Furthermore, analysis of quantitative PCR data demonstrated a significant downregulation of Sema3e gene expression in bronchial epithelial cells from patients with severe asthma (Fig 2, B) compared ...with cells from healthy individuals. ...we revealed that Sema3E expression is reduced in bronchial epithelial cells from patients with severe asthma. Because the functional form of Sema3E is a secreted protein, we then studied in vivo secretion of Sema3E protein into the airways by comparing its level in human bronchoalveolar lavage fluid (BALF) obtained from healthy donors and patients with severe asthma by ELISA. Under asthmatic conditions, along with augmented epithelial inflammatory response,7 we found decreased expression of Sema3E in the airway epithelium. ...it is plausible that Sema3E may negatively regulate the release of inflammatory mediators from the epithelial cells and recruitment of inflammatory effector cells. ...slides were developed using Fast Red (Sigma-Aldrich Canada Ltd, Oakville, Ontario, Canada) and counterstained with modified Mayer's hematoxylin (Fisher Scientific, Fair Lawn, NJ).
The Alliance for Academic Internal Medicine (AAIM) supports the need for a uniform subspecialty fellowship training and advanced residency training start date. At present, training programs and their ...sponsoring institutions vary widely in the timing of institutional orientation and fellowship/advanced residency training start dates. Some institutions conduct orientation programs before the scheduled completion of the initial training program, which leads to conflicts for the resident between current and future obligations. AAIM believes that requiring residents to report for fellowship before completion of residency training is disruptive to medical education, creates unnecessary stress for the residents, and risks, violating federal labor laws and Center for Medicare and Medicaid Services graduate medical education funding rules. Adoption of Jul 1, 2015 as the earliest start date for all training and orientation activities can be endorsed internally by AAIM institutions and would resolve these conflicts. Here, Barrett et al examine AAIM adoption of a uniform subspecialty fellowship and other advanced training.
Background We previously reported an interaction between maternal asthma and the child's HLA-G genotype on the child's subsequent risk for asthma. The implicated single nucleotide polymorphism ...at +3142 disrupted a target site for the microRNA (miR)-152 family. We hypothesized that the interaction effect might be mediated by these miRs. Objective The objective of this study was to test this hypothesis in adults with asthma who are a subset of the same subjects who participated in our earlier family-based studies. Methods We measured soluble HLA-G (sHLA-G) concentrations in bronchoalveolar lavage fluid (n = 36) and plasma (n = 57) from adult asthmatic subjects with and without a mother with asthma, and HLA-G and miR-152 family ( miR-148a , miR-148b , and miR-152 ) transcript levels in airway epithelial cells from the same subjects. Results miR-148b levels were significantly increased in airway epithelial cells from asthmatic subjects with an asthmatic mother compared with those seen in asthmatic subjects without an asthmatic mother, and +3142 genotypes were associated with sHLA-G concentrations in bronchoalveolar lavage fluid among asthmatic subjects with an asthmatic mother but not among those with a nonasthmatic mother. Neither effect was observed in the plasma (sHLA-G) or white blood cells (miRNA). Conclusion These combined results are consistent with +3142 allele–specific targeting of HLA-G by the miR-152 family and support our hypothesis that miRNA regulation of sHLA-G in the airway is influenced by both the asthma status of the subject's mother and the subject's genotype. Moreover, we demonstrate that the effects of maternal asthma on the gene regulatory landscape in the airways of the mother's children persist into adulthood.
Background Pneumonia is the leading infectious cause of death. Early deterioration and death commonly result from progressive sepsis, shock, respiratory failure, and cardiac complications. Recent ...data suggest that cardiac arrest may also be common, yet few previous studies have addressed this. Accordingly, we sought to characterize early cardiac arrest in patients who are hospitalized with coexisting pneumonia. Methods We performed a retrospective analysis of a multicenter cardiac arrest database, with data from > 500 North American hospitals. We included in-hospital cardiac arrest events that occurred in community-dwelling adults with pneumonia within the first 72 h after hospital admission. We compared patient and event characteristics for patients with and without pneumonia. For patients with pneumonia, we also compared events according to event location. Results We identified 4,453 episodes of early cardiac arrest in patients who were hospitalized with pneumonia. Among patients with preexisting pneumonia, only 36.5% were receiving mechanical ventilation and only 33.3% were receiving infusions of vasoactive drugs prior to cardiac arrest. Only 52.3% of patients on the ward were receiving ECG monitoring prior to cardiac arrest. Shockable rhythms were uncommon in all patients with pneumonia (ventricular tachycardia or fibrillation, 14.8%). Patients on the ward were significantly older than patients in the ICU. Conclusions In patients with preexisting pneumonia, cardiac arrest may occur in the absence of preceding shock or respiratory failure. Physicians should be alert to the possibility of abrupt cardiopulmonary collapse, and future studies should address this possibility. The mechanism may involve myocardial ischemia, a maladaptive response to hypoxia, sepsis-related cardiomyopathy, or other phenomena.
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