Cardiac Rehabilitation Intervention and Quality of Life Indicators: A Validation Estimate of Ware's Model

Author Institution: Dept. of Counseling & Mental Health Services, University of Toledo, OHAuthor Institution: Dept. of Educational Foundations & Leadership, University of Akron, OHAuthor Institution: Dept. of Counseling, Summa Health System, University of Akron, OHAuthor Institution: Cardiac Rehabilitation Institute, Summa Health System, University of Akron, OHThe present study tests Ware’s (1987, 1990) prediction that patient evaluations of quality of life (QOL) are related to physical ability. QOL data from 302 patients were collected prior to initiation and upon completion of a 12-week cardiac rehabilitation program. Physical ability was measured in metabolic equivalents (METS). Pearson product moment correlation coefficients were calculated for the variables under study. Multiple regression analyses were conducted to test these relationships covarying patient diagnosis, and pre-treatment QOL score and patient demographics. Significant improvements from pre- to post-CR were found for METs and all QOL variables. Improvements in physical ability were significantly correlated with improvements in physical health related QOL indices, but not with mental health QOL indices. These relationships were present even when moderating variables were co-varied. Improvements in physical ability were predictive of decreased expectations that physical health would interfere with work or other daily activities. As the physical capabilities of our patients increased, they reported feeling less physical pain and were less limited by any pain they did experience. And, increased physical ability was associated with a brighter outlook on current and expected future health status. These findings provide support for Ware’s theory of QOL

Planetary surface exploration: MESUR/autonomous lunar rover

Planetary surface exploration micro-rovers for collecting data about the Moon and Mars was designed by the Department of Mechanical Engineering at the University of Idaho. The goal of both projects was to design a rover concept that best satisfied the project objectives for NASA-Ames. A second goal was to facilitate student learning about the process of design. The first micro-rover is a deployment mechanism for the Mars Environmental SURvey (MESUR) Alpha Particle/Proton/X-ray instruments (APX). The system is to be launched with the sixteen MESUR landers around the turn of the century. A Tubular Deployment System and a spiked-legged walker was developed to deploy the APX from the lander to the Martian surface. While on Mars the walker is designed to take the APX to rocks to obtain elemental composition data of the surface. The second micro-rover is an autonomous, roving vehicle to transport a sensor package over the surface of the moon. The vehicle must negotiate the lunar-terrain for a minimum of one year by surviving impacts and withstanding the environmental extremes. The rover is a reliable track-driven unit that operates regardless of orientation which NASA can use for future lunar exploratory missions. A detailed description of the designs, methods, and procedures which the University of Idaho design teams followed to arrive at the final designs are included

Planetary surface exploration MESUR/autonomous lunar rover

Planetary surface exploration micro-rovers for collecting data about the Moon and Mars have been designed by the Department of Mechanical Engineering at the University of Idaho. The goal of both projects was to design a rover concept that best satisfied the project objectives for NASA/Ames. A second goal was to facilitate student learning about the process of design. The first micro-rover is a deployment mechanism for the Mars Environmental Survey (MESUR) Alpha Particle/Proton/X-ray (APX) Instrument. The system is to be launched with the 16 MESUR landers around the turn of the century. A Tubular Deployment System and a spiked-legged walker have been developed to deploy the APX from the lander to the Martian Surface. While on Mars, the walker is designed to take the APX to rocks to obtain elemental composition data of the surface. The second micro-rover is an autonomous, roving vehicle to transport a sensor package over the surface of the moon. The vehicle must negotiate the lunar terrain for a minimum of one year by surviving impacts and withstanding the environmental extremes. The rover is a reliable track-driven unit that operates regardless of orientation that NASA can use for future lunar exploratory missions. This report includes a detailed description of the designs and the methods and procedures which the University of Idaho design teams followed to arrive at the final designs

Stiripentol in D ravet syndrome: Results of a retrospective U . S . study

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/100157/1/epi12303.pd

The Role of Auxin Transport in Plant Patterning Mechanisms

In plants, many patterning processes involve the phytohormone auxin, and controlling how it moves around plays a critical role in pattern formation

RUNX super-enhancer control through the Notch pathway by Epstein-Barr virus transcription factors regulates B cell growth

In B cells infected by the cancer-associated Epstein-Barr virus (EBV), RUNX3 and RUNX1 transcription is manipulated to control cell growth. The EBV-encoded EBNA2 transcription factor (TF) activates RUNX3 transcription leading to RUNX3-mediated repression of the RUNX1 promoter and the relief of RUNX1-directed growth repression. We show that EBNA2 activates RUNX3 through a specific element within a −97 kb super-enhancer in a manner dependent on the expression of the Notch DNA-binding partner RBP-J. We also reveal that the EBV TFs EBNA3B and EBNA3C contribute to RUNX3 activation in EBV-infected cells by targeting the same element. Uncovering a counter-regulatory feed-forward step, we demonstrate EBNA2 activation of a RUNX1 super-enhancer (−139 to −250 kb) that results in low-level RUNX1 expression in cells refractory to RUNX1-mediated growth inhibition. EBNA2 activation of the RUNX1 super-enhancer is also dependent on RBP-J. Consistent with the context-dependent roles of EBNA3B and EBNA3C as activators or repressors, we find that these proteins negatively regulate the RUNX1 super-enhancer, curbing EBNA2 activation. Taken together our results reveal cell-type-specific exploitation of RUNX gene super-enhancers by multiple EBV TFs via the Notch pathway to fine tune RUNX3 and RUNX1 expression and manipulate B-cell growth

MAO-inhibitors in Parkinson's Disease

Monoamine oxidase inhibitors (MAO-I) belong to the earliest drugs tried in Parkinson's disease (PD). They have been used with or without levodopa (L-DOPA). Non-selective MAO-I due to their side-effect/adverse reaction profile, like tranylcypromine have limited use in the treatment of depression in PD, while selective, reversible MAO-A inhibitors are recommended due to their easier clinical handling. For the treatment of akinesia and motor fluctuations selective irreversible MAO-B inhibitors selegiline and rasagiline are recommended. They are safe and well tolerated at the recommended daily doses. Their main differences are related to (1) metabolism, (2) interaction with CYP-enzymes and (3) quantitative properties at the molecular biological/genetic level. Rasagiline is more potent in clinical practise and has a hypothesis driven more favourable side effect/adverse reaction profile due to its metabolism to aminoindan. Both selegiline and rasagiline have a neuroprotective and neurorestaurative potential. A head-to head clinical trial would be of utmost interest from both the clinical outcome and a hypothesis-driven point of view. Selegiline is available as tablet and melting tablet for PD and as transdermal selegiline for depression, while rasagiline is marketed as tablet for PD. In general, the clinical use of MAO-I nowadays is underestimated. There should be more efforts to evaluate their clinical potency as antidepressants and antidementive drugs in addition to the final proof of their disease-modifying potential. In line with this are recent innovative developments of MAO-I plus inhibition of acetylcholine esterase for Alzheimer's disease as well as combined MAO-I and iron chelation for PD

RNA polymerase II stalling promotes nucleosome occlusion and pTEFb recruitment to drive immortalization by Epstein-Barr virus

Epstein-Barr virus (EBV) immortalizes resting B-cells and is a key etiologic agent in the development of numerous cancers. The essential EBV-encoded protein EBNA 2 activates the viral C promoter (Cp) producing a message of ~120 kb that is differentially spliced to encode all EBNAs required for immortalization. We have previously shown that EBNA 2-activated transcription is dependent on the activity of the RNA polymerase II (pol II) C-terminal domain (CTD) kinase pTEFb (CDK9/cyclin T1). We now demonstrate that Cp, in contrast to two shorter EBNA 2-activated viral genes (LMP 1 and 2A), displays high levels of promoter-proximally stalled pol II despite being constitutively active. Consistent with pol II stalling, we detect considerable pausing complex (NELF/DSIF) association with Cp. Significantly, we observe substantial Cp-specific pTEFb recruitment that stimulates high-level pol II CTD serine 2 phosphorylation at distal regions (up to +75 kb), promoting elongation. We reveal that Cp-specific pol II accumulation is directed by DNA sequences unfavourable for nucleosome assembly that increase TBP access and pol II recruitment. Stalled pol II then maintains Cp nucleosome depletion. Our data indicate that pTEFb is recruited to Cp by the bromodomain protein Brd4, with polymerase stalling facilitating stable association of pTEFb. The Brd4 inhibitor JQ1 and the pTEFb inhibitors DRB and Flavopiridol significantly reduce Cp, but not LMP1 transcript production indicating that Brd4 and pTEFb are required for Cp transcription. Taken together our data indicate that pol II stalling at Cp promotes transcription of essential immortalizing genes during EBV infection by (i) preventing promoter-proximal nucleosome assembly and ii) necessitating the recruitment of pTEFb thereby maintaining serine 2 CTD phosphorylation at distal regions

Modulation of enhancer looping and differential gene targeting by Epstein-Barr virus transcription factors directs cellular reprogramming

Epstein-Barr virus (EBV) epigenetically reprogrammes B-lymphocytes to drive immortalization and facilitate viral persistence. Host-cell transcription is perturbed principally through the actions of EBV EBNA 2, 3A, 3B and 3C, with cellular genes deregulated by specific combinations of these EBNAs through unknown mechanisms. Comparing human genome binding by these viral transcription factors, we discovered that 25% of binding sites were shared by EBNA 2 and the EBNA 3s and were located predominantly in enhancers. Moreover, 80% of potential EBNA 3A, 3B or 3C target genes were also targeted by EBNA 2, implicating extensive interplay between EBNA 2 and 3 proteins in cellular reprogramming. Investigating shared enhancer sites neighbouring two new targets (WEE1 and CTBP2) we discovered that EBNA 3 proteins repress transcription by modulating enhancer-promoter loop formation to establish repressive chromatin hubs or prevent assembly of active hubs. Re-ChIP analysis revealed that EBNA 2 and 3 proteins do not bind simultaneously at shared sites but compete for binding thereby modulating enhancer-promoter interactions. At an EBNA 3-only intergenic enhancer site between ADAM28 and ADAMDEC1 EBNA 3C was also able to independently direct epigenetic repression of both genes through enhancer-promoter looping. Significantly, studying shared or unique EBNA 3 binding sites at WEE1, CTBP2, ITGAL (LFA-1 alpha chain), BCL2L11 (Bim) and the ADAMs, we also discovered that different sets of EBNA 3 proteins bind regulatory elements in a gene and cell-type specific manner. Binding profiles correlated with the effects of individual EBNA 3 proteins on the expression of these genes, providing a molecular basis for the targeting of different sets of cellular genes by the EBNA 3s. Our results therefore highlight the influence of the genomic and cellular context in determining the specificity of gene deregulation by EBV and provide a paradigm for host-cell reprogramming through modulation of enhancer-promoter interactions by viral transcription factors