Breast tumor cells with PI3K mutation or HER2 amplification are selectively addicted to Akt signaling.

Background: Dysregulated PI3K/Akt signaling occurs commonly in breast cancers and is due to HER2 amplification, PI3K mutation or PTEN inactivation. The objective of this study was to determine the role of Akt activation in breast cancer as a function of mechanism of activation and whether inhibition of Akt signaling is a feasible approach to therapy.

Methodology/principal Findings: A selective allosteric inhibitor of Akt kinase was used to interrogate a panel of breast cancer cell lines characterized for genetic lesions that activate PI3K/Akt signaling: HER2 amplification or PI3K or PTEN mutations in order to determine the biochemical and biologic consequences of inhibition of this pathway.

Differential response of primary tumor versus lymphatic metastasis to VEGFR-2 and VEGFR-3 kinase inhibitors cediranib and vandetanib.

Blood vessels are required for a tumor to grow and functional lymphatic vessels are required for it to disseminate to lymph nodes. In an attempt to eradicate both the primary tumor and its lymphatic metastasis, we targeted both blood and lymphatic vessels using two different tyrosine kinase inhibitors (TKIs): cediranib and vandetanib, which block vascular endothelial growth factor receptor (VEGFR)-2 and -3 in enzymatic assays. We found that although both cediranib and vandetanib slowed the growth rate of primary tumors and reduced blood vessel density, neither agent was able to prevent lymphatic metastasis when given after tumor cells had seeded the lymph node.

Genotoxic damage in Solea senegalensis exposed to sediments from the Sado Estuary (Portugal): effects of metallic and organic contaminants.

Juvenile Solea senegalensis (Senegalese sole) were exposed to freshly collected sediments from three sites of the Sado Estuary (West-Portuguese coast) in 28-day laboratory assays in order to assess the ecological risk from sediment contaminants, by measuring two genotoxicity biomarkers in peripheral blood: the percentage of Erythrocyte Nuclear Abnormalities (ENA) by use of an adaptation of the micronucleus test, and the percentage of DNA strand-breakage (DNA-SB) with the Comet assay. Sediments were surveyed for metallic (Cr, Ni, Cu, Zn, As, Cd and Pb) and organic (PAHs (polycyclic aromatic hydrocarbons), PCBs (polychlorinated biphenyls) and DDTs (dichloro-diphenyl-trichloroethane)) contaminants. Sediments from site A (farthest from hotspots of contamination) were found to be the least contaminated and weaker inducers of genotoxic damage, whereas sediments from sites B (urban influence) and C (affected by industrial effluents and agricultural runoffs) were responsible for a very significant increase in both ENA and DNA-SB, site B being most contaminated with metals and site C mainly with organic pollutants, especially PAHs and PCBs .

Electronegative LDL and lipid abnormalities in patients undergoing hemodialysis and peritoneal dialysis.

Background: Oxidative modification of low-density lipoprotein (LDL) has been demonstrated in patients with end-stage renal disease, where it is associated with oxidative stress and plays a key role in the pathogenesis of atherosclerosis. In this context, the generation of minimally oxidized LDL, also called electronegative LDL [LDL(-)], has been associated with active disease, and is a detectable sign of atherogenic tendencies. The purpose of this study was to evaluate serum LDL(-) levels and anti-LDL(-) IgG autoantibodies in end-stage renal disease patients on dialysis, comparing patients on hemodialysis (HD), peritoneal dialysis (PD) and a control group.

[Prognostic value of electrocardiographic findings in hemodynamically stable patients with acute symptomatic pulmonary embolism].

Introduction And Objectives: The aim of this study was to determine the prognostic value of electrocardiography in hemodynamically stable patients with a diagnosis of acute symptomatic pulmonary embolism (PE).

Methods: This prospective study included all hemodynamically stable outpatients who were diagnosed with PE at a university hospital. The electrocardiographic abnormalities investigated were: a) sinus tachycardia (>100 beats/min); b) ST-segment or T-wave abnormalities; c) right bundle branch block; d) an S1Q3T3 pattern, and e) recent-onset atrial arrhythmia.

Clinical predictors for fatal pulmonary embolism in 15,520 patients with venous thromboembolism: findings from the Registro Informatizado de la Enfermedad TromboEmbolica venosa (RIETE) Registry.

Background: Clinical predictors for fatal pulmonary embolism (PE) in patients with venous thromboembolism have never been studied.

Methods And Results: Using data from the international prospective Registro Informatizado de la Enfermedad TromboEmbolica venosa (RIETE) registry about patients with objectively confirmed symptomatic acute venous thromboembolism, we determined independent predictive factors for fatal PE. Between March 2001 and July 2006, 15 520 consecutive patients (mean age+/-SD, 66.

Development of a regional model of care for ambulatory total shoulder arthroplasty: a pilot study.

Unlabelled: Total shoulder arthroplasty (TSA) has traditionally been performed as inpatient surgery to provide adequate postoperative analgesia via intermittent opioid administration. We developed a regional model for ambulatory TSA using continuous brachial plexus nerve block (CBPNB). We asked whether this regional model would allow us to select patients to undergo outpatient TSA using CBPNB while providing similar outcomes to those patients who were managed with CBPNB and a one-night or longer inpatient hospital stay.

The effectiveness of Iberian protected areas in conserving terrestrial biodiversity.

The Iberian Peninsula harbors about 50% of European plant and terrestrial vertebrate species and more than 30% of European endemic species. Despite the global recognition of its importance, the selection of protected areas has been ad hoc and the effectiveness of such choices has rarely been assessed. We compiled the most comprehensive distributional data set of Iberian terrestrial plant and vertebrate species available to date and used it to assess the degree of species representation within existing protected areas.

3'-deoxy-3'-[18F]fluorothymidine positron emission tomography is a sensitive method for imaging the response of BRAF-dependent tumors to MEK inhibition.

Activating mutations of BRAF occur in approximately 7% of all human tumors and in the majority of melanomas. These tumors are very sensitive to pharmacologic inhibition of mitogen-activated protein kinase/extracellular signal-regulated kinase kinase (MEK), which causes loss of D-cyclin expression, hypophosphorylation of Rb, and G(1) arrest. Growth arrest is followed by differentiation or senescence and, in a subset of BRAF mutant tumors, by apoptosis.

Compressed matrix core tablet as a quick/slow dual-component delivery system containing ibuprofen.

The purpose of the present research was to produce a quick/slow biphasic delivery system for ibuprofen. A dual-component tablet made of a sustained release tableted core and an immediate release tableted coat was prepared by direct compression. Both the core and the coat contained a model drug (ibuprofen).

Cardiac function after CPAP therapy in patients with chronic heart failure and sleep apnea: a multicenter study.

Background And Purpose: Continuous positive airway pressure (CPAP) is an effective treatment for sleep apnea (SA), although the evidence for improving chronic heart failure (CHF) is inconclusive. Our aim was to evaluate the effect of CPAP treatment on the left ventricle ejection fraction (LVEF) among other cardiological variables in a randomized, multicenter, placebo (sham-CPAP)-controlled study.

Methods: After the selection procedure, 60 patients with CHF with LVEF<45% and SA with an apnea-hypopnea index (AHI)>10/h were evaluated at baseline, and after 3 months of treatment with optimal CPAP or sham-CPAP.

A global evaluation of metabolic theory as an explanation for terrestrial species richness gradients.

We compiled 46 broadscale data sets of species richness for a wide range of terrestrial plant, invertebrate, and ectothermic vertebrate groups in all parts of the world to test the ability of metabolic theory to account for observed diversity gradients. The theory makes two related predictions: (1) In-transformed richness is linearly associated with a linear, inverse transformation of annual temperature, and (2) the slope of the relationship is near -0.65.

Treatment of prostate cancer local recurrence after radical retropubic prostatectomy with 17-gauge interstitial transperineal cryoablation: initial experience.

Objectives: Interstitial transperineal cryoablation with 17-gauge cryoprobes is an accepted treatment modality for localized prostate cancer. The effectiveness of cryoablation in the treatment of local prostate cancer recurrence after radical retropubic prostatectomy (RRP) is unknown.

Methods: We reviewed the outcome of cryoablative treatment in 15 patients for biopsy-proven locally recurrent prostate cancer after RRP.

E. coli multiresistant meningitis after transrectal prostate biopsy.

Escherichia coli meningitis is a frequent pathology in children younger than 3 years old, but is an uncommon disease in adults. E. coli infection is the main cause of intrahospital bacteremia as a consequence of the employment of different medical procedures.

Limitations of biodiversity databases: case study on seed-plant diversity in Tenerife, Canary Islands.

Databases on the distribution of species can be used to describe the geographic patterns of biodiversity. Nevertheless, they have limitations. We studied three of these limitations: (1) inadequacy of raw data to describe richness patterns due to sampling bias, (2) lack of survey effort assessment (and lack of exhaustiveness in compiling data about survey effort), and (3) lack of coverage of the geographic and environmental variations that affect the distribution of organisms.

Growth, innovation, scaling, and the pace of life in cities.

Humanity has just crossed a major landmark in its history with the majority of people now living in cities. Cities have long been known to be society's predominant engine of innovation and wealth creation, yet they are also its main source of crime, pollution, and disease. The inexorable trend toward urbanization worldwide presents an urgent challenge for developing a predictive, quantitative theory of urban organization and sustainable development.

Clinical syndromes and clinical outcome in patients with pulmonary embolism: findings from the RIETE registry.

Introduction: The influence of the clinical syndromes of pulmonary embolism (PE) on clinical outcome has not been evaluated.

Patients And Methods: The Registro Informatizado de la Enfermedad TromboEmbólica (RIETE) is an ongoing registry of consecutive patients with acute venous thromboembolism. In this study, all enrolled patients with acute PE without preexisting cardiac or pulmonary disease were classified into three clinical syndromes: pulmonary infarction, isolated dyspnea, or circulatory collapse.

Electronic structure of C60 on Au(887).

We present an analysis of the electronic structure of C60 adsorbed on a vicinal Au(111) surface at different fullerene coverages using photoemission, x-ray absorption, and scanning tunneling microscopy/spectroscopy (STS). STS provides a straightforward determination of the highest occupied molecular orbital (HOMO) and the lowest unoccupied molecular orbital (LUMO) levels with respect to the Fermi energy. At C60 coverages of 0.

Effects of forest fragmentation on phenological patterns and reproductive success of the tropical dry forest tree Ceiba aesculifolia.

Spatial isolation caused by forest fragmentation and temporal isolation caused by asynchronous flowering of plants have been proposed as important factors that affect the reproduction ofplant populations. In a 4-year study, we determined the effects of forest fragmentation and spatial isolation on flowering phenology and reproductive success of the tropical tree Ceiba aesculifolia ([Kunth] Britton & Rose). We conducted our study in the dry forest of Mexico and compared populations in two habitat conditions based on density and environmental conditions: (1) disturbed habitat (four populations of < or =3 reproductive individuals/ha surrounded by agriculturalfields or pastures) and (2) undisturbed habitat (three populations of groups of >6 reproductive individuals/ha surrounded by undisturbed mature forest).

Venous thromboembolism in very elderly patients: findings from a prospective registry (RIETE).

Background And Objectives: Elderly patients with venous thromboembolism (VTE) have an increased rate of bleeding complications on therapeutic doses of anticoagulant therapy.

Design And Methods: Using data in RIETE, an international registry of consecutive patients with objectively confirmed, symptomatic acute VTE, we analyzed the clinical characteristics and outcome within 90 days of therapy of all enrolled patients aged > or = 80 years old.

Results: Of the 13,011 patients with VTE enrolled in RIETE up tp September 2005, 2890 (22%) were aged > or = 80 years old.

Compressed mini-tablets as a biphasic delivery system.

Compressed mini-tablets systems are presented as a biphasic delivery system designed for zero-order sustained drug release. The outer layer that fills the void spaces between the mini-tablets was formulated to release the drug in a very short time (fast release), while the mini-tablets provided a prolonged release. Different composition (HPMC or EC) and number (10 or 21) of mini-tablets were used to obtain different drug release rates.