An In Vivo Functional Screen Uncovers miR-150-Mediated Regulation of Hematopoietic Injury Response

SummaryHematopoietic stem and progenitor cells are often undesired targets of chemotherapies, leading to hematopoietic suppression requiring careful clinical management. Whether microRNAs control hematopoietic injury response is largely unknown. We report an in vivo gain-of-function screen and the identification of miR-150 as an inhibitor of hematopoietic recovery upon 5-fluorouracil-induced injury. Utilizing a bone marrow transplant model with a barcoded microRNA library, we screened for barcode abundance in peripheral blood of recipient mice before and after 5-fluorouracil treatment. Overexpression of screen-candidate miR-150 resulted in significantly slowed recovery rates across major blood lineages, with associated impairment of bone marrow clonogenic potential. Conversely, platelets and myeloid cells from miR-150 null marrow recovered faster after 5-fluorouracil treatment. Heterozygous knockout of c-myb, a conserved target of miR-150, partially phenocopied miR-150-forced expression. Our data highlight the role of microRNAs in controlling hematopoietic injury response and demonstrate the power of in vivo functional screens for studying microRNAs in normal tissue physiology

Baseline Q-Wave Surpasses Time From Symptom Onset as a Prognostic Marker in ST-Segment Elevation Myocardial Infarction Patients Treated With Primary Percutaneous Coronary Intervention

ObjectivesWe assessed the incremental value of baseline Q waves over time from symptom onset as a marker of clinical outcome in ST-segment elevation myocardial infarction (STEMI).BackgroundTime from symptom onset is a central focus in STEMI patients. The presence of Q waves on the baseline electrocardiogram (ECG) has been suggested to be of incremental value to time from symptom onset in evaluating clinical outcomes.MethodsWe evaluated baseline Q waves and ST-segment resolution 30 min after primary percutaneous intervention (PCI) ECGs in 4,530 STEMI patients without prior infarction. Additionally, peak biomarkers; 90-day mortality; and the composite of death, congestive heart failure (CHF), or cardiogenic shock were assessed.ResultsFifty-six percent of patients had baseline Q waves: they were older, more frequently male and diabetic, and had a more advanced Killip class. Patients with baseline Q waves had greater mortality and a higher composite rate of death, CHF, and shock versus patients without baseline Q waves at 90 days (5.3% vs. 2.1% and 12.1% vs. 4.8%, respectively, both p < 0.001). Complete ST-segment resolution was highest, whereas 90-day mortality and the composite outcome were lowest among those randomized ≤3 h without baseline Q waves. After multivariable adjustment, baseline Q-wave but not time from symptom onset was significantly associated with a 78% relative increase in the hazard of 90-day mortality and a 90% relative increase in the hazard of death, shock, and CHF.ConclusionsBaseline Q waves in STEMI patients treated with primary PCI provide an independent prognostic marker of clinical outcome. These data might be useful in designing future clinical trials as well as in evaluating patients for triage and potential transfer for planned primary PCI. (Pexelizumab in Conjunction With Angioplasty in Acute Myocardial Infarction [APEX-AMI]; NCT00091637

Predicting sexual problems in women: The relevance of sexual excitation and sexual inhibition

This is the post-print version of the article. The official published version can be obtained from the link below.Data from a non-clinical sample of 540 heterosexual women were used to examine the relationships between scores on the Sexual Excitation/Sexual Inhibition Inventory for Women (SESII-W) and ratings of current sexual problems, lifetime arousal difficulty, lifetime orgasm difficulty, and lifetime problems with low sexual interest. Multiple regression analyses also included several demographic/background variables as predictors: age, full-time employment, completed college, children in household, married, health ratings, importance of sex, and whether the woman was in a sexual relationship. The strongest statistical predictors of both current and lifetime sexual problems were the SESII-W inhibition factors Arousal Contingency and Concerns about Sexual Function. Demographic factors did not feature largely in any of the models predicting sexual problems even when statistically significant relationships were found. If future research supports the predictive utility of the SESII-W in identifying women who are more likely to experience sexual difficulties, these scales may be used as prognostic factors in treatment studies.This study was funded, in part, by a grant from the Lilly Centre for Women's Health

ACC/AHA 2007 Guidelines for the Management of Patients With Unstable Angina/Non–ST-Elevation Myocardial Infarction A Report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Writing Committee to Revise the 2002 Guidelines for the Management of Patients With Unstable Angina/Non–ST-Elevation Myocardial Infarction) Developed in Collaboration with the American College of Emergency Physicians, the Society for Cardiovascular Angiography and Interventions, and the Society of Thoracic Surgeons Endorsed by the American Association of Cardiovascular and Pulmonary Rehabilitation and the Society for Academic Emergency Medicine

"The ACC/AHA Task Force on Practice Guidelines was formed to make recommendations regarding the diagnosis and treatment of patients with known or suspected cardiovascular disease (CVD). Coronary artery disease (CAD) is the leading cause of death in the United States. Unstable angina (UA) and the closely related condition of non–ST-segment elevation myocardial infarction (NSTEMI) are very common manifestations of this disease. The committee members reviewed and compiled published reports through a series of computerized literature searches of the English-language literature since 2002 and a final manual search of selected articles. Details of the specific searches conducted for particular sections are provided when appropriate. Detailed evidence tables were developed whenever necessary with the specific criteria outlined in the individual sections. The recommendations made were based primarily on these published data. The weight of the evidence was ranked highest (A) to lowest (C). The final recommendations for indications for a diagnostic procedure, a particular therapy, or an intervention in patients with UA/NSTEMI summarize both clinical evidence and expert opinion.

Fundamentos e aplicações da metodologia de ensaios não destrutivos com células bacterianas

Os Ensaios Não Destrutivos (END) são determinantes para a fiabilidade de materiais cuja integridade é de extrema importância. A técnica de Ensaios Não Destrutivos com células bacterianas (CB) tem demonstrado viabilidade para deteção de defeitos superficiais, com espessuras e profundidades inferiores a 5 μm em vários materiais de engenharia. O conhecimento adquirido sobre esta técnica já é significativo mas alguns aspetos necessitam de mais desenvolvimentos, como a interação bactéria-defeito e a viabilidade da técnica para condições de superfície diferentes das já ensaiadas. O objetivo deste trabalho é alargar a técnica a uma maior gama de materiais de engenharia com condições de superfície diferentes, assim como, desenvolver o conhecimento sobre a interação bactéria-defeito. A bactéria Rhodococcus erythropolis foi usada na inspeção de vários materiais como Alumínio Liga 1100, Estanho, Ouro, Prata, INCONEL 9095, Aço revestido com Nickel, Cobre revestido com Ouro, Alumínio revestido com Cobre, Polímero com nano tubos de carbono, entre outros, e com condições de superfície diferentes como superfícies anodizadas e revestidas. Foram também caracterizados os campos magnéticos de dois equipamentos desenvolvidos para esta técnica de Ensaios Não Destrutivos. Os resultados experimentais mostraram que a utilização de campos magnéticos contribui positivamente para a deteção de defeitos e que provetes com revestimentos superficiais diferentes revelam resultados diferentes apesar de terem o mesmo material base

Homogeneous nonrelativistic geometries as coset spaces

We generalize the coset procedure of homogeneous spacetimes in (pseudo-) Riemannian geometry to non-Lorentzian geometries. These are manifolds endowed with nowhere vanishing invertible vielbeins that transform under local non-Lorentzian tangent space transformations. In particular we focus on nonrelativistic symmetry algebras that give rise to (torsional) Newton-Cartan geometries, for which we demonstrate how the Newton-Cartan metric complex is determined by degenerate co- and contravariant symmetric bilinear forms on the coset. In specific cases we also show the connection of the resulting nonrelativistic coset spacetimes to pseudo-Riemannian cosets via Inonu-Wigner contraction of relativistic algebras as well as null reduction. Our construction is of use for example when considering limits of the AdS/CFT correspondence in which nonrelativistic spacetimes appear as gravitational backgrounds for nonrelativistic string or gravity theories