spinal cord perfusion pressure and performed filling cystometry. Patients were followed up for 12 months on average., Results: The 13 patients had 63 fill cycles; 38 cycles had unfavorable urodynamics, i.e., dangerously low compliance (< 20 mL/cmH2O), detrusor overactivity, or dangerously high end-fill pressure (> 40 cmH2O). Unfavorable urodynamics correlated with periods of injury site hypoperfusion (spinal cord perfusion pressure < 60 mm Hg), hyperperfusion (spinal cord perfusion pressure > 100 mm Hg), tissue glucose < 3 mM, and tissue lactate to pyruvate ratio > 30. Increasing spinal cord perfusion pressure from 67.0 ± 2.3 mm Hg (average ± SE) to 92.1 ± 3.0 mm Hg significantly reduced, from 534 to 365 mL, the median bladder volume at which the desire to void was first experienced. All patients with dangerously low average initial bladder compliance (< 20 mL/cmH2O) maintained low compliance at follow-up, whereas all patients with high average initial bladder compliance (> 100 mL/cmH2O) maintained high compliance at follow-up., Conclusions: We conclude that unfavorable urodynamics develop within days of traumatic spinal cord injury, thus challenging the prevailing notion that the detrusor is initially acontractile. Urodynamic studies performed acutely identify patients with dangerously low bladder compliance likely to benefit from early intervention. At this early stage, bladder function is dynamic and is influenced by fluctuations in the physiology and metabolism at the injury site; therefore, optimizing spinal cord perfusion is likely to improve urological outcome in patients with acute severe traumatic spinal cord injury.

Sudden unexpected death in epilepsy (SUDEP) is the most common cause of death in patients with refractory epilepsy. The pathophysiology of SUDEP is unknown. Postictal phenomena such as postconvulsive immobility (PI), postictal generalized electroencephalography (EEG) suppression (PGES), arousal deficits, cardiac arrhythmias, central apneas, and obstructive apneas due to laryngospasms have been suggested to contribute to SUDEP. We present, to our knowledge, the first case of a near-SUDEP event in a patient undergoing intracranial, stereotactic EEG (sEEG) monitoring. This case spotlights potential mediators of SUDEP, most notably the striking PGES and postictal apnea. The nature of the sEEG investigation illustrates the extent of cortical and subcortical postictal EEG suppression and showcases a transient return of cerebral activity likely to be missed on scalp-EEG recording. Critically, this case emphasizes the importance of continuous cardiorespiratory monitoring and underscores the importance of postictal arousal as a pathophysiological mechanism in SUDEP., (© 2021 International League Against Epilepsy.)

Nano-sized hematite (α-Fe 2 O 3 ) is not well suited for magnetic heating via an alternating magnetic field (AMF) because it is not superparamagnetic-at its best, it is weakly ferromagnetic. However, manipulating the magnetic properties of nano-sized hematite (i.e., magnetic saturation (Ms), magnetic remanence (Mr), and coercivity (Hc)) can make them useful for nanomedicine (i.e., magnetic hyperthermia) and nanoelectronics (i.e., data storage). Herein we study the effects of size, shape, and crystallinity on hematite nanoparticles to experimentally determine the most crucial variable leading to enhancing the radio frequency (RF) heating properties. We present the synthesis, characterization, and magnetic behavior to determine the structure-property relationship between hematite nano-magnetism and RF heating. Increasing particle shape anisotropy had the largest effect on the specific adsorption rate (SAR) producing SAR values more than 6 × greater than the nanospheres (i.e., 45.6 ± 3 W/g of α-Fe 2 O 3 nanorods vs. 6.89 W/g of α-Fe 2 O 3 nanospheres), indicating α-Fe 2 O 3 nanorods can be useful for magnetic hyperthermia.

Background: Values of fractional flow reserve (FFR CT ) by coronary computed tomography angiography (CTA) decline from the ostium to the terminal vessel, irrespective of stenosis severity. The purpose of this study is to determine if the site of measurement of FFR CT impacts assessment of ischemia and its diagnostic performance relative to invasive FFR (FFR INV )., Methods: 1484 patients underwent FFR CT ; 1910 vessels were stratified by stenosis severity (normal; <25%, 25-50%, 50-70%, and >70% stenosis). The rates of positive FFR CT (≤0.8) were determined by measuring FFR CT from the terminal vessel and from distal-to-the-lesion. Reclassification rates from positive to negative FFR CT were calculated. Diagnostic performance of FFR CT relative to FFR INV was evaluated in 182 vessels using linear regression, Bland Altman analysis, and receiver operating characteristic (ROC) curves., Results: Positive FFR CT was identified in 24.9% of vessels using terminal vessel FFR CT and 10.1% using FFR CT distal-to-the-lesion (p ​< ​0.001). FFR CT obtained distal-to-the-lesion resulted in reclassification of 59.6% of positive terminal FFR CT to negative FFR CT . Relative to FFR INV , there were improvements in specificity (50% to 86%, p ​< ​0.001), diagnostic accuracy (65% to 88%, p ​< ​0.001), positive predictive value (50% to 78%, p ​< ​0.001), and area-under-the-curve (AUC, 0.83 to 0.91, p ​< ​0.001) when FFR CT was measured distal-to-the-lesion., Conclusion: FFR CT values from the terminal vessel should not be used to assess lesion-specific ischemia due to high rates of false positive results. FFR CT measured distal-to-the-lesion improves the diagnostic performance of FFR CT relative to FFR INV , ensures that FFR CT values are due to lesion-specific ischemia, and could reduce the rate of unnecessary invasive procedures., Competing Interests: Declaration of competing interest Drs. Cami, Chinnaiyan, and Safian receive research grant support from HeartFlow Inc. Drs. Chinnaiyan and Safian are members of the Medical Advisory Board for HeartFlow, Inc but do not receive any compensation except for reimbursement for travel expenses., (Copyright © 2020. Published by Elsevier Inc.)

Epileptic activity in genetic generalized epilepsy (GGE) patients preferentially appears during sleep and its mechanism remains unknown. Here, we found that sleep-like slow-wave oscillations (0.5 Hz SWOs) potentiated excitatory and inhibitory synaptic currents in layer V cortical pyramidal neurons from wild-type (wt) mouse brain slices. In contrast, SWOs potentiated excitatory, but not inhibitory, currents in cortical neurons from a heterozygous (het) knock-in (KI) Gabrg2+Q/390X model of Dravet epilepsy syndrome. This created an imbalance between evoked excitatory and inhibitory currents to effectively prompt neuronal action potential firings. Similarly, physiologically similar up-/down-state induction (present during slow-wave sleep) in cortical neurons also potentiated excitatory synaptic currents within brain slices from wt and het KI mice. Moreover, this state-dependent potentiation of excitatory synaptic currents entailed some signaling pathways of homeostatic synaptic plasticity. Consequently, in het KI mice, in vivo SWO induction (using optogenetic methods) triggered generalized epileptic spike-wave discharges (SWDs), being accompanied by sudden immobility, facial myoclonus, and vibrissa twitching. In contrast, in wt littermates, SWO induction did not cause epileptic SWDs and motor behaviors. To our knowledge, this is the first mechanism to explain why epileptic SWDs preferentially happen during non rapid eye-movement sleep and quiet-wakefulness in human GGE patients., (© The Author(s) 2020. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permission@oup.com.)

Carbon nanotubes (CNTs) have unique physical and chemical properties that drive their use in a variety of commercial and industrial applications. CNTs are commonly oxidized prior to their use to enhance dispersion in polar solvents by deliberately grafting oxygen-containing functional groups onto CNT surfaces. In addition, CNT surface oxides can be unintentionally formed or modified after CNTs are released into the environment through exposure to reactive oxygen species and/or ultraviolet irradiation. Consequently, it is important to understand the impact of CNT surface oxidation on the environmental fate, transport, and toxicity of CNTs. In this review, we describe the specific role of oxygen-containing functional groups on the important environmental behaviors of CNTs in aqueous media (e.g., colloidal stability, adsorption, and photochemistry) as well as their biological impact. We place special emphasis on the value of systematically varying and quantifying surface oxides as a route to identifying quantitative structure-property relationships. The role of oxygen-containing functional groups in regulating the efficacy of CNT-enabled water treatment technologies and the influence of surface oxides on other carbon-based nanomaterials are also evaluated and discussed.

Introduction: Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2)-infected patients commonly have elevated troponin and D-dimer levels, but limited imaging exists to support most likely etiologies in efforts to avoid staff exposure. The purpose of this study was to report transthoracic echocardiographic (TTE) findings in SARS-CoV-2 patients with correlating troponin and D-dimer levels., Methods: We identified 66 SARS-CoV-2 patients (mean age 60 ± 15.7 years) admitted within a large, eight-hospital healthcare system over a 6-week period with a TTE performed. TTE readers were blinded to laboratory data with intra-observer and inter-observer analysis assessed., Results: Sixty-six of 1780 SARS-CoV-2 patients were included and represented a high-risk population as 38 (57.6%) were ICU-admitted, 47 (71.2%) had elevated D-dimer, 41 (62.1%) had elevated troponin, and 25 (37.9%) died. Right ventricular (RV) dilation was present in 49 (74.2%) patients. The incidence and average D-dimer elevation was similar between moderate/severe vs. mild/no RV dilation (69.6% vs 67.6%, P = 1.0; 3736 ± 2986 vs 4141 ± 3351 ng/mL, P = .679). Increased left ventricular (LV) wall thickness was present in 46 (69.7%) with similar incidence of elevated troponin and average troponin levels compared to normal wall thickness (66.7% vs 52.4%, P = .231; 0.88 ± 1.9 vs 1.36 ± 2.4 ng/mL, P = .772). LV dilation was rare (n = 6, 9.1%), as was newly reduced LV ejection fraction (n = 2, 3.0%)., Conclusion: TTE in SARS-CoV-2 patients is scarce, technically difficult, and reserved for high-risk patients. RV dilation is common in SARS-CoV-2 but does not correlate with elevated D-dimer levels. Increased LV wall thickness is common, while newly reduced LV ejection fraction is rare, and neither correlates with troponin levels., (© 2020 Wiley Periodicals LLC.)

Coronavirus disease 2019 is a global pandemic affecting >3 million people in >170 countries, resulting in >200 000 deaths; 35% to 40% of patients and deaths are in the United States. The coronavirus disease 2019 crisis is placing an enormous burden on health care in the United States, including residency and fellowship training programs. The balance between mitigation, training and education, and patient care is the ultimate determinant of the role of cardiology fellows in training during the coronavirus disease 2019 crisis. On March 24, 2020, the Accreditation Council for Graduate Medical Education issued a formal response to the pandemic crisis and described a framework for operation of graduate medical education programs. Guidance for deployment of cardiology fellows in training during the coronavirus disease 2019 crisis is based on the principles of a medical mission, and adherence to preparation, protection, and support of our fellows in training. The purpose of this review is to describe our departmental strategic deployment of cardiology fellows in training using the Accreditation Council for Graduate Medical Education framework for pandemic preparedness.

General methods to achieve better physical insight about nanoparticle aggregation and assembly are needed because of the potential role of aggregation in a wide range of materials, environmental, and biological outcomes. Scanning electron microscopy (SEM) is fast and affordable compared to transmission electron microscopy, but SEM micrographs lack contrast and resolution due to lower beam energy, topographic contrast, edge effects, and charging. We present a new segmentation algorithm called SEMseg that is robust to the challenges inherent in SEM micrograph analysis and demonstrate its utility for analyzing gold (Au) nanorod aggregates. SEMseg not only supports nanoparticle size analysis for dispersed nanoparticles, but also discriminates between nanoparticles within an aggregate. We compare our algorithm to those incorporated into the commonly used software ImageJ and demonstrate improved segmentation of aggregate structures. New physical insight about aggregation is demonstrated by the introduction of an order parameter describing side-by-side structure in nanoparticle aggregates. We also present the segmentation and fitting algorithms included in SEMseg within a user-friendly graphical user interface. The resulting code is provided with an open-source interface to provide quantitative image processing tools for researchers to characterize both dispersed nanoparticles and nanoparticle assemblies in SEM micrographs with high throughput.

In five patients with acute, severe thoracic traumatic spinal cord injuries (TSCIs), American spinal injuries association Impairment Scale (AIS) grades A-C, we induced cord hypothermia (33 °C) then rewarming (37 °C). A pressure probe and a microdialysis catheter were placed intradurally at the injury site to monitor intraspinal pressure (ISP), spinal cord perfusion pressure (SCPP), tissue metabolism and inflammation. Cord hypothermia-rewarming, applied to awake patients, did not cause discomfort or neurological deterioration. Cooling did not affect cord physiology (ISP, SCPP), but markedly altered cord metabolism (increased glucose, lactate, lactate/pyruvate ratio (LPR), glutamate; decreased glycerol) and markedly reduced cord inflammation (reduced IL1β, IL8, MCP, MIP1α, MIP1β). Compared with pre-cooling baseline, rewarming was associated with significantly worse cord physiology (increased ICP, decreased SCPP), cord metabolism (increased lactate, LPR; decreased glucose, glycerol) and cord inflammation (increased IL1β, IL8, IL4, IL10, MCP, MIP1α). The study was terminated because three patients developed delayed wound infections. At 18-months, two patients improved and three stayed the same. We conclude that, after TSCI, hypothermia is potentially beneficial by reducing cord inflammation, though after rewarming these benefits are lost due to increases in cord swelling, ischemia and inflammation. We thus urge caution when using hypothermia-rewarming therapeutically in TSCI.

In some centers, monitoring lumbar cerebrospinal fluid (CSF) is used to guide management of patients with acute traumatic spinal cord injuries (TSCI) and draining lumbar CSF to improve spinal cord perfusion. Here, we investigate whether the lumbar CSF provides accurate information about the injury site and the effect of draining lumbar CSF on injury site perfusion. In 13 TSCI patients, we simultaneously monitored lumbar CSF pressure (CSFP) and intraspinal pressure (ISP) from the injury site. Using CSFP or ISP, we computed spinal cord perfusion pressure (SCPP), vascular pressure reactivity index (sPRx) and optimum SCPP (SCPP opt ). We also assessed the effect on ISP of draining 10 mL CSF. Metabolites at the injury site were compared with metabolites in the lumbar CSF. We found that ISP was pulsatile, but CSFP had low pulse pressure and was non-pulsatile 21% of the time. There was weak or no correlation between CSFP versus ISP ( R  = -0.11), SCPP (csf) versus SCPP (ISP) ( R  = 0.39), and sPRx (csf) versus sPRx (ISP) ( R  = 0.45). CSF drainage caused no significant change in ISP in 7/12 patients and a significant drop of <5 mm Hg in 4/12 patients and of ∼8 mm Hg in 1/12 patients. Metabolite concentrations in the CSF versus the injury site did not correlate for lactate ( R  = 0.00), pyruvate ( R  = -0.12) or lactate-to-pyruvate ratio ( R  = -0.05) with weak correlations noted for glucose ( R  = 0.31), glutamate ( R  = 0.61), and glycerol ( R  = 0.56). We conclude that, after a severe TSCI, monitoring from the lumbar CSF provides only limited information about the injury site and that lumbar CSF drainage does not effectively reduce ISP in most patients.

The unique physicochemical and luminescent properties of carbon dots (CDs) have motivated research efforts toward their incorporation into commercial products. Increased use of CDs will inevitably lead to their release into the environment where their fate and persistence will be influenced by photochemical transformations, the nature of which is poorly understood. This knowledge gap motivated the present investigation of the effects of direct and indirect photolysis on citric and malic acid-based CDs. Our results indicate that natural sunlight will rapidly and non-destructively photobleach CDs into optically inactive carbon nanoparticles. We demonstrate that after photobleaching, • OH exposure degrades CDs in a two-step process that will span several decades in natural waters. The first step, occurring over several years of • OH exposure, involves depolymerization of the CD structure, characterized by volatilization of over 60% of nascent carbon atoms and the oxidation of nitrogen atoms into nitro groups. This is followed by a slower oxidation of residual carbon atoms first into carboxylic acids and then volatile carbon species, while nitrogen atoms are oxidized into nitrate ions. Considered alongside related CD studies, our findings suggest that the environmental behavior of CDs will be strongly influenced by the molecular precursors used in their synthesis.

Purpose: To investigate the effect of increasing spinal cord perfusion pressure (SCPP) on sensory evoked potentials (SEPs) and injury site metabolism in patients with severe traumatic spinal cord injury TSCI., Materials and Methods: In 12 TSCI patients we placed a pressure probe, a microdialysis catheter and a strip electrode with 8 contacts on the surface of the injured cord. We monitored SCPP, lactate-to-pyruvate ratio (LPR) and SEPs (after median or posterior tibial nerve stimulation)., Results: Increase in SCPP by ~20 mmHg produced a heterogeneous response in SEPs and injury site metabolism. In some patients, SEP amplitudes increased and the LPR decreased indicating improved tissue metab olism. In others, SEP amplitudes decreased and the LPR increased indicating more impaired metabolism. Compared with patients who did not improve at follow-up, those who improved had significantly more electrode contacts with SEP amplitude increase in response to increasing SCPP., Conclusions: Increasing SCPP after acute, severe TSCI may be beneficial (if associated with increase in SEP amplitude) or detrimental (if associated with decrease in SEP amplitude). Our findings support individualized management of patients with acute, severe TSCI guided by monitoring from the injury site rather than applying universal blood pressure targets as is current clinical practice., Competing Interests: Declaration of Competing Interest There are no conflicts of interest., (Copyright © 2019 Elsevier Inc. All rights reserved.)