Reserve autophagic capacity in alveolar epithelia provides a replicative niche for influenza A virus.

Autophagy contributes to cellular homeostasis through metabolite recycling and degradation of cytotoxic protein aggregates and damaged organelles. Although recent studies have established that the requirement for basal autophagy is largely tissue specific, the importance of autophagy for alveolar epithelial cell homeostasis remains an important knowledge gap. In the present study we generated two mouse models, with > 90% or > 50% recombination at the Atg5 locus in the distal respiratory epithelium, to assess the effect of dose-dependent decreases in autophagy on alveolar homeostasis. A 90% decrease in autophagy was well tolerated in young adult mice but resulted in alveolar septal thickening and altered lung mechanics in aged animals, consistent with accumulation of damage over time. By comparison, a 50% decrease in autophagy had no effect on alveolar structure or function throughout the murine life span, indicating that basal autophagy in this compartment exceeds that required for homeostasis. A 50% decrease in autophagy in the bronchoalveolar epithelium significantly attenuated influenza A/H3N2 viral replication, leading to improved lung structure and function and reduced morbidity and mortality after infection. The reserve of autophagic capacity in the alveolar epithelium may provide a niche for replication of influenza A virus.

Evaluating an inclusive trauma system using linked population-based data.

BACKGROUND: Federal and professional programs require "inclusive" trauma systems. We wished to evaluate an inclusive trauma system using administrative data combined from multiple sources. METHODS: Ambulance reports, outpatient/inpatient discharge data, and/or death certificates were obtained for persons with injury diagnoses who received hospital services and/or died in Maine during 1998 to 2000. Records were unduplicated and joined using probabilistic record-linkage software. Case outcomes, determined from one or more linked records, included place of hospitalization, discharge status, and 30-day mortality. RESULTS: Per 100,000 population annually, 11,100 injured persons were treated and released, 573 were admitted, and 51.3 died. Trauma centers received 37.0% of major cases directly and another 15.4% in transfer; 51.4% of injury deaths occurred without medical intervention, 21.2% occurred in trauma centers, 20.4% occurred in other hospitals, and 7.0% occurred after discharge from a hospital. Database queries produced comparative hospital statistics and identification of questionable outcomes. CONCLUSION: Record linkage allows inexpensive description of an inclusive trauma system and may contribute to quality improvement.