Sustained deep-tissue voltage recording using a fast indicator evolved for two-photon microscopy.

Genetically encoded voltage indicators are emerging tools for monitoring voltage dynamics with cell-type specificity. However, current indicators enable a narrow range of applications due to poor performance under two-photon microscopy, a method of choice for deep-tissue recording. To improve indicators, we developed a multiparameter high-throughput platform to optimize voltage indicators for two-photon microscopy. Using this system, we identified JEDI-2P, an indicator that is faster, brighter, and more sensitive and photostable than its predecessors. We demonstrate that JEDI-2P can report light-evoked responses in axonal termini of Drosophila interneurons and the dendrites and somata of amacrine cells of isolated mouse retina. JEDI-2P can also optically record the voltage dynamics of individual cortical neurons in awake behaving mice for more than 30 min using both resonant-scanning and ULoVE random-access microscopy. Finally, ULoVE recording of JEDI-2P can robustly detect spikes at depths exceeding 400 µm and report voltage correlations in pairs of neurons.

State-dependent pupil dilation rapidly shifts visual feature selectivity.

To increase computational flexibility, the processing of sensory inputs changes with behavioural context. In the visual system, active behavioural states characterized by motor activity and pupil dilation1,2 enhance sensory responses, but typically leave the preferred stimuli of neurons unchanged2-9. Here we find that behavioural state also modulates stimulus selectivity in the mouse visual cortex in the context of coloured natural scenes. Using population imaging in behaving mice, pharmacology and deep neural network modelling, we identified a rapid shift in colour selectivity towards ultraviolet stimuli during an active behavioural state. This was exclusively caused by state-dependent pupil dilation, which resulted in a dynamic switch from rod to cone photoreceptors, thereby extending their role beyond night and day vision. The change in tuning facilitated the decoding of ethological stimuli, such as aerial predators against the twilight sky10. For decades, studies in neuroscience and cognitive science have used pupil dilation as an indirect measure of brain state. Our data suggest that, in addition, state-dependent pupil dilation itself tunes visual representations to behavioural demands by differentially recruiting rods and cones on fast timescales.

The Year in Cardiothoracic and Vascular Anesthesia: Selected Highlights from 2022.

This special article is the 15th in an annual series for the Journal of Cardiothoracic and Vascular Anesthesia. The authors thank the editor-in-chief Dr. Kaplan and the editorial board for the opportunity to continue this series, namely the research highlights of the past year in the specialties of cardiothoracic and vascular anesthesiology. The major themes selected for 2022 are outlined in this introduction, and each highlight is reviewed in detail in the main body of the article. The literature highlights, in the specialties for 2022, begin with an update on COVID-19 therapies, with a focus on the temporal updates in a wide range of therapies, progressing from medical to the use of extracorporeal membrane oxygenation and, ultimately, with lung transplantation in this high-risk group. The second major theme is focused on medical cardiology, with the authors discussing new insights into the life cycle of coronary disease, heart failure treatments, and outcomes related to novel statin therapy. The third theme is focused on mechanical circulatory support, with discussions focusing on both right-sided and left-sided temporary support outcomes and the optimal timing of deployment. The fourth and final theme is an update on cardiac surgery, with a discussion of the diverse aspects of concomitant valvular surgery and the optimal approach to procedural treatment for coronary artery disease. The themes selected for this 15th special article are only a few of the diverse advances in the specialties during 2022. These highlights will inform the reader of key updates on a variety of topics, leading to the improvement of perioperative outcomes for patients with cardiothoracic and vascular disease.

Spatial Interactions in Interocular and Monocular "Blur Suppression".

SIGNIFICANCE: The suppression of blurred images in one eye by clear images in the other eye is thought to contribute to the success of monovision correction. We show that interocular suppression occurs also for low-contrast targets that are not blurred and, to a lesser extent, when clear and low-contrast targets are presented to the same eye. PURPOSE: A blurred target presented to one eye may be suppressed when a clear target is presented to the other eye. We sought to determine how this interocular suppression varies according to the separation between the blurred and clear targets and the magnitude of imposed blur. In addition, we examined whether a similar suppression occurs when the clear and blurred targets are imaged in the same eye. METHODS: Subjects (N = 4) viewed a clear 20/40 Sloan letter surrounded by four 2 × 10 min-arc flanking bars. In different blocks of trials, the gap between the letter and flanking bars varied from 0.5 to 4 bar widths. In addition, the flanking bars were either clear or spatially filtered to simulate 0.5 to 2 D of blur. The contrast required to detect the flanking bars was determined when the letter and flanking bars were presented either dichoptically or monoptically and compared with the thresholds for the bar targets presented alone. RESULTS: In both dichoptic and monoptic viewing conditions, detection thresholds for the blurred flanking bars are highest for the smallest spatial gap and decrease systematically as the gap increases. Thresholds are uniformly higher during dichoptic than monocular viewing, but the proportional change with the bar-to-letter separation is similar in both conditions. Surprisingly, the magnitude of imposed blur has very little influence on the magnitude of threshold elevation in either the dichoptic or monoptic viewing conditions. CONCLUSIONS: Because threshold elevation is nearly the same in the presence of 0 to 2 D of blur, we prefer to designate the phenomenon we studied as "contrast suppression." The similar spatial characteristics of suppression during dichoptic and monoptic viewing are consistent with contributions from a common neural mechanism.

The Year in Graduate Medical Education: Selected Highlights From 2021.

This special article is the first in a planned annual series for the Journal of Cardiothoracic and Vascular Anesthesia that will highlight significant literature from the world of graduate medical education (GME) that was published over the past year. The major themes selected for this inaugural review are the educational value of simulation and training workshops, the expanding role of social media and other information technologies in GME and recruitment, the state of residency and fellowship training before the COVID-19 pandemic, and the inevitable effects COVID-19 has had on graduate medical education. The authors would like to thank the editorial board for allowing us to shine a light on a small subset of the writing and research produced in this field, so that educators may understand how best to educate and train the next generation of anesthesiologists.

The Year in Cardiothoracic and Vascular Anesthesia: Selected Highlights from 2021.

This special article is the fourteenth in an annual series for the Journal of Cardiothoracic and Vascular Anesthesia. The authors thank the Editor-in-Chief, Dr. Kaplan, and the editorial board for the opportunity to continue this series; namely, the research highlights of the past year in the specialty of cardiothoracic and vascular anesthesiology. The major themes selected for 2021 are outlined in this introduction, and each highlight is reviewed in detail in the main body of the article. The literature highlights in the specialty for 2021 begin with an update on structural heart disease, with a focus on updates in arrhythmia and aortic valve disorders. The second major theme is an update on coronary artery disease, with discussion of both medical and procedural management. The third major theme is focused on the perioperative management of patients with COVID-19, with the authors highlighting literature discussing the impact of the disease on the right ventricle and thromboembolic events. The fourth and final theme is an update in heart failure, with discussion of diverse aspects of this area. The themes selected for this fourteenth special article are only a few of the diverse advances in the specialty during 2021. These highlights will inform the reader of key updates on a variety of topics, leading to improvement of perioperative outcomes for patients with cardiothoracic and vascular disease.

Reducing Opioid Use in Patients Undergoing Cardiac Surgery - Preoperative, Intraoperative, and Critical Care Strategies.

Patients undergoing cardiothoracic surgery are exposed to opioids in the operating room and intensive care unit and after hospital discharge. Opportunities exist to reduce perioperative opioid use at all stages of care and include alternative oral and intravenous medications, novel intraoperative regional anesthetic techniques, and postoperative opioid-sparing sedative and analgesic strategies. In this review, currently used and investigational strategies to reduce the opioid burden for cardiothoracic surgical patients are explored.

The Year in Cardiothoracic and Vascular Anesthesia: Selected Highlights from 2020.

THIS SPECIAL article is the 13th in an annual series for the Journal of Cardiothoracic and Vascular Anesthesia. The authors thank the editor-in-chief, Dr Kaplan, and the editorial board for the opportunity to continue this series; namely, the research highlights of the past year in the specialty of cardiothoracic and vascular anesthesiology.1 The major themes selected for 2020 are outlined in this introduction, and each highlight is reviewed in detail in the main body of the article. The literature highlights in the specialty for 2020 begin with an update on valvular disease, with a focus on updates in management of aortic and mitral valve disorders. The second major theme is an update on coronary artery disease, with discussion of both medical and surgical management. The third major theme is focused on the perioperative management of patients with coronavirus disease 2019 (COVID-19), with the authors highlighting literature discussing medical, surgical, and anesthetic considerations for their cardiac care. The fourth major theme is an update in heart failure, with discussion of medical, psychosocial, and procedural aspects of this complicated disease process. The fifth and final theme focuses on the latest analyses regarding survival in heart transplantation. The themes selected for this 13th special article are only a few of the diverse advances in the specialty during 2020. These highlights will inform the reader of key updates on a variety of topics, leading to improvement of perioperative outcomes for patients with cardiothoracic and vascular disease.

Plasma of Acute Lymphoblastic Leukemia Patients React to the Culture of a Mycovirus Containing Aspergillus flavus.

Acute lymphoblastic leukemia (ALL) is the most common cancer in children and is also seen in adults. Currently, no plasma-based test for the detection of ALL is available. We have cultured the home of a patient with ALL and isolated a mycovirus containing Aspergillus flavus. This culture was subjected to electron microscopy, purification, and mass spectrometry. Using enzyme-linked immunosorbent assay technique, plasma of patients with ALL and long-term survivors of this disease were tested for antibodies, utilizing supernatant of the culture of this organism. The results were compared with 3 groups of controls, including healthy individuals, patients with sickle cell disease, and solid tumors. Using electron microscopy, the isolated A. flavus contained mycovirus particles. In chemical analysis, this organism did not produce any aflatoxin. Using an enzyme-linked immunosorbent assay technique, the supernatant of the culture of the mycovirus containing A. flavus could differentiate ALL patients from each group of controls (P<0.001). These studies provide a new technique for the detection of ALL and may add information for future research regarding leukemogenesis.

Differential benefits of olanzapine on executive function in schizophrenia patients: Preliminary findings.

OBJECTIVE: Schizophrenia patients show executive function (EF) impairments in voluntary orienting as measured by eye-movements. We tested 14 inpatients to investigate the effects of the antipsychotic olanzapine on EF, as measured by antisaccade eye-movement performance. METHODS: Patients were tested at baseline (before olanzapine), 3-5 days post-medication, and 12-14 days post-medication. Patients were also assessed on the Positive and Negative Syndrome Scale (PANSS) to measure the severity of schizophrenia-related symptoms, and administered the Stroop task, a test of EF. Nine matched controls were also tested on the antisaccade and Stroop. RESULTS: Both groups showed improvement on Stroop and antisaccade; however, the schizophrenia group improved significantly more on antisaccade, indicating an additional benefit of olanzapine on EF performance. Patients with poorer baseline antisaccade performance (High-Deficit) showed significantly greater improvement on the antisaccade task than patients with better baseline performance (Low-Deficit), suggesting that baseline EF impairment predicts the magnitude of cognitive improvement with olanzapine. These subgroups showed significant and equivalent improvement on PANSS scores, indicating that improvement on the antisaccade task with olanzapine was not a result of differences in magnitude of clinical improvement. CONCLUSIONS: This preliminary study provides evidence that olanzapine may be most advantageous for patients with greater baseline EF deficits.

Pilot Study Suggests Smartphone Application Knowledge Improves Resident Transesophageal Echocardiography Knowledge: A Randomized Controlled Trial.

OBJECTIVE: The objective of this study was to determine whether an asynchronous smartphone-based application with image-based questions would improve anesthesiology resident transesophageal echocardiography (TEE) knowledge compared with standard intraoperative teaching alone. DESIGN: Prospective, single-blinded, pilot, randomized controlled trial. SETTING: Large university teaching hospital. PARTICIPANTS: Participants were anesthesiology residents on their cardiac anesthesiology rotation. INTERVENTIONS: EchoEducator, a TEE image-based smartphone application of learning content through questions, was developed. Content was derived from the Examination of Special Competence in Basic Perioperative Transesophageal Echocardiography and the Objective Structured Clinical Examination portion of the APPLIED Examination and focused on identification of basic TEE views, cardiac structures, and pathology. Residents were randomly assigned to receive access to either the application or to standard intraoperative teaching. Thirty residents met inclusion criteria, and 18 residents completed the study. A pre-intervention assessment was given at the beginning of the rotation, and a post-intervention assessment was given after 2 weeks. MEASUREMENTS: The primary outcome was the difference between the post-test score and the pre-test score. Standard bivariate statistics and the chi-square test were used for categorical variables, and the Student t test was used for continuous variables. Tests were 2-sided, and statistical significance was set at p < 0.05. The intervention group demonstrated a greater increase in score; (+19.19% [95% confidence interval 4.14%-34.24%]; p = 0.02) compared with the control group. CONCLUSIONS: This study supports the hypothesis that use of a smartphone-based asynchronous educational application improves TEE knowledge compared with traditional modalities alone. This supports an opportunity to improve medical education by expanding the role of web-based asynchronous learning.

Faster processing of moving compared with flashed bars in awake macaque V1 provides a neural correlate of the flash lag illusion.

When the brain has determined the position of a moving object, because of anatomical and processing delays the object will have already moved to a new location. Given the statistical regularities present in natural motion, the brain may have acquired compensatory mechanisms to minimize the mismatch between the perceived and real positions of moving objects. A well-known visual illusion-the flash lag effect-points toward such a possibility. Although many psychophysical models have been suggested to explain this illusion, their predictions have not been tested at the neural level, particularly in a species of animal known to perceive the illusion. To this end, we recorded neural responses to flashed and moving bars from primary visual cortex (V1) of awake, fixating macaque monkeys. We found that the response latency to moving bars of varying speed, motion direction, and luminance was shorter than that to flashes, in a manner that is consistent with psychophysical results. At the level of V1, our results support the differential latency model positing that flashed and moving bars have different latencies. As we found a neural correlate of the illusion in passively fixating monkeys, our results also suggest that judging the instantaneous position of the moving bar at the time of flash-as required by the postdiction/motion-biasing model-may not be necessary for observing a neural correlate of the illusion. Our results also suggest that the brain may have evolved mechanisms to process moving stimuli faster and closer to real time compared with briefly appearing stationary stimuli. NEW & NOTEWORTHY We report several observations in awake macaque V1 that provide support for the differential latency model of the flash lag illusion. We find that the equal latency of flash and moving stimuli as assumed by motion integration/postdiction models does not hold in V1. We show that in macaque V1, motion processing latency depends on stimulus luminance, speed and motion direction in a manner consistent with several psychophysical properties of the flash lag illusion.

Stroke After Transcatheter Aortic Valve Replacement: Incidence, Definitions, Etiologies and Management Options.

Neurologic complications after transcatheter aortic valve replacement are devastating. The etiologies of stroke in this setting are best addressed in an integrated fashion during each phase of the perioperative pathway. The conduct of this triphasic approach will continue to be refined to reduce the stroke risks even further, given the major focus on aspects such as embolic protection devices and valve thrombosis. This neurologic focus in transcatheter aortic valve replacement has transformed the investigational approach to neurologic events in cardiovascular clinical trials, resulting in novel guidelines for the diagnosis and assessment of neurologic injury after cardiovascular interventions.