Human epididymis protein 4 (HE4) levels inversely correlate with lung function improvement (delta FEV1) in cystic fibrosis patients receiving ivacaftor treatment

Background

We have recently shown that human epididymis protein 4 (HE4) levels correlate with the severity of cystic fibrosis (CF) lung disease. However, there are no data on how HE4 levels alter in patients receiving CFTR modulating therapy.

The human major histocompatibility complex class Ib molecule HLA-E binds signal sequence-derived peptides with primary anchor residues at positions 2 and 9

Human histocompatibility leukocyte antigen E (HLA-E) and mouse major histocompatibility complex (MHC) class Ib antigen, Qa-1, share the same substitutions at two normally conserved positions 143 and 147, which are likely to affect binding of the C terminus of peptides. Qa-1 is able to bind a peptide derived from the leader sequence of H-2 D and H-2 L molecules. We developed a peptide binding assay in vitro to compare the binding specificity of HLA-E with the mouse MHC class Ib molecule Qa-1. We demonstrate that HLA-E binds, although poorly, the peptide which binds to Qa-1 and that it also binds nonamer signal sequence-derived peptides from human MHC class I molecules. Using alanine and glycine substitutions, we could define primary anchor residues at positions 2 and 9 and secondary anchor residues at position 7 and possibly 3.     

Flecainide versus quinidine in the prevention of paroxysms of atrial fibrillation

We compared the efficacy of flecainide versus quinidine in preventing paroxysms of atrial fibrillation in a randomized open crossover study. Twenty-six patients with weekly attacks of atrial fibrillation during the last 3 months, objectified by 24-h holter monitoring or 12-lead electrocardiogram (ECG) were treated for a period of 3 months with flecainide 100 mg b.i.d. or quinidine 500 mg b.i.d. Efficacy was assessed by 24-h holter monitoring and a questionnaire at the end of each month. Dosage was adjusted to flecainide 100 mg t.i.d. or quinidine 500 mg t.i.d. if patients still had symptomatic paroxysms of atrial fibrillation according to a questionnaire or on holter monitoring. In 46% of the patients, flecainide 100 mg b.i.d. caused total abolition of supraventricular tachycardia; after dose adjustment it caused 50% total abolition. For quinidine, the figures are 16% (p less than 0.05) and 32% (NS), respectively. Side effects occurred with flecainide only after dose adjustment (23%), but on quinidine they occurred before (8%) and after dose adjustment (20%). We conclude that flecainide suppresses paroxysms of atrial fibrillation significantly more often as compared with quinidine in the lower dosage regimen. Optimal treatment dosage of flecainide is 100 mg b.i.d. After quinidine dose adjustment, the difference in efficacy is no longer significant. However, side effects necessitating discontinuation of quinidine developed in 20% of the patients as compared to none in patients treated with flecainide 100 mg b.i.d.     

Youth Tobacco Access and Possession Policy Interventions: Effects on Observed and Perceived Tobacco Use

This study evaluated the effects of tobacco Purchase, Use and Possession (PUP) laws on student perceptions of adolescent tobacco use within towns and schools. Twenty‐four towns were randomly assigned into two conditions, the experimental condition (E PUP) involved efforts to increase both PUP law enforcement and reduce minors' access to commercial sources of tobacco, whereas the control condition (C) focused only on efforts to reduce minors' access to commercial sources of tobacco. A hierarchical linear modeling analytical approach was selected due to the multilevel data and nested design. The present study found that over time, youth in the experimental PUP condition observed less youth tobacco usage at school and in their town, and perceived lower rates of tobacco among their peers at school and among friends than youth in the control condition. The findings suggest that PUP law enforcement might be used to strengthen community norms against youth tobacco use.