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Laura J Hoodless, Christopher D Lucas, Rodger Duffin, Martin A Denvir, Christopher Haslett, Carl S Tucker, Adriano G Rossi
Neutrophilic inflammation is tightly regulated and subsequently resolves to limit tissue damage and promote repair. When the timely resolution of inflammation is dysregulated, tissue damage and disease results. One key control mechanism is neutrophil apoptosis, followed by apoptotic cell clearance by phagocytes such as macrophages. Cyclin-dependent kinase (CDK) inhibitor drugs induce neutrophil apoptosis in vitro and promote resolution of inflammation in rodent models. Here we present the first in vivo evidence, using pharmacological and genetic approaches, that CDK9 is involved in the resolution of neutrophil-dependent inflammation...
November 11, 2016: Scientific Reports
Kevin Sam, Boris Peltenburg, John Conklin, Olivia Sobczyk, Julien Poublanc, Adrian P Crawley, Daniel M Mandell, Lakshmikumar Venkatraghavan, James Duffin, Joseph A Fisher, Sandra E Black, David J Mikulis
OBJECTIVE: To compare the diffusion and perfusion MRI metrics of normal-appearing white matter (NAWM) with and without impaired cerebrovascular reactivity (CVR). METHODS: Seventy-five participants with moderate to severe leukoaraiosis underwent blood oxygen level-dependent CVR mapping using a 3T MRI system with precise carbon dioxide stimulus manipulation. Several MRI metrics were statistically compared between areas of NAWM with positive and negative CVR using one-way analysis of variance with Bonferroni correction for multiple comparisons...
October 28, 2016: Neurology
Kristina Callis Duffin, Michael Bukhalo, Margaret A Bobonich, David Shrom, Fangyi Zhao, James R Kershner, Anne Gill, Beth Pangallo, Catherine L Shuler, Jerry Bagel
BACKGROUND: Most biologic therapies for psoriasis are delivered via subcutaneous injection. Ixekizumab, an anti-interleukin 17A monoclonal antibody approved for patients with moderate-to-severe plaque psoriasis, is delivered subcutaneously via prefilled syringe or autoinjector. Here we report the results of an ixekizumab autoinjector usability study as well as the patient-reported experience with the autoinjector in a clinical trial. METHODS: The usability study enrolled 49 subjects (patients with a range of autoimmune conditions or their caregivers)...
2016: Medical Devices: Evidence and Research
Daniel V Christophersen, Nicklas R Jacobsen, Maria H G Andersen, Shea P Connell, Kenneth K Barfod, Morten B Thomsen, Mark R Miller, Rodger Duffin, Jens Lykkesfeldt, Ulla Vogel, Håkan Wallin, Steffen Loft, Martin Roursgaard, Peter Møller
Exposure to high aspect ratio nanomaterials, such as multi-walled carbon nanotubes (MWCNTs) may be associated with increased risk of atherosclerosis, pulmonary disease, and cancer. In the present study, we investigated the cardiovascular and pulmonary health effects of 10 weeks of repeated oral or pulmonary exposures to MWCNTs (4 or 40μg each week) in Apolipoprotein E-deficient (ApoE(-/-)) mice fed a Western-type diet. Intratracheal instillation of MWCNTs was associated with oxidative damage to DNA in lung tissue and elevated levels of lipid peroxidation products in plasma, whereas the exposure only caused a modest pulmonary inflammation in terms of increased numbers of lymphocytes in bronchoalveolar lavage fluid...
October 8, 2016: Toxicology
Jackie Leung, James Duffin, Joseph A Fisher, Andrea Kassner
OBJECTIVES: Cerebrovascular reactivity (CVR) measures the ability of cerebral blood vessels to change their diameter and, hence, their capacity to regulate regional blood flow in the brain. High resolution quantitative maps of CVR can be produced using blood-oxygen level-dependent (BOLD) magnetic resonance imaging (MRI) in combination with a carbon dioxide stimulus, and these maps have become a useful tool in the clinical evaluation of cerebrovascular disorders. However, conventional CVR analysis does not fully characterize the BOLD response to a stimulus as certain regions of the brain are slower to react to the stimulus than others, especially in disease...
2016: NeuroImage: Clinical
James Voelker, Paul H Berg, Matthew Sheetz, Kevin Duffin, Tong Shen, Brian Moser, Tom Greene, Samuel S Blumenthal, Ivan Rychlik, Yoram Yagil, Philippe Zaoui, Julia B Lewis
TGF-β has been implicated as a major pathogenic factor in diabetic nephropathy. This randomized, double-blind, phase 2 study assessed whether modulating TGF-β1 activity with a TGF-β1-specific, humanized, neutralizing monoclonal antibody (TGF-β1 mAb) is safe and more effective than placebo in slowing renal function loss in patients with diabetic nephropathy on chronic stable renin-angiotensin system inhibitor treatment. We randomized 416 patients aged ≥25 years with type 1 or type 2 diabetes, a serum creatinine (SCr) level of 1...
September 19, 2016: Journal of the American Society of Nephrology: JASN
Ana-Maria Orbai, Maarten de Wit, Philip Mease, Judy A Shea, Laure Gossec, Ying Ying Leung, William Tillett, Musaab Elmamoun, Kristina Callis Duffin, Willemina Campbell, Robin Christensen, Laura Coates, Emma Dures, Lihi Eder, Oliver FitzGerald, Dafna Gladman, Niti Goel, Suzanne Dolwick Grieb, Sarah Hewlett, Pil Hoejgaard, Umut Kalyoncu, Chris Lindsay, Neil McHugh, Bev Shea, Ingrid Steinkoenig, Vibeke Strand, Alexis Ogdie
OBJECTIVE: To identify a core set of domains (outcomes) to be measured in psoriatic arthritis (PsA) clinical trials that represent both patients' and physicians' priorities. METHODS: We conducted (1) a systematic literature review (SLR) of domains assessed in PsA; (2) international focus groups to identify domains important to people with PsA; (3) two international surveys with patients and physicians to prioritise domains; (4) an international face-to-face meeting with patients and physicians using the nominal group technique method to agree on the most important domains; and (5) presentation and votes at the Outcome Measures in Rheumatology (OMERACT) conference in May 2016...
September 9, 2016: Annals of the Rheumatic Diseases
K Callis Duffin, J Bagel, M Bukhalo, I J Clement, S L Choi, F Zhao, A Gill, B Pangallo, C Shuler, L Mallbris, K Jackson
BACKGROUND: The efficacy of ixekizumab, an anti-interleukin-17A (anti-IL-17A) monoclonal IgG4 antibody, was demonstrated in moderate-to-severe psoriasis patients when administered via prefilled syringe (PFS). OBJECTIVE: To evaluate the effect of two drug delivery devices on the pharmacokinetics (PK) of ixekizumab as well as efficacy and safety with both devices. METHODS: In the first 12 weeks of an open-label, phase 3 study, moderate-to-severe psoriasis patients were randomized to ixekizumab delivery via PFS or autoinjector device...
August 8, 2016: Journal of the European Academy of Dermatology and Venereology: JEADV
K Sam, A P Crawley, J Poublanc, J Conklin, O Sobczyk, D M Mandell, J Duffin, L Venkatraghavan, J A Fisher, S E Black, D J Mikulis
BACKGROUND AND PURPOSE: The pathogenesis of leukoaraiosis has long been debated. This work addresses a less well-studied mechanism, cerebrovascular reactivity, which could play a leading role in the pathogenesis of this disease. Our aim was to evaluate blood flow dysregulation and its relation to leukoaraiosis. MATERIALS AND METHODS: Cerebrovascular reactivity, the change in the blood oxygen level-dependent 3T MR imaging signal in response to a consistently applied step change in the arterial partial pressure of carbon dioxide, was measured in white matter hyperintensities and their contralateral spatially homologous normal-appearing white matter in 75 older subjects (age range, 50-91 years; 40 men) with leukoaraiosis...
August 4, 2016: AJNR. American Journal of Neuroradiology
Paul M Duffin, Daniel A Barber
Natural transformation is the main means of horizontal genetic exchange in the obligate human pathogen Neisseria gonorrhoeae and drives the spread of antibiotic resistance and virulence determinants. Transformation can be divided into four steps: (1) DNA binding, (2) DNA uptake, (3) DNA processing and (4) DNA recombination into the chromosome. The DNA processing enzyme DprA has been shown to shuttle incoming ssDNA to the recombination enzyme RecA during transformation in Bacillus subtilis and Streptococcus pneumoniae...
September 2016: Microbiology
W Alan C Mutch, Michael J Ellis, Lawrence N Ryner, Marc P Morissette, Philip J Pries, Brenden Dufault, Marco Essig, David J Mikulis, James Duffin, Joseph A Fisher
BACKGROUND: Advanced neuroimaging studies in concussion have been limited to detecting group differences between concussion patients and healthy controls. In this small pilot study, we used brain magnetic resonance imaging (MRI) CO2 stress testing to longitudinally assess cerebrovascular responsiveness (CVR) in individual sports-related concussion (SRC) patients. METHODS: Six SRC patients (three males and three females; mean age = 15.7, range = 15-17 years) underwent longitudinal brain MRI CO2 stress testing using blood oxygen level-dependent (BOLD) MRI and model-based prospective end-tidal CO2 targeting under isoxic conditions...
2016: Frontiers in Neurology
Kevin Sam, John Conklin, Kenneth R Holmes, Olivia Sobczyk, Julien Poublanc, Adrian P Crawley, Daniel M Mandell, Lakshmikumar Venkatraghavan, James Duffin, Joseph A Fisher, Sandra E Black, David J Mikulis
PURPOSE: To evaluate the relationship between both dynamic and steady-state measures of cerebrovascular reactivity (CVR) and the progression of age-related white matter disease. METHODS: Blood oxygen level-dependent (BOLD) MRI CVR scans were acquired from forty-five subjects (age range: 50-90 years, 25 males) with moderate to severe white matter disease, at baseline and one-year follow-up. To calculate the dynamic (τ) and steady-state (ssCVR) components of the BOLD signal response, the PETCO2 signal waveform was convolved with an exponential decay function...
2016: NeuroImage: Clinical
Christopher J Duffin
No abstract text is available yet for this article.
December 2015: Pharmaceutical Historian
Kevin Sam, Adrian P Crawley, John Conklin, Julien Poublanc, Olivia Sobczyk, Daniel M Mandell, Lakshmikumar Venkatraghavan, James Duffin, Joseph A Fisher, Sandra E Black, David J Mikulis
OBJECTIVE: White matter hyperintensities (WMH) observed on neuroimaging of elderly individuals are associated with cognitive decline and disability. However, the pathogenesis of WMH remains poorly understood. We observed that regions of reduced cerebrovascular reactivity (CVR) in the white matter of young individuals correspond to the regions most susceptible to WMH in the elderly. This finding prompted us to consider that reduced CVR may play a role in the pathogenesis of WMH. We hypothesized that reduced CVR precedes development of WMH...
August 2016: Annals of Neurology
Gina Eom, Paul Grootendorst, Jacalyn Duffin
No abstract text is available yet for this article.
June 13, 2016: CMAJ: Canadian Medical Association Journal, Journal de L'Association Medicale Canadienne
Jacalyn Duffin
No abstract text is available yet for this article.
June 2016: South African Medical Journal, Suid-Afrikaanse Tydskrif Vir Geneeskunde
Saro D Farra, Cathie Kessler, James Duffin, Greg D Wells, Ira Jacobs
Exercise- and hypoxia-induced hyperventilation decreases the partial pressure of end-tidal carbon dioxide (PETCO2), which in turn exerts many physiological effects. Several breathing circuits that control PETCO2 have been previously described, but their designs are not satisfactory for exercise studies where changes in inspired oxygen (FIO2) may be desired. This study is the first report of a breathing system that can maintain PETCO2 constant within a single session of graded submaximal exercise and graded hypoxia...
September 2016: Respiratory Physiology & Neurobiology
Michael J Ellis, Lawrence N Ryner, Olivia Sobczyk, Jorn Fierstra, David J Mikulis, Joseph A Fisher, James Duffin, W Alan C Mutch
Concussion is a form of traumatic brain injury (TBI) that presents with a wide spectrum of subjective symptoms and few objective clinical findings. Emerging research suggests that one of the processes that may contribute to concussion pathophysiology is dysregulation of cerebral blood flow (CBF) leading to a mismatch between CBF delivery and the metabolic needs of the injured brain. Cerebrovascular reactivity (CVR) is defined as the change in CBF in response to a measured vasoactive stimulus. Several magnetic resonance imaging (MRI) techniques can be used as a surrogate measure of CBF in clinical and laboratory studies...
2016: Frontiers in Neurology
Dafna D Gladman, Philip J Mease, Wolf-Henning Boehncke, Philip S Helliwell, Kristina Callis Duffin
In preparation for strategic planning of the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA), a special session titled the Presidential Round Table took place during the GRAPPA annual meeting in Stockholm, Sweden, in July 2015. During this session, past, current, and incoming presidents of GRAPPA reflected on GRAPPA's history and provided insights about GRAPPA's future, followed by general discussion by the membership.
May 2016: Journal of Rheumatology
Philip J Mease, Philip S Helliwell, Wolf-Henning Boehncke, Laura C Coates, Oliver FitzGerald, Dafna D Gladman, Atul A Deodhar, Kristina Callis Duffin
At the 2015 annual meeting of the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA), attendees were presented with brief updates on several ongoing initiatives, including educational projects. Updates were presented on the treatment recommendations project, the development of simple criteria to identify inflammatory musculoskeletal disease, new patient/physician Delphi exercises, and BIODAM (identifying biomarkers that predict progressive structural joint damage). The publication committee also gave a report...
May 2016: Journal of Rheumatology
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