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https://www.readbyqxmd.com/read/29244866/molecular-dynamics-simulations-of-the-glucocorticoid-receptor-dna-binding-domain-suggest-a-role-of-the-lever-arm-mobility-in-transcriptional-output
#1
Lautaro Damián Álvarez, Diego Martín Presman, Adalí Pecci
One of the first and essential steps in gene expression regulation involves the recruitment of transcription factors (TFs) to specific response elements located at enhancers and/or promoters of targeted genes. These DNA elements have a certain variability in both sequence and length, which may affect the final transcriptional output. The molecular mechanisms in which TFs integrate the subtle differences within specific recognition sequences to offer different transcriptional responses is still largely unknown...
2017: PloS One
https://www.readbyqxmd.com/read/29244829/cost-effectiveness-analysis-of-introducing-malaria-diagnostic-testing-in-drug-shops-a-cluster-randomised-trial-in-uganda
#2
Kristian Schultz Hansen, Siân E Clarke, Sham Lal, Pascal Magnussen, Anthony K Mbonye
BACKGROUND: Private sector drug shops are an important source of malaria treatment in Africa, yet diagnosis without parasitological testing is common among these providers. Accurate rapid diagnostic tests for malaria (mRDTs) require limited training and present an opportunity to increase access to correct diagnosis. The present study was a cost-effectiveness analysis of the introduction of mRDTs in Ugandan drug shops. METHODS: Drug shop vendors were trained to perform and sell subsidised mRDTs and artemisinin-based combination therapies (ACTs) in the intervention arm while vendors offered ACTs following presumptive diagnosis of malaria in the control arm...
2017: PloS One
https://www.readbyqxmd.com/read/29244686/high-thoracic-disc-herniation-causing-horner-syndrome-with-the-intraoperative-finding-of-conjoined-nerve-root-compression-a-case-report
#3
Amit K Bhandutia, Zachary Zuzek, Matthew J Schessler, Nestor D Tomycz, Daniel T Altman
CASE: A 29-year-old man presented with right medial arm pain with paresthesia, as well as right-sided ptosis, miosis, and anhidrosis. Magnetic resonance imaging revealed a right paracentral disc herniation at the T1-T2 level. The patient underwent a hemilaminectomy with a medial facetectomy through a posterolateral approach to the T1-T2 disc space, followed by a discectomy. Intraoperative findings were notable for a conjoined nerve root. CONCLUSION: Although high thoracic disc herniation is rare, its diagnosis should be considered when patients present with radicular arm pain and Horner syndrome...
January 2017: JBJS Case Connector
https://www.readbyqxmd.com/read/29244674/thrower-s-fracture-of-the-humerus-an-investigation-of-risk-factors-following-an-unlikely-scenario-a-case-report
#4
Kyle D Morgenstern, Gonzalo Barinaga, Paul J Cagle
CASE: A 26-year-old amateur baseball player without prodromal arm pain sustained a thrower's fracture of the humerus on a warm-up throw performed with submaximal effort. The fracture occurred during the first throwing session following a 6-week layoff. The patient was treated nonoperatively and made a full recovery, but he elected to not return to throwing sports. CONCLUSION: Because of the lack of risk factors in this case, we suggest that time off or irregularity in throwing may play a greater role in a thrower's fracture than previously established...
April 2017: JBJS Case Connector
https://www.readbyqxmd.com/read/29244528/phase-iii-randomized-study-of-dual-human-epidermal-growth-factor-receptor-2-her2-blockade-with-lapatinib-plus-trastuzumab-in-combination-with-an-aromatase-inhibitor-in-postmenopausal-women-with-her2-positive-hormone-receptor-positive-metastatic-breast-cancer
#5
Stephen R D Johnston, Roberto Hegg, Seock-Ah Im, In Hae Park, Olga Burdaeva, Galina Kurteva, Michael F Press, Sergei Tjulandin, Hiroji Iwata, Sergio D Simon, Sarah Kenny, Severine Sarp, Miguel A Izquierdo, Lisa S Williams, William J Gradishar
Purpose Human epidermal growth factor receptor 2 (HER2) targeting plus endocrine therapy (ET) improved clinical benefit in HER2-positive, hormone receptor (HR)-positive metastatic breast cancer (MBC) versus ET alone. Dual HER2 blockade enhances clinical benefit versus single HER2 blockade. The ALTERNATIVE study evaluated the efficacy and safety of dual HER2 blockade plus aromatase inhibitor (AI) in postmenopausal women with HER2-positive/HR-positive MBC who received prior ET and prior neo(adjuvant)/first-line trastuzumab (TRAS) plus chemotherapy...
December 15, 2017: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
https://www.readbyqxmd.com/read/29244235/new-therapy-for-refractory-chronic-mechanical-low-back-pain-restorative-neurostimulation-to-activate-the-lumbar-multifidus-one-year-results-of-a-prospective-multicenter-clinical-trial
#6
REVIEW
Kristiaan Deckers, Kris De Smedt, Bruce Mitchell, David Vivian, Marc Russo, Peter Georgius, Matthew Green, John Vieceli, Sam Eldabe, Ashish Gulve, Jean-Pierre van Buyten, Iris Smet, Vivek Mehta, Shankar Ramaswamy, Ganesan Baranidharan, Richard Sullivan, Robert Gassin, James Rathmell, Chris Gilligan
OBJECTIVES: The purpose of the international multicenter prospective single arm clinical trial was to evaluate restorative neurostimulation eliciting episodic contraction of the lumbar multifidus for treatment of chronic mechanical low back pain (CMLBP) in patients who have failed conventional therapy and are not candidates for surgery or spinal cord stimulation (SCS). MATERIALS AND METHODS: Fifty-three subjects were implanted with a neurostimulator (ReActiv8, Mainstay Medical Limited, Dublin, Ireland)...
December 15, 2017: Neuromodulation: Journal of the International Neuromodulation Society
https://www.readbyqxmd.com/read/29244149/subcutaneous-tocilizumab-in-rheumatoid-arthritis-findings-from-the-common-framework-phase-4-study-programme-tozura-conducted-in-22-countries
#7
Ernest Choy, Roberto Caporali, Ricardo Xavier, Bruno Fautrel, Raimón Sanmarti, Min Bao, Corrado Bernasconi, Attila Pethö-Schramm
Objectives: The aim of this pooled analysis of the TOZURA study programme was to evaluate the efficacy and safety of subcutaneous tocilizumab (TCZ-SC) as monotherapy or in combination with conventional synthetic DMARDs (csDMARDs) in patients with moderate to severe RA who had an inadequate response to csDMARD or anti-TNF agent therapy or who were MTX naïve. Methods: TOZURA is a multinational, open-label, single-arm, common-framework, phase 4 study programme (11 protocols, 22 countries)...
December 13, 2017: Rheumatology
https://www.readbyqxmd.com/read/29243996/validation-of-the-visual-analog-scale-in-the-cervical-spine
#8
Anna MacDowall, Martin Skeppholm, Yohan Robinson, Claes Olerud
OBJECTIVE The visual analog scale (VAS) is frequently used to measure treatment outcome in patients with cervical spine disorders. The minimum clinically important difference (MCID) is the smallest change in a score that has clinical importance to the patient. Although it has been established for other medical fields, knowledge of the VAS MCID for the cervical spine is sparse, and it has rarely been considered in relation to measurement noise. The goals in this study were as follows: 1) to validate the VAS-neck and VAS-arm instruments for the cervical spine (e...
December 15, 2017: Journal of Neurosurgery. Spine
https://www.readbyqxmd.com/read/29243948/shanghai-health-study-2001-2009-what-was-learned-about-benzene-health-effects
#9
Sherilyn A Gross, Dennis J Paustenbach
The Shanghai Health Study (SHS) was a large epidemiology study conducted as a joint effort between the University of Colorado and Fudan University in Shanghai, China. The study was funded by members of the American Petroleum Institute between 2001 and 2009 and was designed to evaluate the human health effects associated with benzene exposure. Two arms of the SHS included: an occupational-based molecular epidemiology study and several hospital-based case control studies. Consistent with historical literature, following sufficient exposure to relatively high airborne concentrations and years of exposure, the SHS concluded that exposure to benzene resulted in an increased risk of various blood and bone marrow abnormalities such as benzene poisoning, aplastic anemia (AA), myelodysplastic syndrome (MDS), and acute myeloid leukemia (AML)...
December 15, 2017: Critical Reviews in Toxicology
https://www.readbyqxmd.com/read/29243854/a-coordination-chemistry-approach-to-fine-tune-the-physicochemical-parameters-of-lanthanide-complexes-relevant-to-medical-applications
#10
Mariane Le Fur, Enikő Molnár, Maryline Beyler, Ferenc K Kálmán, Olivier Fougère, David Esteban-Gómez, Olivier Rousseaux, Raphaël Tripier, Gyula Tircsó, C Platas-Iglesias
The geometric features of two pyclen-based ligands possessing identical donor atoms but different site organization have a profound impact in their complexation properties toward lanthanide ions. The ligand containing two acetate groups and a picolinate arm arranged in a symmetrical fashion (L1) forms a Gd3+ complex being two orders of magnitude less stable than its dissymmetric analogue GdL2. Besides, GdL1 experiences a much faster dissociation following the acid-catalyzed mechanism than GdL2. On the contrary, GdL1 exhibits a lower exchange rate of the coordinated water molecule compared to GdL2...
December 15, 2017: Chemistry: a European Journal
https://www.readbyqxmd.com/read/29243137/activation-of-ankle-muscles-following-rapid-displacement-of-a-light-touch-contact-during-treadmill-walking
#11
Tania Shiva, John E Misiaszek
The first exposure of a rapid displacement of a light touch reference induces an inappropriate balance corrective response during standing in a proportion of participants that is extinguished with repeated exposures. We hypothesized that if the spatial touch reference was critical to performing of a task the evoked response would be more consistently expressed across participants and observed with repeated exposures to the disturbance. To test this, 20 participants received either forward (N = 10) or backward right-touch displacements at right-heel strike during motorized treadmill walking without visual feedback...
December 15, 2017: Experimental Brain Research. Experimentelle Hirnforschung. Expérimentation Cérébrale
https://www.readbyqxmd.com/read/29243031/prospective-randomization-of-post-remission-therapy-comparing-autologous-peripheral-blood-stem-cell-transplantation-versus-high-dose-cytarabine-consolidation-for-acute-myelogenous-leukemia-in-first-remission
#12
Toshihiro Miyamoto, Koji Nagafuji, Tomoaki Fujisaki, Naoyuki Uchida, Kosei Matsue, Hideho Henzan, Ryosuke Ogawa, Ken Takase, Takatoshi Aoki, Michihiro Hidaka, Takanori Teshima, Shuichi Taniguchi, Koichi Akashi, Mine Harada
We prospectively compared outcomes of autologous stem cell transplantation (ASCT) versus high-dose cytarabine (HiDAC) consolidation as post-remission therapy for favorable- and intermediate-risk acute myelogenous leukemia (AML) in first complete remission (CR1). Two-hundred-forty patients under 65 years with AML-M1, M2, M4, or M5 subtypes were enrolled. After induction, 153 patients did not undergo randomization, while the remaining 87 who achieved CR1 were prospectively randomized to HiDAC (n = 45) or ASCT arm (n = 42)...
December 14, 2017: International Journal of Hematology
https://www.readbyqxmd.com/read/29242976/a-rare-case-of-concomitant-cervical-disc-herniation-and-intradural-meningioma-treated-with-one-stage-posterior-surgery
#13
Xiaojian Hu, Zhong Chen, Yue Wang
STUDY DESIGN: Case report. PURPOSE: To present a rare case of cervical disc herniation concomitant with intradural meningioma which was successfully treated using a single one-stage posterior surgery of tumor resection and transdural discectomy. Coexistence of symptomatic disc herniation and intra-spinal tumor in the same cervical segment is extremely rare. Usually, two-stage anterior and posterior surgeries are needed to treat two conditions, respectively. One-stage posterior surgery to treat two pathologies simultaneously has not been reported in the literature...
December 14, 2017: European Spine Journal
https://www.readbyqxmd.com/read/29242937/paclitaxel-with-and-without-pazopanib-for-persistent-or-recurrent-ovarian-cancer-a-randomized-clinical-trial
#14
Debra L Richardson, Michael W Sill, Robert L Coleman, Anil K Sood, Michael L Pearl, Siobhan M Kehoe, Michael E Carney, Parviz Hanjani, Linda Van Le, Xun C Zhou, Angeles Alvarez Secord, Heidi J Gray, Lisa M Landrum, Heather A Lankes, Wei Hu, Carol Aghajanian
Importance: Ovarian cancer is the leading cause of gynecologic cancer deaths in the United States. Pazopanib is an oral, multitarget kinase inhibitor of vascular endothelial growth factor receptors 1, 2, and 3; platelet-derived growth factor receptors α and β; and proto-oncogene receptor tyrosine kinase (c-KIT). Objective: To estimate the progression-free survival (PFS) hazard ratio (HR) of weekly paclitaxel and pazopanib compared with weekly paclitaxel and placebo in women with recurrent ovarian cancer...
December 14, 2017: JAMA Oncology
https://www.readbyqxmd.com/read/29242786/radius-and-ulna-stress-fractures-in-a-patient-with-neuromyelitis-optica-a-case-report
#15
George J M Hourston, Hadyn K N Kankam, Phillip Johnston
Introduction: Stress fractures are more common in the weight-bearing bones of the lower limb and are particularly prevalent in athletes. Whereas, those of the upper limb are usually reported as unique events in rare circumstances. Case Report: We present a case of a 40-year-old White British female with neuromyelitis optica (NMO) who mobilized in a wheelchair and presented to our center in April 2016 with a week-long history of a hot, swollen, and unstable right forearm...
September 2017: Journal of Orthopaedic Case Reports
https://www.readbyqxmd.com/read/29242281/fda-benefit-risk-assessment-of-osimertinib-for-the-treatment-of-metastatic-non-small-cell-lung-cancer-harboring-epidermal-growth-factor-receptor-t790m-mutation
#16
Lauretta Odogwu, Luckson Mathieu, Kirsten B Goldberg, Gideon M Blumenthal, Erin Larkins, Mallorie H Fiero, Lisa Rodriguez, Karen Bijwaard, Eunice Y Lee, Reena Philip, Ingrid Fan, Martha Donoghue, Patricia Keegan, Amy McKee, Richard Pazdur
On March 30, 2017, the U.S. Food and Drug Administration (FDA) approved osimertinib for the treatment of patients with metastatic, epidermal growth factor receptor (EGFR) T790M mutation-positive, non-small cell lung cancer (NSCLC), as detected by an FDA-approved test, whose disease has progressed following EGFR tyrosine kinase inhibitor (TKI) therapy. Approval was based on demonstration of a statistically significant difference in the primary endpoint of progression-free survival (PFS) when comparing osimertinib with chemotherapy in an international, multicenter, open-label, randomized trial (AURA3)...
December 14, 2017: Oncologist
https://www.readbyqxmd.com/read/29242159/an-implantable-depot-capable-of-in-situ-generation-of-micelles-to-achieve-controlled-and-targeted-tumor-chemotherapy
#17
Xiaoming Luo, Maohua Chen, Zhoujiang Chen, Songzhi Xie, Nan He, Tao Wang, Xiaohong Li
Camptothecin (CPT)-containing promicelle polymers (PMCPT) based on 4-armed poly(ethylene glycol) (PEG) were developed previously to self-assemble into folate-targeted and glutathione (GSH)-sensitive micelles (MCPT). To address severe systemic toxicity and lack of tumor specificity implicated in the intravenous administration of MCPT, a micelle-generating depot has been developed by blend electrospinning of PEG-poly(lactide) (PELA) copolymers, PMCPT and polyethylene oxide (PEO). Upon implantation of the depot onto the tumor, PMCPT are sustainably released to spontaneously form MCPT on the tumor site...
December 11, 2017: Acta Biomaterialia
https://www.readbyqxmd.com/read/29242108/a-multi-level-intervention-in-worksites-to-increase-fruit-and-vegetable-access-and-intake-rationale-design-and-methods-of-the-good-to-go-cluster-randomized-trial
#18
Patricia M Risica, Gemma Gorham, Laura Dionne, William Nardi, Doug Ng, Reese Middler, Jennifer Mello, Rahmet Akpolat, Katelyn Gettens, Kim M Gans
BACKGROUND: Fruit and vegetable (F&V) consumption is an important contributor to chronic disease prevention. However, most Americans do not eat adequate amounts. The worksite is an advantageous setting to reach large, diverse segments of the population with interventions to increase F&V intake, but research gaps exist. No studies have evaluated the implementation of mobile F&V markets at worksites nor compared the effectiveness of such markets with or without nutrition education. METHODS: This paper describes the protocol for Good to Go (GTG), a cluster randomized trial to evaluate F&V intake change in employees from worksites randomized into three experimental arms: discount, fresh F&V markets (Access Only arm); markets plus educational components including campaigns, cooking demonstrations, videos, newsletters, and a web site (Access Plus arm); and an attention placebo comparison intervention on physical activity and stress reduction (Comparison)...
December 11, 2017: Contemporary Clinical Trials
https://www.readbyqxmd.com/read/29241979/acalabrutinib-in-relapsed-or-refractory-mantle-cell-lymphoma-ace-ly-004-a-single-arm-multicentre-phase-2-trial
#19
Michael Wang, Simon Rule, Pier Luigi Zinzani, Andre Goy, Olivier Casasnovas, Stephen D Smith, Gandhi Damaj, Jeanette Doorduijn, Thierry Lamy, Franck Morschhauser, Carlos Panizo, Bijal Shah, Andrew Davies, Richard Eek, Jehan Dupuis, Eric Jacobsen, Arnon P Kater, Steven Le Gouill, Lucie Oberic, Taduesz Robak, Todd Covey, Richa Dua, Ahmed Hamdy, Xin Huang, Raquel Izumi, Priti Patel, Wayne Rothbaum, J Greg Slatter, Wojciech Jurczak
BACKGROUND: Bruton tyrosine kinase is a clinically validated target in mantle cell lymphoma. Acalabrutinib (ACP-196) is a highly selective, potent Bruton tyrosine kinase inhibitor developed to minimise off-target activity. METHODS: In this open-label, phase 2 study, oral acalabrutinib (100 mg twice per day) was given to patients with relapsed or refractory mantle cell lymphoma, until disease progression or unacceptable toxicity. The primary endpoint was overall response assessed according to the Lugano classification, and safety analyses were done in all participants...
December 11, 2017: Lancet
https://www.readbyqxmd.com/read/29241924/effects-of-growth-hormone-plus-gonadotropins-on-controlled-ovarian-stimulation-in-infertile-women-of-advanced-age-poor-responders-and-previous-in%C3%A2-vitro-fertilization-failure-patients
#20
Yao-Kai Ho, Tsung-Hsien Lee, Chun-I Lee, En-Hui Cheng, Chun-Chia Huang, Lii-Shung Huang, Maw-Sheng Lee
OBJECTIVE: To investigate the effects of growth hormone (GH) cotreatment in ovarian stimulation in infertile women of advanced age, poor responders, and patients with one or more previous IVF treatment failures. MATERIALS AND METHODS: We conducted a retrospective observational study of 436 patients undergoing GH cotreatment in ovarian stimulation. The first arm included 134 infertile women of advanced age. The second arm included 236 patients with one or more IVF previous treatment failures, and the third arm included 66 younger poor responders...
December 2017: Taiwanese Journal of Obstetrics & Gynecology
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