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fThe differentiation of Bordetella species, particularly those causing human infection, is problematic. We found that sequence analysis of an internal fragment of nrdA allowed differentiation of the currently named Bordetella species. Analysis of 107 "Bordetella" isolates recovered almost exclusively from human respiratory tract specimens identified several putative novel species.

The hypothesis of this study was that Hdac6 depletion would restore cystic fibrosis (CF) responses to bacterial challenge to more wild type profiles using a CF mouse model. CF mice harboring the F508del Cftr mutation respond to bacterial challenge with 25,000 CFU Pseudomonas aeruginosa embedded into agarose beads to slow clearance. CF mice respond significantly more aggressively to this challenge compared to WT mice with respect to bacterial clearance, weight loss, neutrophil recruitment, and MIP-2 production. Depletion of Hdac6 expression in the CF mice (CF/Hdac6) significantly improves these responses to more WT levels. Weight loss in response to infection is most severe in CF mice and significantly attenuated in CF/Hdac6 mice. Bacterial levels are reduced at a faster rate in CF/Hdac6 mice compared to CF mice where infection persists. Percent neutrophils in lung lavage fluid post-infection are significantly higher in CF mice, but returned to WT levels with CF/Hdac6 mice. Similarly, CF Mip-2 levels are restored to WT levels in the absence of Hdac6 expression. These data demonstrate that Hdac6 depletion restores CF responses to bacterial challenge to WT-like profiles and offer a potential therapeutic avenue for addressing inflammation and infection in CF airways independently of Cftr correction.

Fatigue is a prevalent symptom associated with decreased quality of life and increased mortality in individuals with end stage renal disease (ESRD), yet causes of fatigue in individuals with ESRD remain poorly understood. We examined gene expression of Neuronal PAS Domain Protein 2 (NPAS2) in relation to patient-reported fatigue in 122 individuals with ESRD. Independent samples t-tests were used to examine NPAS2 gene expression profiles of: non-fatigue versus fatigue. Multivariable regression analyses were used to examine the relationship between fatigue and numerous variables including depression. Participants were approximately 58 years old (+/- 13.2 years), 78% African American ( n = 95), and 72% male ( n = 88). The phenotype of fatigue was not significantly associated with gene expression of NPAS2 but was significantly associated with depression ( p< .001). This study suggests that further research should examine the causal mechanism between depression and fatigue in order to identify genetic factors that could explain the high comorbidity of depression and fatigue.

Background Altered pulmonary function is present early in the course of cystic fibrosis (CF), independent of documented infections or onset of pulmonary symptoms. New initiatives in clinical care are focusing on detection and characterization of pre-clinical disease. Thus, animal models are needed which recapitulate the pulmonary phenotype characteristic of early stage CF. Methods We investigated young CF mice to determine if they exhibit pulmonary pathophysiology consistent with the early CF lung phenotype. Lung histology and pulmonary mechanics were examined in 12–16 week old congenic C57bl/6 F508del and R117H CF mice using a forced oscillation technique (flexiVent). Results There were no significant differences in the resistance of the large airways. However, in both CF mouse models, prominent differences in the mechanical properties of the peripheral lung compartment were identified including decreased static lung compliance, increased elastance and increased tissue damping. CF mice also had distal airspace enlargement with significantly increased mean linear intercept distances. Conclusions An impaired ability to stretch and expand the peripheral lung compartment, as well as increased distances between gas exchange surfaces, were present in young CF mice carrying two independent Cftr mutations. This altered pulmonary histopathophysiology in the peripheral lung compartment, which develops in the absence of infection, is similar to the early lung phenotype of CF patients.