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Ryan J Mailloux, Adrian Young, Marisa O'Brien, Robert Morris Gill
It has been reported that mitochondria can contain up to 12 enzymatic sources of reactive oxygen species (ROS). A majority of these sites include flavin-dependent respiratory complexes and dehydrogenases that produce a mixture of superoxide (O2●- ) and hydrogen peroxide (H2O2). Accurate quantification of the ROS-producing potential of individual sites in isolated mitochondria can be challenging due to the presence of antioxidant defense systems and side reactions that also form O2●- /H2O2. Use of nonspecific inhibitors that can disrupt mitochondrial bioenergetics can also compromise measurements by altering ROS release from other sites of production...
February 24, 2018: Journal of Visualized Experiments: JoVE
Kathleen A Quan, Jennifer Yim, Doug Merrill, Usme Khusbu, Keith Madey, Linda Dickey, Amish A Dangodara, Scott E Rudkin, Margaret O'Brien, Daniel Thompson, Nimisha Parekh, C Gregory Albers, William C Wilson, Lauri Thrupp, Cassiana E Bittencourt, Susan S Huang, Shruti K Gohil
No abstract text is available yet for this article.
March 19, 2018: Infection Control and Hospital Epidemiology
Ping Guo, Mendwas Dzingina, Alice M Firth, Joanna M Davies, Abdel Douiri, Suzanne M O'Brien, Cathryn Pinto, Sophie Pask, Irene J Higginson, Kathy Eagar, Fliss E M Murtagh
INTRODUCTION: Provision of palliative care is inequitable with wide variations across conditions and settings in the UK. Lack of a standard way to classify by case complexity is one of the principle obstacles to addressing this. We aim to develop and validate a casemix classification to support the prediction of costs of specialist palliative care provision. METHODS AND ANALYSIS: Phase I: A cohort study to determine the variables and potential classes to be included in a casemix classification...
March 17, 2018: BMJ Open
Maro Ohanian, Ana Tari Ashizawa, Guillermo Garcia-Manero, Naveen Pemmaraju, Tapan Kadia, Elias Jabbour, Farhad Ravandi, Gautam Borthakur, Michael Andreeff, Marina Konopleva, Miranda Lim, Sherry Pierce, Susan O'Brien, Yesid Alvarado, Srdan Verstovsek, William Wierda, Hagop Kantarjian, Jorge Cortes
BACKGROUND: Activating mutations of tyrosine kinases are common in leukaemias. Oncogenic tyrosine kinases use the growth factor receptor-bound protein 2 (Grb2) for signal transduction, leading to activation of mitogen-activated protein kinase (MAPK) 1 and MAPK3 (ERK2 and ERK1). We hypothesised that inhibition of Grb2 would suppress ERK1 and ERK2 activation and inhibit leukaemia progression. To inhibit Grb2, a liposome-incorporated antisense oligodeoxynucleotide that blocks Grb2 protein expression, BP1001, was developed...
March 14, 2018: Lancet Haematology
Lucy M Hinder, Benjamin J Murdock, Meeyoung Park, Diane E Bender, Phillipe D O'Brien, Amy E Rumora, Junguk Hur, Eva L Feldman
Diabetic peripheral neuropathy is the most common complication of diabetes and a source of considerable morbidity. Numerous molecular pathways are linked to neuropathic progression, but it is unclear whether these pathways are altered throughout the course of disease. Moreover, the methods by which these molecular pathways are analyzed can produce significantly different results; as such it is often unclear whether previously published pathways are viable targets for novel therapeutic approaches. In the current study we examine changes in gene expression patterns in the sciatic nerve (SCN) and dorsal root ganglia (DRG) of db/db diabetic mice at 8, 16, and 24 weeks of age using microarray analysis...
March 14, 2018: Experimental Neurology
Amir Koolivand, Stephan Clayton, Halie Rion, Armin Oloumi, Ariel O'Brien, Morteza G Khaledi
As previously reported, fluoroalcohols can induce coacervation in aqueous solutions of amphiphilic compounds with subsequent formation of two-phase systems, where one phase is enriched in amphiphile and fluoroalcohol and the other is primarily an aqueous - rich phase. This study focuses on the use of simple coacervates made of a single component amphiphile induced by a fluoroalcohol for extraction and enrichment of proteins. 1,1,1,3,3,3-Hexafluoroisopropanol (HFIP) and 2,2,2-trifluoroethanol (TFE) were used to induce coacervation in the aqueous solutions of a cationic amphiphile, cetyltrimethylammonium bromide (CTAB) or tetra-n-butylammonium bromide (TBAB)...
March 3, 2018: Journal of Chromatography. B, Analytical Technologies in the Biomedical and Life Sciences
Suvi Härmälä, Constantinos Parisinos, Laura Shallcross, Alastair O'Brien, Andrew Hayward
INTRODUCTION: In advanced chronic liver disease, diseases caused by common bacteria Streptococcus pneumoniae or influenza virus put people at an increased risk of serious health complications and death. The effectiveness of the available vaccines in reducing the risk of poor health outcomes, however, is less clear. METHODS AND ANALYSIS: We will search Medline (Ovid), Embase (Ovid), PubMed and Cochrane Central Register of Controlled Trials for published reports on randomised controlled trials and observational studies on the effectiveness of pneumococcal and influenza vaccines in people with chronic liver disease...
March 16, 2018: BMJ Open
Lisa Barbera, Rinku Sutradhar, Anna Chu, Hsien Seow, Doris Howell, Craig C Earle, Mary Ann O'Brien, Deb Dudgeon, Clare Atzema, Amna Husain, Ying Liu, Carlo DeAngelis
BACKGROUND: Opioid prescribing has been increasingly scrutinized among non-cancer patients. As an unintended consequence, opioids may be under-prescribed for cancer patients. The purpose of this study was to compare trends in opioid prescribing in younger adults with and without cancer. METHODS: From 2004 to 2013, Ontario residents 18-64 years eligible for government paid pharmacare were annually stratified into 3 groups: no cancer history, cancer diagnosis >5 years ago and cancer diagnosis ≤5 years ago...
March 13, 2018: Journal of Pain and Symptom Management
Ajeet K Sharma, Nabeel Ahmed, Edward P O'Brien
Ribosome profiling experiments have found greater than 100-fold variation in ribosome density along mRNA transcripts, indicating that individual codon elongation rates can vary to a similar degree. This wide range of elongation times, coupled with differences in codon usage between transcripts, suggests that the average codon translation-rate per gene can vary widely. Yet, ribosome run-off experiments have found that the average codon translation rate for different groups of transcripts in mouse stem cells is constant at 5...
February 2018: Physical Review. E
Byron J Schneider, Zachary McCormick, David O'Brien, Michael Bunch, Clark C Smith
No abstract text is available yet for this article.
March 14, 2018: Pain Medicine: the Official Journal of the American Academy of Pain Medicine
Souheil El-Chemaly, Kevin J O'Brien, Steven D Nathan, Gerald L Weinhouse, Hilary J Goldberg, Jean M Connors, Ye Cui, Todd L Astor, Philip C Camp, Ivan O Rosas, Merte Lemma, Vladislav Speransky, Melissa A Merideth, William A Gahl, Bernadette R Gochuico
Pulmonary fibrosis is a progressive, fatal manifestation of Hermansky-Pudlak syndrome (HPS). Some patients with advanced HPS pulmonary fibrosis undergo lung transplantation despite their disease-associated bleeding tendency; others die while awaiting donor organs. The objective of this study is to determine the clinical management and outcomes of a cohort with advanced HPS pulmonary fibrosis who were evaluated for lung transplantation. Six patients with HPS-1 pulmonary fibrosis were evaluated at the National Institutes of Health Clinical Center and one of two regional lung transplant centers...
2018: PloS One
Martin D Cheatle, Rollin M Gallagher, Charles P O'Brien
No abstract text is available yet for this article.
March 13, 2018: Pain Medicine: the Official Journal of the American Academy of Pain Medicine
Katie M O'Brien, Dale P Sandler, Min Shi, Quaker E Harmon, Jack A Taylor, Clarice R Weinberg
Genetic factors likely influence individuals' concentrations of 25-hydroxyvitamin D [25(OH)D], a biomarker of vitamin D exposure previously linked to reduced risk of several chronic diseases. We conducted a genome-wide association study of serum 25(OH)D (assessed using liquid chromatography-tandem mass spectrometry) and 386,449 single nucleotide polymorphisms (SNPs). Our sample consisted of 1,829 participants randomly selected from the Sister Study, a cohort of women who had a sister with breast cancer but had never had breast cancer themselves...
2018: Frontiers in Genetics
Luis R Peraza, Ruth Cromarty, Xenia Kobeleva, Michael J Firbank, Alison Killen, Sara Graziadio, Alan J Thomas, John T O'Brien, John-Paul Taylor
Dementia with Lewy bodies (DLB) and Alzheimer's disease (AD) require differential management despite presenting with symptomatic overlap. Currently, there is a need of inexpensive DLB biomarkers which can be fulfilled by electroencephalography (EEG). In this regard, an established electrophysiological difference in DLB is a decrease of dominant frequency (DF)-the frequency with the highest signal power between 4 and 15 Hz. Here, we investigated network connectivity in EEG signals acquired from DLB patients, and whether these networks were able to differentiate DLB from healthy controls (HCs) and associated dementias...
March 15, 2018: Scientific Reports
Daniel E O'Brien, Douglas M Shaw, Hyekyung P Cho, Alan J Cross, Steven S Wesolowski, Andrew S Felts, Jonas Bergare, Charles S Elmore, Craig W Lindsley, Colleen M Niswender, P Jeffrey Conn
Allosteric modulation of metabotropic glutamate receptor 2 (mGlu2) has demonstrated efficacy in preclinical rodent models of several brain disorders, leading to industry and academic drug discovery efforts. Although the pharmacology and binding sites of some mGlu2 allosteric modulators have been characterized previously, questions remain about the nature of the allosteric mechanism of cooperativity with glutamate and whether structurally diverse allosteric modulators bind in an identical manner to specific allosteric sites...
March 15, 2018: Molecular Pharmacology
Sarah Donnelly, Emer Begley, Marita O'Brien
In recent years, there have been national and international policy advances around capacity and decision-making and an apparent burgeoning rights-based approach to the issue, all of which have the potential to impact on the experience for people with dementia in Ireland. There is little evidence however on whether these policies and principles are being translated into practice and whether traditional paternalistic approaches to decision-making are being challenged. To gain insight into current practice, research was undertaken with social workers working with older people in Ireland; reporting on the involvement of people living with dementia in care-planning processes...
January 1, 2018: Dementia
Ava I Kikut, Joan M O'Brien
No abstract text is available yet for this article.
March 15, 2018: JAMA Ophthalmology
Alexandra J Harvey, Carmel O'Brien, Jack Lambshead, John R Sheedy, Joy Rathjen, Andrew L Laslett, David K Gardner
Reprogramming somatic cells to a pluripotent cell state (induced Pluripotent Stem (iPS) cells) requires reprogramming of metabolism to support cell proliferation and pluripotency, most notably changes in carbohydrate turnover that reflect a shift from oxidative to glycolytic metabolism. Some aspects of iPS cell metabolism differ from embryonic stem (ES) cells, which may reflect a parental cell memory, or be a consequence of the reprogramming process. In this study, we compared the metabolism of 3 human iPS cell lines to assess the fidelity of metabolic reprogramming...
2018: PloS One
Christopher John Kiely, Paul Pavli, Claire Louise O'Brien
Studies of the human intestinal microbiome in patients with inflammatory bowel disease (IBD) consistently show that there are differences (an abnormal or unbalanced microbiome, "dysbiosis") when compared to healthy subjects. We sought to describe changes in the microbiome in individual patients over time, and determine the clinical factors that are associated with significant alteration. Forty-two mucosal biopsies were collected from 20 patients that were spaced an average of 2.4 years apart. These were analysed using bacterial 16S rRNA gene high-throughput sequencing methods...
March 15, 2018: Gut Microbes
Young Hwa Kim, Karen M O'Brien
The purpose of the study was to examine the factor structure, measurement invariance, and psychometric properties of a commonly used measure of perceived career barriers (The Perception of Barriers Scale; Luzzo & McWhirter, 2001) with racially diverse college women. The results supported a 9-factor structure for the Perception of Barriers Scale; configural, metric, and scalar invariance for the 9-factors were found with Asian, African American, Latina, and White college women. All groups of women of color reported higher career barriers due to racism and higher educational barriers due to racial discrimination than White women...
March 2018: Journal of Counseling Psychology
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