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  • Ostomy telehealth for cancer survivors: Design of the Ostomy Self-management Training (OSMT) randomized trial

    Sun, Virginia; Ercolano, Elizabeth; McCorkle, Ruth; Grant, Marcia; Wendel, Christopher S.; Tallman, Nancy J.; Passero, Frank; Raza, Sabreen; Cidav, Zuleyha; Holcomb, Michael; Weinstein, Ronald S.; Hornbrook, Mark C.; Krouse, Robert S.; Univ Arizona (ELSEVIER SCIENCE INC, 2018-01)
    Purpose: An ostomy adversely affects health-related quality of life (HRQOL) in a diverse population of cancer survivors and their caregivers. Hit-or-miss ostomy care, nurse counseling, and community referral have been the primary modes of self-management education and support in the pert-operative setting. Few evidence-based, systematic ostomy self-management programs are available to ensure optimal post-operative care. This paper describes the study design of a telehealth-based Ostomy Self-management Training (OSMT) program for cancer survivors and their caregivers. Methods: The study is a three-year, randomized trial that tests the effectiveness of the OSMT program on survivor activation, self-efficacy, and HRQOL. The intervention integrates goal setting and problem-solving approaches to enhance survivor activation and self-efficacy to carry out ostomy care. The curriculum is delivered via four group sessions administered by trained ostomy certified nurses (WOCNs) and peer ostomates. An additional session is offered to caregivers to address their needs in relation to ostomy care. Telehealth approaches through videoconferencing are used to enhance program delivery to participants in three different geographic areas across two time zones. Participants join sessions via real-time videoconferencing from their homes. Conclusions: The OSMT program has high potential to make a positive impact on the unique physical, psychological, social, and spiritual needs of cancer survivors living with a permanent ostomy. The study design, process, and telehealth approach contributes to the success of future dissemination efforts of the intervention into diverse clinical and community settings.
  • Epigenetic modulation of Nrf2 and Ogg1 gene expression in testicular germ cells by methyl parathion exposure

    Hernandez-Cortes, D.; Alvarado-Cruz, I.; Solís-Heredia, M.J.; Quintanilla-Vega, B.; Univ Arizona, Coll Pharm, Dept Pharmacol & Toxicol (ACADEMIC PRESS INC ELSEVIER SCIENCE, 2018-05)
    Methyl parathion (Me-Pa) is an oxidizing organophosphate (OP) pesticide that generates reactive oxygen species (ROS) through its biotransformation. Some studies have also suggested that OP pesticides have the capacity to alkylate biomolecules, including DNA. In general, DNA methylation in gene promoters represses transcription. NRF2 is a key transcription factor that regulates the expression of antioxidant, metabolic and detoxifying genes through the antioxidant response element (ARE) situated in promoters of regulated genes. Furthermore, DNA repair genes, including 8-oxoguanine DNA glycosidase (OGG1), have been proposed as NRF2 target genes. Me-Pa exposure produces poor semen quality, genetic and oxidative damage in sperm cells, and reduced fertility. However, the Me-Pa effects on the methylation status and the expression of antioxidant (Nrf2) or DNA repair (Ogg1) genes in male germ cells have not been investigated. Therefore, mice were exposed to Me-Pa to evaluate the global (%5-mC) and specific methylation of Nrf2 and 0:4:1 genes using pyrosequencing, gene expression, and total protein carbonylation in male germ cells. The results showed that Me-Pa significantly decreased the global DNA methylation pattern and significantly increased the methylation of two CpG sites within Ogg1 promoter and one CpG site within Nrf2 promoter, In addition, Ogg1 or Nrf2 expression did not change after Me-Pa exposure despite the oxidative damage produced. Altogether, our data suggest that Me-Pa toxicity alters Ogg1 and Nrf2 promoter methylation in male germ cells that may be modulating their gene expression.
  • TDP-43 pathology disrupts nuclear pore complexes and nucleocytoplasmic transport in ALS/FTD

    Chou, Ching-Chieh; Zhang, Yi; Umoh, Mfon E.; Vaughan, Spencer W.; Lorenzini, Ileana; Liu, Feilin; Sayegh, Melissa; Donlin-Asp, Paul G.; Chen, Yu Han; Duong, Duc M.; Seyfried, Nicholas T.; Powers, Maureen A.; Kukar, Thomas; Hales, Chadwick M.; Gearing, Marla; Cairns, Nigel J.; Boylan, Kevin B.; Dickson, Dennis W.; Rademakers, Rosa; Zhang, Yong-Jie; Petrucelli, Leonard; Sattler, Rita; Zarnescu, Daniela C.; Glass, Jonathan D.; Rossoll, Wilfried; Univ Arizona, Dept Mol & Cellular Biol (NATURE PUBLISHING GROUP, 2018-02)
    The cytoplasmic mislocalization and aggregation of TAR DNA-binding protein-43 (TDP-43) is a common histopathological hallmark of the amyotrophic lateral sclerosis and frontotemporal dementia disease spectrum (ALS/FTD). However, the composition of aggregates and their contribution to the disease process remain unknown. Here we used proximity-dependent biotin identification (BioID) to interrogate the interactome of detergent-insoluble TDP-43 aggregates and found them enriched for components of the nuclear pore complex and nucleocytoplasmic transport machinery. Aggregated and disease-linked mutant TDP-43 triggered the sequestration and/or mislocalization of nucleoporins and transport factors, and interfered with nuclear protein import and RNA export in mouse primary cortical neurons, human fibroblasts and induced pluripotent stem cell-derived neurons. Nuclear pore pathology is present in brain tissue in cases of sporadic ALS and those involving genetic mutations in TARDBP and C9orf72. Our data strongly implicate TDP-43-mediated nucleocytoplasmic transport defects as a common disease mechanism in ALS/FTD.
  • 16S rRNA gene sequencing on a benchtop sequencer: accuracy for identification of clinically important bacteria.

    Watts, G S; Youens-Clark, K; Slepian, M J; Wolk, D M; Oshiro, M M; Metzger, G S; Dhingra, D; Cranmer, L D; Hurwitz, B L; Univ Arizona, Ctr Canc; Univ Arizona, Dept Pharmacol; Univ Arizona, Dept Agr & Biosyst Engn; Univ Arizona, Dept Med; Univ Arizona, Dept Biomed Engn; Univ Arizona, Arizona Ctr Accelerated Biomed Innovat (WILEY, 2017-12-01)
    Test the choice of 16S rRNA gene amplicon and data analysis method on the accuracy of identification of clinically important bacteria utilizing a benchtop sequencer. Nine 16S rRNA amplicons were tested on an Ion Torrent PGM to identify 41 strains of clinical importance. The V1-V2 region identified 40 of 41 isolates to the species level. Three data analysis methods were tested, finding that the Ribosomal Database Project's SequenceMatch outperformed BLAST and the Ion Reporter Metagenomics analysis pipeline. Lastly, 16S rRNA gene sequencing mixtures of four species through a six log range of dilution showed species were identifiable even when present as 0·1% of the mixture. Sequencing the V1-V2 16S rRNA gene region, made possible by the increased read length Ion Torrent PGM sequencer's 400 base pair chemistry, may be a better choice over other commonly used regions for identifying clinically important bacteria. In addition, the SequenceMatch algorithm, freely available from the Ribosomal Database Project, is a good choice for matching filtered reads to organisms. Lastly, 16S rRNA gene sequencing's sensitivity to the presence of a bacterial species at 0·1% of a mixture suggests it has sufficient sensitivity for samples in which important bacteria may be rare. We have validated 16S rRNA gene sequencing on a benchtop sequencer including simple mixtures of organisms; however, our results highlight deficits for clinical application in place of current identification methods.
  • Search for new high-mass phenomena in the dilepton final state using 36 fb(-1) of proton-proton collision data at root s=13 TeV with the ATLAS detector

    Aaboud, M.; Cheu, E.; Delitzsch, C. M.; Johns, K. A.; Jones, S.; Lampl, W.; LeBlanc, M.; Lei, X.; Leone, R.; Loch, P.; Nayyar, R.; Rutherfoord, J. P.; Varnes, E. W.; Zhou, Y.; Univ Arizona, Dept Phys (SPRINGER, 2017-10-26)
    A search is conducted for new resonant and non-resonant high-mass phenomena in dielectron and dimuon fi nal states. The search uses 36 : 1 fb(-1) of proton-proton collision data, collected at root s = 13TeV by the ATLAS experiment at the LHC in 2015 and 2016. No signi fi cant deviation from the Standard Model prediction is observed. Upper limits at 95% credibility level are set on the cross-section times branching ratio for resonances decaying into dileptons, which are converted to lower limits on the resonance mass, up to 4.1 TeV for the E-6 -motivated Z(X)'. Lower limits on the qqll contact interaction scale are set between 2.4 TeV and 40 TeV, depending on the model.

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