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https://www.readbyqxmd.com/read/28231491/effect-of-granulocyte-colony-stimulating-factor-on-outcomes-in-patients-with-non-m3-acute-myelogenous-leukemia-treated-with-anthracycline-based-induction-7-3-regimen-chemotherapies
#1
Ka-Won Kang, Dae Sik Kim, Se Ryeon Lee, Hwa Jung Sung, Seok Jin Kim, Chul Won Choi, Byung Soo Kim, Yong Park
We analyzed the effects of granulocyte colony-stimulating factor (G-CSF) on outcomes in 315 anthracycline-based induction chemotherapy-treated patients with non-M3 acute myelogenous leukemia (AML). Patients were classified as follows: no G-CSF administration during induction (no G-CSF group; 112 patients); administration immediately upon neutropenia onset (absolute neutrophil counts (ANC)<1000/μL), but before febrile neutropenia (preemptive group; 74 patients); and administration following febrile neutropenia development (therapeutic group; 129 patients)...
February 8, 2017: Leukemia Research
https://www.readbyqxmd.com/read/28230986/design-synthesis-and-evaluation-of-a-novel-series-of-oxadiazine-gamma-secretase-modulators-for-familial-alzheimer-s-disease
#2
Matthew G Bursavich, Bryce A Harrison, Raksha Acharya, Donald E Costa, Emily A Freeman, Hilliary E Hodgdon, Lori A Hrdlicka, Hong Jin, Sudarshan Kapadnis, Jeffrey S Moffit, Deirdre A Murphy, Scott Nolan, Holger Patzke, Cuyue Tang, Melody Wen, Gerhard Koenig, Jean-François Blain, Duane A Burnett
Herein we describe the design, synthesis and evaluation of a novel series of oxadiazine-based gamma secretase modulators obtained via isosteric amide replacement and critical consideration of conforma-tional restriction. Oxadiazine lead 47 possesses good in vitro potency with excellent predicted CNS drug-like properties and desirable ADME/PK profile. This lead compound demonstrated robust Aβ42 reductions and subsequent Aβ37 increases in both rodent brain and CSF at 30 mg/kg dosed orally.
February 23, 2017: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28228714/narrative-organization-deficit-in-lewy-body-disorders-is-related-to-alzheimer-pathology
#3
Murray Grossman, David J Irwin, Charles Jester, Amy Halpin, Sharon Ash, Katya Rascovsky, Daniel Weintraub, Corey T McMillan
Background: Day-to-day interactions depend on conversational narrative, and we examine here the neurobiological basis for difficulty organizing narrative discourse in patients with Lewy body disorders (LBD). Method: Narrative organization was examined in 56 non-aphasic LBD patients, including a non-demented cohort (n = 30) with Parkinson's disease (PD) or PD-Mild Cognitive Impairment PD-MCI,) and a cohort with mild dementia (n = 26) including PD-dementia (PDD) and dementia with Lewy bodies (DLB), with similar age and education but differing in MMSE (p < 0...
2017: Frontiers in Neuroscience
https://www.readbyqxmd.com/read/28228280/autocrine-loop-involving-il-6-family-member-lif-lif-receptor-and-stat4-drives-sustained-fibroblast-production-of-inflammatory-mediators
#4
Hung N Nguyen, Erika H Noss, Fumitaka Mizoguchi, Christine Huppertz, Kevin S Wei, Gerald F M Watts, Michael B Brenner
Fibroblasts are major contributors to and regulators of inflammation and dominant producers of interleukin-6 (IL-6) in inflammatory diseases like rheumatoid arthritis. Yet, compared to leukocytes, the regulation of inflammatory pathways in fibroblasts is largely unknown. Here, we report that analyses of genes coordinately upregulated with IL-6 pointed to STAT4 and leukemia inhibitory factor (LIF) as potentially linked. Gene silencing revealed that STAT4 was required for IL-6 transcription. STAT4 was recruited to the IL-6 promoter after fibroblast activation, and LIF receptor (LIFR) and STAT4 formed a molecular complex that, together with JAK1 and TYK2 kinases, controlled STAT4 activation...
February 21, 2017: Immunity
https://www.readbyqxmd.com/read/28226605/semi-automated-image-analysis-of-gel-electrophoresis-of-cerebrospinal-fluid-for-oligoclonal-band-detection
#5
S Boudet, L Peyrodie, Z Wang, G Forzy, S Boudet, L Peyrodie, Z Wang, G Forzy, Z Wang, L Peyrodie, S Boudet, G Forzy
Detection of oligoclonal electrophoretic bands in cerebrospinal fluid (CSF) is an important diagnostic tool for Multiple Sclerosis (MS). Electrophoretic profiles are difficult to interpret due to low contrast and artefacts. A semi-automated method to ease analysis and to reduce subjectivity is presented. The method sequentially converts color images to grayscale, realigns bands, removes artifacts, then converts 2D images to a signal, before detecting, thresholding and editing peaks to optimize profiles. Such treated profiles (21 positive and 15 negative) are compared to ground truth analysis of an expert biologist...
August 2016: Conference Proceedings: Annual International Conference of the IEEE Engineering in Medicine and Biology Society
https://www.readbyqxmd.com/read/28225337/multiple-cytokines-for-the-detection-of-mycobacterium-tuberculosis-infection-in-children-with-tuberculosis
#6
N Nausch, C Lundtoft, G Schulz, H Henckel, E Mayatepek, B Fleischer, F M Marx, M Jacobsen
SETTING: Interferon-gamma (IFN-γ) release assays (IGRAs) play an important role in the diagnosis of Mycobacterium tuberculosis infection. However, in children with tuberculosis (TB), some studies have shown increased frequencies of false-negative or indeterminate IGRA results. OBJECTIVE: To analyse the spectrum of different cytokines to improve the diagnostic accuracy of IGRAs in latent tuberculous infection (LTBI) and active TB. DESIGN: We performed multiplex cytokine expression analysis of QuantiFERON® Gold In-Tube supernatants in children with active TB (n = 21) and disease-free contacts with (n = 15) and without LTBI (n = 12), to determine the sensitivity and specificity of the modified tests...
March 1, 2017: International Journal of Tuberculosis and Lung Disease
https://www.readbyqxmd.com/read/28224485/incidence-of-varicella-zoster-virus-infections-of-the-central-nervous-system-in-the-elderly-a-large-tertiary-hospital-based-series-2007-2014
#7
M Arruti, L D Piñeiro, Y Salicio, G Cilla, M A Goenaga, A López de Munain
The aim of the study was to describe the clinical and epidemiological characteristics of the central nervous system (CNS) infection by varicella zoster virus (VZV) in patients older than 65 years in a tertiary community hospital. We retrospectively analysed the results of cerebrospinal fluid (CSF) testing in patients older than 65 years between 2007 and 2014 with clinically suspected VZV infection with CNS involvement. Patients whose CSF samples were positive for VZV DNA were included, as were those with negative results who simultaneously presented herpes zoster and CSF or magnetic resonance imaging findings suggestive of CNS infection, and in whom other possible aetiologies had been ruled out...
February 21, 2017: Journal of Neurovirology
https://www.readbyqxmd.com/read/28222797/melanoma-antigen-specific-effector-t-cell-cytokine-secretion-patterns-in-patients-treated-with-ipilimumab
#8
Yana G Najjar, Fei Ding, Yan Lin, Robert VanderWeele, Lisa H Butterfield, Ahmad A Tarhini
BACKGROUND: In a previously reported study, patients with regionally advanced melanoma were treated with neoadjuvant ipilimumab (ipi) (Tarhini in PLoS ONE 9(2): e87705, 3). Significant changes in circulating myeloid derived suppressor cells (MDSC), regulatory T cells (Treg) and peptide specific type I CD4(+) and CD8(+) T cells were noted at week 6 that correlated with clinical outcome. Characterization of antigen-specific effector T cell secreted cytokines may shed insights into ipi associated T cell activation and function...
February 21, 2017: Journal of Translational Medicine
https://www.readbyqxmd.com/read/28220745/is-it-possible-to-differentiate-tuberculous-and-cryptococcal-meningitis-in-hiv-infected-patients-using-only-clinical-and-basic-cerebrospinal-fluid-characteristics
#9
J E Vidal, E J F Peixoto de Miranda, J Gerhardt, M Croda, D R Boulware
BACKGROUND: Tuberculous and cryptococcal meningitis (TBM and CM) are the most common causes of opportunistic meningitis in HIVinfected patients from resource-limited settings, and the differential diagnosis is challenging. OBJECTIVE: To compare clinical and basic cerebrospinal fluid (CSF) characteristics between TBM and CM in HIV-infected patients. METHODS: A retrospective analysis was conducted of clinical, radiological and laboratory records of 108 and 98 HIV-infected patients with culture-proven diagnosis of TBM and CM, respectively...
January 30, 2017: South African Medical Journal, Suid-Afrikaanse Tydskrif Vir Geneeskunde
https://www.readbyqxmd.com/read/28220120/neutrophil-extracellular-traps-and-its-implications-in-inflammation-an-overview
#10
REVIEW
Vidal Delgado-Rizo, Marco A Martínez-Guzmán, Liliana Iñiguez-Gutierrez, Alejandra García-Orozco, Anabell Alvarado-Navarro, Mary Fafutis-Morris
In addition to physical barriers, neutrophils are considered a part of the first line of immune defense. They can be found in the bloodstream, with a lifespan of 6-8 h, and in tissue, where they can last up to 7 days. The mechanisms that neutrophils utilize for host defense are phagocytosis, degranulation, cytokine production, and, the most recently described, neutrophil extracellular trap (NET) production. NETs are DNA structures released due to chromatin decondensation and spreading, and they thus occupy three to five times the volume of condensed chromatin...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28219470/comparing-external-ventricular-drains-related-ventriculitis-surveillance-definitions
#11
Maria M Reyes, Satish Munigala, Emily L Church, Tobias B Kulik, Salah G Keyrouz, Gregory J Zipfel, David K Warren
OBJECTIVE To evaluate the agreement between the current National Healthcare Safety Network (NHSN) definition for ventriculitis and others found in the literature among patients with an external ventricular drain (EVD) DESIGN Retrospective cohort study from January 2009 to December 2014 SETTING Neurology and neurosurgery intensive care unit of a large tertiary-care center PATIENTS Patients with an EVD were included. Patients with an infection prior to EVD placement or a permanent ventricular shunt were excluded...
February 21, 2017: Infection Control and Hospital Epidemiology
https://www.readbyqxmd.com/read/28218904/the-protumorigenic-potential-of-fty720-by-promoting-extramedullary-hematopoiesis-and-mdsc-accumulation
#12
Y Li, T Zhou, Y Wang, C Ning, Z Lv, G Han, J C Morris, E N Taylor, R Wang, H Xiao, C Hou, Y Ma, B Shen, J Feng, R Guo, Y Li, G Chen
FTY720 (also called fingolimod) is recognized as an immunosuppressant and has been approved by the Food and Drug Administration to treat refractory multiple sclerosis. However, long-term administration of FTY720 potentially increases the risk for cancer in recipients. The underlying mechanisms remain poorly understood. Herein, we provided evidence that FTY720 administration potentiated tumor growth. Mechanistically, FTY720 enhanced extramedullary hematopoiesis and massive accumulation of myeloid-derived suppressor cells (MDSCs), which actively suppressed antitumor immune responses...
February 20, 2017: Oncogene
https://www.readbyqxmd.com/read/28217607/concurrent-central-nervous-system-infective-pathology-in-a-severely-immunocompromised-patient
#13
Thein Swe, Bordes P Laurent, Nickul N Shah
To our knowledge and literature search, concurrent cryptococcal meningitis and neurosyphilis in a patient have rarely been reported. Here, we report a 37-year-old male with HIV infection presented with headache and dizziness for 5 days along with memory difficulty and personality changes for about 1 week. During the hospital stay, cryptococcal meningitis was confirmed with positive cerebral spinal fluid (CSF) cryptococcal antigen titer (1:320) and positive CSF culture. Diagnosis of neurosyphilis was made based upon CSF white blood cell count of 85 cells/μL, with CSF total protein of 87 mg/dL, reactive CSF treponemal antibody, and fluorescent treponemal antibody...
July 2016: Journal of Family Medicine and Primary Care
https://www.readbyqxmd.com/read/28217183/affection-of-the-respiratory-muscles-in-combined-complex-i-and-iv-deficiency
#14
Josef Finsterer, Helmut Rauschka, Liane Segal, Gabor G Kovacs, Boris Rolinski
OBJECTIVES: Combined complex I+IV deficiency has rarely been reported to manifest with the involvement of the respiratory muscles. CASE REPORT: A 45y male was admitted for hypercapnia due to muscular respiratory insufficiency. He required intubation and mechanical ventilation. He had a previous history of ophthalmoparesis since age 6y, ptosis since age 23y, and anterocollis since at least age 40y. Muscle biopsy from the right deltoid muscle at age 41y was indicative of mitochondrial myopathy...
2017: Open Neurology Journal
https://www.readbyqxmd.com/read/28216660/results-of-the-randomized-phase-iib-admire-trial-of-fcr-with-or-without-mitoxantrone-in-previously-untreated-cll
#15
T Munir, D R Howard, L McParland, C Pocock, A C Rawstron, A Hockaday, A Varghese, M Hamblin, A Bloor, A Pettitt, C Fegan, J Blundell, J G Gribben, D Phillips, P Hillmen
ADMIRE was a multi-center, randomized-controlled, open, phase IIB superiority trial in previously untreated Chronic Lymphocytic Leukemia (CLL). Conventional frontline therapy in fit patients is fludarabine, cyclophosphamide and rituximab (FCR). Initial evidence from non-randomized Phase II trials suggested that the addition of mitoxantrone to FCR (FCM-R) improved remission rates. 215 patients were recruited to assess the primary endpoint of complete remission (CR) rates according to IWCLL criteria. Secondary endpoints were progression-free survival (PFS), overall survival (OS), overall response rate, minimal residual disease (MRD) negativity and safety...
February 20, 2017: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/28216393/predicting-progression-to-dementia-in-persons-with-mild-cognitive-impairment-using-cerebrospinal-fluid-markers
#16
Ron L H Handels, Stephanie J B Vos, Milica G Kramberger, Vesna Jelic, Kaj Blennow, Mark van Buchem, Wiesje van der Flier, Yvonne Freund-Levi, Harald Hampel, Marcel Olde Rikkert, Ania Oleksik, Zvezdan Pirtosek, Philip Scheltens, Hilkka Soininen, Charlotte Teunissen, Magda Tsolaki, Asa K Wallin, Bengt Winblad, Frans R J Verhey, Pieter Jelle Visser
BACKGROUND: We aimed to determine the added value of cerebrospinal fluid (CSF) to clinical and imaging tests to predict progression from mild cognitive impairment (MCI) to any type of dementia. METHODS: The risk of progression to dementia was estimated using two logistic regression models based on 250 MCI participants: the first included standard clinical measures (demographic, clinical, and imaging test information) without CSF biomarkers, and the second included standard clinical measures with CSF biomarkers...
February 16, 2017: Alzheimer's & Dementia: the Journal of the Alzheimer's Association
https://www.readbyqxmd.com/read/28214758/comparative-analysis-of-viral-shedding-in-pediatric-and-adult-subjects-with-central-nervous-system-associated-enterovirus-infections-from-2013-to-2015-in-switzerland
#17
S Cordey, M Schibler, A G L'Huillier, N Wagner, A R Gonçalves, J Ambrosioni, S Asner, L Turin, K M Posfay-Barbe, L Kaiser
BACKGROUND: Several enterovirus (EV) genotypes can result in aseptic meningitis, but their routes of access to the central nervous system remain to be elucidated and may differ between the pediatric and adult populations. OBJECTIVE: To assess the pattern of viral shedding in pediatric and adult subjects with acute EV meningitis and to generate EV surveillance data for Switzerland. STUDY DESIGN: All pediatric and adult subjects admitted to the University Hospitals of Geneva with a diagnosis of EV meningitis between 2013 and 2015 were enrolled...
February 7, 2017: Journal of Clinical Virology: the Official Publication of the Pan American Society for Clinical Virology
https://www.readbyqxmd.com/read/28209190/the-effects-of-different-familial-alzheimer-s-disease-mutations-on-app-processing-in-vivo
#18
Steinunn Thordardottir, Anne Kinhult Ståhlbom, Ove Almkvist, Håkan Thonberg, Maria Eriksdotter, Henrik Zetterberg, Kaj Blennow, Caroline Graff
BACKGROUND: Disturbed amyloid precursor protein (APP) processing is considered to be central to the pathogenesis of Alzheimer's disease (AD). The autosomal dominant form of the disease, familial AD (FAD), may serve as a model for the sporadic form of AD. In FAD the diagnosis of AD is reliable and presymptomatic individuals carrying FAD mutations can give valuable insights into the earliest stages of the disease where therapeutic interventions are thought to be the most effective. METHODS: In the current cross-sectional study, products of APP processing (e...
February 16, 2017: Alzheimer's Research & Therapy
https://www.readbyqxmd.com/read/28209068/urinary-cytokines-chemokines-after-magnetic-resonance-guided-high-intensity-focused-ultrasound-for-palliative-treatment-of-painful-bone-metastases
#19
Ahmad Bushehri, Gregory Czarnota, Liying Zhang, Kullervo Hynynen, Yuexi Huang, Michael Chan, William Chu, Kristopher Dennis, Charles Mougenot, Jennifer Coccagna, Arjun Sahgal, Edward Chow, Carlo DeAngelis
BACKGROUND: Pain is experienced by 50-75% of patients with bone metastases, representing a major source of morbidity amongst cancer patients. Magnetic resonance-guided high intensity focused ultrasound (MRgHIFU) is a new, non-invasive, outpatient treatment modality for painful bone metastases. The aim of this study was to analyze urinary cytokines/chemokines pattern after MRgHIFU for palliative treatment of painful bone metastases. The findings were compared to the cytokines/chemokines pattern post single 8 Gy fraction radiation from our previous study...
January 2017: Annals of Palliative Medicine
https://www.readbyqxmd.com/read/28206782/process-dissociation-analyses-of-memory-changes-in-healthy-aging-preclinical-and-very-mild-alzheimer-disease-evidence-for-isolated-recollection-deficits
#20
Peter R Millar, David A Balota, Geoffrey B Maddox, Janet M Duchek, Andrew J Aschenbrenner, Anne M Fagan, Tammie L S Benzinger, John C Morris
OBJECTIVE: Recollection and familiarity are independent processes that contribute to memory performance. Recollection is dependent on attentional control, which has been shown to be disrupted in early stage Alzheimer's disease (AD), whereas familiarity is independent of attention. The present longitudinal study examines the sensitivity of recollection estimates based on Jacoby's (1991) process dissociation procedure to AD-related biomarkers in a large sample of well-characterized cognitively normal middle-aged and older adults (N = 519) and the extent to which recollection discriminates these individuals from individuals with very mild symptomatic AD (N = 64)...
February 16, 2017: Neuropsychology
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