Contraction of small arteries is regulated by the sympathetic nervous system, but the Ca2+ transients during neurally stimulated contraction of intact small arteries have not yet been recorded. We loaded rat mesenteric small arteries with the fluorescent Ca2+ indicator fluo‐4 and mounted them in a myograph that permitted simultaneous (i) high‐speed confocal imaging of fluorescence from individual smooth muscle cells, (ii) electrical stimulation of perivascular nerves, and (iii) recording of isometric tension. Sympathetic neuromuscular transmission was achieved by electrical field stimulation (EFS) (frequency, 10 Hz; pulse voltage, 40 V; pulse duration, 0.2 ms) in the presence of capsaicin and scopolamine (to inhibit ‘sensory’ and cholinergic nerves, respectively). During the first 20 s of EFS, force rose to a small peak and then declined. During this time, junctional Ca2+ transients (jCaTs) were present at relatively high frequency. We have previously attributed jCaTs to influx of Ca2+ through post‐junctional P2X receptors activated by ATP. Propagating asynchronous Ca2+ waves, previously associated with bath‐applied α1‐adrenoceptor agonists, were not initially present. During the next 2.5 min of EFS, force rose slowly, and asynchronous propagating Ca2+ waves appeared. The selective α1‐adrenoceptor antagonist prazosin abolished both the slowly developing contraction and the Ca2+ waves, but reduced the initial transient contraction by only ∼25 %. During 3 min of EFS in prazosin, the frequency of jCaTs declined markedly; at sites at which at least one jCaT occurred, the average probability of a jCaT was 0.008 ± 0.002 pulse−1 in the first 20 s and 0.0007 ± 0.0002 pulse−1 in the last 20 s. We suggest that (i) ATP released from sympathetic varicosities activates the initial, transient, contraction and the activator Ca2+ is derived largely from jCaTs, and (ii) sympathetically released noradrenaline (NA) activates the later, major contraction through mechanisms involving α1‐adrenoceptors and which are associated with propagating Ca2+ waves.

Adenovirus (AdV) is an increasingly recognized threat to recipients of allogeneic hematopoietic stem cell transplantation (allo-HCT), particularly when infection is prolonged and unresolved. AdVance is the first multinational, multicenter study to evaluate the incidence of AdV infection in both pediatric and adult allo-HCT recipients across European transplantation centers. Medical records for patients undergoing first allo-HCT between January 2013 and September 2015 at 50 participating centers were reviewed. The cumulative incidence of AdV infection (in any sample using any assay) during the 6 months after allo-HCT was 32% (95% confidence interval [CI], 30.9% to 33.4%) among pediatric allo-HCT recipients (n = 1736) and 6% (95% CI, 4.7% to 6.4%) among adult allo-HCT recipients (n = 2540). The incidence of AdV viremia 1000 copies/mL (a common threshold for initiation of preemptive treatment) was 14% (95% CI, 13.0% to 14.8%) in pediatric recipients and 1.5% (95% CI, 1.1% to 2.0%) in adult recipients. Baseline risk factors for developing AdV viremia 1000 copies/mL included younger age, use of T cell depletion, and donor type other than matched related. Baseline demographic factors were broadly comparable across patients of all ages and identified by multivariate analyses. Notably, the incidence of AdV infection decreased stepwise with increasing age; younger adults (age 18 to 34 years) had a similar incidence as older pediatric patients (<18 years). This study provides a contemporary multicenter understanding of the incidence and risk factors for AdV infection following allo-HCT. Our findings may help optimize infection screening and intervention criteria, particularly for younger at-risk adults.

This multivariable analysis from the AdVance multicenter observational study assessed adenovirus (AdV) viremia peak, duration, and overall AdV viral burden-measured as time-averaged area under the viremia curve over 16 weeks (AAUC 0-16 ) -as predictors of all-cause mortality in pediatric allo-HCT recipients with AdV viremia. In the 6 months following allo-HCT, 241 patients had AdV viremia ≥ 1000 copies/ml. Among these, 18% (43/241) died within 6 months of first AdV ≥ 1000 copies/ml. Measures of AdV viral peak, duration, and overall burden of infection consistently correlate with all-cause mortality. In multivariable analyses, controlling for lymphocyte recovery, patients with AdV AAUC 0-16 in the highest quartile had a hazard ratio of 11.1 versus the lowest quartile (confidence interval 5.3-23.6); for peak AdV viremia, the hazard ratio was 2.2 for the highest versus lowest quartile. Both the peak level and duration of AdV viremia were correlated with short-term mortality, independent of other known risk factors for AdV-related mortality, such as lymphocyte recovery. AdV AAUC 0-16 , which assesses both peak and duration of AdV viremia, is highly correlated with mortality under the current standard of care. New therapeutic agents that decrease AdV AAUC 0-16 have the potential of reducing mortality in this at-risk patient population.

ObjectiveAdenovirus (AdV) infections are potentially life‐threatening for allogeneic hematopoietic stem cell transplant (allo‐HCT) recipients. The AdVance study aimed to evaluate the incidence, management, and outcomes of AdV infections in European allo‐HCT recipients.MethodsAs part of the study, physician surveys were conducted to determine current AdV screening and treatment practices at their center.ResultsAll of the 28 respondents who treat pediatric patients reported routine AdV screening practices, with 93% screening all allo‐HCT recipients and others screening those with transplant‐related risk factors. Nearly all centers take a pre‐emptive approach to AdV treatment in both high‐ (89%) and low‐risk patients (75%). Among the 14 respondents who treat adult patients, 5 (36%) reported routine screening practices and few (21%) screen all allo‐HCT recipients unless risk factors are present. In adults, pre‐emptive AdV treatment is uncommon and quantitative AdV thresholds are rare. Typical treatment for all patients with symptomatic AdV infection is off‐label intravenous cidofovir.ConclusionsOur findings confirm that screening for AdV is more common in pediatric patients. Antiviral treatment is employed in both pediatric and adult patients, although adults are generally treated when AdV disease is diagnosed. The approach to AdV screening and treatment is risk‐based and consistent with clinical guidelines.

Background-Multiple measures of endothelial progenitor cells (EPCs) have been described, but there has been limited study of the comparability of these assays. We sought to determine the reproducibility of and correlation between alternative EPC assay methodologies.