Thrombopoietin stimulates megakaryocytopoiesis, myelopoiesis, and expansion of CD34+ progenitor cells from single CD34+Thy-1+Lin- primitive progenitor cells

Thrombopoietin (TPO) or MpI ligand is known to stimulate megakaryocyte (MK) proliferation and differentiation. To identify the earliest human hematopoietic cells on which TPO acts, we cultured single CD34+Thy- 1+Lin- adult bone marrow cells in the presence of TPO alone, with TPO and interleukin-3 (IL-3), or with TPO and c-kit ligand (KL) in the presence of a murine stromal cell line (Sys1). Two distinct growth morphologies were observed: expansion of up to 200 blast cells with subsequent differentiation to large refractile CD41b+ MKs within 3 weeks or expansion to 200-10,000 blast cells, up to 25% of which expressed CD34. The latter blast cell expansions occurred over a 3- to 6-week period without obvious MK differentiation. Morphological staining, analysis of surface marker expression, and colony formation analysis revealed that these populations consisted predominantly of cells committed to the myelomonocytic lineage. The addition of IL-3 to TPO-containing cultures increased the extent of proliferation of single cells, whereas addition of KL increased the percentage of CD34+ cells among the expanding cell populations. Production of multiple colony- forming unit-MK from single CD34+Thy-1+Lin- cells in the presence of TPO was also demonstrated. In limiting dilution assays of CD34+Lin- cells, TPO was found to increase the size and frequency of cobblestone areas at 4 weeks in stromal cultures in the presence of leukemia inhibitory factor and IL-6. In stroma-free cultures, TPO activated a quiescent CD34+Lin-Rhodamine 123lo subset of primitive hematopoietic progenitor cells into cycle, without loss of CD34 expression. These data demonstrate that TPO acts directly on and supports division of cells more primitive than those committed to the MK lineage.     

Computer-based interventions for sexual health promotion: systematic review and meta-analyses

This systematic review was conducted to determine the effects of self-help interactive computer-based interventions (ICBIs) for sexual health promotion. We searched 40 databases for randomized controlled trials (RCTs) of computer-based interventions, defining 'interactive' as programmes that require contributions from users to produce personally relevant material. We conducted searches and analysed data using Cochrane Collaboration methods. Results of RCTs were pooled using a random-effects model with standardized mean differences for continuous outcomes and odds ratios (ORs) for binary outcomes, with heterogeneity assessed using the I(2) statistic. We identified 15 RCTs of ICBIs (3917 participants). Comparing ICBIs to minimal interventions, there were significant effects on sexual health knowledge (standardized mean difference [SMD] 0.72, 95% confidence interval [CI] 0.27-1.18); safer sex self-efficacy (SMD 0.17, 95% CI 0.05-0.29); safer-sex intentions (SMD 0.16, 95% CI 0.02-0.30); and sexual behaviour (OR 1.75, 95% CI 1.18-2.59). ICBIs had a greater impact on sexual health knowledge than face-to-face interventions did (SMD 0.36, 95% CI 0.13-0.58). ICBIs are effective tools for learning about sexual health, and show promising effects on self-efficacy, intention and sexual behaviour. More data are needed to analyse biological outcomes and cost-effectiveness.     

Differentiation of cardiac and noncardiac dyspnea using bioelectrical impedance vector analysis (BIVA)

BackgroundThere is no gold standard for the differential diagnosis of acute dyspnea despite the usefulness of N-terminal pro–B-type natriuretic peptide (NT-proBNP) and lung ultrasound. No study has evaluated the contribution of bioelectrical impedance vector analysis (BIVA) in discriminating between cardiac and noncardiac dyspnea. We sought to determine whether a relationship exists between ultrasound detection of lung congestion, NT-proBNP, and BIVA in patients with acute dyspnea.Methods and ResultsEligible patients were between 50 and 95 years, with an estimated glomerular filtration rate of ≥30 mL min^?1 1.73 m^?2, who presented to an emergency department with dyspnea. Dyspnea was classified by reviewers blinded to BIVA as cardiac or noncardiac based on physical examination, electrocardiogram, chest X-ray, NT-proBNP, and B-lines of lung congestion on ultrasound. Overall, 315 patients were enrolled (median age 77 years, 48% male). An adjudicated diagnosis of cardiac dyspnea was established in 169 (54%). Using BIVA, vector positions below ?1 SD of the Z-score of reactance were associated with peripheral congestion (χ² = 115; P < .001). BIVA measures were reasonably accurate in discriminating cardiac and noncardiac dyspnea (69% sensitivity, 79% specificity, 80% area under the receiver operating characteristic curve).ConclusionsIn patients presenting with acute dyspnea, the combination of BIVA and lung ultrasound may provide a rapid noninvasive method to determine the cause of dyspnea.