In human airways diseases, including cystic fibrosis (CF) and chronic obstructive pulmonary disease (COPD), host defense is compromised and airways inflammation and infection often result. Mucus clearance and trapping of inhaled pathogens constitute key elements of host defense. Clearance rates are governed by mucus viscous and elastic moduli at physiological driving frequencies, whereas transport of trapped pathogens in mucus layers is governed by diffusivity. There is a clear need for simple and effective clinical biomarkers of airways disease that correlate with these properties. We tested the hypothesis that mucus solids concentration, indexed as weight percent solids (wt%), is such a biomarker. Passive microbead rheology was employed to determine both diffusive and viscoelastic properties of mucus harvested from human bronchial epithelial (HBE) cultures. Guided by sputum from healthy (1.5–2.5 wt%) and diseased (COPD, CF; 5 wt%) subjects, mucus samples were generated in vitro to mimic in vivo physiology, including intermediate range wt% to represent disease progression. Analyses of microbead datasets showed mucus diffusive properties and viscoelastic moduli scale robustly with wt%. Importantly, prominent changes in both biophysical properties arose at ∼4 wt%, consistent with a gel transition (from a more viscous-dominated solution to a more elastic-dominated gel). These findings have significant implications for: (1) penetration of cilia into the mucus layer and effectiveness of mucus transport; and (2) diffusion vs. immobilization of micro-scale particles relevant to mucus barrier properties. These data provide compelling evidence for mucus solids concentration as a baseline clinical biomarker of mucus barrier and clearance functions.

Objectives: To identify the time at which point of care ultrasound static image recognition and image acquisition skills decay in novice learners. Setting: The University of Iowa Hospitals and Clinics. Subjects: Twenty-four subjects (23 first-year medical students and one first-year physician assistant student). Design: The subjects completed an initial didactic and hands-on session with immediate testing of learned image acquisition and static image identification skills. Interventions: Retesting occurred at 1, 4, and 8 weeks after the initial training session with no retraining in between. Image acquisition skills were obtained on the same healthy male volunteers, and the students were given no immediate feedback on their performance. The image identification skills were assessed with a 10 question test at each follow-up session. Measurements and Main Results: For pleural ultrasound by 4 weeks, there was a significant decline of the ability to identify A-lines (p = 0.0065). For pleural image acquisition, there was no significant decline in the ability to demonstrate lung sliding. Conversely, cardiac image recognition did not significantly decline throughout the study, while the ability to demonstrate cardiac images at 4 weeks (parasternal short axis view) did (p = 0.0008). Conclusions: Motor and cognitive skills decay at different times for pleural and cardiac images. Future ultrasound curricula should retrain skills at a maximum of 8 weeks from initial training. They should focus more on didactic sessions related to image identification for pleural images, and more hands-on image acquisition training for cardiac images, which represents a novel finding.

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BACKGROUND: Epidemiological studies support the hypothesis that diabetes alters pulmonary responses to air pollutants like ozone (O 3). The mechanism(s) underlying these associations and potential links among diabetes, O 3 , and lung inflammation and remodeling are currently unknown. OBJECTIVES: The goal was to determine whether pulmonary responses to repetitive ozone exposures are exacerbated in murine strains that are hyperglycemic and insulin resistant. METHODS: Normoglycemic and insulin-sensitive C57BL/6J mice; hyperglycemic, but mildly insulin-resistant, KK mice; and hyperglycemic and markedly insulin-resistant KKAy mice were used for ozone exposure studies. All animals were exposed to filtered air (FA) or repetitive ozone (0:5 ppm O 3 , 4 h/d, for 13 consecutive weekdays). Tissue analysis was performed 24 h following the final exposure. This analysis included bronchoalveolar lavage (BAL) for cell and fluid analysis, and tissue for pathology, immunohistology, mRNA, and hydroxyproline. RESULTS: Following repetitive O 3 exposure, higher bronchoalveolar lavage fluid inflammatory cells were observed in all mice (KKAy >KK >C57BL=6), with a notable influx of neutrophils and eosinophils in KK and KKAy mice. Although the lungs of O 3-exposed C57BL/6J and KK mice had minimal centriacinar histological changes without fibrosis, the lungs of O 3-exposed KKAy mice contained marked epithelial hyperplasia in proximal alveolar ducts and adjacent alveoli with associated centriacinar fibrosis. Fibrosis in O 3-exposed KKAy lungs was confirmed with immunohistochemistry, tissue hydroxyproline content, and tissue mRNA expression of fibrosis-associated genes (Ccl11, Il13, and Mmp12). Immunofluorescence staining and confocal microscopy revealed alterations in the structure and composition of the airway and alveolar epithelium in regions of fibrosis. DISCUSSION: Our results demonstrate that in diabetic animal strains repetitive ambient ozone exposure led to early and exaggerated pulmonary inflammation and remodeling. Changes in distal and interstitial airspaces and the activation of Th2 inflammatory and profibrotic pathways in experimental animals provide a preliminary, mechanistic framework to support the emerging epidemiological associations among air pollution, diabetes, and lung disease.

Hemolytic uremic syndrome (HUS) is a well-described process that is known to cause severe renal dysfunction, thrombocytopenia, and anemia. HUS is typically associated with toxins (shiga-like and shigella toxin) found in strains of E. coli and Shigella spp [1], [2], [3]. We present a case of a 27 year-old man with jaundice, thrombocytopenia, and renal dysfunction who was found to have HUS in the setting of Shigella sonnei infection. Outside of developing countries, cases of HUS related to S. sonnei are largely unreported.