REST Controls Self-Renewal and Tumorigenic Competence of Human Glioblastoma Cells

The Repressor Element 1 Silencing Transcription factor (REST/NRSF) is a master repressor of neuronal programs in non-neuronal lineages shown to function as a central regulator of developmental programs and stem cell physiology. Aberrant REST function has been associated with a number of pathological conditions. In cancer biology, REST has been shown to play a tumor suppressor activity in epithelial cancers but an oncogenic role in brain childhood malignancies such as neuroblastoma and medulloblastoma. Here we examined REST expression in human glioblastoma multiforme (GBM) specimens and its role in GBM cells carrying self-renewal and tumorigenic competence. We found REST to be expressed in GBM specimens, its presence being particularly enriched in tumor cells in the perivascular compartment. Significantly, REST is highly expressed in self-renewing tumorigenic-competent GBM cells and its knock down strongly reduces their self-renewal in vitro and tumor-initiating capacity in vivo and affects levels of miR-124 and its downstream targets. These results indicate that REST contributes to GBM maintenance by affecting its self-renewing and tumorigenic cellular component and that, hence, a better understanding of these circuitries in these cells might lead to new exploitable therapeutic targets

Year in review in Intensive Care Medicine 2010: I. Acute renal failure, outcome, risk assessment and ICU performance, sepsis, neuro intensive care and experimentals

SCOPUS: re.jinfo:eu-repo/semantics/publishe

Cardio-metabolic responses during horse riding at three different speeds

Purpose: The purpose of the present investigation was to study the metabolic demand and cardiovascular response during a typical horse riding session. Methods: To this aim, 19 (9 male, 10 female) riders, regularly participating in competitions, were enrolled. They underwent a preliminary, incremental exercise test on a cycle-ergometer to assess their anaerobic threshold (AT) and VO2max. Then, participants underwent a riding training session, which comprised periods of walking, trotting, and cantering for a total of 20 min. Oxygen uptake (VO2), carbon dioxide production (VCO2), and heart rate (HR) were obtained throughout the preliminary and riding test by means of a portable metabolic system. Moreover, excess of CO2 production (CO2excess) and oxygen pulse (OP) were also calculated to obtain an estimate of anaerobic glycolysis and stroke volume. Results: The main result was that all collected parameters remained below the AT level throughout the riding session, with the exception of HR that approached the AT level only during cantering. In detail, during cantering, average VO2, VCO2, HR, CO2excess, and OP values were 1289 ± 331 mL min−1, 1326 ± 266 mL min−1, 158 ± 22 bpm, 215 ± 119 mL min−1, and 7.8 ± 1.6 mL/bpm, respectively. Conclusions: It was concluded that riding imposes only light to moderate stress on the aerobic and anaerobic energy systems. Moreover, cardiovascular reserve is only moderately recruited in terms of inotropism, while chronotropism can be stimulated mor

Predicting In-Hospital Treatment Failure (<= 7 days) in Patients with COPD Exacerbation Using Antibiotics and Systemic Steroids

Although pharmacological treatment of COPD exacerbation (COPDE) includes antibiotics and systemic steroids, a proportion of patients show worsening of symptoms during hospitalization that characterize treatment failure. The aim of our study was to determine in-hospital predictors of treatment failure (7 days). Prospective data on 110 hospitalized COPDE patients, all treated with antibiotics and systemic steroids, were collected; on the seventh day of hospitalization, patients were divided into treatment failure (n = 16) or success (n = 94). Measures of inflammatory serum biomarkers were recorded at admission and at day 3; data on clinical, laboratory, microbiological, and severity, as well data on mortality and readmission, were also recorded. Patients with treatment failure had a worse lung function, with higher serum levels of C-reactive protein (CRP), procalcitonin (PCT), tumour necrosis factor-alpha (TNF-), interleukin (IL) 8, and IL-10 at admission, and CRP and IL-8 at day 3. Longer length of hospital stay and duration of antibiotic therapy, higher total doses of steroids and prevalence of deaths and readmitted were found in the treatment failure group. In the multivariate analysis, +1 mg/dL of CRP at admission (OR, 1.07; 95% CI, 1.01 to 1.13) and use of penicillins or cephalosporins (OR, 5.63; 95% CI, 1.26 to 25.07) were independent variables increasing risk of treatment failure, whereas cough at admission (OR, 0.20; 95%CI, 0.05 to 0.75) reduces risk of failure. In hospitalized COPDE patients CRP at admission and use of specific class of antibiotics predict in-hospital treatment failure, while presence of cough has a protective role