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https://www.readbyqxmd.com/read/29778696/renal-pre-competitive-consortium-rpc-2-discovering-therapeutic-targets-together
#1
Mark Tomilo, Heather Ascani, Barbara Mirel, Maria Chiara Magnone, Carol Moreno Quinn, Anil Karihaloo, Kevin Duffin, Uptal D Patel, Matthias Kretzler
Despite significant effort, patients with kidney disease have not seen their outcomes improved significantly over the past two decades. This has motivated clinicians and researchers to consider alternative methods to identifying risk factors, disease progression markers, and effective therapies. Genome-scale data sets from patients with renal disease can be used to establish a platform to improve understanding of the molecular basis of disease; however, such studies require expertise and resources. To overcome these challenges, we formed an academic-industry consortium to share molecular target identification efforts and expertise across academia and the pharmaceutical industry...
May 17, 2018: Drug Discovery Today
https://www.readbyqxmd.com/read/29776990/effect-of-2-psoriasis-treatments-on-vascular-inflammation-and-novel-inflammatory-cardiovascular-biomarkers-a-randomized-placebo-controlled-trial
#2
Nehal N Mehta, Daniel B Shin, Aditya A Joshi, Amit K Dey, April W Armstrong, Kristina Callis Duffin, Zelma Chiesa Fuxench, Charlotte L Harrington, Rebecca A Hubbard, Robert E Kalb, Alan Menter, Daniel J Rader, Muredach P Reilly, Eric L Simpson, Junko Takeshita, Drew A Torigian, Thomas J Werner, Andrea B Troxel, Stephen K Tyring, Suzette Baez Vanderbeek, Abby S Van Voorhees, Martin P Playford, Mark A Ahlman, Abass Alavi, Joel M Gelfand
BACKGROUND: Psoriasis is a chronic inflammatory disease associated with dyslipidemia, cardiovascular events, and mortality. We aimed to assess and compare the effect of treatment of moderate-to-severe psoriasis with adalimumab or phototherapy on vascular inflammation and cardiovascular biomarkers. METHODS AND RESULTS: Randomized, double-blind, trial of adalimumab, phototherapy, and placebo (1:1:1) for 12 weeks, with crossover to adalimumab for 52 weeks total. Outcomes included vascular inflammation by 18 F-fluorodeoxyglucose positron emission tomography/computed tomography and biomarkers of inflammation, insulin resistance, and lipoproteins...
June 2018: Circulation. Cardiovascular Imaging
https://www.readbyqxmd.com/read/29747232/efficacy-and-safety-of-ixekizumab-in-a-randomized-double-blinded-placebo-controlled-phase-3b-study-of-patients-with-moderate-to-severe-genital-psoriasis
#3
C Ryan, A Menter, L Guenther, A Blauvelt, R Bissonnette, K Meeuwis, J Sullivan, J C Cather, G Yosipovitch, A B Gottlieb, J F Merola, K Callis Duffin, S Fretzin, O O Osuntokun, R Burge, A N Naegeli, F E Yang, C-Y Lin, K Todd, A Potts Bleakman
BACKGROUND: Genital psoriasis (GenPs) is a common, debilitating, and difficult to treat manifestation of plaque psoriasis. However, few controlled, interventional studies of GenPs exist. OBJECTIVE: To determine the efficacy of ixekizumab versus placebo in patients with moderate-to-severe GenPs with BSA≥1%. METHODS: Subjects with moderate-to-severe GenPs (defined as a baseline static Physician's Global Assessment of Genitalia [sPGA-G] score of ≥3) with BSA≥1% were randomized 1:1 to receive placebo (N=74) or the recommended dosing of ixekizumab (N=75)...
May 10, 2018: British Journal of Dermatology
https://www.readbyqxmd.com/read/29681886/importance-of-collateralization-in-patients-with-large-artery-intracranial-occlusive-disease-long-term-longitudinal-assessment-of-cerebral-hemodynamic-function
#4
Larissa McKetton, Lakshmikumar Venkatraghavan, Julien Poublanc, Olivia Sobczyk, Adrian P Crawley, Casey Rosen, Frank L Silver, James Duffin, Joseph A Fisher, David J Mikulis
Patients with large artery intracranial occlusive disease (LAICOD) are at risk for both acute ischemia and chronic hypoperfusion. Collateral circulation plays an important role in prognosis, and imaging plays an essential role in diagnosis, treatment planning, and prognosis of patients with LAICOD. In addition to standard structural imaging, assessment of cerebral hemodynamic function is important to determine the adequacy of collateral supply. Among the currently available methods of assessment of cerebral hemodynamic function, measurement of cerebrovascular reactivity (CVR) using blood oxygen level-dependent (BOLD) MRI and precisely controlled CO2 has shown to be a safe, reliable, reproducible, and clinically useful method for long-term assessment of patients...
2018: Frontiers in Neurology
https://www.readbyqxmd.com/read/29589016/on-surface-synthesis-of-polyethylenedioxythiophene
#5
Iolanda Di Bernardo, Peter Hines, Maryam Abyazisani, Nunzio Motta, Jennifer MacLeod, Josh Lipton-Duffin
On-surface synthesis of conjugated polymers is made challenging by the need to promote the desired reaction while preventing or minimizing unwanted ancillary reactions that compromise the product integrity. We perform a comprehensive study of the reactions of 2,5-dichloro-3,4-ethylenedioxythiophene on coinage metal surfaces, and demonstrate that only on Ag(111) can we obtain a planar polymer product, polyethylenedioxythiophene (PEDOT).
March 28, 2018: Chemical Communications: Chem Comm
https://www.readbyqxmd.com/read/29574419/facilitation-of-il-22-production-from-innate-lymphoid-cells-by-prostaglandin-e-2-prevents-experimental-lung-neutrophilic-inflammation
#6
Jennifer M Felton, Rodger Duffin, Calum T Robb, Siobhan Crittenden, Stephen M Anderton, Sarah E M Howie, Moira K B Whyte, Adriano G Rossi, Chengcan Yao
Acute lung injury is a neutrophil-dominant, life-threatening disease without effective therapies and better understanding of the pathophysiological mechanisms involved is an urgent need. Here we show that interleukin (IL)-22 is produced from innate lymphoid cells (ILC) and is responsible for suppression of experimental lung neutrophilic inflammation. Blocking prostaglandin E2 (PGE2 ) synthesis reduces lung ILCs and IL-22 production, resulting in exacerbation of lung neutrophilic inflammation. In contrast, activation of the PGE2 receptor EP4 prevents acute lung inflammation...
March 24, 2018: Thorax
https://www.readbyqxmd.com/read/29559344/longitudinal-study-of-the-psoriasis-associated-skin-microbiome-during-therapy-with-ustekinumab-in-a-randomized-phase-3b-clinical-trial
#7
Michael Loesche, Kamyar Farahi, Kimberly Capone, Steven Fakharzadeh, Andrew Blauvelt, Kristina Callis Duffin, Samuel E DePrimo, Ernesto J Muñoz-Elías, Carrie Brodmerkel, Bidisha Dasgupta, Marc Chevrier, Kevin Smith, Joseph Horwinski, Amanda Tyldsley, Elizabeth A Grice
BACKGROUND: Plaque psoriasis, a chronic inflammatory disease primarily affecting the skin, is thought to have a multifactorial etiology, including innate immune system dysregulation, environmental triggers, and genetic susceptibility. PURPOSE: We sought to further understand the role of skin microbiota in psoriasis pathogenesis, as well as their response to therapy. We systematically analyzed dynamic microbiota colonizing psoriasis lesions and adjacent nonlesional skin in 114 patients prior to and during ustekinumab treatment in a Phase 3b clinical trial...
March 17, 2018: Journal of Investigative Dermatology
https://www.readbyqxmd.com/read/29481660/jak1-jak2-inhibition-by-baricitinib-in-diabetic-kidney-disease-results-from-a-phase-2-randomized-controlled-clinical-trial
#8
Katherine R Tuttle, Frank C Brosius, Sharon G Adler, Matthias Kretzler, Ravindra L Mehta, James A Tumlin, Yoshiya Tanaka, Masakazu Haneda, Jiajun Liu, Maria E Silk, Tracy E Cardillo, Kevin L Duffin, Joseph V Haas, William L Macias, Fabio P Nunes, Jonathan M Janes
Background: Inflammation signaled by Janus kinases (JAKs) promotes progression of diabetic kidney disease (DKD). Baricitinib is an oral, reversible, selective inhibitor of JAK1 and JAK2. This study tested the efficacy of baricitinib versus placebo on albuminuria in adults with Type 2 diabetes at high risk for progressive DKD. Methods: In this Phase 2, double-blind, dose-ranging study, participants were randomized 1:1:1:1:1 to receive placebo or baricitinib (0.75 mg daily; 0...
February 22, 2018: Nephrology, Dialysis, Transplantation
https://www.readbyqxmd.com/read/29463325/paediatric-obstructive-sleep-apnoea-is-our-operative-management-evidence-based
#9
L Pabla, J Duffin, L Flood, K Blackmore
BACKGROUND: Despite the plethora of publications on the subject of paediatric obstructive sleep apnoea, there seems to be wide variability in the literature and in practice, regarding recourse to surgery, the operation chosen, the benefits gained and post-operative management. This may reflect a lack of high-level evidence. METHODS: A systematic review of four significant controversies in paediatric ENT was conducted from the available literature: tonsillectomy versus tonsillotomy, focusing on the evidence base for each; anaesthetic considerations in paediatric obstructive sleep apnoea surgery; the objective evidence for the benefits of surgical treatment for obstructive sleep apnoea; and the medical treatment options for residual obstructive sleep apnoea after surgical treatment...
April 2018: Journal of Laryngology and Otology
https://www.readbyqxmd.com/read/29462231/efficacy-and-safety-of-apremilast-in-systemic-and-biologic-naive-patients-with-moderate-plaque-psoriasis-52-week-results-of-unveil
#10
Linda Stein Gold, Jerry Bagel, Mark Lebwohl, J Mark Jackson, Rongdean Chen, Joana Goncalves, Eugenia Levi, Kristina Callis Duffin
<p>BACKGROUND: Many patients with moderate plaque psoriasis are undertreated despite broadening treatment options. In the phase IV UNVEIL study, oral apremilast demonstrated efficacy and safety in systemic-naive patients with chronic moderate plaque psoriasis with lower psoriasis-involved body surface area (BSA; 5%-10%) during the 16-week, double-blind, placebo-controlled phase. We describe efficacy and safety of apremilast in this population through week 52 in UNVEIL.</p> <p>METHODS: Patients with moderate plaque psoriasis (BSA 5%-10%; static Physician's Global Assessment [sPGA] score of 3 [moderate]) and naive to systemic therapies for psoriasis were randomized (2:1) to receive apremilast 30 mg twice daily or placebo for 16 weeks...
February 1, 2018: Journal of Drugs in Dermatology: JDD
https://www.readbyqxmd.com/read/29460710/doctors-as-stewards-of-medicare-or-not-camsi-mrg-cdm-drhc-and-the-thin-alphabet-soup-of-physician-support
#11
Jacalyn Duffin
Physicians are deeply involved in Canadian medicare because it is through medicare that they are paid. However, from its origins to the present physicians -as a profession - have not been strong supporters of medicare. Fearing loss of income and individual autonomy, they have frequently opposed it with criticisms, strikes, threatened job action and lawsuits. Some opponents are unaware that medicare was a boon to physician income, and many fail to connect medicare with responsibility for improving the health status of the country...
February 20, 2018: Health Economics, Policy, and Law
https://www.readbyqxmd.com/read/29450908/aquagenic-pruritus-successfully-treated-with-omalizumab
#12
B Murphy, M Duffin, J Tolland
No abstract text is available yet for this article.
February 16, 2018: Clinical and Experimental Dermatology
https://www.readbyqxmd.com/read/29439747/paediatric-obstructive-sleep-apnoea-can-our-identification-of-surgical-candidates-be-evidence-based
#13
L Pabla, J Duffin, L Flood, K Blackmore
BACKGROUND: Paediatric obstructive sleep apnoea is a common clinical condition managed by most ENT clinicians. However, despite the plethora of publications on the subject, there is wide variability, in the literature and in practice, on key aspects such as diagnostic criteria, the impact of co-morbidities and the indications for surgical correction. METHODS: A systematic review is presented, addressing four key questions from the available literature: (1) what is the evidence base for any definition of paediatric obstructive sleep apnoea?; (2) does it cause serious systemic illness?; (3) what co-morbidities influence the severity of paediatric obstructive sleep apnoea?; and (4) is there a medical answer? RESULTS AND CONCLUSION: There is a considerable lack of evidence regarding most of these fundamental questions...
April 2018: Journal of Laryngology and Otology
https://www.readbyqxmd.com/read/29428392/mer-mediated-eosinophil-efferocytosis-regulates-resolution-of-allergic-airway-inflammation
#14
Jennifer M Felton, Christopher D Lucas, David A Dorward, Rodger Duffin, Tiina Kipari, Sonja Vermeren, Calum T Robb, Kenneth G MacLeod, Bryan Serrels, Jürgen Schwarze, Christopher Haslett, Ian Dransfield, Adriano G Rossi
BACKGROUND: Eosinophils play a central role in propagation of allergic diseases, including asthma. Both recruitment and retention of eosinophils regulate pulmonary eosinophilia, but the question of whether alterations in apoptotic cell clearance by phagocytes contributes directly to resolution of allergic airway inflammation remains unexplored. OBJECTIVES: In this study we investigated the role of the receptor tyrosine kinase Mer in mediating apoptotic eosinophil clearance and allergic airway inflammation resolution in vivo to establish whether apoptotic cell clearance directly affects the resolution of allergic airway inflammation...
February 8, 2018: Journal of Allergy and Clinical Immunology
https://www.readbyqxmd.com/read/29416525/patient-specific-alterations-in-co-2-cerebrovascular-responsiveness-in-acute-and-sub-acute-sports-related-concussion
#15
W Alan C Mutch, Michael J Ellis, Lawrence N Ryner, Patrick J McDonald, Marc P Morissette, Philip Pries, Marco Essig, David J Mikulis, James Duffin, Joseph A Fisher
Background: Preliminary studies suggest that sports-related concussion (SRC) is associated with alterations in cerebral blood flow (CBF) regulation. Here, we use advanced magnetic resonance imaging (MRI) techniques to measure CBF and cerebrovascular responsiveness (CVR) in individual SRC patients and healthy control subjects. Methods: 15 SRC patients (mean age = 16.3, range 14-20 years) and 27 healthy control subjects (mean age = 17.6, range 13-21 years) underwent anatomical MRI, pseudo-continuous arterial spin labeling (pCASL) MRI and model-based prospective end-tidal targeting (MPET) of CO2 during blood oxygenation level-dependent (BOLD) MRI...
2018: Frontiers in Neurology
https://www.readbyqxmd.com/read/29398132/markers-of-early-progressive-renal-decline-in-type-2-diabetes-suggest-different-implications-for-etiological-studies-and-prognostic-tests-development
#16
Natalia Nowak, Jan Skupien, Adam M Smiles, Masayuki Yamanouchi, Monika A Niewczas, Andrzej T Galecki, Kevin L Duffin, Matthew D Breyer, Nick Pullen, Joseph V Bonventre, Andrzej S Krolewski
To identify determinants of early progressive renal decline in type 2 diabetes a range of markers was studied in 1032 patients enrolled into the 2nd Joslin Kidney Study. eGFR slopes estimated from serial measurements of serum creatinine during 5-12 years of follow-up were used to define early renal decline. At enrollment, all patients had normal eGFR, 58% had normoalbuminuria and 42% had albuminuria. Early renal decline developed in 6% and in 18% patients, respectively. As determinants, we examined baseline values of clinical characteristics, circulating markers: TNFR1, KIM-1, and FGF23, and urinary markers: albumin, KIM-1, NGAL, MCP-1, EGF (all normalized to urinary creatinine) and the ratio of EGF to MCP-1...
May 2018: Kidney International
https://www.readbyqxmd.com/read/29376834/quasi-free-standing-epitaxial-graphene-fabrication-on-3c-sic-si-111
#17
Mojtaba Amjadipour, Anton Tadich, John J Boeckl, Josh Lipton-Duffin, Jennifer MacLeod, Francesca Iacopi, Nunzio Motta
Growing graphene on SiC thin films on Si is a cheaper alternative to the growth on bulk SiC, and for this reason it has been recently intensively investigated. Here we study the effect of hydrogen intercalation on epitaxial graphene obtained by high temperature annealing on 3C-SiC/Si(111) in ultra-high vacuum. By using a combination of core-level photoelectron spectroscopy, low energy electron diffraction, and near-edge x-ray absorption fine structure (NEXAFS) we find that hydrogen saturates the Si atoms at the topmost layer of the substrate, leading to free-standing graphene on 3C-SiC/Si(111)...
April 6, 2018: Nanotechnology
https://www.readbyqxmd.com/read/29374211/low-altitude-solar-magnetic-reconnection-type-iii-solar-radio-bursts-and-x-ray-emissions
#18
I H Cairns, V V Lobzin, A Donea, S J Tingay, P I McCauley, D Oberoi, R T Duffin, M J Reiner, N Hurley-Walker, N A Kudryavtseva, D B Melrose, J C Harding, G Bernardi, J D Bowman, R J Cappallo, B E Corey, A Deshpande, D Emrich, R Goeke, B J Hazelton, M Johnston-Hollitt, D L Kaplan, J C Kasper, E Kratzenberg, C J Lonsdale, M J Lynch, S R McWhirter, D A Mitchell, M F Morales, E Morgan, S M Ord, T Prabu, A Roshi, N Udaya Shankar, K S Srivani, R Subrahmanyan, R B Wayth, M Waterson, R L Webster, A R Whitney, A Williams, C L Williams
Type III solar radio bursts are the Sun's most intense and frequent nonthermal radio emissions. They involve two critical problems in astrophysics, plasma physics, and space physics: how collective processes produce nonthermal radiation and how magnetic reconnection occurs and changes magnetic energy into kinetic energy. Here magnetic reconnection events are identified definitively in Solar Dynamics Observatory UV-EUV data, with strong upward and downward pairs of jets, current sheets, and cusp-like geometries on top of time-varying magnetic loops, and strong outflows along pairs of open magnetic field lines...
January 26, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29346929/numerical-estimation-of-structure-constants-in-the-three-dimensional-ising-conformal-field-theory-through-markov-chain-uv-sampler
#19
Victor Herdeiro
Herdeiro and Doyon [Phys. Rev. E 94, 043322 (2016)2470-004510.1103/PhysRevE.94.043322] introduced a numerical recipe, dubbed uv sampler, offering precise estimations of the conformal field theory (CFT) data of the planar two-dimensional (2D) critical Ising model. It made use of scale invariance emerging at the critical point in order to sample finite sublattice marginals of the infinite plane Gibbs measure of the model by producing holographic boundary distributions. The main ingredient of the Markov chain Monte Carlo sampler is the invariance under dilation...
September 2017: Physical Review. E
https://www.readbyqxmd.com/read/29316616/revitalising-silver-nitrate-for-caries-management
#20
REVIEW
Sherry Shiqian Gao, Irene Shuping Zhao, Steve Duffin, Duangporn Duangthip, Edward Chin Man Lo, Chun Hung Chu
Silver nitrate has been adopted for medical use as a disinfectant for eye disease and burned wounds. In dentistry, it is an active ingredient of Howe's solution used to prevent and arrest dental caries. While medical use of silver nitrate as a disinfectant became subsidiary with the discovery of antibiotics, its use in caries treatment also diminished with the use of fluoride in caries prevention. Since then, fluoride agents, particularly sodium fluoride, have gained popularity in caries prevention. However, caries is an infection caused by cariogenic bacteria, which demineralise enamel and dentine...
January 6, 2018: International Journal of Environmental Research and Public Health
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