ABSTRACT
Clinical studies indicate that patients infected with SARS-CoV-2 develop hyperinflammation, which correlates with increased mortality. The SARS-CoV-2/COVID-19-dependent inflammation is thought to occur via increased cytokine production and hyperactivity of RAGE in several cell types, a phenomenon observed for other disorders and diseases. Metabolic reprogramming has been shown to contribute to inflammation and is considered a hallmark of cancer, neurodegenerative diseases, and viral infections. Malfunctioning glycolysis, which normally aims to convert glucose into pyruvate, leads to the accumulation of advanced glycation end products (AGEs). Being aberrantly generated, AGEs then bind to their receptor, RAGE, and activate several pro-inflammatory genes, such as IL-1b and IL-6, thus, increasing hypoxia and inducing senescence. Using the lung epithelial cell (BEAS-2B) line, we demonstrated that SARS-CoV-2 proteins reprogram the cellular metabolism and increase pyruvate kinase muscle isoform 2 (PKM2). This deregulation promotes the accumulation of AGEs and senescence induction. We showed the ability of the PKM2 stabilizer, Tepp-46, to reverse the observed glycolysis changes/alterations and restore this essential metabolic process.
Subject(s)
COVID-19 , Pneumonia , Humans , Inflammation , Pyridazines , Pyrroles , SARS-CoV-2ABSTRACT
In 1995, Dr Martin Dalton published a recounting of his involvement with the first human lung transplant in the Annals of Thoracic Surgery. As recalled in that account, the first lung transplant took place in the summer of 1963 in the context of another historical event, the assassination of Medgar Evers. This article is written in follow-up to Dalton's report in hopes of providing more insight into the events surrounding the assassination. This review will discuss the details of the assassination, attempted resuscitation, and the medical evidence presented in the trial of his assassin.
Subject(s)
Homicide/history , History, 20th Century , Homicide/legislation & jurisprudence , Mississippi , Wounds, Gunshot/history , Wounds, Gunshot/therapyABSTRACT
On June 5, 1968, having won the Democratic Party presidential primary in California, Senator Robert F. Kennedy delivered a victory speech to supporters at the Ambassador Hotel in downtown Los Angeles. Just after 12:15 am (Pacific daylight savings time), a lone assassin shot Kennedy 3 times at point-blank range. One of the bullets struck Kennedy in the right posterior auricular region. Within the ensuing 26 hours, Kennedy was transported to 2 hospitals, underwent emergency surgery, and eventually died of severe brain injury. Although this story has been repeated in the press and recounted in numerous books, this is the first analysis of the senator's injuries and subsequent surgical care to be reported in the medical literature. The authors review eyewitness reports on the mechanism of injury, the care rendered for 3 hours prior to the emergency craniotomy, the clinical course, and, ultimately, the autopsy.
