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https://www.readbyqxmd.com/read/29844014/an-allosteric-propofol-binding-site-in-kinesin-disrupts-kinesin-mediated-processive-movement-on-microtubules
#1
Kellie A Woll, Stephanie Guzik-Lendrum, Brandon M Bensel, Natarajan V Bhanu, William P Dailey, Benjamin A Garcia, Susan P Gilbert, Roderic G Eckenhoff
Microtubule-based molecular motors mediate transport of intracellular cargo to subdomains in neurons. Previous evidence has suggested that the anesthetic propofol decreases the average run-length potential of the major anterograde transporters kinesin-1 and kinesin-2 without altering their velocity. This effect on kinesin has not been observed with other inhibitors, stimulating considerable interest in the underlying mechanism. Here, we used a photoactive derivative of propofol, meta-azipropofol (AziPm), to search for potential propofol-binding sites in kinesin...
May 29, 2018: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/29782425/increased-arterial-stiffness-in-a-cohort-of-pediatric-takayasu-arteritis-patients-in-toronto-adversely-affects-left-ventricular-mechanics
#2
Heynric B Grotenhuis, Florence A Aeschlimann, Wei Hui, Cameron Slorach, Rae S M Yeung, Susanne M Benseler, Timothy J Bradley, Lars Grosse-Wortmann
BACKGROUND/OBJECTIVE: Takayasu arteritis (TA) is characterized by extensive aortic, large and midsize arterial wall inflammation. The aim of this study was to assess the morphological and elastic properties of the aorta and large arteries and the impact on left ventricular (LV) mechanics in children with TA. METHODS: Seven pediatric TA patients (6 female patients, 13.8 ± 3.2 years) were assessed with magnetic resonance imaging, vascular ultrasound, applanation tonometry, and echocardiography from February 2015 until July 2017 and compared with 7 age- and sex-matched controls...
May 19, 2018: Journal of Clinical Rheumatology: Practical Reports on Rheumatic & Musculoskeletal Diseases
https://www.readbyqxmd.com/read/29622301/cluster-and-multiple-correspondence-analyses-in-rheumatology-paths-to-uncovering-relationships-in-a-sea-of-data
#3
REVIEW
Lu Han, Susanne M Benseler, Pascal N Tyrrell
Rheumatic diseases encompass a wide range of conditions caused by inflammation and dysregulation of the immune system resulting in organ damage. Research in these heterogeneous diseases benefits from multivariate methods. The aim of this review was to describe and evaluate current literature in rheumatology regarding cluster analysis and correspondence analysis. A systematic review showed an increase in studies making use of these 2 methods. However, standardization in how these methods are applied and reported is needed...
May 2018: Rheumatic Diseases Clinics of North America
https://www.readbyqxmd.com/read/29483003/comparison-of-facemask-and-mouthpiece-interfaces-for-multiple-breath-washout-measurements
#4
Paul D Robinson, Sooky Lum, Courtney Moore, Kate M Hardaker, Nick Benseler, Paul Aurora, Peter Cooper, Dominic Fitzgerald, Renee Jensen, Reginald McDonald, Hiran Selvadurai, Felix Ratjen, Sanja Stanojevic
BACKGROUND: Different interfaces (mouthpiece/nose clip vs. facemask) are used during multiple breath washout (MBW) tests in young children. METHODS: We investigated the effect of interface choice and breathing modalities on MBW outcomes in healthy adults and preschool children. RESULTS: In adults (n = 26) facemask breathing significantly increased LCI, compared to mouthpiece use (mean difference (95% CI) 0.4 (0.2; 0.6)), with results generalizable across sites and different equipment...
February 23, 2018: Journal of Cystic Fibrosis: Official Journal of the European Cystic Fibrosis Society
https://www.readbyqxmd.com/read/29478390/beyond-circles-of-support-fearless-an-open-peer-to-peer-mutual-support-group-for-sex-offense-registrants-and-their-family-members
#5
Lisa L Sample, Brooke N Cooley, Tusty Ten Bensel
The term sex offender carries expectations that include a continuous level of sexual criminal risk and untreatable mental health conditions that govern sex offending behaviors. These role expectations by the public can socially isolate individuals who have been convicted of a crime and the people who love them. This is likely to contribute to negative self-images that can result in loneliness, isolation, and depression, and, subsequently, contribute to discontinuing support for sex offender's loved ones and reoffending...
February 1, 2018: International Journal of Offender Therapy and Comparative Criminology
https://www.readbyqxmd.com/read/29317618/development-of-an-oral-once-weekly-drug-delivery-system-for-hiv-antiretroviral-therapy
#6
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
https://www.readbyqxmd.com/read/29259297/hyperstretching-dna
#7
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
https://www.readbyqxmd.com/read/29174857/the-utility-of-collaterals-as-a-biomarker-in-pediatric-unilateral-intracranial-arteriopathy
#8
Jorina Elbers, Derek Armstrong, Susanne M Benseler, Nomazulu Dlamini, Gary K Steinberg, Kristen W Yeom
BACKGROUND: Intracranial arteriopathies are frequent causes of pediatric stroke and important risk factors for stroke recurrence. Without tissue diagnosis, vascular imaging is relied upon to identify the underlying etiology and prognosis. We hypothesized that children with unilateral intracranial arteriopathy with lenticulostriate collaterals would demonstrate distinct vascular outcomes compared with children without collaterals. METHODS: We retrospectively identified children with unilateral intracranial arteriopathy from two institutions...
January 2018: Pediatric Neurology
https://www.readbyqxmd.com/read/29166923/childhood-takayasu-arteritis-disease-course-and-response-to-therapy
#9
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
https://www.readbyqxmd.com/read/29051063/defining-optimal-permeant-characteristics-for-ultrasound-mediated-gastrointestinal-delivery
#10
Carl M Schoellhammer, Yiyun Chen, Cody Cleveland, Daniel Minahan, Taylor Bensel, June Y Park, Sarah Saxton, Young-Ah Lucy Lee, Lucas Booth, Robert Langer, Giovanni Traverso
Ultrasound-mediated drug delivery in the gastrointestinal (GI) tract is a bourgeoning area of study. Localized, low-frequency ultrasound has recently been shown to enable significant enhancement in delivery of a broad set of active pharmaceutical ingredients including small molecules, proteins, and nucleic acids without any formulation or encapsulation of the therapeutic. Traditional chemical formulations are typically required to protect, stabilize, and enable the successful delivery of a given therapeutic...
December 28, 2017: Journal of Controlled Release: Official Journal of the Controlled Release Society
https://www.readbyqxmd.com/read/29021237/recommendations-for-collaborative-paediatric-research-including-biobanking-in-europe-a-single-hub-and-access-point-for-paediatric-rheumatology-in-europe-share-initiative
#11
Jasmin B Kuemmerle-Deschner, Sandra Hansmann, Nico M Wulffraat, Sebastiaan J Vastert, Kristien Hens, Jordi Anton, Tadej Avcin, Alberto Martini, Isabelle Koné-Paut, Yosef Uziel, Angelo Ravelli, Carine Wouters, David Shaw, Seza Özen, Andreas Eikelberg, Berent J Prakken, Nicolino Ruperto, Gerd Horneff, Tamas Constantin, Michael W Beresford, Marijn Sikken, Helen E Foster, Iris Haug, Sabrina Schuller, Christine Jägle, Susanne M Benseler
Innovative research in childhood rheumatic diseases mandates international collaborations. However, researchers struggle with significant regulatory heterogeneity; an enabling European Union (EU)-wide framework is missing. The aims of the study were to systematically review the evidence for best practice and to establish recommendations for collaborative research. The Paediatric Rheumatology European Single Hub and Access point for paediatric Rheumatology in Europe (SHARE) project enabled a scoping review and expert discussion, which then informed the systematic literature review...
March 2018: Annals of the Rheumatic Diseases
https://www.readbyqxmd.com/read/28870142/validation-of-the-standardized-universal-pain-evaluations-for-rheumatology-providers-for-children-and-youth-super-kidz
#12
Nadia J Luca, Jennifer N Stinson, Brian M Feldman, Susanne M Benseler, Dorcas Beaton, Sarah Campillo, Claire LeBlanc, Margaret van Wyk, Ahmed M Bayoumi
Study Design Longitudinal observational clinimetric study with repeated measures. Background No validated multidimensional pain measure for children and youth with juvenile idiopathic arthritis exists. Objective To determine the test-retest reliability, construct validity, and responsiveness of English and French versions of the Standardized Universal Pain Evaluations for Rheumatology Providers for Children and Youth (SUPER-KIDZ). Methods Measurement properties of the SUPER-KIDZ (older child, younger child, and parent versions) were prospectively evaluated in patients (aged 4 to 18 years) with juvenile idiopathic arthritis at 2 centers...
October 2017: Journal of Orthopaedic and Sports Physical Therapy
https://www.readbyqxmd.com/read/28830457/growth-and-weight-gain-in-children-with-juvenile-idiopathic-arthritis-results-from-the-reacch-out-cohort
#13
MULTICENTER STUDY
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
https://www.readbyqxmd.com/read/28807967/l%C3%A2-acide-ac%C3%A3-tylsalicylique-pour-les-enfants-atteints-de-la-maladie-de-kawasaki
#14
Teeranai Sakulchit, Susanne M Benseler, Ran D Goldman
No abstract text is available yet for this article.
August 2017: Canadian Family Physician Médecin de Famille Canadien
https://www.readbyqxmd.com/read/28807954/acetylsalicylic-acid-for-children-with-kawasaki-disease
#15
REVIEW
Teeranai Sakulchit, Susanne M Benseler, Ran D Goldman
Question A 7-year-old child in my office was recently discharged from the hospital after receiving intravenous immunoglobulin for Kawasaki disease. Should I continue treatment with acetylsalicylic acid (ASA), and if so, what is the appropriate dose? Answer The role of ASA for Kawasaki disease during the acute febrile phase has recently been called into question. According to several studies, ASA might reduce the duration of fever but it does not appear to directly reduce the incidence of coronary artery complications...
August 2017: Canadian Family Physician Médecin de Famille Canadien
https://www.readbyqxmd.com/read/28729171/exercise-therapy-in-juvenile-idiopathic-arthritis-a-systematic-review-and-meta-analysis
#16
REVIEW
Gregor Kuntze, Colleen Nesbitt, Jackie L Whittaker, Alberto Nettel-Aguirre, Clodagh Toomey, Shane Esau, Patricia K Doyle-Baker, Jena Shank, Julia Brooks, Susanne Benseler, Carolyn A Emery
OBJECTIVE: To conduct a systematic review to evaluate the efficacy of exercise interventions in improving outcomes across domains of functioning and disability in children and adolescents with juvenile idiopathic arthritis (JIA). DATA SOURCES: Seven electronic databases were systematically searched up to November 16, 2016. STUDY SELECTION: Original data, analytic prospective design, physical therapy-led exercise intervention evaluation, children and adolescents with JIA, and assessment of functional, structural, activity, participation, or quality of life outcomes...
January 2018: Archives of Physical Medicine and Rehabilitation
https://www.readbyqxmd.com/read/28692792/clinical-and-molecular-phenotypes-of-low-penetrance-variants-of-nlrp3-diagnostic-and-therapeutic-challenges
#17
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
https://www.readbyqxmd.com/read/28556862/therapeutic-hypothermia-to-treat-a-newborn-with-perinatal-hypoxic-ischemic-encephalopathy
#18
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
https://www.readbyqxmd.com/read/28503078/variations-in-the-clinical-practice-of-physicians-managing-takayasu-arteritis-a-nationwide-survey
#19
Lillian Barra, Patrick Liang, Susanne M Benseler, David A Cabral, Aurore Fifi-Mah, Yueyang Li, Nataliya Milman, Marinka Twilt, Elaine Yacyshyn, Christian Pagnoux
OBJECTIVE: Takayasu arteritis (TAK) is a large vessel vasculitis that predominately affects young women and can cause severe ischemic complications. Given the rarity of TAK, the management of this condition is challenging. We aim to describe current rheumatologist practices for the management of TAK and identify discrepancies and gaps in knowledge. METHODS: An online survey (developed by the Canadian Vasculitis Network and approved by the Canadian Rheumatology Association) containing 48 questions with regard to the diagnosis, monitoring and treatment of TAK was distributed to 495 Canadian adult and pediatric rheu-matologists by email...
2017: Open Access Rheumatology: Research and Reviews
https://www.readbyqxmd.com/read/28484025/common-general-anesthetic-propofol-impairs-kinesin-processivity
#20
Brandon M Bensel, Stephanie Guzik-Lendrum, Erin M Masucci, Kellie A Woll, Roderic G Eckenhoff, Susan P Gilbert
Propofol is the most widely used i.v. general anesthetic to induce and maintain anesthesia. It is now recognized that this small molecule influences ligand-gated channels, including the GABAA receptor and others. Specific propofol binding sites have been mapped using photoaffinity ligands and mutagenesis; however, their precise target interaction profiles fail to provide complete mechanistic underpinnings for the anesthetic state. These results suggest that propofol and other common anesthetics, such as etomidate and ketamine, may target additional protein networks of the CNS to contribute to the desired and undesired anesthesia end points...
May 23, 2017: Proceedings of the National Academy of Sciences of the United States of America
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