Baricitinib in the Treatment of a Critical Patient with COVID-19 Pneumonia: a case report

A 72-year-old male presented to the emergency department with a chief complaint of diarrhea after having tested positive for COVID-19 two days prior. He initially had minimal respiratory complaints, but was eventually transferred to the intensive care unit for acute hypoxic respiratory failure. In addition to dexamethasone, remdesivir, and antibiotics, the patient was treated with baricitinib, a Janus kinase inhibitor that was recently granted emergency use authorization by the Food and Drug Administration for treatment of hospitalized patients with COVID-19. He had an extensive and complicated hospital course and had to be placed on mechanical ventilation, ultimately undergoing tracheostomy. After 78 days of hospitalization, his family withdrew life-sustaining measures and the patient died shortly thereafter. This case details the use of baricitinib for treatment of COVID-19 pneumonia, and demonstrates the need for additional studies regarding the efficacy of this drug

COVID-19-associated pulmonary aspergillosis: a case report from the COVID-19 surveillance program.

A 72-year-old male was brought to the hospital following a motorcycle crash and was admitted for multiple trauma management. His initial course of hospitalization was complicated by mild hypoxemia and altered mental status. Respiratory workup and imaging were consistent with SARS-CoV-2 pneumonia. He completed a five-day course of remdesivir and a ten-day course of dexamethasone. Twenty days later, he developed a low-grade fever. His chest computerized tomography (CT) showed gas and fluid containing parenchymal collection in the anteromedial right middle lobe measuring up to 4.8 cm, most consistent with a pulmonary abscess. Antimicrobial treatment was started. The patient became hypoxic and was intubated and mechanically ventilated. Bronchoalveolar lavage fluid was positive for galactomannan assay, a diagnostic marker for possible aspergillosis. A repeat chest CT showed a cavitary lesion with a positive air crescent sign, a common CT finding of invasive pulmonary aspergillosis. The patient was diagnosed with COVID-19-associated pulmonary aspergillosis and was started on antifungal treatment. He improved clinically and was successfully extubated

RSV-induced Guillain–Barré Syndrome

A patient with respiratory syncytial virus-induced Guillain–Barré Syndrome and acute disseminated encephalomyelitis is presented. This virus is the most common cause of upper respiratory infections, and it can become an etiology for extra-pulmonary pathology with serious complications. Such a case is rare, but the possibility of adverse comorbidities makes early diagnosis and treatment important

Unveiling the cerium(III)/(IV) structures and charge transfer mechanism in sulfuric acid

The Ce3+/Ce4+ redox couple has a charge transfer (CT) with extreme asymmetry and a large shift in redox potential depending on electrolyte composition. The redox potential shift and CT behavior are difficult to understand because neither the cerium structures nor the CT mechanism are well understood, limiting efforts to improve the Ce3+/Ce4+ redox kinetics in applications such as energy storage. Herein, we identify the Ce3+ and Ce4+ structures and CT mechanism in sulfuric acid via extended X-ray absorption fine structure spectroscopy (EXAFS), kinetic measurements, and density functional theory (DFT) calculations. We show EXAFS evidence that confirms that Ce3+ is coordinated by nine water molecules and suggests that Ce4+ is complexed by water and three bisulfates in sulfuric acid. Despite the change in complexation within the first coordination shell between Ce3+ and Ce4+, we show that the kinetics are independent of the electrode, suggesting outer-sphere electron-transfer behavior. We identify a two-step mechanism where Ce4+ exchanges the bisulfate anions with water in a chemical step followed by a rate-determining electron transfer step that follows Marcus theory (MT). This mechanism is consistent with all experimentally observed structural and kinetic data. The asymmetry of the Ce3+/Ce4+ CT and the observed shift in the redox potential with acid is explained by the addition of the chemical step in the CT mechanism. The fitted parameters from this rate law qualitatively agree with DFT-predicted free energies and the reorganization energy. The combination of a two-step mechanism with MT should be considered for other metal ion CT reactions whose kinetics have not been appropriately described.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/176715/1/jacsau.2c00484_-_Dylan_Herrera.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/176715/2/annotated-Herrera_Dylan_Design_Expo_-_Dylan_Herrera.pd

Semi-automated counting of axon regeneration in poly(lactide co-glycolide) spinal cord bridges.

BackgroundSpinal cord injury (SCI) is a debilitating event with multiple mechanisms of degeneration leading to life-long paralysis. Biomaterial strategies, including bridges that span the injury and provide a pathway to reconnect severed regions of the spinal cord, can promote partial restoration of motor function following SCI. Axon growth through the bridge is essential to characterizing regeneration, as recovery can occur via other mechanisms such as plasticity. Quantitative analysis of axons by manual counting of histological sections can be slow, which can limit the number of bridge designs evaluated. In this study, we report a semi-automated process to resolve axon numbers in histological sections, which allows for efficient analysis of large data sets.New methodAxon numbers were estimated in SCI cross-sections from animals implanted with poly(lactide co-glycolide) (PLG) bridges with multiple channels for guiding axons. Immunofluorescence images of histological sections were filtered using a Hessian-based approach prior to threshold detection to improve the signal-to-noise ratio and filter out background staining associated with PLG polymer.ResultsSemi-automated counting successfully recapitulated average axon densities and myelination in a blinded PLG bridge implantation study.Comparison with existing methodsAxon counts obtained with the semi-automated technique correlated well with manual axon counts from blinded independent observers across sections with a wide range of total axons.ConclusionsThis semi-automated detection of Hessian-filtered axons provides an accurate and significantly faster alternative to manual counting of axons for quantitative analysis of regeneration following SCI

Semi-automated counting of axon regeneration in poly(lactide co-glycolide) spinal cord bridges.

BackgroundSpinal cord injury (SCI) is a debilitating event with multiple mechanisms of degeneration leading to life-long paralysis. Biomaterial strategies, including bridges that span the injury and provide a pathway to reconnect severed regions of the spinal cord, can promote partial restoration of motor function following SCI. Axon growth through the bridge is essential to characterizing regeneration, as recovery can occur via other mechanisms such as plasticity. Quantitative analysis of axons by manual counting of histological sections can be slow, which can limit the number of bridge designs evaluated. In this study, we report a semi-automated process to resolve axon numbers in histological sections, which allows for efficient analysis of large data sets.New methodAxon numbers were estimated in SCI cross-sections from animals implanted with poly(lactide co-glycolide) (PLG) bridges with multiple channels for guiding axons. Immunofluorescence images of histological sections were filtered using a Hessian-based approach prior to threshold detection to improve the signal-to-noise ratio and filter out background staining associated with PLG polymer.ResultsSemi-automated counting successfully recapitulated average axon densities and myelination in a blinded PLG bridge implantation study.Comparison with existing methodsAxon counts obtained with the semi-automated technique correlated well with manual axon counts from blinded independent observers across sections with a wide range of total axons.ConclusionsThis semi-automated detection of Hessian-filtered axons provides an accurate and significantly faster alternative to manual counting of axons for quantitative analysis of regeneration following SCI

Amyloid formation and depolymerization of tumor suppressor p16INK4a are regulated by a thiol-dependent redox mechanism

The conversion of a soluble protein into polymeric amyloid structures is a process that is poorly understood. Here, we describe a fully redox-regulated amyloid system in which cysteine oxidation of the tumor suppressor protein p16INK4a leads to rapid amyloid formation. We identify a partially-structured disulfide-bonded dimeric intermediate species that subsequently assembles into fibrils. The stable amyloid structures disassemble when the disulfide bond is reduced. p16INK4a is frequently mutated in cancers and is considered highly vulnerable to single-point mutations. We find that multiple cancer-related mutations show increased amyloid formation propensity whereas mutations stabilizing the fold prevent transition into amyloid. The complex transition into amyloids and their structural stability is therefore strictly governed by redox reactions and a single regulatory disulfide bond