Evaluation of off-label rapamycin use on oral health.

Rapamycin (sirolimus) is an FDA approved drug with immune modulating properties that is being prescribed off-label in adults as a preventative therapy to maintain healthspan. We recently published one of the first reports on 333 adults with a history of off-label rapamycin use. Along with presenting evidence that rapamycin can be used safely in adults of normal health status, we discovered that about 26% of rapamycin users also reported oral health changes.

Strong toll-like receptor responses in cystic fibrosis patients are associated with higher lung function.

Background: Cystic fibrosis (CF) airways disease varies widely among patients with identical cystic fibrosis transmembrane conductance regulator (CFTR) genotypes. Robust airway inflammation is thought to be deleterious in CF; inter-individual variation in Toll-like receptor (TLR)-mediated innate immune inflammatory responses (TMIIR) might account for a portion of the phenotypic variation. We tested if TMIIR in people with CF are different than those of healthy controls, and whether higher TMIIR in people with CF are associated with reduced lung function.

Alveolar Macrophage Transcriptional Programs Are Associated with Outcomes in Acute Respiratory Distress Syndrome.

Serial measurements of alveolar macrophage (AM) transcriptional changes in patients with acute respiratory distress syndrome (ARDS) could identify cell-specific biological programs that are associated with clinical outcomes. To determine whether AM transcriptional programs are associated with prolonged mechanical ventilation and 28-day mortality in individuals with ARDS. We performed genome-wide transcriptional profiling of AMs purified from BAL fluid collected from 35 subjects with ARDS.

Glycan targeted polymeric antibiotic prodrugs for alveolar macrophage infections.

Alveolar macrophages resident in the lung are prominent phagocytic effector cells of the pulmonary innate immune response, and paradoxically, are attractive harbors for pathogens. Consequently, facultative intracellular bacteria, such as Francisella tularensis, can cause severe systemic disease and sepsis, with high morbidity and mortality associated with pulmonary infection. Current clinical treatment, which involves exhaustive oral or intravenous antibiotic therapy, has limitations such as systemic toxicity and off-target effects.