Oxidative stress and COVID-19-associated neuronal dysfunction: mechanisms and therapeutic implications.

Severe acute respiratory syndrome (SARS)-CoV-2 virus causes novel coronavirus disease 2019 (COVID-19), and there is a possible role for oxidative stress in the pathophysiology of neurological diseases associated with COVID-19. Excessive oxidative stress could be responsible for the thrombosis and other neuronal dysfunctions observed in COVID-19. This review discusses the role of oxidative stress associated with SARS-CoV-2 and the mechanisms involved. Furthermore, the various therapeutics implicated in treating COVID-19 and the oxidative stress that contributes to the etiology and pathogenesis of COVID-19-induced neuronal dysfunction are discussed. Further mechanistic and clinical research to combat COVID-19 is warranted to understand the exact mechanisms, and its true clinical effects need to be investigated to minimize neurological complications from COVID-19.

Arid1a Loss Drives Nonalcoholic Steatohepatitis in Mice Through Epigenetic Dysregulation of Hepatic Lipogenesis and Fatty Acid Oxidation.

Nonalcoholic steatohepatitis (NASH) is a rapidly growing cause of chronic liver damage, cirrhosis, and hepatocellular carcinoma. How fatty liver pathogenesis is subject to epigenetic regulation is unknown. We hypothesized that chromatin remodeling is important for the pathogenesis of fatty liver disease. AT-rich interactive domain-containing protein 1A (ARID1A), a DNA-binding component of the SWItch/sucrose nonfermentable adenosine triphosphate-dependent chromatin-remodeling complex, contributes to nucleosome repositioning and access by transcriptional regulators. Liver-specific deletion of Arid1a (Arid1a liver knockout [LKO]) caused the development of age-dependent fatty liver disease in mice. Transcriptome analysis revealed up-regulation of lipogenesis and down-regulation of fatty acid oxidation genes. As evidence of direct regulation, ARID1A demonstrated direct binding to the promoters of many of these differentially regulated genes. Additionally, Arid1a LKO mice were more susceptible to high-fat diet-induced liver steatosis and fibrosis. We deleted Pten in combination with Arid1a to synergistically drive fatty liver progression. Inhibition of lipogenesis using CAT-2003, a potent sterol regulatory element-binding protein inhibitor, mediated improvements in markers of fatty liver disease progression in this Arid1a/Pten double knockout model. Conclusion: ARID1A plays a role in the epigenetic regulation of hepatic lipid homeostasis, and its suppression contributes to fatty liver pathogenesis. Combined Arid1a and Pten deletion shows accelerated fatty liver disease progression and is a useful mouse model for studying therapeutic strategies for NASH.

Evaluation of Transmission Near the Christiansen Wavelength for Dynamic Sand Samples.

Many optical applications, including free-space optical communications, lidar, and astronomical measurements, are impacted by the presence of light-scattering particles also known as obscurants. Scattering from particles consisting of sand, dust, dirt, and other substances can significantly degrade optical signals. For many obscurants, the index of refraction is dependent on the wavelength of light, and there exists a Christiansen wavelength (λc) at which scattering is at a minimum. At λc the index of refraction of the scattering particles (ns) matches that of the surrounding medium, in this case air (with refractive index na). This condition makes the scattering particulates almost invisible to the propagating light, minimizing scattering and increasing transmission at λc. Previously, the authors showed a technique for measuring the index of refraction n(λ) and the extinction coefficient k(λ) using spectroscopic ellipsometry for various sand samples. Spectroscopic measurements on static sand samples demonstrated good agreement with the predicted spectral properties and highlighted the presence of a Christiansen feature near 8 µm. However, in outdoor environments, the scattering particles are never stationary but in a constant state of motion. In this work, spectroscopic measurements on dynamic sand samples (sand that is falling through the optical beam path) show two Christiansen features seen previously in predicted and observed static sand measurements. Additionally, we characterize, for the first time, transmission around a Christiansen feature using a tunable laser and show results consistent with other spectroscopic measurements.

The Role of Vitamin C in Human Immunity and Its Treatment Potential Against COVID-19: A Review Article.

The outbreak of the COVID-19 pandemic has left clinicians around the world searching for viable prevention and treatment options to use against the virus. The important physiologic properties of vitamin C have been well documented regarding its use by immune cells and its role as an antioxidant. It has previously shown potential as a prophylactic and treatment option for other respiratory viruses, and because of this, there has been intrigue into whether these positive outcomes translate into a cost-effective prevention and treatment option for COVID-19. To this point, there have only been a few clinical trials performed to assess the validity of this notion, with very few showing definitive positive outcomes when vitamin C has been incorporated into prophylactic or treatment protocols to use against coronavirus. When being used to specifically treat the severe complications that arise from COVID-19, vitamin C is a reliable option to treat COVID-19-induced sepsis but not pneumonia or acute respiratory distress syndrome (ARDS). As a treatment option, high-dose therapy has shown flashes of promise in a few studies although investigators in these studies often subject the testing group to multimodal therapies that include vitamin C as opposed to just vitamin C alone. Given the role that vitamin C has shown to uphold regarding the human immune response, it is currently advised for all individuals to maintain a normal physiologic range of plasma vitamin C through diet or supplements for adequate prophylactic protection against the virus. More research with definitive outcomes will be needed before it is recommended to provide high-dose vitamin C therapy to prevent or treat COVID-19.

Quantifying Intubation Forces on Incisors and Tongue Base Across Exposure Difficulty and Experience in a Simulator.

OBJECTIVE: Laryngoscopy simulators quantifying forces on critical structures in progressively challenging airways and operator expertise are lacking. We aimed to quantify laryngoscopy forces across expertise and exposure difficulty. STUDY DESIGN: Prospective observational study Setting: Tertiary care medical center Methods: Force gauges were affixed to a difficult airway mannequin to quantify teeth and tongue forces across increasingly challenging airway exposure. Medical students (n=10), residents (n=11), and otolaryngology staff (n=10) performed direct laryngoscopy using a Miller size 3 laryngoscope with 1) normal neck/jaw mobility, 2) restricted neck extension, 3) restricted jaw opening, and 4) restricted neck/jaw mobility. Incisor and tongue pounds of force (lbf) were continuously measured. RESULTS: As the difficulty setting increased, forces exerted by the students, residents, and staff on the incisors and tongue base increased (p=0.01). Between normal and maximally restricted settings, force delivered to the incisors increased by 6.95 lbf (standard error (SE) 1.29), 5.93 lbf (SE 0.98), and 5.94 lbf (SE 0.70) for the students, residents, and staff, respectively. At the tongue base, force increased by 0.37 lbf (SE 0.18), 0.46 lbf (SE 0.14), and 0.73 lbf (SE 0.15) for the students, residents, and staff, respectively. Esophageal intubations occurred in 50% of the students, 23% of the residents, and 45% of the otolaryngology staff at maximal difficulty, with none at the easiest setting (p=0.33). Compared to the residents, the staff applied significantly increased pressure on the tongue base during laryngoscopy (p=0.02). CONCLUSION: Forces exerted on the incisors and tongue base varied across exposure difficulty and expertise levels, suggesting that they may be useful markers for training and competence assessment.

Nickel-Catalyzed Formation of α-Substituted γ-Amino Ketones via Alkene Carboacylation.

Herein, we report Ni-catalyzed intramolecular carboacylation of imides containing a tethered alkene and tetraarylborate nucleophiles. Using a nickel-phosphine catalyst system, α-substituted, γ-amino ketones are generated in up to 92% yield with site selectivity. Deprotection and cyclization of the γ-amino ketone product afforded a cyclic imine in 71% yield, and a stereoselective reduction formed the ß-substituted, δ-amino alcohol in 66% yield with 2.3:1 d.r. and 94% ee (major diastereomer).

An Assessment of the Impact of SARS-CoV-2 on a Level 1 Trauma Center Including Subgroup Analysis of Orthopedic Injuries and Mechanism of Injury.

Background and objective There is a paucity of medical literature describing the preparedness of hospital institutions to withstand the population effects of a pandemic. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus that causes coronavirus disease 2019 (COVID-19), has had a global impact on all facets of medicine, which has ultimately affected the medical community in a significant manner. Furthermore, there is a scarcity of research regarding the effects of COVID-19 on trauma and acute care surgery injury and admission rates. We conducted this study to examine the effects of the COVID-19 pandemic on both pediatric and adult trauma admissions, injury types, and mechanisms of injury. Materials and methods Data from the Trauma Registry was extracted for all adult (>15 years) and pediatric (<15 years) patients who consulted trauma surgery, acute care surgery, or orthopedic surgery at our center in the year immediately prior to the pandemic (March 1, 2019-February 29, 2020) and during the COVID-19 pandemic (March 1, 2020-February 28, 2021). Patient demographics, cause of injury, injury type and mechanism, and procedures performed were recorded. Results We documented a 4.2% increase in adult encounters compared to the preceding year. There was a significant difference in the distribution of mechanism of injury of adult patients between the two time periods, with the most changes seen in motor-vehicle auto, gunshot, and other vehicle injuries. However, no significant difference was seen in trauma type or intent (assault, self-inflicted, unintentional). Pediatric encounters increased by 6.4% during the COVID-19 pandemic compared to the pre-COVID-19 period. Overall, there was no detectable association between the distribution of encounters by the mechanism of injury and the time period for pediatric encounters. Conclusion This retrospective review of trauma encounters through both pre-COVID-19 and COVID-19 periods outlines the differences in factors such as demographics, injury mechanisms, and injury types between the two time periods. Overall, we expected a decrease in orthopedic-related trauma admissions during the COVID-19 pandemic; however, there was actually an increase of 4.1% in adult encounters and that of 6.4% in pediatric encounters. Our study lays out possible trends in injury patterns that can be correlated with the COVID-19 pandemic and the lockdown period. This information is useful for the healthcare system in that it demonstrates that resources should not be cut down or removed from surgical specialties. At level I facilities, resources need to be allocated for and continued to be provided to emergency rooms and operative services, including supplies and staffing. These departments need to be well-equipped to handle an increased number of trauma patients.

Glenoid bone augmentation: a contemporary and comprehensive systematic review of open procedures.

Introduction: There is a trend towards arthroscopically treating shoulder instability with glenoid deficiency. Despite this, there remains the option for treatment through an open technique. Multiple bone augmentation options are available for recurrent anterior shoulder instability. Objective: To provide a systematic review of recent studies for recurrent anterior shoulder instability necessitating glenoid bone augmentation specifically through open procedures using coracoid bone or free bone blocks [iliac crest bone autograft/allograft or distal tibia allograft (DTA)]. Methods: PubMed, Cochrane, EMBASE, and Google Scholar were searched for studies reporting open glenoid bone augmentation procedures with iliac crest, tibia, or coracoid bones within 10 years. Extracted data included study/patient characteristics, techniques, prior surgeries, prior dislocations, radiographic findings, range of motion (ROM), recurrent instability, patient-reported outcomes, and complications. Results: 92 met inclusion criteria (5693 total patients). Six were studies of iliac crest bone, four of DTA, and 84 using the coracoid bone. 29 studies measured postoperative arthritis showing no development or mild arthritis. 26 studies reported postoperative graft position. 62 studies reported ROM noting decline in internal/external rotation. 87 studies measured postoperative instability with low rates. Rowe Scores with noted improvement across 31/59 (52.5%) studies were seen. Common post operative complications included infection, hematoma, graft fracture, nerve injury, pain, and screw-related irritation. Conclusion: Despite a trend towards arthroscopic management of recurrent anterior shoulder instability with glenoid deficiency, open procedures continue to provide satisfactory outcomes. Additionally, studies have demonstrated safe and efficacious use of free bone block graft options in the primary and revision setting.

Arid1a loss potentiates pancreatic ß-cell regeneration through activation of EGF signaling.

The dynamic regulation of ß-cell abundance is poorly understood. Since chromatin remodeling plays critical roles in liver regeneration, these mechanisms could be generally important for regeneration in other tissues. Here, we show that the ARID1A mammalian SWI/SNF complex subunit is a critical regulator of ß-cell regeneration. Arid1a is highly expressed in quiescent ß-cells but is physiologically suppressed when ß-cells proliferate during pregnancy or after pancreas resection. Whole-body Arid1a knockout mice are protected against streptozotocin-induced diabetes. Cell-type and temporally specific genetic dissection show that ß-cell-specific Arid1a deletion can potentiate ß-cell regeneration in multiple contexts. Transcriptomic and epigenomic profiling of mutant islets reveal increased neuregulin-ERBB-NR4A signaling. Chemical inhibition of ERBB or NR4A1 blocks increased regeneration associated with Arid1a loss. Mammalian SWI/SNF (mSWI/SNF) complex activity is a barrier to ß-cell regeneration in physiologic and disease states.

Lumbopelvic Muscle Changes Following Long-Duration Spaceflight.

Long-duration spaceflight has been shown to negatively affect the lumbopelvic muscles of crewmembers. Through analysis of computed tomography scans of crewmembers on 4- to 6-month missions equipped with the interim resistive exercise device, the structural deterioration of the psoas, quadratus lumborum, and paraspinal muscles was assessed. Computed tomography scans of 16 crewmembers were collected before and after long-duration spaceflight. The volume and attenuation of lumbar musculature at the L2 vertebral level were measured. Percent changes in the lumbopelvic muscle volume and attenuation (indicative of myosteatosis, or intermuscular fat infiltration) following spaceflight were calculated. Due to historical studies demonstrating only decreases in the muscles assessed, a one-sample t test was performed to determine if these decreases persist in more recent flight conditions. Crewmembers on interim resistive exercise device-equipped missions experienced an average 9.5% (2.0% SE) decrease in volume and 6.0% (1.5% SE) decrease in attenuation in the quadratus lumborum muscles and an average 5.3% (1.0% SE) decrease in volume and 5.3% (1.6% SE) decrease in attenuation in the paraspinal muscles. Crewmembers experienced no significant changes in psoas muscle volume or attenuation. No significant changes in intermuscular adipose tissue volume or attenuation were found in any muscles. Long-duration spaceflight was associated with preservation of psoas muscle volume and attenuation and significant decreases in quadratus lumborum and paraspinal muscle volume and attenuation.