International Journal of Anesthesia and Critical Care

Chronic, non-healing, or slow to heal wounds present a significant and growing health problem in the United States, with an estimated 6.5 million people affected, at an annual cost of US $20 billion, with the highest risk groups represented by the elderly and the increasing prevalence of lifestyle diseases such as diabetes and obesity.

Amyotrophic Lateral Sclerosis (ALS) is a devastating and progressive neurodegenerative disease with a complex, multifactorial pathophysiology, culminating in death of motor neurons. We introduce a new mechanism of ALS pathogenesis via study of a novel drug-like small molecule series that targets a subset of protein disulfide isomerase (PDI) within a previously largely unappreciated transient and energy-dependent multi-protein complex enriched for proteins of the ALS interactome. This drug, found by a novel phenotypic screen, has activity in cellular models for both familial and sporadic ALS, as well as in transgenic worms, flies, and mice bearing a diversity of human genes with ALS-associated mutations. 

Antimicrobial resistance is a significant global issue, posing a serious threat to the effective prevention and treatment of a growing range of resistant bacterial infections. While resistance trends vary among populations, evidence shows that the prevalence of multi-drug resistance (MDR) is increasing. Infections caused by MDR organisms can lead to higher treatment costs, longer hospital stays, and increased mortality rates. Recently, there has been a rise in resistance among Gram-positive and Gram-negative pathogens causing both community and hospital-based infections.

Background: Sepsis arises when an uncontrolled systemic immune response to infection leads to life-threatening organ dysfunction. Despite available therapies, sepsis remains a major global health challenge with high mortality. Further research into molecular mechanisms, diagnostic and prognostic biomarkers, and novel treatments is critical to improve outcomes.