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Host proteases have been suggested to be crucial for dissemination of MERS, SARS-CoV, and SARS-CoV-2 coronaviruses, but the relative contribution of membrane versus intracellular proteases remains controversial. Transmembrane serine protease 2 (TMPRSS2) is regarded as one of the main proteases implicated in the coronavirus S protein priming, an important step for binding of the S protein to the angiotensin-converting enzyme 2 (ACE2) receptor before cell entry.

We developed a cell-based assay to identify TMPRSS2 inhibitors. Inhibitory activity was established in SARS-CoV-2 viral load systems.

We identified the human extracellular serine protease inhibitor (serpin) alpha 1 anti-trypsin (A1AT) as a novel TMPRSS2 inhibitor. Structural modeling revealed that A1AT docked to an extracellular domain of TMPRSS2 in a conformation that is suitable for catalysis, resembling similar serine protease inhibitor complexes. Inhibitory activity of A1AT was established in a SARS-CoV-2 viral load system. Notably, plasma A1AT levels were associated with COVID-19 disease severity.

Our data support the key role of extracellular serine proteases in SARS CoV-2 infections and indicate that treatment with serpins, particularly the FDA-approved drug A1AT, may be effective in limiting SARS-CoV-2 dissemination by affecting the surface of the host cells.

Our data support the key role of extracellular serine proteases in SARS CoV-2 infections and indicate that treatment with serpins, particularly the FDA-approved drug A1AT, may be effective in limiting SARS-CoV-2 dissemination by affecting the surface of the host cells.Viral infections have historically had a complex relationship with autoimmune diseases. For patients with preexisting autoimmune disorders, often complicated by immunosuppressive therapies, there are numerous potential effects of COVID-19, a disease of complex immunobiology, including the potential for an altered natural history of COVID-19 when infected. In addition, individuals without recognized autoimmune disease may be vulnerable to virally induced autoimmunity in the forms of autoantibody formation, as well as the development of clinical immune-mediated inflammatory diseases. Until quite recently in the pandemic, this relationship between COVID-19 and autoimmune diseases has been relatively underexplored; yet such investigation offers potential insights into immunopathogenesis as well as for the development of new immune-based therapeutics. Our review examines this relationship through exploration of a series of questions with relevance to both immunopathogenic mechanisms as well as some clinical implications.Cell-cell communication is a fundamental process that shapes biological tissue. Historically, studies of cell-cell communication have been feasible for one or two cell types and a few genes. With the emergence of single-cell transcriptomics, we are now able to examine the genetic profiles of individual cells at unprecedented scale and depth. The availability of such data presents an exciting opportunity to construct a more comprehensive description of cell-cell communication. This review discusses the recent explosion of methods that have been developed to infer cell-cell communication from non-spatial and spatial single-cell transcriptomics, two promising technologies which have complementary strengths and limitations. We propose several avenues to propel this rapidly expanding field forward in meaningful ways.BRASH syndrome is a syndrome characterized by bradycardia, renal failure, usage of atrioventricular (AV) nodal blocker, shock, and hyperkalemia (BRASH). It is more common among patients with multiple comorbidities such as cardiac disease, kidney dysfunction, and hypertension requiring AV nodal blockers. Akt inhibitor Cardiac conduction abnormalities are frequently caused by severe hyperkalemia. However, it may also occur in mild-to-moderate hyperkalemia with concomitant use of AV nodal blockers due to the synergistic effects between these two factors in the presence of renal insufficiency. It is essential for the physician to identify BRASH syndrome as the treatment may differ from standard advanced cardiovascular life support (ACLS) protocol. We report the two cases of patient who presented with BRASH syndrome who failed to respond to standard ACLS protocol.Glufosinate ammonium (GLA) is widely used as a commercial herbicide in many countries. Neurotoxicity of GLA has been associated with serious neurological complications such as loss of consciousness, convulsions, and memory impairment. Late-onset memory impairment due to GLA-induced hippocampal lesions is the most distinct clinical feature in GLA poisoning. However, the lesion of the splenium of the corpus callosum (SCC) is a rare condition in GLA poisoning, so the clinical features are not well known. We report the case of a 57-year-old male patient who developed SCC damage after GLA poisoning. The patient had various late-onset neurotoxic symptoms, including prolonged overall cognitive dysfunction and psychosis-like symptoms. Emergency physicians should be aware that GLA-induced SCC lesions may be associated with various late-onset neurotoxic symptoms.Arterial bleeding due to pelvic fracture can be life-threatening, and angiographic embolization is the gold standard for its control. Various materials have been described, but most of them are not widely available, mainly because of the high costs. Here, we report a case of use of autologous subcutaneous fat tissue for successfully controlling bleeding in a patient with an anterior-posterior pelvic fracture.Administration of sub-dissociative doses of ketamine is used via intranasal (IN) and intravenous routes in the pediatric emergency department for managing acute pain. Due to difficulties in both obtaining intravenous access and compliance with IN medications in children, administration of ketamine via breath-actuated nebulizer can serve as a valuable modality for timely analgesia in children where dosing titration is patient controlled. We describe five pediatric patients who received ketamine via breath-actuated nebulizer at 0.75 mg/kg, 1 mg/kg, and 1.5 mg/kg, with all patients experiencing a decrease in pain score. This case series introduces ketamine inhalation as a modality for managing pain in children.