Left ventricular geometric patterns and adaptations to hemodynamics are similar in elderly men and women

<p>Abstract</p> <p>Background</p> <p>Common conditions such as obesity and hypertension result in hemodynamic alterations that will induce remodeling of the left ventricle (LV). However, differences between the genders in the relationship of hemodynamics to LV geometry are not well known.</p> <p>The present study aims to investigate differences between the genders in this respect, in a sample of elderly persons.</p> <p>Methods</p> <p>Echocardiography and Doppler was performed in a population-based sample aged 70 - The Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS) study (n = 922).</p> <p>Hemodynamic patterns obtained by echocardiography and Doppler were evaluated in relation to four LV geometric groups (normal, concentric remodeling, eccentric hypertrophy and concentric hypertrophy).</p> <p>Results</p> <p>No significant difference between the genders was observed regarding the prevalence of the LV geometric groups.</p> <p>Mean values of most evaluated echocardiography and Doppler variables differed between men and women, such as LA, IVS, LVEDD and IVRT, but the relationship of hemodynamic variables to LV geometric groups did not differ between the genders.</p> <p>Conclusions</p> <p>Although mean values of many echocardiographic variables differed between men and women, the LV geometric adaptations to a given hemodynamic load appear similar in both genders.</p

Low Walking Impairment Questionnaire score after a recent myocardial infarction identifies patients with polyvascular disease

Objectives: To evaluate whether the Walking Impairment Questionnaire score could identify patients with polyvascular disease in a population with recent myocardial infarction and their association with cardiovascular events during two-year follow-up. Design: A prospective observational study. Setting: Patients admitted to the acute coronary care unit, the Department of Cardiology, Uppsala University Hospital. Participants: Patients admitted with acute Non-STEMI- or STEMI-elevation myocardial infarction. Main outcome measures: The Walking Impairment Questionnaire, developed as a self-administered instrument to assess walking distance, speed, and stair climbing in patients with peripheral artery disease, predicts future cardiovascular events and mortality. Two hundred and sixty-three patients with recent myocardial infarction answered Walking Impairment Questionnaire. Polyvascular disease was defined as abnormal findings in the coronary- and carotid arteries and an abnormal ankle-brachial index. The calculated score for each of all three categories were divided into quartiles with the lowest score in first quartile. Results: The lowest (worst) quartile in all three Walking Impairment Questionnaire categories was associated with polyvascular disease, fully adjusted; distance, odds ratio (OR) 5.4 (95% confidence interval (CI) 1.8-16.1); speed, OR 7.4 (95% CI 1.5-36.5); stair climbing, OR 8.4 (95% CI 1.0-73.6). In stair climbing score, patients with the lowest (worst) score had a higher risk for the composite cardiovascular endpoint compared to the highest (best) score; hazard ratio 5.3 (95% CI 1.5-19.0). The adherence to medical treatment was high (between 81.7% and 99.2%). Conclusions: The Walking Impairment Questionnaire is a simple tool to identify myocardial infarction patients with more widespread atherosclerotic disease and although well treated medically, stair climbing predicts cardiovascular events

Targeting p53 in Vivo: A First-in-Human Study With p53-Targeting Compound APR-246 in Refractory Hematologic Malignancies and Prostate Cancer.

PURPOSEAPR-246 (PRIMA-1MET) is a novel drug that restores transcriptional activity of unfolded wild-type or mutant p53. The main aims of this first-in-human trial were to determine maximum-tolerated dose (MTD), safety, dose-limiting toxicities (DLTs), and pharmacokinetics (PK) of APR-246. PATIENTS AND METHODSAPR-246 was administered as a 2-hour intravenous infusion once per day for 4 consecutive days in 22 patients with hematologic malignancies and prostate cancer. Acute myeloid leukemia (AML; n = 7) and prostate cancer (n = 7) were the most frequent diagnoses. Starting dose was 2 mg/kg with dose escalations up to 90 mg/kg.ResultsMTD was defined as 60 mg/kg. The drug was well tolerated, and the most common adverse effects were fatigue, dizziness, headache, and confusion. DLTs were increased ALT/AST (n = 1), dizziness, confusion, and sensory disturbances (n = 2). PK showed little interindividual variation and were neither dose nor time dependent; terminal half-life was 4 to 5 hours. Tumor cells showed cell cycle arrest, increased apoptosis, and upregulation of p53 target genes in several patients. Global gene expression analysis revealed changes in genes regulating proliferation and cell death. One patient with AML who had a p53 core domain mutation showed a reduction of blast percentage from 46% to 26% in the bone marrow, and one patient with non-Hodgkin's lymphoma with a p53 splice site mutation showed a minor response. CONCLUSIONWe conclude that APR-246 is safe at predicted therapeutic plasma levels, shows a favorable pharmacokinetic profile, and can induce p53-dependent biologic effects in tumor cells in vivo

Higher levels of multiple ecosystem services are found in forests with more tree species

Forests are of major importance to human society, contributing several crucial ecosystem services. Biodiversity is suggested to positively influence multiple services but evidence from natural systems at scales relevant to management is scarce. Here, across a scale of 400,000 km(2), we report that tree species richness in production forests shows positive to positively hump-shaped relationships with multiple ecosystem services. These include production of tree biomass, soil carbon storage, berry production and game production potential. For example, biomass production was approximately 50% greater with five than with one tree species. In addition, we show positive relationships between tree species richness and proxies for other biodiversity components. Importantly, no single tree species was able to promote all services, and some services were negatively correlated to each other. Management of production forests will therefore benefit from considering multiple tree species to sustain the full range of benefits that the society obtains from forests