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https://www.readbyqxmd.com/read/28340349/structure-reveals-mechanisms-of-viral-suppressors-that-intercept-a-crispr-rna-guided-surveillance-complex
#1
Saikat Chowdhury, Joshua Carter, MaryClare F Rollins, Sarah M Golden, Ryan N Jackson, Connor Hoffmann, Lyn'Al Nosaka, Joseph Bondy-Denomy, Karen L Maxwell, Alan R Davidson, Elizabeth R Fischer, Gabriel C Lander, Blake Wiedenheft
Genetic conflict between viruses and their hosts drives evolution and genetic innovation. Prokaryotes evolved CRISPR-mediated adaptive immune systems for protection from viral infection, and viruses have evolved diverse anti-CRISPR (Acr) proteins that subvert these immune systems. The adaptive immune system in Pseudomonas aeruginosa (type I-F) relies on a 350 kDa CRISPR RNA (crRNA)-guided surveillance complex (Csy complex) to bind foreign DNA and recruit a trans-acting nuclease for target degradation. Here, we report the cryo-electron microscopy (cryo-EM) structure of the Csy complex bound to two different Acr proteins, AcrF1 and AcrF2, at an average resolution of 3...
March 23, 2017: Cell
https://www.readbyqxmd.com/read/28340251/thermal-qst-phenotypes-associated-with-response-to-lumbar-epidural-steroid-injections-a-pilot-study
#2
Dermot P Maher, Weihua Ding, Sarabdeep Singh, Arissa Opalacz, Claire Fishman, Mary Houghton, Shihab Ahmed, Lucy Chen, Jianren Mao, Yi Zhang
Objective.:  Response to lumbar epidural steroid injection in lumbar radicular pain varies. The purpose of this study is to characterize the changes in quantitative sensory testing (QST) phenotypes of subjects and compare the QST characteristics in patients who do respond to treatment of radicular pain with a lumbar epidural steroid injection (ESI). Design.:  Prospective, observational pilot study. Setting.:  Outpatient pain center. Methods...
March 13, 2017: Pain Medicine: the Official Journal of the American Academy of Pain Medicine
https://www.readbyqxmd.com/read/28339574/arm-paralysis-after-routine-childhood-vaccinations-application-of-advanced-molecular-methods-to-the-causality-assessment-of-an-adverse-event-after-immunization
#3
Jana Shaw, Neal A Halsey, Adriana Weinberg, D Scott Schmid, Kirsten St George, William C Weldon, Michael Jordan, Patrick W Bryant, Philip S LaRussa, Deborah Y Bradshaw, Theresa Harrington, Anne Gershon
Post-licensure surveillance for adverse events following immunizations (AEFI) can identify rare complications of vaccinations and rigorous vaccine adverse event causality assessments can help to identify possible causal relationships. We report the development of arm paralysis after varicella vaccination in a 1-year-old child. Paralysis was initially presumed to be due to vOka because of the temporal relationship between vaccination and onset of arm weakness; however, molecular studies identified wild-type varicella zoster virus VZV (WT-VZV) in the CSF, leading the authors to conclude that WT-VZV was the probable cause...
January 25, 2017: Journal of the Pediatric Infectious Diseases Society
https://www.readbyqxmd.com/read/28335271/distribution-of-iron-oxide-core-titanium-dioxide-shell-nanoparticles-in-vx2-tumor-bearing-rabbits-introduced-by-two-different-delivery-modalities
#4
Tamer Refaat, Derek West, Samar El Achy, Vamsi Parimi, Jasmine May, Lun Xin, Kathleen R Harris, William Liu, Michael Beau Wanzer, Lydia Finney, Evan Maxey, Stefan Vogt, Reed A Omary, Daniele Procissi, Andrew C Larson, Tatjana Paunesku, Gayle E Woloschak
This work compares intravenous (IV) versus fluoroscopy-guided transarterial intra-catheter (IC) delivery of iron oxide core-titanium dioxide shell nanoparticles (NPs) in vivo in VX2 model of liver cancer in rabbits. NPs coated with glucose and decorated with a peptide sequence from cortactin were administered to animals with developed VX2 liver cancer. Two hours after NPs delivery tumors, normal liver, kidney, lung and spleen tissues were harvested and used for a series on histological and elemental analysis tests...
August 3, 2016: Nanomaterials
https://www.readbyqxmd.com/read/28334684/biochemical-signaling-by-remote-ischemic-conditioning-of-the-arm-versus-thigh-is-one-raise-of-the-cuff-enough
#5
Cameron Dezfulian, Maia Taft, Catherine Corey, Gabrielle Hill, Nicholas Krehel, Jon C Rittenberger, Frank X Guyette, Sruti Shiva
Remote Ischemic Conditioning (RIC), induced by brief cycles of ischemia and reperfusion, protects vital organs from a prolonged ischemic insult. While several biochemical mediators have been implicated in RIC's mechanism of action, it remains unclear whether the localization or "dose" of RIC affects the extent of protective signaling. In this randomized crossover study of healthy individuals, we tested whether the number of cycles of RIC and its localization (arm versus thigh) determines biochemical signaling and cytoprotection...
March 18, 2017: Redox Biology
https://www.readbyqxmd.com/read/28333010/quantitative-assessment-of-breast-cosmetic-outcome-after-whole-breast-irradiation
#6
Jay P Reddy, Xiudong Lei, Sheng-Cheng Huang, Krista M Nicklaus, Michelle C Fingeret, Simona F Shaitelman, Kelly K Hunt, Thomas A Buchholz, Fatima Merchant, Mia K Markey, Benjamin D Smith
PURPOSE: To measure, by quantitative analysis of digital photographs, breast cosmetic outcome within the setting of a randomized trial of conventionally fractionated (CF) and hypofractionated (HF) whole-breast irradiation (WBI), to identify how quantitative cosmesis metrics were associated with patient- and physician-reported cosmesis and whether they differed by treatment arm. METHODS AND MATERIALS: From 2011 to 2014, 287 women aged ≥40 with ductal carcinoma in situ or early invasive breast cancer were randomized to HF-WBI (42...
April 1, 2017: International Journal of Radiation Oncology, Biology, Physics
https://www.readbyqxmd.com/read/28332826/packaged-and-free-stmv-rna-genomes-adopt-distinct-conformational-states
#7
Bridget C Larman, Elizabeth A Dethoff, Kevin M Weeks
The RNA genomes of viruses likely undergo multiple functionally important conformational changes during their replication cycles, changes that are poorly understood at present. We used two complementary in-solution RNA structure probing strategies (SHAPE-MaP and RING-MaP) to examine the structure of the RNA genome of satellite tobacco mosaic virus inside authentic virions and in a capsid-free state. Both RNA states feature similar three-domain architectures in which each major replicative function - translation, capsid coding, and genome synthesis - fall into distinct domains...
March 23, 2017: Biochemistry
https://www.readbyqxmd.com/read/28330808/germline-genetic-biomarkers-of-sunitinib-efficacy-in-advanced-renal-cell-carcinoma-results-from-the-renal-effect-trial
#8
Robert J Motzer, Robert A Figlin, Jean-François Martini, Subramanian Hariharan, Neeraj Agarwal, Chun Xiao Li, J Andrew Williams, Thomas E Hutson
BACKGROUND: Sunitinib, the vascular endothelial growth factor pathway inhibitor, is an established standard-of-care for advanced renal cell carcinoma (RCC). This study aimed to assess correlations between candidate germline single nucleotide polymorphisms (SNPs) and sunitinib efficacy in patients from the RENAL EFFECT trial (NCT00267748), a randomized phase II study in patients with metastatic RCC comparing the 4-weeks-on/2-weeks-off schedule and a continuous daily dosing schedule. PATIENTS AND METHODS: Informed consent for pharmacogenetics research was obtained from 202 out of 289 treated patients in the trial...
February 27, 2017: Clinical Genitourinary Cancer
https://www.readbyqxmd.com/read/28329844/the-influence-of-exercise-on-cognitive-function-in-older-hispanic-latino-adults-results-from-the-%C3%A2-caminemos-study
#9
Lissette M Piedra, Flavia C D Andrade, Rosalba Hernandez, Seth William Boughton, Laura Trejo, Catherine A Sarkisian
Purpose of the Study: We examined the prospective effect of an evidence-based exercise intervention (¡Caminemos!) on cognitive function among older Hispanic/Latino adults and the potential synergistic effects (if any) of an attribution-retraining intervention given to a random sample to counter negative ascriptions of the aging process. Design and Methods: We analyzed baseline and follow-up (1- and 2-year) data collected from Hispanics/Latinos ≥60 years (N = 571) who participated in ¡Caminemos! across 27 senior centers...
March 15, 2017: Gerontologist
https://www.readbyqxmd.com/read/28329624/actinic-keratoses-progress-more-quickly-to-squamous-cell-carcinoma-than-basal-cell-carcinoma
#10
Julia A Siegal, Joanna L Walker, Moniyka Sachar, Robert A Lew, Suephy C Chen, Susan M Swetter, Robert P Dellavalle, George P Stricklin, Martin A Weinstock
Actinic keratoses (AK) are common, costly, and may evolve to keratinocyte carcinoma (KC): basal cell (BCC) and squamous cell carcinoma (SCC) of the skin. Time to malignant transformation is controversial. We used data from the placebo arm (n=166) of a randomized trial of veterans with multiple prior KCs. Study dermatologists examined participants' faces/ears at enrollment and semiannual visits. Clinically diagnosed AKs were marked, photographed, and treated with cryotherapy (starting at 6 months). Lesions suspicious for KC were marked, photographed, and biopsied...
September 15, 2016: Dermatology Online Journal
https://www.readbyqxmd.com/read/28329617/extensive-unilateral-nevus-comedonicus-without-genetic-abnormality
#11
Anca Chiriac, Luminita Paduraru, Gorduza Vlad Eusebiu, Constantine A Stratakis, Christos C Zouboulis
Nevus comedonicus is considered a genodermatosis characterized by the presence of multiple groups of dilated pilosebaceous orifices filled with black keratin plugs, with sharply unilateral distribution mostly on the face, neck, trunk, upper arms. Lesions can appear at any age, frequently before the age of 10 years, but they are usually present at birth. We present a 2.7-year-old girl with a very severe form of nevus comedonicus. She exhibited lesions located initially at the left side of the body with a linear characteristic, following Blascko lines T1/T2, T5, T7, S1 /S2, but progressively developed lesions on the right side of the scalp and left gluteal area...
September 15, 2016: Dermatology Online Journal
https://www.readbyqxmd.com/read/28329483/the-use-of-a-sunscreen-containing-dna-photolyase-in-the-treatment-of-patients-with-field-cancerization-and-multiple-actinic-keratoses-a-case-series
#12
C Navarrete-Dechent, M Molgó
Cutaneous field cancerization (CFC) is associated witha high-risk of developing cutaneous squamous cellcarcinoma (cSCC). It manifests as actinic keratoses(AK) as one of the few macroscopic alterations in CFCpatients. A prospective, single-arm, case-series wasperformed to evaluate the utility of a novel sunscreencontaining DNA-photolyase for treatment of CFCin nine subjects (mean age 70.6 years, male: femaleratio 5:4). The cream was applied topically twicedaily on CFC/AK areas and patients were followedup for three months, with no other treatments...
January 15, 2017: Dermatology Online Journal
https://www.readbyqxmd.com/read/28329286/short-course-tlr9-agonist-treatment-impacts-innate-immunity-and-plasma-viremia-in-individuals-with-hiv-infection
#13
Line Vibholm, Mariane H Schleimann, Jesper F Højen, Thomas Benfield, Rasmus Offersen, Katrine Rasmussen, Rikke Olesen, Anders Dige, Jørgen Agnholt, Judith Grau, Maria Buzon, Burghardt Wittig, Mathias Lichterfeld, Andreas Munk Petersen, Xutao Deng, Mohammed Abdel-Mohsen, Satish K Pillai, Sofie Rutsaert, Wim Trypsteen, Ward De Spiegelaere, Linos Vandekerchove, Lars Østergaard, Thomas A Rasmussen, Paul W Denton, Martin Tolstrup, Ole S Søgaard
Background: Treatment with latency reversing agents (LRA) enhances HIV-1 transcription in vivo but only leads to modest reductions in the size of the reservoir, possibly due to insufficient immune-mediated elimination of infected cells. We hypothesized that a single drug molecule - a novel toll-like receptor 9 (TLR9) agonist, MGN1703 - could function as an enhancer of innate immunity and an LRA in vivo. Methods: We conducted a single-arm, open-label study, where 15 virologically suppressed HIV-1 infected individuals on antiretroviral therapy received 60 mg MGN1703 s...
March 9, 2017: Clinical Infectious Diseases: An Official Publication of the Infectious Diseases Society of America
https://www.readbyqxmd.com/read/28327988/efficacy-and-safety-of-nilotinib-in-patients-with-kit-mutated-metastatic-or-inoperable-melanoma-final-results-from-the-global-single-arm-phase-ii-team-trial
#14
J Guo, R D Carvajal, R Dummer, A Hauschild, A Daud, B C Bastian, S N Markovic, P Queirolo, A Arance, C Berking, V Camargo, D Herchenhorn, T M Petrella, D Schadendorf, W Sharfman, A Testori, S Novick, S Hertle, C Nourry, Q Chen, F S Hodi
Background.: The single-arm, phase II Tasigna Efficacy in Advanced Melanoma (TEAM) trial evaluated the KIT-selective tyrosine kinase inhibitor nilotinib in patients with KIT -mutated advanced melanoma without prior KIT inhibitor treatment. Patients and Methods.: Forty-two patients with KIT -mutated advanced melanoma were enrolled and treated with nilotinib 400 mg twice daily. TEAM originally included a comparator arm of dacarbazine (DTIC)-treated patients; the design was amended to a single-arm trial due to an observed low number of KIT -mutated melanomas...
March 6, 2017: Annals of Oncology: Official Journal of the European Society for Medical Oncology
https://www.readbyqxmd.com/read/28327934/pazopanib-or-placebo-in-completely-resected-stage-i-nsclc-patients-results-of-the-phase-ii-ifct-0703-trial
#15
B Besse, J Mazières, L Ribassin-Majed, F Barlesi, J Bennouna, R Gervais, L Moreau, H Berard, D Debieuvre, O Molinier, D Moro-Sibilot, P J Souquet, S Jacquot, L Petit, H Lena, J P Pignon, B Lacas, F Morin, B Milleron, G Zalcman, J C Soria
Background: Adjuvant treatment in resected stage I non-small cell lung cancer (NSCLC) is generally not recommended. Pazopanib is an oral tyrosine kinase inhibitor of VEGFR-1/2/3 and PDGFR-α/β. We explored the feasibility and efficacy of adjuvant pazopanib in this population. Patients and methods: In this double-blind phase II/III trial, patients with resected stage I NSCLC were randomized to placebo or pazopanib 800 mg/d (P800) for 6 months with a two-step Fleming design...
February 23, 2017: Annals of Oncology: Official Journal of the European Society for Medical Oncology
https://www.readbyqxmd.com/read/28327923/heart-dose-exposure-as-prognostic-marker-after-radiotherapy-for-resectable-stage-iiia-b-non-small-cell-lung-cancer-secondary-analysis-of-a-randomised-trial
#16
M Guberina, W Eberhardt, M Stuschke, T Gauler, F Heinzelmann, D Cheufou, M Kimmich, G Friedel, H Schmidberger, K Darwiche, V Jendrossek, M Schuler, G Stamatis, C Pöttgen
BACKGROUND: Heart exposure to ionizing irradiation can cause ischemic heart disease. The partial heart volume receiving ≥5 Gy (heartV5) was supposed to be an independent prognostic factor for survival after radiochemotherapy for locally advanced non-small cell lung cancer (NSCLC). But validation of the latter hypothesis is needed under the concurrent risks of lung cancer patients. PATIENTS AND METHODS: The ESPATUE phase III trial recruited patients with potentially operable IIIA(N2)/selected IIIB NSCLC between 01/2004 and 01/2013...
February 21, 2017: Annals of Oncology: Official Journal of the European Society for Medical Oncology
https://www.readbyqxmd.com/read/28327917/fifth-ovarian-cancer-consensus-conference-of-the-gynecologic-cancer-intergroup-first-line-interventions
#17
A Karam, J A Ledermann, J-W Kim, J Sehouli, K Lu, C Gourley, N Katsumata, R A Burger, B-H Nam, M Bacon, C Ng, J Pfisterer, R L M Bekkers, A Casado Herráez, A Redondo, H Fujiwara, N Gleeson, O Rosengarten, G Scambia, J Zhu, A Okamoto, G Stuart, K Ochiai
The consensus statements regarding first-line therapies in women with ovarian cancer, reached at the Fifth Ovarian Cancer Consensus Conference held in Tokyo, Japan, in November 2015 are reported. Three topics were reviewed and the following statements are recommended: (i) Surgery: the subgroups that should be considered in first-line ovarian cancer clinical trials should be (a) patients undergoing primary debulking surgery and (b) patients receiving neo-adjuvant chemotherapy. The amount of residual disease following surgery should further stratify patients into those with absent gross residual disease and others...
February 21, 2017: Annals of Oncology: Official Journal of the European Society for Medical Oncology
https://www.readbyqxmd.com/read/28327907/a-randomized-open-label-phase-2-study-of-everolimus-in-combination-with-pasireotide-lar-or-everolimus-alone-in-advanced-well-differentiated-progressive-pancreatic-neuroendocrine-tumors-cooperate-2-trial
#18
M H Kulke, P Ruszniewski, E Van Cutsem, C Lombard-Bohas, J W Valle, W W De Herder, M Pavel, E Degtyarev, J C Brase, L Bubuteishvili-Pacaud, M Voi, R Salazar, I Borbath, N Fazio, D Smith, J Capdevila, R P Riechelmann, J C Yao
Background: Several studies have demonstrated the antitumor activity of first-generation somatostatin analogs (SSAs), primarily targeting somatostatin receptor (sstr) subtypes 2 and 5, in neuroendocrine tumors (NET). Pasireotide, a second-generation SSA, targets multiple sstr subtypes. We compared the efficacy and safety of pasireotide plus everolimus to everolimus alone in patients with advanced, well-differentiated, progressive pancreatic NET (pNET). Patients and methods: Patients were randomized 1:1 to receive a combination of everolimus (10 mg/d, orally) and pasireotide long-acting release (LAR; 60 mg/28 d, intramuscularly) or everolimus alone (10 mg/d, orally); stratified by prior SSA use, and baseline serum chromogranin A and neuron-specific enolase...
March 6, 2017: Annals of Oncology: Official Journal of the European Society for Medical Oncology
https://www.readbyqxmd.com/read/28327586/cellular-preservation-of-musculoskeletal-specializations-in-the-cretaceous-bird-confuciusornis
#19
Baoyu Jiang, Tao Zhao, Sophie Regnault, Nicholas P Edwards, Simon C Kohn, Zhiheng Li, Roy A Wogelius, Michael J Benton, John R Hutchinson
The hindlimb of theropod dinosaurs changed appreciably in the lineage leading to extant birds, becoming more 'crouched' in association with changes to body shape and gait dynamics. This postural evolution included anatomical changes of the foot and ankle, altering the moment arms and control of the muscles that manipulated the tarsometatarsus and digits, but the timing of these changes is unknown. Here, we report cellular-level preservation of tendon- and cartilage-like tissues from the lower hindlimb of Early Cretaceous Confuciusornis...
March 22, 2017: Nature Communications
https://www.readbyqxmd.com/read/28327161/rehabilitation-of-hand-function-after-spinal-cord-injury-using-a-novel-handgrip-device-a-pilot-study
#20
Haydn Hoffman, Tiffany Sierro, Tianyi Niu, Melanie E Sarino, Majid Sarrafzadeh, David McArthur, V Reggie Edgerton, Daniel C Lu
BACKGROUND: Activity-based therapy (ABT) for patients with spinal cord injury (SCI), which consists of repetitive use of muscles above and below the spinal lesion, improves locomotion and arm strength. Less data has been published regarding its effects on hand function. We sought to evaluate the effects of a weekly hand-focused therapy program using a novel handgrip device on grip strength and hand function in a SCI cohort. METHODS: Patients with SCI were enrolled in a weekly program that involved activities with the MediSens (Los Angeles, CA) handgrip...
March 21, 2017: Journal of Neuroengineering and Rehabilitation
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