Severe and persistent bacterial lung infections characterize cystic fibrosis (CF). While several studies have documented the microbial diversity within CF lung mucus, we know much less about the inorganic chemistry that constrains microbial metabolic processes and their distribution. We hypothesized that sputum is chemically heterogeneous both within and between patients. To test this, we measured microprofiles of oxygen and sulfide concentrations as well as pH and oxidation-reduction potentials in 48 sputum samples from 22 pediatric patients with CF. Inorganic ions were measured in 20 samples from 12 patients. In all cases, oxygen was depleted within the first few millimeters below the sputum-air interface. Apart from this steep oxycline, anoxia dominated the sputum environment. Different sputum samples exhibited a broad range of redox conditions, with either oxidizing (16 mV to 355 mV) or reducing (−300 to −107 mV) potentials. The majority of reduced samples contained hydrogen sulfide and had a low pH (2.9 to 6.5). Sulfide concentrations increased at a rate of 0.30 µM H2S/min. Nitrous oxide was detected in only one sample that also contained sulfide. Microenvironmental variability was observed both within a single patient over time and between patients. Modeling oxygen dynamics within CF mucus plugs indicates that anoxic zones vary as a function of bacterial load and mucus thickness and can occupy a significant portion of the mucus volume. Thus, aerobic respiration accounts only partially for pathogen survival in CF sputum, motivating research to identify mechanisms of survival under conditions that span fluctuating redox states, including sulfidic environments.
More than half the patients who received bleomycin had subclinical pulmonary dysfunction as evidenced by abnormalities in pulmonary function tests, although the incidence of clinical symptoms was low.
A variety of genetic techniques have been devised to determine cell lineage relationships during tissue development. Some of these systems monitor cell lineages spatially and/or temporally without regard to gene expression by the cells, whereas others correlate gene expression with the lineage under study. The GAL4 Technique for Real-time and Clonal Expression (G-TRACE) system allows for rapid, fluorescent protein-based visualization of both current and past GAL4 expression patterns and is therefore amenable to genome-wide expression-based lineage screens. Here we describe the results from such a screen, performed by undergraduate students of the University of California, Los Angeles (UCLA) Undergraduate Research Consortium for Functional Genomics (URCFG) and high school summer scholars as part of a discovery-based education program. The results of the screen, which reveal novel expression-based lineage patterns within the brain, the imaginal disc epithelia, and the hematopoietic lymph gland, have been compiled into the G-TRACE Expression Database (GED), an online resource for use by the Drosophila research community. The impact of this discovery-based research experience on student learning gains was assessed independently and shown to be greater than that of similar programs conducted elsewhere. Furthermore, students participating in the URCFG showed considerably higher STEM retention rates than UCLA STEM students that did not participate in the URCFG, as well as STEM students nationwide.
After severe neurocognitive decline developed in an otherwise healthy 63-year-old man, brain magnetic resonance imaging showed eosinophilic meningoencephalitis and enhancing lesions. The patient tested positive for antibodies to Baylisascaris spp. roundworms, was treated with albendazole and dexamethasone, and showed improvement after 3 months. Baylisascariasis should be considered for all patients with eosinophilic meningitis.
Background Symptoms of pulmonary injury following lung irradiation may not manifest clinically in childhood. We performed comprehensive pulmonary evaluation of patients who had received lung irradiation for treatment of cancer. Methods Patients underwent a focused history and physical examination, computed tomography (CT) of the chest, pulmonary function test (PFT) and cardio-pulmonary exercise stress test (CPET). Health related quality of life (HRQOL) was also measured. Results Fourteen patients were recruited with median age of 16 years (range 6-21 years). Median time from pulmonary radiation to testing was 5 years (range 2-11 years). Five patients reported pulmonary symptoms. Twelve patients (85.7%) had at least one PFT abnormality. Nine patients demonstrated CPET abnormalities; seven patients had abnormal pulmonary limitation to exercise, and five patients had exercise-induced bronchospasm. The pulmonary limitations included abnormal ventilatory response to exercise in five patients, and gas exchange abnormalities in four patients. Chest CT demonstrated grade 1-2 radiation induced lung changes in four patients, and grade 3 abnormalities in one patient. Conclusion Significant pulmonary dysfunction was observed in childhood cancer survivors who had received lung irradiation. CPET is feasible in childhood cancer survivors and can be valuable for assessment of pulmonary function and exercise capacity.
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