31 research outputs found

    SARS-CoV-2 infection causes dopaminergic neuron senescence

    Get PDF
    COVID-19 patients commonly present with signs of central nervous system and/or peripheral nervous system dysfunction. Here, we show that midbrain dopamine (DA) neurons derived from human pluripotent stem cells (hPSCs) are selectively susceptible and permissive to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. SARS-CoV-2 infection of DA neurons triggers an inflammatory and cellular senescence response. High-throughput screening in hPSC-derived DA neurons identified several FDA-approved drugs that can rescue the cellular senescence phenotype by preventing SARS-CoV-2 infection. We also identified the inflammatory and cellular senescence signature and low levels of SARS-CoV-2 transcripts in human substantia nigra tissue of COVID-19 patients. Furthermore, we observed reduced numbers of neuromelanin+ and tyrosine-hydroxylase (TH)+ DA neurons and fibers in a cohort of severe COVID-19 patients. Our findings demonstrate that hPSC-derived DA neurons are susceptible to SARS-CoV-2, identify candidate neuroprotective drugs for COVID-19 patients, and suggest the need for careful, long-term monitoring of neurological problems in COVID-19 patients.</p

    SARS-CoV-2 infection causes dopaminergic neuron senescence

    Get PDF
    COVID-19 patients commonly present with signs of central nervous system and/or peripheral nervous system dysfunction. Here, we show that midbrain dopamine (DA) neurons derived from human pluripotent stem cells (hPSCs) are selectively susceptible and permissive to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. SARS-CoV-2 infection of DA neurons triggers an inflammatory and cellular senescence response. High-throughput screening in hPSC-derived DA neurons identified several FDA-approved drugs that can rescue the cellular senescence phenotype by preventing SARS-CoV-2 infection. We also identified the inflammatory and cellular senescence signature and low levels of SARS-CoV-2 transcripts in human substantia nigra tissue of COVID-19 patients. Furthermore, we observed reduced numbers of neuromelanin+ and tyrosine-hydroxylase (TH)+ DA neurons and fibers in a cohort of severe COVID-19 patients. Our findings demonstrate that hPSC-derived DA neurons are susceptible to SARS-CoV-2, identify candidate neuroprotective drugs for COVID-19 patients, and suggest the need for careful, long-term monitoring of neurological problems in COVID-19 patients.</p

    Factors Associated with Revision Surgery after Internal Fixation of Hip Fractures

    Get PDF
    Background: Femoral neck fractures are associated with high rates of revision surgery after management with internal fixation. Using data from the Fixation using Alternative Implants for the Treatment of Hip fractures (FAITH) trial evaluating methods of internal fixation in patients with femoral neck fractures, we investigated associations between baseline and surgical factors and the need for revision surgery to promote healing, relieve pain, treat infection or improve function over 24 months postsurgery. Additionally, we investigated factors associated with (1) hardware removal and (2) implant exchange from cancellous screws (CS) or sliding hip screw (SHS) to total hip arthroplasty, hemiarthroplasty, or another internal fixation device. Methods: We identified 15 potential factors a priori that may be associated with revision surgery, 7 with hardware removal, and 14 with implant exchange. We used multivariable Cox proportional hazards analyses in our investigation. Results: Factors associated with increased risk of revision surgery included: female sex, [hazard ratio (HR) 1.79, 95% confidence interval (CI) 1.25-2.50; P = 0.001], higher body mass index (fo

    Vision Guided Lane Transition

    Full text link
    Many systems have been created which can keep an autonomous vehicle within a driving lane, but little experimental work has been reported that describes methods to transition a vehicle between lanes. Three techniques to accomplish lane transition using the ALVINN lane keeping system are reported here. The most basic involves intelligently switching between two trained ALVINN networks. The other techniques use active control of virtual camera views to move the vehicle into the destination lane. Introduction Much progress has been made toward solving the autonomous lane keeping problem using vision-based methods. Systems have been demonstrated which can drive robot vehicles at high speeds for long distances. The current challenge for vision-based on-road navigation researchers is to create systems that maintain the performance of the existing lane-keeping systems, while adding the ability to execute tactical level driving tasks like transitioning from one lane to another. Lane transiti..

    Automated Highways And The Free Agent Demonstration

    Full text link
    In August of 1997, The US National Automated Highway System Consortium (NAHSC) presented a proof of technical feasibility demonstration of automated driving. The 97 Demo took place on car-pool lanes on I15 in San Diego, California. Members of the Consortium demonstrated many different functions, including: Vision-based road following Lane departure warning Magnetic nail following Radar reflective strip following Radar-based headway maintenance Ladar-based headway maintenance Partial automation and evolutionary systems Close vehicle following (platooning) Cooperative maneuvering Obstacle detection and avoidance Mixed automated and manual driving Mixed automated cars and buses Semi-automated maintenance operations Carnegie Mellon University (CMU) led the effort to build the Free Agent Demonstration (FAD). The FAD involved two fully-automated cars, one partially-automated car, and two fullyautomated city buses. The scenario demonstrated speed and headway control, lane follow..
    corecore