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Ameya R Kirtane, Omar Abouzid, Daniel Minahan, Taylor Bensel, Alison L Hill, Christian Selinger, Anna Bershteyn, Morgan Craig, Shirley S Mo, Hormoz Mazdiyasni, Cody Cleveland, Jaimie Rogner, Young-Ah Lucy Lee, Lucas Booth, Farhad Javid, Sarah J Wu, Tyler Grant, Andrew M Bellinger, Boris Nikolic, Alison Hayward, Lowell Wood, Philip A Eckhoff, Martin A Nowak, Robert Langer, Giovanni Traverso
The efficacy of antiretroviral therapy is significantly compromised by medication non-adherence. Long-acting enteral systems that can ease the burden of daily adherence have not yet been developed. Here we describe an oral dosage form composed of distinct drug-polymer matrices which achieved week-long systemic drug levels of the antiretrovirals dolutegravir, rilpivirine and cabotegravir in a pig. Simulations of viral dynamics and patient adherence patterns indicate that such systems would significantly reduce therapeutic failures and epidemiological modelling suggests that using such an intervention prophylactically could avert hundreds of thousands of new HIV cases...
January 9, 2018: Nature Communications
Koen Schakenraad, Andreas S Biebricher, Maarten Sebregts, Brian Ten Bensel, Erwin J G Peterman, Gijs J L Wuite, Iddo Heller, Cornelis Storm, Paul van der Schoot
The three-dimensional structure of DNA is highly susceptible to changes by mechanical and biochemical cues in vivo and in vitro. In particular, large increases in base pair spacing compared to regular B-DNA are effected by mechanical (over)stretching and by intercalation of compounds that are widely used in biophysical/chemical assays and drug treatments. We present single-molecule experiments and a three-state statistical mechanical model that provide a quantitative understanding of the interplay between B-DNA, overstretched DNA and intercalated DNA...
December 19, 2017: Nature Communications
Florence A Aeschlimann, Simon W M Eng, Shehla Sheikh, Ronald M Laxer, Diane Hebert, Damien Noone, Marinka Twilt, Christian Pagnoux, Susanne M Benseler, Rae S M Yeung
BACKGROUND: Takayasu arteritis (TAK) is a large vessel vasculitis that rarely affects children. Data on childhood TAK are scarce. The aim of this study was to analyze the presenting features, course and outcome of children with TAK, compare efficacy of treatment regimens and identify high-risk factors for adverse outcome. METHODS: A single-center cohort study of consecutive children fulfilling the EULAR/PRINTO/PReS criteria for childhood TAK between 1986 and 2015 was performed...
November 22, 2017: Arthritis Research & Therapy
Jaime Guzman, Tristan Kerr, Leanne M Ward, Jinhui Ma, Kiem Oen, Alan M Rosenberg, Brian M Feldman, Gilles Boire, Kristin Houghton, Paul Dancey, Rosie Scuccimarri, Alessandra Bruns, Adam M Huber, Karen Watanabe Duffy, Natalie J Shiff, Roberta A Berard, Deborah M Levy, Elizabeth Stringer, Kimberly Morishita, Nicole Johnson, David A Cabral, Maggie Larché, Ross E Petty, Ronald M Laxer, Earl Silverman, Paivi Miettunen, Anne-Laure Chetaille, Elie Haddad, Lynn Spiegel, Stuart E Turvey, Heinrike Schmeling, Bianca Lang, Janet Ellsworth, Suzanne E Ramsey, Johannes Roth, Sarah Campillo, Susanne Benseler, Gaëlle Chédeville, Rayfel Schneider, Shirley M L Tse, Roxana Bolaria, Katherine Gross, Debbie Feldman, Bonnie Cameron, Roman Jurencak, Jean Dorval, Claire LeBlanc, Claire St Cyr, Michele Gibbon, Rae S M Yeung, Ciarán M Duffy, Lori B Tucker
BACKGROUND: With modern treatments, the effect of juvenile idiopathic arthritis (JIA) on growth may be less than previously reported. Our objective was to describe height, weight and body mass index (BMI) development in a contemporary JIA inception cohort. METHODS: Canadian children newly-diagnosed with JIA 2005-2010 had weight and height measurements every 6 months for 2 years, then yearly up to 5 years. These measurements were used to calculate mean age- and sex-standardized Z-scores, and estimate prevalence and cumulative incidence of growth impairments, and the impact of disease activity and corticosteroids on growth...
August 22, 2017: Pediatric Rheumatology Online Journal
J B Kuemmerle-Deschner, D Verma, T Endres, L Broderick, A A de Jesus, F Hofer, N Blank, K Krause, C Rietschel, G Horneff, I Aksentijevich, P Lohse, R Goldbach-Mansky, H M Hoffman, S M Benseler
OBJECTIVE: Cryopyrin-associated periodic syndromes (CAPS) result from gain-of-function mutations in the NLRP3 gene, which causes excessive release of interleukin-1β (IL-1β) and systemic inflammation. While pathogenetic NLRP3 variant phenotypes are well-characterized, low-penetrance NLRP3 variants represent a significant clinical challenge. The aims of this study were to determine the clinical phenotype, the in vitro biologic phenotype, and the effect of anti-IL-1 treatment in patients with low-penetrance NLRP3 variants...
November 2017: Arthritis & Rheumatology
Todd R Fredricks, Christopher Gibson, Francis Essien, Jeffrey S Benseler
Hypoxic-ischemic encephalopathy is caused by neonatal asphyxia and can lead to mortality or long-term neurodevelopmental morbidity in neonates. Therapeutic hypothermia (TH) is one of the few effective ways to manage mitigating neurologic sequelae. The authors describe the case of a neonate who had a perinatal hypoxic insult and sustained no long-term sequelae after being treated with TH. It is important that osteopathic physicians who provide obstetric and gynecologic, perinatal, and emergency medical care are able to recognize a perinatal hypoxic event, understand the stratification of hypoxic-ischemic encephalopathy risk factors, and implement early TH protocols...
June 1, 2017: Journal of the American Osteopathic Association
Kimberly A Morishita, Lakshmi N Moorthy, Joanna M Lubieniecka, Marinka Twilt, Rae S M Yeung, Mary B Toth, Susan Shenoi, Goran Ristic, Susan M Nielsen, Raashid A Luqmani, Suzanne C Li, Tzielan Lee, Erica F Lawson, Mikhail M Kostik, Marisa Klein-Gitelman, Adam M Huber, Aimee O Hersh, Dirk Foell, Melissa E Elder, Barbara A Eberhard, Paul Dancey, Sirirat Charuvanij, Susanne M Benseler, David A Cabral
OBJECTIVE: To characterize the early disease course in childhood-onset antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) and the 12-month outcomes in children with AAV. METHODS: Eligible subjects were children entered into the Pediatric Vasculitis Initiative study who were diagnosed before their eighteenth birthday as having granulomatosis with polyangiitis (Wegener's), microscopic polyangiitis, eosinophilic granulomatosis with polyangiitis (Churg-Strauss), or ANCA-positive pauci-immune glomerulonephritis...
July 2017: Arthritis & Rheumatology
Kiem Oen, Jaime Guzman, Brenden Dufault, Lori B Tucker, Natalie J Shiff, Karen Watanabe Duffy, Jennifer J Y Lee, Brian M Feldman, Roberta A Berard, Paul Dancey, Adam M Huber, Rosie Scuccimarri, David A Cabral, Kimberly A Morishita, Suzanne E Ramsey, Alan M Rosenberg, Gilles Boire, Susanne M Benseler, Bianca Lang, Kristin Houghton, Paivi M Miettunen, Gaëlle Chédeville, Deborah M Levy, Alessandra Bruns, Heinrike Schmeling, Elie Haddad, Rae S M Yeung, Ciarán M Duffy
OBJECTIVE: To describe changes in health-related quality of life (HRQoL) over time in children with juvenile idiopathic arthritis (JIA), relative to other outcomes, and to identify predictors of unfavorable HRQoL trajectories. METHODS: Children with JIA in the Research in Arthritis in Canadian Children emphasizing Outcomes (ReACCh-Out) cohort were included. The Juvenile Arthritis Quality of Life Questionnaire (JAQQ, a standardized instrument), health-related Quality of My Life (HRQoML, an instrument based on personal valuations), and JIA core variables were completed serially...
January 2018: Arthritis Care & Research
Nienke M Ter Haar, Kim V Annink, Sulaiman M Al-Mayouf, Gayane Amaryan, Jordi Anton, Karyl S Barron, Susanne M Benseler, Paul A Brogan, Luca Cantarini, Marco Cattalini, Alexis-Virgil Cochino, Fabrizio De Benedetti, Fatma Dedeoglu, Adriana A De Jesus, Ornella Della Casa Alberighi, Erkan Demirkaya, Pavla Dolezalova, Karen L Durrant, Giovanna Fabio, Romina Gallizzi, Raphaela Goldbach-Mansky, Eric Hachulla, Veronique Hentgen, Troels Herlin, Michaël Hofer, Hal M Hoffman, Antonella Insalaco, Annette F Jansson, Tilmann Kallinich, Isabelle Koné-Paut, Anna Kozlova, Jasmin B Kuemmerle-Deschner, Helen J Lachmann, Ronald M Laxer, Alberto Martini, Susan Nielsen, Irina Nikishina, Amanda K Ombrello, Seza Ozen, Efimia Papadopoulou-Alataki, Pierre Quartier, Donato Rigante, Ricardo Russo, Anna Simon, Maria Trachana, Yosef Uziel, Angelo Ravelli, Marco Gattorno, Joost Frenkel
OBJECTIVES: Autoinflammatory diseases cause systemic inflammation that can result in damage to multiple organs. A validated instrument is essential to quantify damage in individual patients and to compare disease outcomes in clinical studies. Currently, there is no such tool. Our objective was to develop a common autoinflammatory disease damage index (ADDI) for familial Mediterranean fever, cryopyrin-associated periodic syndromes, tumour necrosis factor receptor-associated periodic fever syndrome and mevalonate kinase deficiency...
May 2017: Annals of the Rheumatic Diseases
Tania Cellucci, Jaime Guzman, Ross E Petty, Michelle Batthish, Susanne M Benseler, Janet E Ellsworth, Kristin M Houghton, Claire M A LeBLANC, Adam M Huber, Nadia Luca, Heinrike Schmeling, Natalie J Shiff, Gordon S Soon, Shirley M L Tse
No abstract text is available yet for this article.
October 2016: Journal of Rheumatology
Florence A Aeschlimann, Lars Grosse-Wortmann, Susanne M Benseler, Ronald M Laxer, Diane Hebert, Rae S M Yeung
BACKGROUND: Arterial vessel wall dissection is a rare, life-threatening and rarely described complication in childhood Takayasu Arteritis (cTA). Prevalence and risk factors for arterial dissection in cTA are unknown. We sought to study the prevalence and analyse risk factors for arterial dissection in cTA. FINDINGS: A single center retrospective review of all children with cTA was performed. Patients with arterial dissection at cTA diagnosis were reported in detail and compared to the remaining single center retrospective cohort of children without dissection...
September 22, 2016: Pediatric Rheumatology Online Journal
David A Cabral, Debra L Canter, Eyal Muscal, Kabita Nanda, Dawn M Wahezi, Steven J Spalding, Marinka Twilt, Susanne M Benseler, Sarah Campillo, Sirirat Charuvanij, Paul Dancey, Barbara A Eberhard, Melissa E Elder, Aimee Hersh, Gloria C Higgins, Adam M Huber, Raju Khubchandani, Susan Kim, Marisa Klein-Gitelman, Mikhail M Kostik, Erica F Lawson, Tzielan Lee, Joanna M Lubieniecka, Deborah McCurdy, Lakshmi N Moorthy, Kimberly A Morishita, Susan M Nielsen, Kathleen M O'Neil, Andreas Reiff, Goran Ristic, Angela B Robinson, Angelyne Sarmiento, Susan Shenoi, Mary B Toth, Heather A Van Mater, Linda Wagner-Weiner, Jennifer E Weiss, Andrew J White, Rae S M Yeung
OBJECTIVE: To uniquely classify children with microscopic polyangiitis (MPA), to describe their demographic characteristics, presenting clinical features, and initial treatments in comparison to patients with granulomatosis with polyangiitis (Wegener's) (GPA). METHODS: The European Medicines Agency (EMA) classification algorithm was applied by computation to categorical data from patients recruited to the ARChiVe (A Registry for Childhood Vasculitis: e-entry) cohort, with the data censored to November 2015...
October 2016: Arthritis & Rheumatology
Todd R Fredricks, Jeffrey S Benseler
BACKGROUND: Bicuspid aortic valve disease (BAV) is the most common cardiac valve pathology. BAV is associated with aortic root disorders. The literature has few case reports identifying this condition during routine physical exam. CASE REPORT: A 42-yr-old military reservist flight medic presented for his annual military flight physical. He was found to have a faint cardiac murmur. His past family and medical history were remarkable for familial essential hypertension and being told at age 9 that he had a "murmur...
May 2016: Aerospace Medicine and Human Performance
J B Kümmerle-Deschner, J Thomas, S M Benseler
BACKGROUND: The primary vasculitides are rare conditions in childhood. The most common disease subtypes are Schönlein-Henoch purpura and Kawasaki's syndrome, which frequently have a self-limiting course. In the majority of vasculitides, the etiology remains unknown. Environmental exposure, including infections, is suspected to trigger an autoinflammatory response in predisposed individuals. GOAL: The aim of this review is to present the various aspects of childhood vasculitis...
December 2015: Zeitschrift Für Rheumatologie
Lucy McGeoch, Marinka Twilt, Leilani Famorca, Volodko Bakowsky, Lillian Barra, Susan M Benseler, David A Cabral, Simon Carette, Gerald P Cox, Navjot Dhindsa, Christine S Dipchand, Aurore Fifi-Mah, Michelle Goulet, Nader Khalidi, Majed M Khraishi, Patrick Liang, Nataliya Milman, Christian A Pineau, Heather N Reich, Nooshin Samadi, Kam Shojania, Regina Taylor-Gjevre, Tanveer E Towheed, Judith Trudeau, Michael Walsh, Elaine Yacyshyn, Christian Pagnoux
OBJECTIVE: The Canadian Vasculitis research network (CanVasc) is composed of physicians from different medical specialties and researchers with expertise in vasculitis. One of its aims is to develop recommendations for the diagnosis and management of antineutrophil cytoplasm antibody (ANCA)-associated vasculitides (AAV) in Canada. METHODS: Diagnostic and therapeutic questions were developed based on the results of a national needs assessment survey. A systematic review of existing non-Canadian recommendations and guidelines for the diagnosis and management of AAV and studies of AAV published after the 2009 European League Against Rheumatism/European Vasculitis Society recommendations (publication date: January 2009) until November 2014 was performed in the Medline database, Cochrane library, and main vasculitis conference proceedings...
January 2016: Journal of Rheumatology
Gregory S Day, Harald Prüss, Susanne M Benseler, Tara A Paton, Andrew D Paterson, Danielle M Andrade
OBJECTIVE: To determine whether distinct single nucleotide polymorphisms (SNPs) within the glutamate receptor ionotropic NMDA 1 gene (GRIN1) are associated with NMDA receptor (NMDAR) encephalitis and whether these same variants are associated with variability in the clinical presentation and course of affected patients. METHODS: We performed clinical follow-up on 48 patients with NMDAR encephalitis and NMDAR autoantibodies detected in serum or CSF. All RefSeq GRIN1 coding exons were sequenced in 39 Caucasian-European patients, and the frequencies of SNPs were compared with those of an ethnically similar population using a case-control study design...
October 2015: Neurology® Neuroimmunology & Neuroinflammation
Nienke M ter Haar, Marlen Oswald, Jerold Jeyaratnam, Jordi Anton, Karyl S Barron, Paul A Brogan, Luca Cantarini, Caroline Galeotti, Gilles Grateau, Veronique Hentgen, Michael Hofer, Tilmann Kallinich, Isabelle Kone-Paut, Helen J Lachmann, Huri Ozdogan, Seza Ozen, Ricardo Russo, Anna Simon, Yosef Uziel, Carine Wouters, Brian M Feldman, Sebastiaan J Vastert, Nico M Wulffraat, Susanne M Benseler, Joost Frenkel, Marco Gattorno, Jasmin B Kuemmerle-Deschner
: Autoinflammatory diseases are characterised by fever and systemic inflammation, with potentially serious complications. Owing to the rarity of these diseases, evidence-based guidelines are lacking. In 2012, the European project Single Hub and Access point for paediatric Rheumatology in Europe (SHARE) was launched to optimise and disseminate regimens for the management of children and young adults with rheumatic diseases, facilitating the clinical practice of paediatricians and (paediatric) rheumatologists...
September 2015: Annals of the Rheumatic Diseases
J Bichler, S M Benseler, M Krumrey-Langkammerer, J-P Haas, B Hügle
OBJECTIVES: Chronic anterior uveitis is a serious complication of juvenile idiopathic arthritis (JIA); disease flares are highly associated with loss of vision. Leflunomide (LEF) is used successfully for JIA joint disease but its effectiveness in uveitis has not been determined. The aim of this study was to determine whether LEF improves flare rates of uveitis in JIA patients compared to preceding methotrexate (MTX) therapy. METHOD: A single-centre retrospective study of consecutive children with JIA and chronic anterior uveitis was performed...
2015: Scandinavian Journal of Rheumatology
Jaime Guzman, Kiem Oen, Adam M Huber, Karen Watanabe Duffy, Gilles Boire, Natalie Shiff, Roberta A Berard, Deborah M Levy, Elizabeth Stringer, Rosie Scuccimarri, Kimberly Morishita, Nicole Johnson, David A Cabral, Alan M Rosenberg, Maggie Larché, Paul Dancey, Ross E Petty, Ronald M Laxer, Earl Silverman, Paivi Miettunen, Anne-Laure Chetaille, Elie Haddad, Kristin Houghton, Lynn Spiegel, Stuart E Turvey, Heinrike Schmeling, Bianca Lang, Janet Ellsworth, Suzanne E Ramsey, Alessandra Bruns, Johannes Roth, Sarah Campillo, Susanne Benseler, Gaëlle Chédeville, Rayfel Schneider, Shirley M L Tse, Roxana Bolaria, Katherine Gross, Brian Feldman, Debbie Feldman, Bonnie Cameron, Roman Jurencak, Jean Dorval, Claire LeBlanc, Claire St Cyr, Michele Gibbon, Rae S M Yeung, Ciarán M Duffy, Lori B Tucker
OBJECTIVE: To describe probabilities and characteristics of disease flares in children with juvenile idiopathic arthritis (JIA) and to identify clinical features associated with an increased risk of flare. METHODS: We studied children in the Research in Arthritis in Canadian Children emphasizing Outcomes (ReACCh-Out) prospective inception cohort. A flare was defined as a recurrence of disease manifestations after attaining inactive disease and was called significant if it required intensification of treatment...
June 2016: Annals of the Rheumatic Diseases
Damien G Noone, Marinka Twilt, Wesley N Hayes, Paul S Thorner, Susanne Benseler, Ronald M Laxer, Rulan S Parekh, Diane Hebert
BACKGROUND AND OBJECTIVES: A proposed histopathologic classification for ANCA-associated GN is predictive of long-term renal outcome in adult populations. This study sought to validate this system in a pediatric cohort. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: This was a retrospective, single-center, cohort study of 40 children diagnosed and followed until their transition to adult care at one institution between 1987 and 2012. Renal biopsy specimens were reviewed by a pathologist blinded to patient outcome and were classified using the new histopathologic classification system of focal, crescentic, mixed, and sclerotic groups...
October 7, 2014: Clinical Journal of the American Society of Nephrology: CJASN
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