Toll-like receptor 2-deficiency on bone marrow-derived cells augments vascular healing of murine arterial lesions.

AIMS: Neointimal hyperplasia contributes to arterial restenosis after percutaneous transluminal coronary angioplasty or vascular surgery. Neointimal thickening after arterial injury is determined by inflammatory processes. We investigated the role of the innate immune receptor toll-like receptor 2 (TLR2) in neointima formation after arterial injury in mice. MATERIALS AND METHODS: Carotid artery injury was induced by 10% ferric chloride in C57Bl/6J wild type (WT), TLR2 deficient (B6.129-Tlr2tm1Kir/J, TLR2-/-) and WT mice treated with a TLR2 blocking antibody. 21 days after injury, carotid arteries were assessed histomorphometrically and for smooth muscle cell (SMC) content. To identify the contribution of circulating cells in mediating the effects of TLR2-deficiency, arterial injury was induced in WT/TLR2-/--chimeric mice and the paracrine modulation of bone marrow-derived cells from WT and TLR2-/- on SMC migration compared in vitro. KEY FINDINGS: TLR2-/- mice and WT mice treated with TLR2 blocking antibodies exhibited reduced neointimal thickening (23.7 ± 4.2 and 6.5 ± 3.0 vs. 43.1 ± 5.9 µm, P < 0.05 and P < 0.01), neointimal area (5491 ± 1152 and 315 ± 76.7 vs. 13,756 ± 2627 µm2, P < 0.05 and P < 0.01) and less luminal stenosis compared to WT mice (8.5 ± 1.6 and 5.0 ± 1.3 vs. 22.4 ± 2.2%, both P < 0.001n = 4-8 mice/group). The phenotypes of TLR2-/- vs. WT mice were completely reverted in WT/TLR2-/- bone marrow chimeric mice (5.9 ± 1.5 µm neointimal thickness, 874.2 ± 290.2 µm2 neointima area and 2.7 ± 0.6% luminal stenoses in WT mice transplanted with TLR2-/- bone marrow vs. 23.6 ± 5.1 µm, 3555 ± 511 µm2 and 12.0 ± 1.3% in WT mice receiving WT bone marrow, all P < 0.05, n = 6/group). Neointimal lesions of WT and WT mice transplanted with TLR2-/- bone marrow chimeric mice showed increased numbers of SMC (10.8 ± 1.4 and 12.6 ± 1.4 vs. 3.8 ± 0.9 in TLR2-/- and 3.5 ± 1.1 cells in WT mice transplanted with TLR2-/- bone marrow, all P < 0.05, n = 6). WT bone marrow cells stimulated SMC migration more than TLR2-deficient bone marrow cells (1.7 ± 0.05 vs. 1.3 ± 0.06-fold, P < 0.05, n = 7) and this effect was aggravated by TLR2 stimulation and diminished by TLR2 blockade (1.1 ± 0.03-fold after stimulation with TLR2 agonists and 0.8 ± 0.02-fold after TLR2 blockade vs. control treated cells defined as 1.0, P < 0.05, n = 7). SIGNIFICANCE: TLR2-deficiency on hematopoietic but not vessel wall resident cells augments vascular healing after arterial injury. Pharmacological blockade of TLR2 may thus be a promising therapeutic option to improve vessel patency after iatrogenic arterial injury.

Digital Communication Technology: Does Offering a Choice of Modality Improve Medication Adherence and Outcomes in a Persistent Asthma Population?

BACKGROUND: Use of digital communication technology has shown potential to improve asthma adherence and outcomes. Few studies have looked at patient preference around mode of medication reminders used to improve and maintain asthma medication adherence. OBJECTIVE: To determine if, in a population already receiving automated medication reminders, offering a choice for preferred mode of reminder (text, email, phone) would improve their adherence and asthma outcomes over a 1-year period. METHODS: This was a pragmatic, randomized controlled trial conducted at Kaiser Permanente Colorado involving 7522 adult patients with persistent asthma. Study patients were randomized to receive usual care or their choice of medication reminder. Differences between the 2 groups in both medication adherence and asthma outcomes were then assessed over the following year. RESULTS: Only 30% of those offered a choice of medication reminder modality responded by making a choice, with 52% preferring text messaging. There was less of a decrease in adherence rate over the 1-year period in those who made a choice regarding the mode of medication refill reminder. There was no difference in asthma outcomes between those who did make a choice compared with those who did not make a choice regarding the mode of medication refill reminder. CONCLUSION: In a patient population already receiving medication reminders, offering a choice about what type of technology-enabled asthma medication reminder patients wanted did not improve outcomes but did enable a subgroup to better maintain their medication adherence.

Effects of typeface characteristics on visual field asymmetries for letter identification in children and adults.

The current study compared the effects of three typeface characteristics (script-likeness, or resemblance to cursive writing; confusability, or likelihood of confusing one letter with another; and difficulty, as indexed by naming latency) on letter identification in a divided visual fields test. It also asked whether and how these effects change with subject age. Subjects were 48 right-handed 9- and 14-year-old boys and undergraduate men--16 in each age group. They orally identified single letters in eight different typefaces presented tachistoscopically to the left or right visual hemifield. The difference between hemifields in threshold presentation time was the dependent measure. For all ages, the direction and degree of the visual field advantage changed with typeface complexity (a composite index of the three characteristics), with the simplest typeface yielding a right visual field/left hemisphere advantage, and with two of the most complex typefaces yielding a left visual field/right hemisphere advantage. There were age differences, though, in the relative contribution of the individual characteristics to this effect. For undergraduates, the strongest predictor of right hemisphere participation was script-likeness, whereas for 9- and 14-year-olds it was typeface difficulty.