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https://www.readbyqxmd.com/read/29346778/diverse-brain-myeloid-expression-profiles-reveal-distinct-microglial-activation-states-and-aspects-of-alzheimer-s-disease-not-evident-in-mouse-models
#1
Brad A Friedman, Karpagam Srinivasan, Gai Ayalon, William J Meilandt, Han Lin, Melanie A Huntley, Yi Cao, Seung-Hye Lee, Patrick C G Haddick, Hai Ngu, Zora Modrusan, Jessica L Larson, Joshua S Kaminker, Marcel P van der Brug, David V Hansen
Microglia, the CNS-resident immune cells, play important roles in disease, but the spectrum of their possible activation states is not well understood. We derived co-regulated gene modules from transcriptional profiles of CNS myeloid cells of diverse mouse models, including new tauopathy model datasets. Using these modules to interpret single-cell data from an Alzheimer's disease (AD) model, we identified microglial subsets-distinct from previously reported "disease-associated microglia"-expressing interferon-related or proliferation modules...
January 16, 2018: Cell Reports
https://www.readbyqxmd.com/read/29346763/derepression-of-the-iroquois-homeodomain-transcription-factor-gene-irx3-confers-differentiation-block-in-acute-leukemia
#2
Tim D D Somerville, Fabrizio Simeoni, John A Chadwick, Emma L Williams, Gary J Spencer, Katalin Boros, Christopher Wirth, Eleni Tholouli, Richard J Byers, Tim C P Somervaille
The Iroquois homeodomain transcription factor gene IRX3 is expressed in the developing nervous system, limb buds, and heart, and transcript levels specify obesity risk in humans. We now report a functional role for IRX3 in human acute leukemia. Although transcript levels are very low in normal human bone marrow cells, high IRX3 expression is found in ∼30% of patients with acute myeloid leukemia (AML), ∼50% with T-acute lymphoblastic leukemia, and ∼20% with B-acute lymphoblastic leukemia, frequently in association with high-level HOXA gene expression...
January 16, 2018: Cell Reports
https://www.readbyqxmd.com/read/29346761/ino80-chromatin-remodeling-coordinates-metabolic-homeostasis-with-cell-division
#3
Graeme J Gowans, Alicia N Schep, Ka Man Wong, Devin A King, William J Greenleaf, Ashby J Morrison
Adaptive survival requires the coordination of nutrient availability with expenditure of cellular resources. For example, in nutrient-limited environments, 50% of all S. cerevisiae genes synchronize and exhibit periodic bursts of expression in coordination with respiration and cell division in the yeast metabolic cycle (YMC). Despite the importance of metabolic and proliferative synchrony, the majority of YMC regulators are currently unknown. Here, we demonstrate that the INO80 chromatin-remodeling complex is required to coordinate respiration and cell division with periodic gene expression...
January 16, 2018: Cell Reports
https://www.readbyqxmd.com/read/29346723/shear-induced-brittle-failure-along-grain-boundaries-in-boron-carbide
#4
Xiaokun Yang, Shawn P Coleman, Jerry Lasalvia, William A Goddard, Qi An
The roles of grain boundaries (GB) in mechanical properties have been examined extensively for metals and alloys; however, for covalent solids their roles in deformation response to applied stress are much less established. We consider here the unusual ceramic, boron carbide (B4C), which is very hard and lightweight but exhibits brittle impact behavior. We used quantum mechanics (QM) simulations to determine the mechanical response in the atomistic structures at GBs under pure shear and also with biaxial shear deformation that mimics indentation stress conditions...
January 18, 2018: ACS Applied Materials & Interfaces
https://www.readbyqxmd.com/read/29346703/pursuing-personal-passion-learner-centered-research-mentoring
#5
William R Phillips
New researchers often face difficulty finding and focusing research questions. I describe a new tool for research mentoring, the Pursuing Personal Passion (P3) interview, and a systematic approach to help learners organize their curiosity and develop researchable questions aligned with their personal and professional priorities. The learner-centered P3 research interview parallels the patient-centered clinical interview. This paper reviews experience with 27 research mentees over the years 2009 to 2016, using the P3 approach to identify their initial research topics, classify their underlying passions and track the evolution into their final research questions...
January 2018: Family Medicine
https://www.readbyqxmd.com/read/29346686/in-the-hands-of-doctors-touch-and-trust-in-medical-care
#6
William Ventres
No abstract text is available yet for this article.
January 2018: Family Medicine
https://www.readbyqxmd.com/read/29346587/are-root-cause-analyses-recommendations-effective-and-sustainable-an-observational-study
#7
Peter D Hibbert, Matthew J W Thomas, Anita Deakin, William B Runciman, Jeffrey Braithwaite, Stephanie Lomax, Jonathan Prescott, Glenda Gorrie, Amy Szczygielski, Tanja Surwald, Catherine Fraser
Objective: To assess the strength of root cause analysis (RCA) recommendations and their perceived levels of effectiveness and sustainability. Design: All RCAs related to sentinel events (SEs) undertaken between the years 2010 and 2015 in the public health system in Victoria, Australia were analysed. The type and strength of each recommendation in the RCA reports were coded by an expert patient safety classifier using the US Department of Veteran Affairs type and strength criteria...
January 16, 2018: International Journal for Quality in Health Care
https://www.readbyqxmd.com/read/29346537/cerebral-mitochondrial-dysfunction-associated-with-deep-hypothermic-circulatory-arrest-in-neonatal-swine
#8
Constantine D Mavroudis, Michael Karlsson, Tiffany Ko, Marco Hefti, Javier I Gentile, Ryan W Morgan, Ross Plyler, Kobina G Mensah-Brown, Timothy W Boorady, Richard W Melchior, Tami M Rosenthal, Brandon C Shade, Kellie L Schiavo, Susan C Nicolson, Thomas L Spray, Robert M Sutton, Robert A Berg, Daniel J Licht, J William Gaynor, Todd J Kilbaugh
OBJECTIVES: Controversy remains regarding the use of deep hypothermic circulatory arrest (DHCA) in neonatal cardiac surgery. Alterations in cerebral mitochondrial bioenergetics are thought to contribute to ischaemia-reperfusion injury in DHCA. The purpose of this study was to compare cerebral mitochondrial bioenergetics for DHCA with deep hypothermic continuous perfusion using a neonatal swine model. METHODS: Twenty-four piglets (mean weight 3.8 kg) were placed on cardiopulmonary bypass (CPB): 10 underwent 40-min DHCA, following cooling to 18°C, 10 underwent 40 min DHCA and 10 remained at deep hypothermia for 40 min; animals were subsequently rewarmed to normothermia...
January 15, 2018: European Journal of Cardio-thoracic Surgery
https://www.readbyqxmd.com/read/29346494/novel-myopia-genes-and-pathways-identified-from-syndromic-forms-of-myopia
#9
D Ian Flitcroft, James Loughman, Christine F Wildsoet, Cathy Williams, Jeremy A Guggenheim
Purpose: To test the hypothesis that genes known to cause clinical syndromes featuring myopia also harbor polymorphisms contributing to nonsyndromic refractive errors. Methods: Clinical phenotypes and syndromes that have refractive errors as a recognized feature were identified using the Online Mendelian Inheritance in Man (OMIM) database. One hundred fifty-four unique causative genes were identified, of which 119 were specifically linked with myopia and 114 represented syndromic myopia (i...
January 1, 2018: Investigative Ophthalmology & Visual Science
https://www.readbyqxmd.com/read/29346471/use-of-single-nucleotide-polymorphisms-and-mammographic-density-plus-classic-risk-factors-for-breast-cancer-risk-prediction
#10
Elke M van Veen, Adam R Brentnall, Helen Byers, Elaine F Harkness, Susan M Astley, Sarah Sampson, Anthony Howell, William G Newman, Jack Cuzick, D Gareth R Evans
Importance: Single-nucleotide polymorphisms (SNPs) have demonstrated an association with breast cancer susceptibility, but there is limited evidence on how to incorporate them into current breast cancer risk prediction models. Objective: To determine whether a panel of 18 SNPs (SNP18) may be used to predict breast cancer in combination with classic risk factors and mammographic density. Design, Setting, and Participants: This cohort study enrolled a subcohort of 9363 women, aged 46 to 73 years, without a previous breast cancer diagnosis from the larger prospective cohort of the PROCAS study (Predicting Risk of Cancer at Screening) specifically to evaluate breast cancer risk-assessment methods...
January 18, 2018: JAMA Oncology
https://www.readbyqxmd.com/read/29346435/influenza-a-virus-hemagglutinin-glycosylation-compensates-for-antibody-escape-fitness-costs
#11
Ivan Kosik, William L Ince, Lauren E Gentles, Andrew J Oler, Martina Kosikova, Matthew Angel, Javier G Magadán, Hang Xie, Christopher B Brooke, Jonathan W Yewdell
Rapid antigenic evolution enables the persistence of seasonal influenza A and B viruses in human populations despite widespread herd immunity. Understanding viral mechanisms that enable antigenic evolution is critical for designing durable vaccines and therapeutics. Here, we utilize the primerID method of error-correcting viral population sequencing to reveal an unexpected role for hemagglutinin (HA) glycosylation in compensating for fitness defects resulting from escape from anti-HA neutralizing antibodies...
January 2018: PLoS Pathogens
https://www.readbyqxmd.com/read/29346412/a-comparative-analysis-of-preservation-techniques-for-the-optimal-molecular-detection-of-hookworm-dna-in-a-human-fecal-specimen
#12
Marina Papaiakovou, Nils Pilotte, Ben Baumer, Jessica Grant, Kristjana Asbjornsdottir, Fabian Schaer, Yan Hu, Raffi Aroian, Judd Walson, Steven A Williams
BACKGROUND: Proper collection and storage of fecal samples is necessary to guarantee the subsequent reliability of DNA-based soil-transmitted helminth diagnostic procedures. Previous research has examined various methods to preserve fecal samples for subsequent microscopic analysis or for subsequent determination of overall DNA yields obtained following DNA extraction. However, only limited research has focused on the preservation of soil-transmitted helminth DNA in stool samples stored at ambient temperature or maintained in a cold chain for extended periods of time...
January 2018: PLoS Neglected Tropical Diseases
https://www.readbyqxmd.com/read/29346377/assessing-the-feasibility-of-interrupting-the-transmission-of-soil-transmitted-helminths-through-mass-drug-administration-the-deworm3-cluster-randomized-trial-protocol
#13
Kristjana Hrönn Ásbjörnsdóttir, Sitara S Rao Ajjampur, Roy M Anderson, Robin Bailey, Iain Gardiner, Katherine E Halliday, Moudachirou Ibikounle, Khumbo Kalua, Gagandeep Kang, D Timothy J Littlewood, Adrian J F Luty, Arianna Rubin Means, William Oswald, Rachel L Pullan, Rajiv Sarkar, Fabian Schär, Adam Szpiro, James E Truscott, Marleen Werkman, Elodie Yard, Judd L Walson
ClinicalTrials.gov NCT03014167.
January 2018: PLoS Neglected Tropical Diseases
https://www.readbyqxmd.com/read/29346185/higher-art-adherence-is-associated-with-lower-systemic-inflammation-in-treatment-na%C3%A3-ve-ugandans-who-achieve-virologic-suppression
#14
Jose R Castillo-Mancilla, Mary Morrow, Yap Boum, Helen Byakwaga, Jessica E Haberer, Jeffrey N Martin, David Bangsberg, Samantha Mawhinney, Nicholas Musinguzi, Yong Huang, Russell P Tracy, Tricia H Burdo, Kenneth Williams, Conrad Muzoora, Peter W Hunt, Mark J Siedner
BACKGROUND: Residual systemic inflammation persists despite suppressive antiretroviral therapy (ART) and is associated with non-AIDS clinical outcomes. We aimed to evaluate the association between ART adherence and inflammation in Ugandans living with HIV who were predominantly receiving nevirapine-based ART with a thymidine analog backbone and were virologically suppressed by conventional assays. METHODS: Plasma concentrations of interleukin-6 (IL-6), D-dimer, soluble (s)CD14, sCD163, the kynurenine/tryptophan (K/T) ratio, in addition to CD8 T-cell activation, were measured at baseline and 6 months after ART initiation in treatment-naïve adults who achieved an undetectable plasma HIV RNA (<400 copies/mL) at their 6-month visit...
January 16, 2018: Journal of Acquired Immune Deficiency Syndromes: JAIDS
https://www.readbyqxmd.com/read/29346180/development-of-a-pd-l1-complementary-diagnostic-immunohistochemistry-assay-sp142-for-atezolizumab
#15
Bharathi Vennapusa, Brian Baker, Marcin Kowanetz, Jennifer Boone, Ina Menzl, Jean-Marie Bruey, Gregg Fine, Sanjeev Mariathasan, Ian McCaffery, Simonetta Mocci, Sandra Rost, Dustin Smith, Eslie Dennis, Szu-Yu Tang, Bita Damadzadeh, Espen Walker, Priti S Hegde, J Andrew Williams, Hartmut Koeppen, Zachary Boyd
Cancer immunotherapies, such as atezolizumab, are proving to be a valuable therapeutic strategy across indications, including non-small cell lung cancer (NSCLC) and urothelial cancer (UC). Here, we describe a diagnostic assay that measures programmed-death ligand 1 (PD-L1) expression, via immunohistochemistry, to identify patients who will derive the most benefit from treatment with atezolizumab, a humanized monoclonal anti-PD-L1 antibody. We describe the performance of the VENTANA PD-L1 (SP142) Assay in terms of specificity, sensitivity, and the ability to stain both tumor cells (TC) and tumor-infiltrating immune cells (IC), in NSCLC and UC tissues...
January 16, 2018: Applied Immunohistochemistry & Molecular Morphology: AIMM
https://www.readbyqxmd.com/read/29346081/reported-balance-confidence-and-movement-reinvestment-of-younger-knee-replacement-patients-are-more-like-younger-healthy-individuals-than-older-patients
#16
Brian D Street, Allan Adkin, William Gage
This study focused on differences between the rapidly growing younger (<65 years old) and older (>65 years old) total knee replacement (TKR) patients for measures of balance confidence, movement reinvestment, and functional mobility. Fifty-nine participants, including twenty-nine primary unilateral TKR patients (six months post-TKR) formed the four experimental groups: 1) Younger TKR Patient (YP), 2) Younger Control (YC), 3) Older TKR Patient (OP), and 4) Older Control (OC). The Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), the Oxford Knee Score (OKS), Activities-specific Balance Confidence scale (ABC), the Movement-Specific Reinvestment Scale (MSRS), and the Timed Up and Go (TUG) test were measured...
January 11, 2018: Gait & Posture
https://www.readbyqxmd.com/read/29346049/microphthalmia-corneal-dermoids-and-congenital-anomalies-resembling-goldenhar-syndrome-in-a-cat
#17
William Berkowski, Ingeborg Langohr, Anthony Pease, Joshua Bartoe
CASE DESCRIPTION An 18-month-old spayed female domestic shorthair cat was evaluated because of conjunctivitis and skin-fold dermatitis secondary to bilateral microphthalmia, corneal dermoids, and ankyloblepharon. CLINICAL FINDINGS Physical examination revealed bilateral microphthalmia, bilaterally symmetrical corneal dermoids, ankyloblepharon, superior and inferior entropion, prognathism, and facial asymmetry with deviation of the nasal septum. Computed tomography revealed malformed, thickened bony orbits with mineralization of the orbital ligament bilaterally...
February 1, 2018: Journal of the American Veterinary Medical Association
https://www.readbyqxmd.com/read/29346048/risk-factors-and-prognostic-indicators-for-surgical-outcome-of-dogs-with-esophageal-foreign-body-obstructions
#18
Brigitte A Brisson, Shannon H Wainberg, Sarah Malek, Stephanie Reabel, Alice Defarges, William C Sears
OBJECTIVE To determine risk factors for surgical intervention, complications, and outcome in dogs with an esophageal foreign body (EFB). DESIGN Retrospective observational study. ANIMALS 224 incidents of EFB in 223 dogs evaluated at a veterinary teaching hospital from 1995 through 2014. PROCEDURES Hospital records were reviewed to collect data regarding signalment, history, clinical signs, EFB type and location, procedures, complications, and outcomes. Breed distributions were compared between dogs with EFB and the entire canine patient population during the study period...
February 1, 2018: Journal of the American Veterinary Medical Association
https://www.readbyqxmd.com/read/29346046/ultrasonographic-characteristics-of-the-reproductive-tract-and-serum-progesterone-and-estradiol-concentrations-in-captive-female-red-wolves-canis-rufus-with-and-without-reproductive-tract-disease
#19
Kadie M Anderson, Mandi W Schook, Karen L Goodrowe, William T Waddell, Karen N Wolf
OBJECTIVE To describe ultrasonographic characteristics of the reproductive tract and serum progesterone and estradiol concentrations in captive female red wolves (Canis rufus) with and without reproductive tract disease. DESIGN Prospective study. ANIMALS 13 adult female red wolves. PROCEDURES Wolves with varying parity and history of contraceptive treatment were anesthetized to facilitate ultrasonographic examination and measurement of the reproductive tract and blood collection for determination of serum progesterone and estradiol concentrations in December 2011 and June 2012...
February 1, 2018: Journal of the American Veterinary Medical Association
https://www.readbyqxmd.com/read/29346041/post-treatment-mortality-after-surgery-and-stereotactic-body-radiotherapy-for-early-stage-non-small-cell-lung-cancer
#20
William A Stokes, Michael R Bronsert, Robert A Meguid, Matthew G Blum, Bernard L Jones, Matthew Koshy, David J Sher, Alexander V Louie, David A Palma, Suresh Senan, Laurie E Gaspar, Brian D Kavanagh, Chad G Rusthoven
Purpose In early-stage non-small cell lung cancer (NSCLC), post-treatment mortality may influence the comparative effectiveness of surgery and stereotactic body radiotherapy (SBRT), with implications for shared decision making among high-risk surgical candidates. We analyzed early mortality after these interventions using the National Cancer Database. Patients and Methods We abstracted patients with cT1-T2a, N0, M0 NSCLC diagnosed between 2004 and 2013 undergoing either surgery or SBRT. Thirty-day and 90-day post-treatment mortality rates were calculated and compared using Cox regression and propensity score-matched analyses...
January 18, 2018: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
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