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This Viewpoint commends the ruling in favor of 340B-covered entities but contemplates if the absence of the Chevron deference will affect future health care-related policy.

The phenoxazine dye resazurin exhibits bactericidal activity against the Gram-negative pathogens Francisella tularensis and Neisseria gonorrhoeae. One resazurin derivative, resorufin pentyl ether, significantly reduces vaginal colonization by Neisseria gonorrhoeae in a mouse model of infection. The narrow spectrum of bacteria susceptible to resazurin and its derivatives suggests these compounds have a novel mode of action. To identify potential targets of resazurin and mechanisms of resistance, we isolated mutants of F. tularensis subsp. holarctica live vaccine strain (LVS) exhibiting reduced susceptibility to resazurin and performed whole genome sequencing. The genes pilD (FTL_0959) and dipA (FTL_1306) were mutated in half of the 46 resazurin-resistant (RZR) strains sequenced. Complementation of select RZR LVS isolates with wild-type dipA or pilD partially restored sensitivity to resazurin. To further characterize the role of dipA and pilD in resazurin susceptibility, a dipA deletion mutant, ΔdipA, and pilD disruption mutant, FTL_0959d, were generated. Both mutants were less sensitive to killing by resazurin compared to wild-type LVS with phenotypes similar to the spontaneous resazurin-resistant mutants. This study identified a novel role for two genes dipA and pilD in F. tularensis susceptibility to resazurin.

Background: Periprocedural myocardial infarction and injury (PM-injury) are the most common complications of percutaneous coronary intervention (PCI) and are associated with future adverse cardiac events. Inflammation plays a pivotal role in the development of PM-injury. In this randomized pilot trial, we assessed the effect of an anti-inflammatory medication colchicine on periprocedural myocardial injury. Methods: Patients undergoing PCI for stable angina or non–ST-segment–elevation myocardial infarction were randomized to oral colchicine (1 mg followed by 0.5 mg 1 hour later) or placebo, 6 to 24 hours preprocedure. Blood samples were taken immediately pre- and 24-hours post-PCI. The primary outcome, periprocedural myocardial infarction, was defined by an increase in post-PCI troponin >5×99th% upper reference limit when the pre-PCI troponin was normal, or >20% increase in post-PCI troponin when the pre-PCI troponin was raised, including supporting evidence of new myocardial ischemia. Major PM-injury was defined as per periprocedural myocardial infarction without supporting evidence of new myocardial ischemia. Minor PM-injury was defined by post-PCI troponin increase >99th% upper reference limit but ≤5×99th% upper reference limit. Results: A total of 196 patients met inclusion criteria and were randomized. One hundred twenty-one patients were excluded (no PCI, unstable troponin before PCI, or poor-quality measurements) leaving a study population of 75 patients. Thirty-six patients were randomized to colchicine and 39 to placebo preprocedure. Forty-four presented with non–ST-segment–elevation myocardial infarction and 31 with stable angina. High-sensitive (hs) troponin-I pre-PCI was similar between treatment groups (colchicine: 79 ng/L [4–1336] versus placebo: 35 [5–448], P =0.42). Absolute change in hs-troponin-I (calculated as 24-hour post-PCI minus pre-PCI measurements) was significantly lower in the colchicine group: 59 (1–221) versus placebo: 166 (53–530), P =0.02. No patients developed periprocedural myocardial infarction in either group. Significantly fewer patients developed major PM-injury: 11 (31%) versus 21 (54%), P =0.04 or minor PM-injury: 21 (58%) versus 33 (85%), P =0.01, if given colchicine pre-PCI. Conclusions: In this randomized pilot trial, colchicine given 6 to 24 hours pre-PCI reduces periprocedural myocardial injury. Registration: URL: https://www.anzctr.org.au ; Unique identifier: ACTRN12615000485538.

Intervertebral disc calcification is rare in the pediatric population and is associated with sudden neurological manifestations. Although commonly symptomatic, conservative management yields excellent prognosis in the vast majority of cases. The following case illustrates the finding of intervertebral disc calcification in a patient with vertebral body segmentation anomaly consistent with Klippel-Feil Syndrome. As both entities are associated with potential neurological sequelae, this case of coexistent pathologies highlights the importance of recognizing the potential presence of intervertebral disc calcifications in pediatric Klippel-Feil Syndrome patients.

In this letter, we investigate the impact of environment on integrated and spatially-resolved stellar kinematics of a sample of massive, quiescent galaxies at intermediate redshift ($0.6, Comment: 10 pages, 5 figures, submitted to ApJ Letters

Summary Aims Despite the guidelines, a “treatment gap” exists in the delivery of pharmacotherapy for secondary prevention. We aimed to analyze the trend in guideline-based medication usage following percutaneous coronary intervention (PCI) using the Melbourne Interventional Group (MIG) registry over a 6-year period (2005–2010). Methods The MIG registry prospectively collects demographical, clinical, and procedural characteristics of consecutive patients undergoing PCI. We assessed medication use (aspirin, clopidogrel, ACE inhibitors, angiotensin receptor blockers, beta-blockers, and lipid-lowering agents) at 30 days and 12 months in patients alive and able to provide the information. Results The cohort consists of 12,813 patients who underwent 14,787 consecutive interventional procedures. They comprised 76% males: 22% were elderly (≥75 years), 23% had diabetes, 2% had severe renal impairment, 2% had severe left ventricular dysfunction, 26% presented with STEMI, and 44% of patients received drug-eluting stent. Follow-up was complete for 97.8% of the cohort at 30 days (2.2% mortality) and 89.1% at 12 months (4% mortality). From 2005 to 2010, the percentage of patients taking all five classes of medications increased each year. In 2010 at 30 days, nearly 60% of patients took all five classes of medications, and by 12 months, 75% of patients were taking four or five classes of medications. Conclusion In conclusion, while the increasing use of cardiovascular medicines in an “at-risk” Australian cohort is encouraging, a treatment gap appears to still exist.

Recent data suggests hospitals fail to meet guideline specified time to PCI for a proportion of STEMI presentations. Implicit in achieving this time is the rapid assembly of crucial catheter laboratory staff. As proof of concept, we integrated traffic congestion data, distance to destination, and