SUMMARY Misfolding of ΔF508 CFTR underlies pathology in most CF patients. F508 resides in the first nucleotide binding domain (NBD1) of CFTR near a predicted interface with the fourth intracellular loop (ICL4). Efforts to identify small molecules that restore function by correcting the folding defect have revealed an apparent efficacy ceiling. To understand the mechanistic basis of this obstacle, positions statistically coupled to 508, in evolved sequences, were identified and assessed for their impact on both NBD1 and CFTR folding. The results indicate that both NBD1 folding and interaction with ICL4 are altered by the ΔF508 mutation and that correction of either individual process is only partially effective. By contrast, combination of mutations that counteract both defects restores ΔF508 maturation and function to wild type levels. These results provide a mechanistic rationale for the limited efficacy of extant corrector compounds and suggest approaches for identifying compounds that correct both defective steps.

Objectives The goal of this study was to examine 2006 to 2010 emergency department (ED) admission rates, hospital procedures, lengths of stay, and costs for acute heart failure (AHF). Background Patients with AHF are often admitted and are associated with high readmissions and cost. Methods We utilized Nationwide Emergency Department Sample AHF data from 2006 to 2010 to describe admission proportion, hospital length of stay (LOS), and ED charges as a surrogate for resource utilization. Results were compared across U.S. regions, patient insurance status, and hospital characteristics. Results There were 958,167 mean yearly ED visits for AHF in the United States. Fifty-one percent of the patients were female, and the median age was 75.1 years (interquartile range [IQR]: 62.5 to 83.7 years). Overall, 83.7% (95% confidence interval: 83.1% to 84.2%) were admitted; the median LOS was 3.4 days (IQR: 1.9 to 5.8 days). Comparing 2006 with 2010, there was a small decrease in median LOS (0.09 days), but the proportion admitted did not change. Odds of admission, adjusting for age, sex, hospital characteristic (academic and safety net status), and insurance (Medicare, Medicaid, private, self-pay/no charge) were highest in the Northeast. Median ED charges were $1,075 (IQR: $679 to $1,665) in 2006 and $1,558 (IQR: $1,018 to $2,335) in 2010. Patients without insurance were more likely to be discharged from the ED, but when admitted, were more likely to receive a major diagnostic or therapeutic procedure. Conclusions A very high proportion of ED patients with AHF are admitted nationally, with significant variation in disposition and procedural decisions based on region of the country and type of insurance, even after adjusting for potential confounding.

The current literature suggests that prehospital cervical immobilisation may not be necessary unless the patient has focal neurological deficits. Studies show that patients with penetrating neck trauma who are haemodynamically stable and exhibit no "hard signs" of vascular injury may be evaluated initially by MDCT imaging even when platysma violation is present. Airway management is evolving, but traditional laryngoscopy continues to be the mainstay of airway stabilisation.

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