The functional neuroanatomy resource (FNAR) at Weill Cornell Medicine

INTRODUCTION. Computer assisted instruction has long proven useful in teaching of neuroanatomy, particularly when accompanied by traditional lecture presentations that present image and text data to students. The work describes the functional neuroanatomy resource (FNAR) innovation created at Weill Cornell Medicine – the first homegrown functional neuroanatomy teaching application developed for iPads by a medical school, including the learning options actively utilized by students and plans for continued development of the app. RESOURCES. Previously the teaching of functional neuroanatomy has relied heavily on gross brain and histological material created at the medical college and presented through computer technology initially server-based and then web-based. When the institution decided to move students to mobile devices, all students were provided with iPads. The functional neuroanatomy faculty and educational computing team accepted the challenge to make the FNAR content available through an iPad app. DESCRIPTION. This first local FNAR app integrates and indexes an image database along with various text resources. The app utilizes mouse-over and overlay technology, allowing users to easily highlight and select different areas of the brain and spinal cord and their related structures; it allows students to access the self-assessment tools onto the image overlays so that students can test their knowledge as they progress. CONCLUSIONS. A recent student evaluation reflects students rating the overall quality and usefulness of the FNAR as “excellent” (3.85 on a 4-point scale). Future plans include incorporating radiographic images and an “on-the-fly image set” technology, allowing students to query the database specifically designed to answer their questions

GRB 221009A, The BOAT

GRB 221009A has been referred to as the Brightest Of All Time (the BOAT). We investigate the veracity of this statement by comparing it with a half century of prompt gamma-ray burst observations. This burst is the brightest ever detected by the measures of peak flux and fluence. Unexpectedly, GRB 221009A has the highest isotropic-equivalent total energy ever identified, while the peak luminosity is at the $\sim99$th percentile of the known distribution. We explore how such a burst can be powered and discuss potential implications for ultra-long and high-redshift gamma-ray bursts. By geometric extrapolation of the total fluence and peak flux distributions GRB 221009A appears to be a once in 10,000 year event. Thus, while it almost certainly not the BOAT over all of cosmic history, it may be the brightest gamma-ray burst since human civilization began.Comment: Resubmitted to ApJ

Deep Multimessenger Search for Compact Binary Mergers in LIGO, Virgo, and Fermi/GBM Data from 2016–2017

GW170817–GRB 170817A provided the first observation of gravitational waves from a neutron star merger with associated transient counterparts across the entire electromagnetic spectrum. This discovery demonstrated the long-hypothesized association between short gamma-ray bursts and neutron star mergers. More joint detections are needed to explore the relation between the parameters inferred from the gravitational wave and the properties of the gamma-ray burst signal. We developed a joint multimessenger analysis of LIGO, Virgo, and Fermi/GBM data designed for detecting weak gravitational-wave transients associated with weak gamma-ray bursts. As such, it does not start from confident (GWTC-1) events only. Instead, we take the full list of existing compact binary coalescence triggers generated with the PyCBC pipeline from the second Gravitational-Wave Observing Run (O2), and reanalyze the entire set of public Fermi/GBM data covering this observing run to generate a corresponding set of gamma-ray burst candidate triggers. We then search for coincidences between the gravitational-wave and gamma-ray burst triggers without requiring a confident detection in any channel. The candidate coincidences are ranked according to a statistic combining each candidate’s strength in gravitational-wave and gamma-ray data, their time proximity, and the overlap of their sky localization. The ranking is then converted to a false alarm rate using time shifts between the gravitational-wave and gamma-ray burst triggers. We present the results using O2 triggers, which allowed us to check the validity of our method against GW170817–GRB 170817A. We also discuss the different configurations tested to maximize the significance of the joint detection

Smoking is associated with increased risk of cardiovascular events, disease severity, and mortality among patients hospitalized for SARS-CoV-2 infections.

The clinical sequalae of SARS-CoV-2 infection are in part dependent upon age and pre-existing health conditions. Although the use of tobacco products decreases cardiorespiratory fitness while increasing susceptibility to microbial infections, limited information is available on how smoking affects COVID-19 severity. Therefore, we examined whether smokers hospitalized for COVID-19 are at a greater risk for developing severe complications than non-smokers. Data were from all hospitalized adults with SARS-CoV-2 infection from the American Heart Association's Get-With-The-Guidelines COVID-19 Registry, from January 2020 to March 2021, which is a hospital-based voluntary national registry initiated in 2019 with 122 participating hospitals across the United States. Patients who reported smoking at the time of admission were classified as smokers. Severe outcome was defined as either death or the use of mechanical ventilation. Of the 31,545 patients in the cohort, 6,717 patients were 1:2 propensity matched (for age, sex, race, medical history, medications, and time-frame of hospital admission) and classified as current smokers or non-smokers according to admission data. In multivariable analyses, after adjusting for sociodemographic characteristics, medical history, medication use, and the time of hospital admission, patients self-identified as current smokers had higher adjusted odds of death (adjusted odds ratio [aOR], 1.41; 95% CI, 1.21-1.64), the use of mechanical ventilation (aOR 1.15; 95% CI 1.01-1.32), and increased risk of major adverse cardiovascular events (aOR, 1.27; 95% CI 1.05-1.52). Independent of sociodemographic characteristics and medical history, smoking was associated with a higher risk of severe COVID-19, including death

Smoking is associated with increased risk of cardiovascular events, disease severity, and mortality among patients hospitalized for SARS-CoV-2 infections.

The clinical sequalae of SARS-CoV-2 infection are in part dependent upon age and pre-existing health conditions. Although the use of tobacco products decreases cardiorespiratory fitness while increasing susceptibility to microbial infections, limited information is available on how smoking affects COVID-19 severity. Therefore, we examined whether smokers hospitalized for COVID-19 are at a greater risk for developing severe complications than non-smokers. Data were from all hospitalized adults with SARS-CoV-2 infection from the American Heart Association's Get-With-The-Guidelines COVID-19 Registry, from January 2020 to March 2021, which is a hospital-based voluntary national registry initiated in 2019 with 122 participating hospitals across the United States. Patients who reported smoking at the time of admission were classified as smokers. Severe outcome was defined as either death or the use of mechanical ventilation. Of the 31,545 patients in the cohort, 6,717 patients were 1:2 propensity matched (for age, sex, race, medical history, medications, and time-frame of hospital admission) and classified as current smokers or non-smokers according to admission data. In multivariable analyses, after adjusting for sociodemographic characteristics, medical history, medication use, and the time of hospital admission, patients self-identified as current smokers had higher adjusted odds of death (adjusted odds ratio [aOR], 1.41; 95% CI, 1.21-1.64), the use of mechanical ventilation (aOR 1.15; 95% CI 1.01-1.32), and increased risk of major adverse cardiovascular events (aOR, 1.27; 95% CI 1.05-1.52). Independent of sociodemographic characteristics and medical history, smoking was associated with a higher risk of severe COVID-19, including death

Chronic E-Cigarette Use Impairs Endothelial Function on the Physiological and Cellular Levels.

BACKGROUND: The harmful vascular effects of smoking are well established, but the effects of chronic use of electronic cigarettes (e-cigarettes) on endothelial function are less understood. We hypothesized that e-cigarette use causes changes in blood milieu that impair endothelial function. METHODS: Endothelial function was measured in chronic e-cigarette users, chronic cigarette smokers, and nonusers. We measured effects of participants sera, or e-cigarette aerosol condensate, on NO and H2O2 release and cell permeability in cultured endothelial cells (ECs). RESULTS: E-cigarette users and smokers had lower flow-mediated dilation (FMD) than nonusers. Sera from e-cigarette users and smokers reduced VEGF (vascular endothelial growth factor)-induced NO secretion by ECs relative to nonuser sera, without significant reduction in endothelial NO synthase mRNA or protein levels. E-cigarette user sera caused increased endothelial release of H2O2, and more permeability than nonuser sera. E-cigarette users and smokers exhibited changes in circulating biomarkers of inflammation, thrombosis, and cell adhesion relative to nonusers, but with distinct profiles. E-cigarette user sera had higher concentrations of the receptor for advanced glycation end products (RAGE) ligands S100A8 and HMGB1 (high mobility group box 1) than smoker and nonuser sera, and receptor for advanced glycation end product inhibition reduced permeability induced by e-cigarette user sera but did not affect NO production. CONCLUSIONS: Chronic vaping and smoking both impair FMD and cause changes in the blood that inhibit endothelial NO release. Vaping, but not smoking, causes changes in the blood that increase microvascular endothelial permeability and may have a vaping-specific effect on intracellular oxidative state. Our results suggest a role for RAGE in e-cigarette-induced changes in endothelial function

Evaluating the effects of pod-based electronic cigarettes on human endothelial cell function

Pod-based electronic (e-) cigarettes more efficiently deliver nicotine using a protonated formulation. The cardiovascular effects associated with these devices are poorly understood. We evaluated whether pod-based e-liquids and their individual components impair endothelial cell function. We isolated endothelial cells from people who are pod users (n=10), tobacco never users (n=7), and combustible cigarette users (n=6). After a structured use, pod users had lower acetylcholine-mediated endothelial nitric oxide synthase (eNOS) activation compared with never users and was similar to levels from combustible cigarette users (overall P=0.008, P=0.01 pod vs never; P=0.96 pod vs combustible cigarette). The effects of pod-based e-cigarettes and their constituents on vascular cell function were further studied in commercially available human aortic endothelial cells (HAECs) incubated with flavored JUUL e-liquids or propylene glycol (PG):vegetable glycerol (VG) at 30:70 ratio with or without 60 mg/mL nicotine salt for 90 min. A progressive increase in cell death with JUUL e-liquid exposure was observed across 0.0001-1% dilutions; PG:VG vehicle with and without nicotine salt-induced cell death. A23187-stimulated nitric oxide production was decreased with all JUUL e-liquid flavors, PG:VG and nicotine salt exposures. Aerosols generated by JUUL e-liquid heating similarly decreased stimulated nitric oxide production. Only mint-flavored e-liquids increased inflammation and menthol-flavored e-liquids enhanced oxidative stress in HAECs. In conclusion, pod e-liquids and their individual components appear to impair endothelial cell function. These findings indicate the potential harm of pod-based devices on endothelial cell function and thus may be relevant to cardiovascular injury in pod-type e-cigarette users.Funding provided by: National Heart, Lung, and Blood InstituteCrossref Funder Registry ID: http://dx.doi.org/10.13039/100000050Award Number: 5P50HL120163Funding provided by: National Heart, Lung, and Blood InstituteCrossref Funder Registry ID: http://dx.doi.org/10.13039/100000050Award Number: U54HL120163Funding provided by: American Heart AssociationCrossref Funder Registry ID: http://dx.doi.org/10.13039/100000968Award Number: 20YVNR35500014Funding provided by: National Heart, Lung, and Blood InstituteCrossref Funder Registry ID: http://dx.doi.org/10.13039/100000050Award Number: K01 HL14314

Chronic E-Cigarette Use Impairs Endothelial Function on the Physiological and Cellular Levels

BackgroundThe harmful vascular effects of smoking are well established, but the effects of chronic use of electronic cigarettes (e-cigarettes) on endothelial function are less understood. We hypothesized that e-cigarette use causes changes in blood milieu that impair endothelial function.MethodsEndothelial function was measured in chronic e-cigarette users, chronic cigarette smokers, and nonusers. We measured effects of participants' sera, or e-cigarette aerosol condensate, on NO and H2O2 release and cell permeability in cultured endothelial cells (ECs).ResultsE-cigarette users and smokers had lower flow-mediated dilation (FMD) than nonusers. Sera from e-cigarette users and smokers reduced VEGF (vascular endothelial growth factor)-induced NO secretion by ECs relative to nonuser sera, without significant reduction in endothelial NO synthase mRNA or protein levels. E-cigarette user sera caused increased endothelial release of H2O2, and more permeability than nonuser sera. E-cigarette users and smokers exhibited changes in circulating biomarkers of inflammation, thrombosis, and cell adhesion relative to nonusers, but with distinct profiles. E-cigarette user sera had higher concentrations of the receptor for advanced glycation end products (RAGE) ligands S100A8 and HMGB1 (high mobility group box 1) than smoker and nonuser sera, and receptor for advanced glycation end product inhibition reduced permeability induced by e-cigarette user sera but did not affect NO production.ConclusionsChronic vaping and smoking both impair FMD and cause changes in the blood that inhibit endothelial NO release. Vaping, but not smoking, causes changes in the blood that increase microvascular endothelial permeability and may have a vaping-specific effect on intracellular oxidative state. Our results suggest a role for RAGE in e-cigarette-induced changes in endothelial function

Updates to the Fermi GBM Targeted Sub-threshold Search in Preparation for the Third Observing Run of LIGO/Virgo

In this document, we detail the improvements made to the Fermi GBM targeted sub-threshold search for counterparts to LIGO/Virgo gravitational-wave triggers. We describe the implemented changes and compare the sensitivity of the O3 search to that of the version of the search that operated during O2. Overall, we have improved both the sensitivity and speed of the targeted search. Further improvements to the search have been made for the O3b observing run, including automated upperlimits estimation and incorporating the updated localization systematic with the new version of the search

Determination of oxidative stress using MitoSOX.

The representative images show two replicates for control, menthol, and mint treated HAECs for 90 minutes and loaded with MitoSOX. (TIF)</p