miRNA-126 Orchestrates an Oncogenic Program in B Cell Precursor Acute Lymphoblastic Leukemia

MicroRNA (miRNA)-126 is a known regulator of hematopoietic stem cell quiescence. We engineered murine hematopoiesis to express miRNA-126 across all differentiation stages. Thirty percent of mice developed monoclonal B cell leukemia, which was prevented or regressed when a tetracycline-repressible miRNA-126 cassette was switched off. Regression was accompanied by upregulation of cell-cycle regulators and B cell differentiation genes, and downregulation of oncogenic signaling pathways. Expression of dominant-negative p53 delayed blast clearance upon miRNA-126 switch-off, highlighting the relevance of p53 inhibition in miRNA-126 addiction. Forced miRNA-126 expression in mouse and human progenitors reduced p53 transcriptional activity through regulation of multiple p53-related targets. miRNA-126 is highly expressed in a subset of human B-ALL, and antagonizing miRNA-126 in ALL xenograft models triggered apoptosis and reduced disease burden

Translating and validating a Training Needs Assessment tool into Greek

<p>Abstract</p> <p>Background</p> <p>The translation and cultural adaptation of widely accepted, psychometrically tested tools is regarded as an essential component of effective human resource management in the primary care arena. The Training Needs Assessment (TNA) is a widely used, valid instrument, designed to measure professional development needs of health care professionals, especially in primary health care. This study aims to describe the translation, adaptation and validation of the TNA questionnaire into Greek language and discuss possibilities of its use in primary care settings.</p> <p>Methods</p> <p>A modified version of the English self-administered questionnaire consisting of 30 items was used. Internationally recommended methodology, mandating forward translation, backward translation, reconciliation and pretesting steps, was followed. Tool validation included assessing item internal consistency, using the alpha coefficient of Cronbach. Reproducibility (test – retest reliability) was measured by the kappa correlation coefficient. Criterion validity was calculated for selected parts of the questionnaire by correlating respondents' research experience with relevant research item scores. An exploratory factor analysis highlighted how the items group together, using a Varimax (oblique) rotation and subsequent Cronbach's alpha assessment.</p> <p>Results</p> <p>The psychometric properties of the Greek version of the TNA questionnaire for nursing staff employed in primary care were good. Internal consistency of the instrument was very good, Cronbach's alpha was found to be 0.985 (p < 0.001) and Kappa coefficient for reproducibility was found to be 0.928 (p < 0.0001). Significant positive correlations were found between respondents' current performance levels on each of the research items and amount of research involvement, indicating good criterion validity in the areas tested. Factor analysis revealed seven factors with eigenvalues of > 1.0, KMO (Kaiser-Meyer-Olkin) measure of sampling adequacy = 0.680 and Bartlett's test of sphericity, p < 0.001.</p> <p>Conclusion</p> <p>The translated and adapted Greek version is comparable with the original English instrument in terms of validity and reliability and it is suitable to assess professional development needs of nursing staff in Greek primary care settings.</p

Single-dose palonosetron for prevention of chemotherapy-induced nausea and vomiting in patients with aggressive non-Hodgkin's lymphoma receiving moderately emetogenic chemotherapy containing steroids: results of a phase II study from the Gruppo Italiano per lo Studio dei Linfomi (GISL)

PURPOSE: The control of nausea and vomiting induced by chemotherapy is paramount for overall treatment success in cancer patients. Antiemetic therapy during chemotherapy in lymphoma patients generally consists of anti-serotoninergic drugs and dexamethasone. The aim of this trial was to evaluate the efficacy of a single dose of palonosetron, a second-generation serotonin type 3 (5-HT(3)) receptor antagonist, in patients with aggressive non-Hodgkin's lymphoma receiving moderately emetogenic chemotherapy (MEC) containing steroids. METHODS: Patients received a single intravenous bolus of palonosetron (0.25 mg) before administration of chemotherapy. Complete response (CR) defined as no vomiting and no rescue therapy during overall phase (0-120 h) was the primary endpoint. Complete control (CC) defined as CR and only mild nausea was a secondary endpoint. RESULTS: Eighty-six evaluable patients entered in the study. A CR was observed in 74 patients (86.0%) during the overall phase; the CR during the acute (0-24 h) and delayed (24-120 h) phases was 90.7% and 88.4%, respectively. CC was 89.5% during the acute and 84.9% during the delayed phase; the overall CC was 82.6%. CONCLUSIONS: This was the first trial, which demonstrated the efficacy of a single dose of palonosetron in control CINV in patients with aggressive non-Hodgkin's lymphoma receiving MEC regimen containing steroids

Toughening mechanisms in elastomer-modified epoxies

The role Of matrix ductility on the toughenability and toughening mechanism of elastomer-modified, diglycidyl ether of bisphenol A (DGEBA)-based epoxies is investigated. Matrix ductility is varied by using epoxide resins of varying epoxide monomer molecular weights. These epoxide resins are cured using 4,4′ diaminodiphenyl sulphone (DDS) and, in some cases, modified with 10 vol% carboxyl-terminated copolymer of butadiene and acrylonitrile (CTBN). Fracture toughness values for the neat epoxies are found to be almost independent of the monomer molecular weight of the epoxide resin used. However, the fracture toughness of the elastomer-modified epoxies is found to be very dependent upon the epoxide monomer molecular weight. Tensile dilatometry indicates that the toughening mechanism, when present, is similar to the mechanism found for piperidine cured, elastomer-modified epoxies studied previously. Scanning electron microscopy and optical microscopy techniques corroborate this finding.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/44695/1/10853_2005_Article_BF01174528.pd