Activity

Coronavirus disease 2019 (COVID-19) is a pandemic that started in China in December 2019 and carries a high risk of morbidity and mortality. To-date (4-22-2020) it affected over 2.6 million people and resulted in nearly 200,000 death worldwide mainly due to severe acute respiratory syndrome coronavirus 2 (SARS-Cov-2). Among the major underlying pathophysiologic mechanisms in COVID 19 is hypercoagulability, leading to increased risk for deep vein thrombosis and pulmonary embolism that contribute to increased morbidity and mortality. In this report, we present the case of a 55-year-old man who presented with COVID-19 pneumonia, and was found to have a thrombus in transit by routine point of care ultrasound (POCUS). While computer tomography (CT) angiography is the test of choice, the utilization of point of care ultrasound (POCUS) has gained traction as an adjunctive means of surveillance for the development of VTE in patients with COVID-19. In this report, we discuss the clinical utility of POCUS in diagnosing thrombus in transit in COVID 19 populations.Right-sided aortic arch with aberrant left subclavian artery is a rare variant of vascular anatomy. Three types of right-sided aortic arches are described and classified based on the arrangement of the aortic arch vessels, the presence or absence of congenital heart abnormalities, the relationship of the aortic arch to the trachea and esophagus, as well as the presence or absence of a complete or incomplete vascular ring. On review of the existing literature, 31 case reports were found with a spectrum of clinical presentation sand outcomes. In this case report, we highlight a case of a young female in her early 20’swho presented with choking spells, shortness of breath along with intermittent dysphagia since childhood. She was otherwise healthy and pregnant at 26 weeks gestational age. A Computed tomography scan with angiography (CTA) of the thorax was performed to rule out a pulmonary embolism (PE) however surprisingly, a right-sided aortic arch with aberrant left subclavian artery was revealed instead. Subsequently, an extensive literature review was carried out to better understand clinical presentation sand treatment strategies for this rather rare disorder.Caveolae are membrane organelles formed by submicron invaginations in the plasma membrane, and are involved in mechanosensing, cell signaling, and endocytosis. Although implicated broadly in physiology and pathophysiology, better tools are required to elucidate the precise role of caveolar processes through selective activation and inactivation of their trafficking. Our group recently reported that thermally-responsive elastin-like polypeptides (ELPs) can trigger formation of ‘genetically engineered protein microdomains (GEPMs)’ functionalized with either Clathrin-light chain or the epidermal growth factor receptor. Cobimetinib mw This manuscript is the first report of this strategy to modulate caveolin-1 (CAV1). By attaching different ELP sequences to CAV1, mild heating can be used to self-assemble CAV1-ELP microdomains inside of cells. The temperature of self-assembly can be controlled by tuning the ELP sequence. The formation of CAV1-ELP microdomains internalizes Cholera Toxin Subunit B, a commonly used marker of caveolae mediated endocytosis. CAV1-ELPs also colocalize with Cavin 1, an essential component of functional caveolae biogenesis. With the emerging significance of caveolae in health and disease and the lack of specific probes to rapidly and reversibly affect caveolar function, CAV1-ELP microdomains are a new tool to rapidly probe caveolae associated processes in endocytosis, cell signaling, and mechanosensing.Direct visualization of the key features of coronavirus genomes can lead to a better understanding of this virus as well as a method to distinguish this type of virus from others. The DNA nucleotide footprint plotter is a tool that makes it possible for straightforward visualization of the characteristics of viral genomes. It can also distinguish different gene types and gene structures. The current project provides a novel tool for biological studies that can contribute to breakthroughs in coronavirus diagnosis, treatment, and prevention.Background Currently lung injury is managed conservatively through supportive care including mechanical ventilation. However, mechanical ventilation can also cause additional lung injury due to over-stretch along with atelectasis and cytokine release. Here we developed an in vitro mechanical ventilation model using cyclic stretch of lung epithelial cells to mimic high and low tidal volume (TV) ventilation strategy, so that we could use this platform for pathophysiology analysis and screening for therapeutic drugs. Method We subjected MLE-15 cells to the following treatments. 1) No treatment, 2) lipopolysaccharide (100 ng/mL) stimulation for 24 hours, 3) mechanical stretch initiated at 6-hour time point for 18 hours, 4) LPS stimulation at time point 0 hour, and mechanical stretch was added at 6-hour time point for 18 hours. Biaxial cyclic stretch with a triangular wave was given via the Flexcell FX-6000 tension system to mimic low and high TV. Anesthetics dexmedetomidine and propofol were also tested. Result Our high TV mimic stretch increased cell death, while low TV mimic stretch did not affect the degree of cell death. Using this system, we examined the effect of sedatives commonly used in intensive care units on cell death and found that dexmedetomidine attenuated necrosis associated with stretch. Conclusion We described the in vitro cyclic stretch system mimicking high and low TV ventilation. High TV mimetic was associated with increased cell death. Dexmedetomidine attenuated the degree of cell death.The chronic ocular toxicity, tolerability, and inflammation following corneal intrastromal injection of saline or escalating doses of an adeno-associated virus (AAV) containing a codon-optimized α-l-iduronidase (AAV-opt-IDUA) expression cassette were evaluated in New Zealand White rabbits. Corneal opacity following corneal intrastromal injection resolved by 24 h. Mild elevation of clinical ocular inflammation was observed 24 h after injection, but it returned to baseline by day 7 and no abnormalities were noted through 6 months of observation after injection. Vector genomes and IDUA cDNA were detected in the injected corneas in a dose-dependent manner. Both the lowest administered AAV-opt-IDUA dose, shown to be effective in mucopolysaccharidosis type I (MPS I) dogs, and a 10-fold higher dose of AAV-opt-IDUA resulted in no detectable immunologic response or adverse effect in rabbits. Vector genomes outside of the eye were rarely detected following corneal intrastromal injection of AAV-opt-IDUA, and neutralizing antibodies to the AAV capsid were not present at the experimental conclusion. This study, combined with our previous studies in MPS I dogs, suggests that AAV-opt-IDUA corneal gene therapy following corneal intrastromal injection of AAV-opt-IDUA has the potential to prevent and reverse blindness in MPS I patients in a safe and effective manner.Thermodynamic integration (TI), a powerful formalism for computing Gibbs free energy, has been implemented for many biophysical processes with alchemical schemes that require delicate human efforts to choose/design biasing potentials for sampling the desired biophysical events and to remove their artifactitious consequences afterwards. Theoretically, an alchemical scheme is exact but practically, an unsophisticated implementation of this exact formula can cause error amplifications. Small relative errors in the input parameters can be amplified many times in their propagation into the computed free energy [due to subtraction of similar numbers such as (105 ± 5)‒(100 ± 5) = 5 ± 7]. In this paper, we present an unsophisticated implementation of TI in 3n dimensions (3nD) (n=1,2,3…) for the potential of mean force along a 3nD path connecting one state in the bound state ensemble to one state in the unbound state ensemble. Fluctuations in these 3nD are integrated in the bound and unbound state ensembles but not along the 3nD path. Using TI3nD, we computed the standard binding free energies of three protein complexes trometamol in Salmonella effector SpvD (n=1), biotin-avidin (n=2), and Colicin E9 endonuclease with cognate immunity protein Im9 (n=3). We employed three different protocols in three independent computations of E9-Im9 to show TI3nD’s robustness. We also computed the hydration energies of ten biologically relevant compounds (n=1 for water, acetamide, urea, glycerol, trometamol, ammonium and n=2 for erythritol, 1,3-propanediol, xylitol, biotin). Each of the 15 computations is accomplishable within one (for hydration) to ten (for E9-Im9) days on an inexpensive GPU workstation. The computed results all agree with the available experimental data.Background The novel coronavirus, SARS-CoV-2, has been responsible for the devastation of hundreds of thousands of lives directly and has caused disruptions globally. Vulnerable populations, specifically those suffering from serious mental illness and homelessness, are at higher risk of contracting COVID-19 infection resulting in medical complications and psychiatric destabilization. In addition, mental health has become increasingly relevant throughout the country given the psychological distress people have been facing due to the spread of COVID-19 and the toll of a more restricted way of living. Although the healthcare industry has quickly integrated novel ways of treating patients with mental illness with technological advances, these technologies are not applicable to different populations equally. There is a clear disparity that is represented within the public county health systems, which leads to a widening gap between those who receive adequate treatment for mental illness and those who do not. Aims ates, serve as a rationale for the need of innovative solutions for the integration of these services in not only emergency situations such as the COVID-19 pandemic, but also in daily non-emergent operations to sufficiently address the needs for those needing mental healthcare.Background The end plate plays an important role in intervertebral disc degeneration progression. The aim of the study was to examine the compositional and structural changes of the end plate with age and to investigate the correlation between end plate and disc degeneration by T1ρ and T2 map magnetic resonance imaging. Methods There were 12 young monkeys (6-7 years old), 20 aged monkeys (14-17 years old) and 12 human participants (30-50 years old) in this study. T1ρ or T2 map values of the nucleus pulposus and end plate cartilage were analyzed according to Pfirrmann grades and age. Afterwards, micro computed tomography and histological analysis were used to confirm the end plate changes in monkeys. Pearson’s correlation was performed to investigate the relationship between end plate and disc degeneration. Results In monkeys, T1ρ (r=-0.794, P less then 0.001) and T2 map values (r=-0.8, P less then 0.001) of the nucleus pulposus were negatively associated with Pfirrmann grades. Moreover, the T2 map was more suitable than T1ρ for the evaluation of end plate degeneration. Age was an important influence factor of end plate and disc degeneration, which was confirmed by microcomputed tomography, Safranin O/fast green staining, and collagen II staining. The T2 map value of lower end plate degeneration positively correlated with that of the intervertebral discs in monkeys (R2=0.3133, P less then 0.001) and humans (R2=0.2092, P less then 0.001). Conclusion This study suggests that the compositional and structural changes of the end plate can be quantitatively evaluated by T2 map. Furthermore, cartilage end plate degeneration is associated with disc degeneration during ageing. The translational potential of this article A better understanding of how the cartilage end plate affects disc degeneration is needed, which may propose a new clinical application using T2 map to evaluate end plate degeneration.