MC4R mutations represent the largest monogenic cause of obesity, resulting mainly from receptor misfolding and intracellular retention by the cellular quality control system. The present study aimed at determining whether pharmacological chaperones (PCs) that restore folding and plasma membrane trafficking by stabilizing near native protein conformation may represent valid therapeutic avenues for the treatment of melanocortin type 4 receptor-linked (MC4R-linked) obesity. To test the therapeutic PC potential, we engineered humanized MC4R (hMC4R) mouse models expressing either the WT human MC4R or a prevalent obesity-causing mutant (R165W).
View Article and Find Full Text PDFSeveral clinical and histological features, usually associated with chronic inflammation could complexify the diagnosis of oral epithelial dysplasia (OED). These changes in response to inflammatory stimuli, or re-epithelialization events, are described as reactive epithelial atypia or dysplasia (REA/D). Within a REA/D scenario (for example in the edges of chronic traumatic ulcers), the diagnosis of OED could be challenging for oral pathologists due to an unfeasibility to accurate the true nature of that changes.
View Article and Find Full Text PDFBackground: Widespread penicillin usage rapidly resulted in the emergence of penicillin resistance in Staphylococcus aureus. However, new data suggest that penicillin susceptibility may be in a period of renaissance. The objective of our study was to quantify penicillin resistance in methicillin-susceptible Staphylococcus aureus (MSSA) bacteremia.
View Article and Find Full Text PDFContext: A 4-year-old girl and a 4-month-old boy presented with hypoglycemia, normal electrolytes, low cortisol, and high ACTH. A diagnosis of primary adrenal insufficiency was made and initial treatment was with glucocorticoids and mineralocorticoids. The genes known to cause ACTH resistance were normal.
View Article and Find Full Text PDFWe compared the performance of 8 Clostridium difficile enzyme immunoassays to cell cytotoxicity neutralization assay and toxigenic culture. The effect of strain type on assay performance was also examined. There were a total of 71 (14.
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