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https://www.readbyqxmd.com/read/28811633/rapid-replacement-by-non-vaccine-pneumococcal-serotypes-may-mitigate-the-impact-of-the-pneumococcal-conjugate-vaccine-on-nasopharyngeal-bacterial-ecology
#1
Brenda Kwambana-Adams, Blake Hanson, Archibald Worwui, Schadrac Agbla, Ebenezer Foster-Nyarko, Fatima Ceesay, Chinelo Ebruke, Uzochukwu Egere, Yanjiao Zhou, Maze Ndukum, Erica Sodergren, Michael Barer, Richard Adegbola, George Weinstock, Martin Antonio
There is growing concern that interventions that alter microbial ecology can adversely affect health. We characterised the impact of the seven-valent pneumococcal conjugate vaccine (PCV7) on pneumococcal carriage and the bacterial component of the nasopharyngeal microbiome during infancy. Newborns were recruited into three groups as follows: Group1 (n = 33) was the control group and comprised infants who received PCV7 after 6 months and came from unvaccinated communities. Group 2 (n = 30) came from unvaccinated communities and Group 3 (n = 39) came from vaccinated communities...
August 15, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28797298/community-characteristics-of-the-gut-microbiomes-of-competitive-cyclists
#2
Lauren M Petersen, Eddy J Bautista, Hoan Nguyen, Blake M Hanson, Lei Chen, Sai H Lek, Erica Sodergren, George M Weinstock
BACKGROUND: Changes in diet and exercise can alter the gut microbiome of humans and mice; however, few studies to date have assessed the microbiomes of highly fit athletes. In this pilot study, we used metagenomic whole genome shotgun (mWGS) and metatranscriptomic (RNA-Seq) sequencing to show what organisms are both present and active in the gut microbiomes of both professional and amateur level competitive cyclists and to determine if any significant differences exist between these two groups...
August 10, 2017: Microbiome
https://www.readbyqxmd.com/read/28768102/chemical-approaches-to-intervening-in-ubiquitin-specific-protease-7-usp7-function-for-oncology-and-immune-oncology-therapies
#3
Jian Wu, Suresh Kumar, Feng Wang, Hui Wang, Lijia Chen, Patrick Arsenault, Michael Mattern, Joseph Weinstock
USP7, the most widely studied among the nearly 100 deubiquitinating enzymes, supports cancer by positively affecting tumor growth and negatively affecting the patient's immune response to tumors. Great interest exists, therefore, in developing USP7 inhibitors for clinical evaluation. While the proteasome inhibitor field has enjoyed clinical success, very few clinically appropriate effectors of deubiquitinating (protease) or ubiquitinating (ligase) enzymes have appeared. The ubiquitin protease/ligase field is moving from the initial discovery of potent, selective modulators with cell proof of concept and/or in vivo activity to the optimization of these molecules to impart drug-like properties or the discovery of new inhibitor scaffolds by improved screening or rational design...
August 2, 2017: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28760895/molecular-epidemiology-and-phylogenomics-of-staphylococcus-aureus-bacteremia-in-latin-america-a-prospective-cohort-multicenter-study-in-nine-countries
#4
Cesar A Arias, Jinnethe Reyes, Lina Paola Carvajal, Sandra Rincon, Lorena Diaz, Diana Panesso, Gabriel Ibarra, Rafael Rios, Jose M Munita, Mauro J Salles, Carlos Alvarez-Moreno, Jaime Labarca, Coralith Garcia, Carlos M Luna, Carlos Mejia-Villatoro, Jeannete Zurita, Manuel Guzman-Blanco, Eduardo Rodriguez-Noriega, Apurva Narechania, Laura J Rojas, Paul J Planet, George M Weinstock, Eduardo Gotuzzo, Carlos Seas
Staphylococcus aureus are important pathogens causing a spectrum of diseases ranging from mild skin and soft tissue infections to life-threatening conditions. Bloodstream infections are particularly important and the treatment approach is complicated by the presence of methicillin resistance among S. aureus isolates (MRSA). Emergence of new genetic lineages of MRSA has occurred in Latin America (LA) with the rise and dissemination of the community-associated USA300 Latin American Variant (USA300-LV). Here, we prospectively characterized bloodstream MRSA recovered from selected hospitals in 9 Latin American countries...
July 31, 2017: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/28749823/rates-of-primary-and-secondary-syphilis-among-white-and-black-non-hispanic-men-who-have-sex-with-men-us-states-2014
#5
Jeremy A Grey, Kyle T Bernstein, Patrick S Sullivan, Sarah E Kidd, Thomas L Gift, Eric W Hall, Abigail Hankin-Wei, Hillard S Weinstock, Eli S Rosenberg
BACKGROUND: Men who have sex with men (MSM) in the United States experience an approximately 100-fold greater rate of primary and secondary (P&S) syphilis diagnoses compared to men who have sex with women only. As in the general population, racial/ethnic disparities in P&S syphilis diagnosis rates may exist among MSM, but MSM-specific P&S syphilis rates by race/ethnicity are unavailable. We enhanced a published modeling approach to estimate area-level MSM populations by race/ethnicity and provide the first estimates of P&S syphilis among black and white non-Hispanic MSM...
July 26, 2017: Journal of Acquired Immune Deficiency Syndromes: JAIDS
https://www.readbyqxmd.com/read/28739787/resistance-to-ceftazidime-avibactam-is-due-to-transposition-of-kpc-in-a-porin-deficient-strain-of-klebsiella-pneumoniae-with-increased-efflux-activity
#6
Kirk Nelson, Peera Hemarajata, Dongxu Sun, Debora Rubio-Aparicio, Ruslan Tsivkovski, Shangxin Yang, Robert Sebra, Andrew Kasarskis, Hoan Nguyen, Blake M Hanson, Shana Leopold, George Weinstock, Olga Lomovskaya, Romney M Humphries
Ceftazidime-avibactam is an antibiotic with activity against serine beta-lactamases, including KPC. Recently, reports have emerged of KPC-producing isolates resistant to this antibiotic, including a report of a wild-type KPC-3 producing sequence type 258 Klebsiella pneumoniae that was resistant to ceftazidime-avibactam. We describe a detailed analysis of this isolate, in the context of two other closely related KPC-3 producing isolates, recovered from the same patient. Both isolates encoded a non-functional OmpK35, whereas we demonstrate a novel T333N mutation in OmpK36, present in the ceftazidime-avibactam resistant isolate, reduced activity of this porin and impacted ceftazidime-avibactam susceptibility...
July 24, 2017: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/28721810/centralized-and-local-color-doppler-ultrasound-reading-agreement-for-diagnosis-of-the-chronic-cerebrospinal-venous-insufficiency-in-patients-with-multiple-sclerosis
#7
Maria Grazia Caprio, Karen Marr, Sirin Gandhi, Dejan Jakimovski, Jesper Hagemeier, Bianca Weinstock-Guttman, Robert Zivadinov, Marcello Mancini
BACKGROUND: An impaired cerebrospinal venous drainage was postulated to be a cofactor in the multifactorial pathogenesis of multiple sclerosis (MS). Chronic cerebrospinal venous insufficiency (CCSVI) is characterized by abnormalities of the main extracranial cerebrospinal venous outflow routes, which can be detected by color Doppler Ultrasound (CDUS) using 5 venous hemodynamic (VH) criteria. Discrepant results between different investigators were reported in the past, therefore the usefulness and applicability of the CCSVI CDUS-based diagnosis in clinical research and practice has been questioned...
July 17, 2017: Current Neurovascular Research
https://www.readbyqxmd.com/read/28719482/teaching-incision-and-drainage-perceived-educational-value-of-abscess-models
#8
Cynthia M Adams, Lise E Nigrovic, Gavin Hayes, Peter H Weinstock, Joshua Nagler
OBJECTIVES: Incision and drainage (I&D) of skin abscesses is an important procedural skill for pediatric emergency medicine providers. Practical skills training using simulation provides an opportunity to learn and gain confidence with this invasive procedure. Our objective was to assess the perceived educational value of 2 versions of an abscess model as part of an educational workshop for teaching I&D. METHODS: A combined didactic and practical skills workshop was developed for use at 2 national conferences...
July 17, 2017: Pediatric Emergency Care
https://www.readbyqxmd.com/read/28706155/characterization-of-midostaurin-as-a-dual-inhibitor-of-flt3-and-syk-and-potentiation-of-flt3-inhibition-against-flt3-itd-driven-leukemia-harboring-activated-syk-kinase
#9
Ellen L Weisberg, Alexandre Puissant, Richard Stone, Martin Sattler, Sara J Buhrlage, Jing Yang, Paul W Manley, Chengcheng Meng, Michael Buonopane, John F Daley, Suzan Lazo, Renee Wright, David M Weinstock, Amanda L Christie, Kimberly Stegmaier, James D Griffin
Oncogenic FLT3 kinase is a clinically validated target in acute myeloid leukemia (AML), and both multi-targeted and selective FLT3 inhibitors have been developed. Spleen tyrosine kinase (SYK) has been shown to be activated and increased in FLT3-ITD-positive AML patients, and has further been shown to be critical for transformation and maintenance of the leukemic clone in these patients. Further, over-expression of constitutively activated SYK causes resistance to highly selective FLT3 tyrosine kinase inhibitors (TKI)...
July 6, 2017: Oncotarget
https://www.readbyqxmd.com/read/28692584/association-between-risk-factors-and-detection-of-cutaneous-melanoma-in-the-setting-of-a-population-based-skin-cancer-screening
#10
Joachim Hübner, Annika Waldmann, Nora Eisemann, Maria Noftz, Alan C Geller, Martin A Weinstock, Beate Volkmer, Rüdiger Greinert, Eckhard W Breitbart, Alexander Katalinic
Early detection is considered to improve the prognosis of cutaneous melanoma. The value of population-based screening for melanoma, however, is still controversial. The aim of this study was to evaluate the predictive power of established risk factors in the setting of a population-based screening and to provide empirical evidence for potential risk stratifications. We reanalyzed data (including age, sex, risk factors, and screening results) of 354 635 participants in the Skin Cancer Research to provide Evidence for Effectiveness of Screening in Northern Germany project conducted in the German state of Schleswig-Holstein (2003-2004)...
July 7, 2017: European Journal of Cancer Prevention
https://www.readbyqxmd.com/read/28659278/pathologists-diagnosis-of-invasive-melanoma-and-melanocytic-proliferations-observer-accuracy-and-reproducibility-study
#11
MULTICENTER STUDY
Joann G Elmore, Raymond L Barnhill, David E Elder, Gary M Longton, Margaret S Pepe, Lisa M Reisch, Patricia A Carney, Linda J Titus, Heidi D Nelson, Tracy Onega, Anna N A Tosteson, Martin A Weinstock, Stevan R Knezevich, Michael W Piepkorn
Objective To quantify the accuracy and reproducibility of pathologists' diagnoses of melanocytic skin lesions.Design Observer accuracy and reproducibility study.Setting 10 US states.Participants Skin biopsy cases (n=240), grouped into sets of 36 or 48. Pathologists from 10 US states were randomized to independently interpret the same set on two occasions (phases 1 and 2), at least eight months apart.Main outcome measures Pathologists' interpretations were condensed into five classes: I (eg, nevus or mild atypia); II (eg, moderate atypia); III (eg, severe atypia or melanoma in situ); IV (eg, pathologic stage T1a (pT1a) early invasive melanoma); and V (eg, ≥pT1b invasive melanoma)...
June 28, 2017: BMJ: British Medical Journal
https://www.readbyqxmd.com/read/28658986/ocrelizumab-a-b-cell-depleting-therapy-for-multiple-sclerosis
#12
Dejan Jakimovski, Bianca Weinstock-Guttman, Murali Ramanathan, Channa Kolb, David Hojnacki, Alireza Minagar, Robert Zivadinov
Multiple sclerosis (MS) is the most common neurological disease responsible for early disability in the young working population. In the last two decades, based on retrospective/prospective data, the use of disease-modifying therapies has been shown to slow the rate of disability progression and prolonged the time to conversion into secondary-progressive MS (SPMS). However, despite the availability of several approved therapies, disability progression cannot be halted significantly in all MS patients. Areas covered: This article reviews the immunopathology of the B-cells, and their role in pathogenesis of MS and their attractiveness as a potential therapeutic target in MS...
July 3, 2017: Expert Opinion on Biological Therapy
https://www.readbyqxmd.com/read/28650342/inflammatory-ly6chi-monocytes-and-their-conversion-to-m2-macrophages-drive-atherosclerosis-regression
#13
Karishma Rahman, Yuliya Vengrenyuk, Stephen A Ramsey, Noemi Rotllan Vila, Natasha M Girgis, Jianhua Liu, Viktoria Gusarova, Jesper Gromada, Ada Weinstock, Kathryn J Moore, P'ng Loke, Edward A Fisher
Atherosclerosis is a chronic inflammatory disease, and developing therapies to promote its regression is an important clinical goal. We previously established that atherosclerosis regression is characterized by an overall decrease in plaque macrophages and enrichment in markers of alternatively activated M2 macrophages. We have now investigated the origin and functional requirement for M2 macrophages in regression in normolipidemic mice that received transplants of atherosclerotic aortic segments. We compared plaque regression in WT normolipidemic recipients and those deficient in chemokine receptors necessary to recruit inflammatory Ly6Chi (Ccr2-/- or Cx3cr1-/-) or patrolling Ly6Clo (Ccr5-/-) monocytes...
August 1, 2017: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/28636448/ebola-virus-training-a-needs-assessment-and-gap-analysis
#14
Kevin Yeskey, Joseph Hughes, Betsy Galluzzo, Nina Jaitly, James Remington, Deborah Weinstock, Joy Lee Pearson, Jonathan D Rosen
In response to the 2014 Ebola virus disease outbreak, the Worker Training Program embarked on an assessment of existing training for those at risk for exposure to the virus. Searches of the recent peer-reviewed literature were conducted for descriptions of relevant training. Federal guidance issued during 2015 was also reviewed. Four stakeholder meetings were conducted with representatives from health care, academia, private industry, and public health to discuss issues associated with ongoing training. Our results revealed few articles about training that provided sufficient detail to serve as models...
May 2017: Health Security
https://www.readbyqxmd.com/read/28632934/a-prospective-microbiome-wide-association-study-of-food-sensitization-and-food-allergy-in-early-childhood
#15
Jessica H Savage, Kathleen A Lee-Sarwar, Joanne Sordillo, Supinda Bunyavanich, Yanjiao Zhou, George O'Connor, Megan Sandel, Leonard B Bacharier, Robert Zeiger, Erica Sodergren, George M Weinstock, Diane R Gold, Scott T Weiss, Augusto A Litonjua
BACKGROUND: Alterations in the intestinal microbiome are prospectively associated with the development of asthma; less is known regarding the role of microbiome alterations in food allergy development. METHODS: Intestinal microbiome samples were collected at age 3-6 months in children participating in the follow-up phase of an interventional trial of high-dose vitamin D given during pregnancy. At age 3, sensitization to foods (milk, egg, peanut, soy, wheat, walnut) was assessed...
June 20, 2017: Allergy
https://www.readbyqxmd.com/read/28628850/indoline-derivatives-mitigate-liver-damage-in-a-mouse-model-of-acute-liver-injury
#16
Efrat Finkin-Groner, Shlomi Finkin, Shani Zeeli, Marta Weinstock
BACKGROUND: Exposure of mice to D-galactosamine (GalN) and lipopolysaccharide (LPS) induces acute liver failure through elevation of TNF-α, which causes liver damage resembling that in humans. The current study evaluated in this model the effect of two indoline derivatives, which have anti-inflammatory activity in macrophages. METHODS: AN1297 and AN1284 (0.025-0.75mg/kg) or dexamethasone (3mg/kg), were injected subcutaneously, 15min before intraperitoneal injection of GalN (800mg) plus LPS (50μg) in male Balb/C mice...
April 12, 2017: Pharmacological Reports: PR
https://www.readbyqxmd.com/read/28625833/colorectal-cancer-cell-line-proteomes-are-representative-of-primary-tumors-and-predict-drug-sensitivity
#17
Jing Wang, Dmitri Mouradov, Xiaojing Wang, Robert N Jorissen, Matthew C Chambers, Lisa J Zimmerman, Suhas Vasaikar, Christopher G Love, Shan Li, Kym Lowes, Karl-Johan Leuchowius, Helene Jousset, Janet Weinstock, Christopher Yau, John Mariadason, Zhiao Shi, Yuguan Ban, Xi Chen, Robert J C Coffey, Robbert J C Slebos, Antony W Burgess, Daniel C Liebler, Bing Zhang, Oliver M Sieber
BACKGROUND AND AIMS: Proteomics holds promise for individualizing cancer treatment. We analyzed to what extent the proteomic landscape of human colorectal cancer (CRC) is maintained in established CRC cell lines and the utility of proteomics for predicting therapeutic responses. METHODS: Proteomic and transcriptomic analyses were performed on 44 CRC cell lines, compared against primary CRCs (n=95) and normal tissues (n=60), and integrated with genomic and drug sensitivity data...
June 15, 2017: Gastroenterology
https://www.readbyqxmd.com/read/28621489/validation-and-comparison-of-quality-of-life-measures-for-topical-5-fluorouracil-treatment-results-from-a-randomized-controlled-trial
#18
H Pomerantz, M-M Chren, R Lew, M A Weinstock
BACKGROUND: Topical 5-fluorouracil (5-FU) is commonly used for high-risk patients with keratinocyte carcinoma (KC). Skindex and Skin Cancer Index (SCI) are validated instruments to measure quality of life (QoL) of patients with KC and those who have had surgical treatment of KCs. AIM: To validate Skindex and SCI for topical 5-fluorouracil (5-FU) application and to compare the two QoL instruments. METHODS: We randomized 932 veterans at high risk for developing a KC to either topical 5-FU or vehicle control cream applied to the face and ears for up to 1 month...
July 2017: Clinical and Experimental Dermatology
https://www.readbyqxmd.com/read/28620490/ketogenic-diet-predictors-of-seizure-control
#19
Nitin Agarwal, Dimitrios Arkilo, Osman Farooq, Cynthia Gillogly, Katelyn S Kavak, Arie Weinstock
BACKGROUND: The ketogenic diet is an effective non-pharmacologic treatment for medically resistant epilepsy. The aim of this study was to identify any predictors that may influence the response of ketogenic diet. METHODS: A retrospective chart review for all patients with medically resistant epilepsy was performed at a tertiary care epilepsy center from 1996 to 2012. Patient- and diet-related variables were evaluated with respect to seizure reduction at 1, 3, 6, 9 and 12-month intervals and divided into four possible outcome classes...
2017: SAGE Open Medicine
https://www.readbyqxmd.com/read/28611866/association-of-cognitive-impairment-in-patients-on-3-hydroxy-3-methyl-glutaryl-coa-reductase-inhibitors
#20
Satyajeet Roy, Joshua Louis Weinstock, Allyse Sachiko Ishino, Jefferson Felix Benites, Samantha Rachel Pop, Christopher David Perez, Edvard Adrian Gumbs, Jennifer Ann Rosenbaum, Mary Kate Roccato, Hely Shah, Gabriela Contino, Krystal Hunter
BACKGROUND: Atherosclerotic cardiovascular diseases are the leading cause of death in the United States. A reduction in cholesterol with 3-hydroxy-3-methyl-glutaryl-CoA reductase inhibitors (statin) significantly reduces mortality and morbidity. Statins may be associated with cognitive impairment or dementia. Our aim was to study the association of cognitive impairment or dementia in patients who were on a statin. METHODS: Electronic medical records of 3,500 adult patients in our suburban internal medicine office were reviewed...
July 2017: Journal of Clinical Medicine Research
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