Mre11 exonuclease activity removes the chain-terminating nucleoside analog gemcitabine from the nascent strand during DNA replication.

The Mre11 nuclease is involved in early responses to DNA damage, often mediated by its role in DNA end processing. MRE11 mutations and aberrant expression are associated with carcinogenesis and cancer treatment outcomes. While, in recent years, progress has been made in understanding the role of Mre11 nuclease activities in DNA double-strand break repair, their role during replication has remained elusive. The nucleoside analog gemcitabine, widely used in cancer therapy, acts as a replication chain terminator; for a cell to survive treatment, gemcitabine needs to be removed from replicating DNA. Activities responsible for this removal have, so far, not been identified. We show that Mre11 3' to 5' exonuclease activity removes gemcitabine from nascent DNA during replication. This contributes to replication progression and gemcitabine resistance. We thus uncovered a replication-supporting role for Mre11 exonuclease activity, which is distinct from its previously reported detrimental role in uncontrolled resection in recombination-deficient cells.

Breast magnetic resonance elastography: a review of clinical work and future perspectives.

This review on magnetic resonance elastography (MRE) of the breast provides an overview of available literature and describes current developments in the field of breast MRE, including new transducer technology for data acquisition and multi-frequency-derived power-law behaviour of tissue. Moreover, we discuss the future potential of breast MRE, which goes beyond its original application as an additional tool in differentiating benign from malignant breast lesions. These areas of ongoing and future research include MRE for pre-operative tumour delineation, staging, monitoring and predicting response to treatment, as well as prediction of the metastatic potential of primary tumours.

Simultaneous MR quantification of hepatic fat content, fatty acid composition, transverse relaxation time and magnetic susceptibility for the diagnosis of non-alcoholic steatohepatitis.

Non-alcoholic steatohepatitis (NASH) is characterized at histology by steatosis, hepatocyte ballooning and inflammatory infiltrates, with or without fibrosis. Although diamagnetic material in fibrosis and inflammation can be detected with quantitative susceptibility imaging, fatty acid composition changes in NASH relative to simple steatosis have also been reported. Therefore, our aim was to develop a single magnetic resonance (MR) acquisition and post-processing scheme for the diagnosis of steatohepatitis by the simultaneous quantification of hepatic fat content, fatty acid composition, T2 * transverse relaxation time and magnetic susceptibility in patients with non-alcoholic fatty liver disease. MR acquisition was performed at 3.0 T using a three-dimensional, multi-echo, spoiled gradient echo sequence. Phase images were unwrapped to compute the B0 field inhomogeneity (ΔB0 ) map. The ΔB0 -demodulated real part images were used for fat-water separation, T2 * and fatty acid composition quantification. The external and internal fields were separated with the projection onto dipole field method. Susceptibility maps were obtained after dipole inversion from the internal field map with single-orientation Bayesian regularization including spatial priors. Method validation was performed in 32 patients with biopsy-proven, non-alcoholic fatty liver disease from which 12 had simple steatosis and 20 NASH. Liver fat fraction and T2 * did not change significantly between patients with simple steatosis and NASH. In contrast, the saturated fatty acid fraction increased in patients with NASH relative to patients with simple steatosis (48 ± 2% versus 44 ± 4%; p < 0.05) and the magnetic susceptibility decreased (-0.30 ± 0.27 ppm versus 0.10 ± 0.14 ppm; p < 0.001). The area under the receiver operating characteristic curve for magnetic susceptibility as NASH marker was 0.91 (95% CI: 0.79-1.0). Simultaneous MR quantification of fat content, fatty acid composition, T2 * and magnetic susceptibility is feasible in the liver. Our preliminary results suggest that quantitative susceptibility imaging has a high diagnostic performance for the diagnosis of NASH.

Comparison of viscoelastic property characterization of plastisol phantoms with magnetic resonance elastography and high-frequency rheometry.

This study aims at evaluating Magnetic Resonance Elastography (MRE) as a reliable technique for the characterization of viscoelastic properties of soft tissues. Three phantoms with different concentrations of plastisol and softener were prepared in order to mechanically mimic a broad panel of healthy and pathological soft tissues. Once placed in a MRI device, each sample was excited by a homemade external driver, inducing shear waves within the medium. The storage (G') and loss (G") moduli of each phantom were then reconstructed from MRE acquisitions over a frequency range from 300 to 1,000 Hz, by applying a 2D Helmholtz inversion algorithm. At the same time, mechanical tests were performed on four samples of each phantom with a High-Frequency piezo-Rheometer (HFR) over an overlapping frequency range (from 160 to 630 Hz) with the same test conditions (temperature, ageing). The comparison between both techniques shows a good agreement in the measurement of the storage and loss moduli, underlying the capability of MRE to noninvasively assess the complex shear modulus G* of a medium and its interest for investigating the viscoelastic properties of living tissues. Moreover, the phantoms with varying concentrations of plastisol used in this study show interesting rheological properties, which make them good candidates to simulate the broad variety of viscoelastic behaviors of healthy and pathological soft tissues.

The effects of hypnosis/guided imagery on the postoperative course of children.

Hypnosis, guided imagery, and relaxation have been shown to improve the postoperative course of adult surgical patients. Children have successfully used hypnosis/guided imagery to significantly reduce the pain associated with invasive procedures and to improve selected medical conditions. The purpose of this study was to examine the effect of hypnosis/guided imagery on the postoperative course of pediatric surgical patients. Fifty-two children (matched for sex, age, and diagnosis) were randomly assigned to an experimental or control group. The experimental group was taught guided imagery by the investigator. Practice of the imagery technique included suggestions for a favorable postoperative course. Significantly lower postoperative pain ratings and shorter hospital stays occurred for children in the experimental group. State anxiety was decreased for the guided imagery group and increased postoperatively for the control group. This study demonstrates the positive effects of hypnosis/guided imagery for the pediatric surgical patient.

Therapeutic relations decision making: the Rainbow Framework.

The giving and receiving of gifts, funeral attendance, post-discharge babysitting, usurping of parental roles, indiscriminate sharing of personal information, and other issues prompted a pediatric tertiary care facility in the Midwest to examine intricacies involved in the promotion and maintenance of therapeutic relationships. A multidisciplinary group developed a therapeutic relations decision-making framework to (a) foster a proactive process of conscious deliberation regarding nurse/patient interactions, and (b) afford a nonthreatening mechanism for retrospective review of apparently non-therapeutic relationships. The framework, based upon an "act utilitarian" approach to moral reasoning, promotes the clarification of personal philosophy and values. The framework provides a basis for deliberate, consistent, and confident nursing care delivery and the impetus for developing of new patient and family care initiatives.

Easing the wait: development of a pager program for families.

Waiting is inevitable for patients and families seeking health care services. Anxiety, frustration, and stress are exacerbated. A pager program, where pagers are loaned free of charge to families, uses a family-centered approach to counteract the aggravation of waiting. Patients and families can leave the hospital room or clinic setting and then be paged to return as needed. In any clinical setting, having choices and control will enhance coping and satisfaction for both patients and families.

Variables that affect the school-age child's reaction to hospitalization and surgery: a review of the literature.

The purpose of this paper has been to identify the variables documented in the literature that affect the school-age child's reaction to hospitalization and surgery. The variables were categorized as pertaining to the child, the parents, or the hospital. Variables in the category pertaining to the child that affect the child's reaction to hospitalization and surgery are developmental level and mechanisms used to cope with hospitalization and surgery. In the parent category, presence of the mother, preparation of the mother, support of the child by the mother, parental values, and socioeconomic status were considered variables that affect the child's reaction to hospitalization and surgery. The hospital environment is generally considered to be threatening to school-age children. The major variables identified in the hospital category that affect the child's reaction to hospitalization and surgery were specific events, length of hospitalization, nature and degree of illness, type of procedure, and method of preparation for the hospital experience.