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https://www.readbyqxmd.com/read/28545238/epigenetic-strategies-to-boost-cancer-immunotherapies
#1
REVIEW
Maria J Barrero
Recently, immunotherapeutic approaches have shown impressive responses in a subset of cancer patients. However, the rate of success is low and a large percentage of treated patients do not experience clinical benefits. Therefore, additional strategies are needed to improve responses and select responsive patients. Emerging data suggest that epigenetic drugs can improve the responses to immunotherapy. Understanding the mechanisms of resistance to immunotherapy and the epigenetic events that take place during immune evasion is critical to providing a rational combined use of immunotherapies and epigenetic drugs...
May 23, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28544891/emergence-of-ultrafast-sparsely-synchronized-rhythms-and-their-responses-to-external-stimuli-in-an-inhomogeneous-small-world-complex-neuronal-network
#2
Sang-Yoon Kim, Woochang Lim
We consider an inhomogeneous small-world network (SWN) composed of inhibitory short-range (SR) and long-range (LR) interneurons, and investigate the effect of network architecture on emergence of synchronized brain rhythms by varying the fraction of LR interneurons plong. The betweenness centralities of the LR and SR interneurons (characterizing the potentiality in controlling communication between other interneurons) are distinctly different. Hence, in view of the betweenness, SWNs we consider are inhomogeneous, unlike the "canonical" Watts-Strogatz SWN with nearly the same betweenness centralities...
April 28, 2017: Neural Networks: the Official Journal of the International Neural Network Society
https://www.readbyqxmd.com/read/28544603/metabolic-reprogramming-of-macrophages-exposed-to-silk-poly-lactic-co-glycolic-acid-and-silica-nanoparticles
#3
Raquel Saborano, Thidarat Wongpinyochit, John D Totten, Blair F Johnston, F Philipp Seib, Iola F Duarte
Monitoring macrophage metabolism in response to nanoparticle exposure provides new insights into biological outcomes, such as inflammation or toxicity, and supports the design of tailored nanomedicines. This paper describes the metabolic signature of macrophages exposed to nanoparticles ranging in diameter from 100 to 125 nm and made from silk, poly(lactic-co-glycolic acid) or silica. Nanoparticles of this size and type are currently at various stages of preclinical and clinical development for drug delivery applications...
May 8, 2017: Advanced Healthcare Materials
https://www.readbyqxmd.com/read/28544459/plaque-removal-with-triple-headed-vs-single-headed-manual-toothbrushes-a-systematic-review
#4
REVIEW
S M Kalf-Scholte, G A Van der Weijden, Ewp Bakker, D E Slot
OBJECTIVE: The aim of this systematic review was to establish the effectiveness of brushing with a triple-headed manual toothbrush compared to a single-headed manual toothbrush on plaque removal. MATERIALS AND METHODS: The MEDLINE-PubMed and Cochrane-CENTRAL databases were searched. The inclusion criteria were clinical trials conducted with humans without fixed orthodontic appliances who were not dental care professionals. Papers that evaluated the effect of toothbrushing with a triple-headed manual toothbrush compared to a single-headed manual toothbrush on plaque removal were included...
May 22, 2017: International Journal of Dental Hygiene
https://www.readbyqxmd.com/read/28544158/molecular-and-physiological-manifestations-and-measurement-of-aging-in-humans
#5
REVIEW
Sadiya S Khan, Benjamin D Singer, Douglas E Vaughan
Biological aging is associated with a reduction in the reparative and regenerative potential in tissues and organs. This reduction manifests as a decreased physiological reserve in response to stress (termed homeostenosis) and a time-dependent failure of complex molecular mechanisms that cumulatively create disorder. Aging inevitably occurs with time in all organisms and emerges on a molecular, cellular, organ, and organismal level with genetic, epigenetic, and environmental modulators. Individuals with the same chronological age exhibit differential trajectories of age-related decline, and it follows that we should assess biological age distinctly from chronological age...
May 23, 2017: Aging Cell
https://www.readbyqxmd.com/read/28544049/tone-identification-behavior-in-rattus-norvergicus-muscarinic-receptor-blockage-lowers-responsiveness-in-non-target-selective-neurons-while-nicotinic-receptor-blockage-selectively-lowers-target-responses
#6
Ezekiel P Carpenter-Hyland, Jackson Griffeth, Kristopher Bunting, Alvin Terry, Almira Vazdarjanova, David T Blake
Learning to associate a stimulus with reinforcement causes plasticity in primary sensory cortex. Neural activity caused by the associated stimulus is paired with reinforcement, but population analyses have not found a selective increase in response to that stimulus. Responses to other stimuli increase as much as, or more than, responses to the associated stimulus. Here, we applied population analysis at a new time point, and additionally evaluated whether cholinergic receptor blockers interacted with the plastic changes in cortex...
May 24, 2017: European Journal of Neuroscience
https://www.readbyqxmd.com/read/28543886/human-hairless-protein-roles-in-skin-hair-and-emerging-connections-to-brain-and-other-cancers
#7
Anas Maatough, G Kerr Whitfield, Lemlem Brook, David Hsieh, Patricia Palade, Jui-Cheng Hsieh
The mammalian hairless protein (HR) is a 130 kDa nuclear transcription factor that is essential for proper skin and hair follicle function. Previous studies have focused on the role of HR in skin maintenance and hair cycling. However, hairless gene (HR) is also expressed in brain and other tissues, where its role remains poorly understood. HR has been reported to contain functional domains that potentially serve in DNA binding, histone demethylation, nuclear translocation signal, and protein-protein interactions...
May 23, 2017: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/28543811/the-structural-flexibility-of-the-human-copper-chaperone-atox1-insights-from-combined-pulsed-epr-studies-and-computations
#8
Ariel R Levy, Meital Turgeman, Lada Gevorkyan-Aiapetov, Sharon Ruthstein
Metallochaperones are responsible for shuttling metal ions to target proteins. Thus, a metallochaperone's structure must be sufficiently flexible both to hold onto its ion while traversing the cytoplasm and to transfer the ion to or from a partner protein. Here, we sought to shed light on the structure of Atox1, a metallochaperone involved in the human copper regulation system. Atox1 shuttles copper ions from the main copper transporter, Ctr1, to the ATP7b transporter in the Golgi apparatus. Conventional biophysical tools such as X-ray or NMR cannot always target the various conformational states of metallochaperones, owing to a requirement for crystallography or low sensitivity and resolution...
May 20, 2017: Protein Science: a Publication of the Protein Society
https://www.readbyqxmd.com/read/28543648/making-the-choices-necessary-to-make-a-difference-the-responsibility-of-national-bioethics-commissions
#9
Christine Grady
In this essay, I offer some reflections on how the topics were identified and approached by the Presidential Commission for the Study of Bioethical Issues, on which I had the honor to serve, in the hope that the reflections may be useful to future national bioethics commissions. In the executive order that established the bioethics commission, President Obama explicitly recognized the ethical imperative to responsibly pursue science, innovation, and advances in biomedical research and health care, and the importance of national attention to these issues...
May 2017: Hastings Center Report
https://www.readbyqxmd.com/read/28543585/a-score-test-for-genetic-class-level-association-with-nonlinear-biomarker-trajectories
#10
Jing Qian, Sara Nunez, Soohyun Kim, Muredach P Reilly, Andrea S Foulkes
Emerging data suggest that the genetic regulation of the biological response to inflammatory stress may be fundamentally different to the genetic underpinning of the homeostatic control (resting state) of the same biological measures. In this paper, we interrogate this hypothesis using a single-SNP score test and a novel class-level testing strategy to characterize protein-coding gene and regulatory element-level associations with longitudinal biomarker trajectories in response to stimulus. Using the proposed class-level association score statistic for longitudinal data, which accounts for correlations induced by linkage disequilibrium, the genetic underpinnings of evoked dynamic changes in repeatedly measured biomarkers are investigated...
May 23, 2017: Statistics in Medicine
https://www.readbyqxmd.com/read/28543419/flu-floods-and-fire-ethical-public-health-preparedness
#11
REVIEW
Alexandra L Phelan, Lawrence O Gostin
Even as public health ethics was developing as a field, major incidents such as 9/11 and the SARS epidemic propelled discourse around public health emergency preparedness and response. Policy and practice shifted to a multidisciplinary approach, recognizing the broad range of potential threats to public health, including biological, physical, radiological, and chemical threats. This propelled the development of surveillance systems to detect incidents, laboratory capacities to rapidly test for potential threats, and therapeutic and social countermeasures to prepare for and respond to a range of hazards...
May 2017: Hastings Center Report
https://www.readbyqxmd.com/read/28543184/a-systematic-review-of-patient-reported-measures-associated-with-vestibular-dysfunction
#12
REVIEW
Vicky M Stewart, M Dilani Mendis, Nancy Low Choy
OBJECTIVES/HYPOTHESIS: Use of clinical questionnaires to assist in the screening of vestibular disorders in the acute hospital setting is needed. The objective is to detail the clinimetric properties and clinical utility of patient-reported questionnaires for quantifying dizziness/vertigo symptoms associated with vestibular dysfunction, and to determine validity and utility for screening dizziness/vertigo in the emergency department. DATA SOURCES: We performed a systematic review of PubMed, CINAHL, Embase, and Web of Science in May 2015...
May 23, 2017: Laryngoscope
https://www.readbyqxmd.com/read/28542929/the-immune-response-to-prevotella-bacteria-in-chronic-inflammatory-disease
#13
REVIEW
Jeppe Madura Larsen
The microbiota plays a central role in human health and disease by shaping immune development, immune responses, metabolism, and protecting from invading pathogens. Technical advances that allow comprehensive characterization of microbial communities by genetic sequencing have sparked the hunt for disease modulating bacteria. Emerging studies in humans have linked increased abundance of Prevotella species at mucosal sites to localized and systemic disease, including periodontitis, bacterial vaginosis, rheumatoid arthritis, metabolic disorders, and low-grade systemic inflammation...
May 19, 2017: Immunology
https://www.readbyqxmd.com/read/28542794/positive-affectivity-and-fear-trajectories-in-infancy-contributions-of-mother-child-interaction-factors
#14
Maria A Gartstein, Gregory R Hancock, Sydney L Iverson
Fear and positive emotionality were considered in a growth modeling context. Mothers, primarily Caucasian (91.9%) and of middle socioeconomic status, participated in play interactions with infants at 4 months (N = 148). Infant fear and positive affectivity were evaluated at 6, 8, 10, and 12 months of age. A linear trajectory was superior in explaining growth for parent report and observation-based indicators of positive affectivity and parent report of fearfulness; a piecewise model explained the nonlinear growth of observation-based fear...
May 24, 2017: Child Development
https://www.readbyqxmd.com/read/28542682/applicant-perspectives-on-the-otolaryngology-residency-application-process
#15
Matthew Ward, Christian Pingree, Adrienne M Laury, Sarah N Bowe
Importance: It has been nearly 25 years since medical students were queried regarding their perspectives on otolaryngology-head and neck surgery (OHNS) residency selection. Understanding this viewpoint is critical to improving the current application process. Objective: To evaluate the perceptions of 2016 OHNS residency applicants regarding the application process and offer suggestions for reform. Design, Setting, and Participants: In this cross-sectional study of anonymous online survey data, a 14-question survey was designed based on resources obtained from a computerized PubMed, Ovid, and GoogleScholar database search of the English language from January 1, 1990, through December 31, 2015, was conducted using the following search terms: (medical student OR applicant) AND (application OR match) AND otolaryngology...
May 25, 2017: JAMA Otolaryngology—Head & Neck Surgery
https://www.readbyqxmd.com/read/28542618/early-and-late-stage-processing-abnormalities-in-autism-spectrum-disorders-an-erp-study
#16
Shanshan Wang, Chunjuan Yang, Yijun Liu, Zhi Shao, Todd Jackson
This research assessed event-related potentials (ERPs) elicited during the processing of different kinds of visual stimuli among children with Autism Spectrum Disorder (ASD) (n = 15) and typically developing (TD) children (n = 19). Within a simple visual oddball paradigm, participating children passively viewed fruit and vegetable images that were used as standard stimuli in addition to images of these foods with their usual colors modified to create novel stimuli and cartoon depictions of these images (i.e...
2017: PloS One
https://www.readbyqxmd.com/read/28542609/potent-and-selective-inhibition-of-pathogenic-viruses-by-engineered-ubiquitin-variants
#17
Wei Zhang, Ben A Bailey-Elkin, Robert C M Knaap, Baldeep Khare, Tim J Dalebout, Garrett G Johnson, Puck B van Kasteren, Nigel J McLeish, Jun Gu, Wenguang He, Marjolein Kikkert, Brian L Mark, Sachdev S Sidhu
The recent Middle East respiratory syndrome coronavirus (MERS-CoV), Ebola and Zika virus outbreaks exemplify the continued threat of (re-)emerging viruses to human health, and our inability to rapidly develop effective therapeutic countermeasures. Many viruses, including MERS-CoV and the Crimean-Congo hemorrhagic fever virus (CCHFV) encode deubiquitinating (DUB) enzymes that are critical for viral replication and pathogenicity. They bind and remove ubiquitin (Ub) and interferon stimulated gene 15 (ISG15) from cellular proteins to suppress host antiviral innate immune responses...
May 18, 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/28542559/fluvastatin-inhibits-age-induced-cell-proliferation-and-migration-via-an-erk5-dependent-nrf2-pathway-in-vascular-smooth-muscle-cells
#18
Ae-Rang Hwang, Jung-Hwa Han, Jae Hyang Lim, Young Jin Kang, Chang-Hoon Woo
Advanced glycation endproduct (AGE)-induced vascular smooth muscle cell (VSMC) proliferation and reactive oxygen species (ROS) production are emerging as important mechanisms of diabetic vasculopathy, but little is known about the molecular mechanism responsible for the antioxidative effects of statins on AGEs. It has been reported that statins exert pleiotropic effects on the cardiovascular system due to decreases in AGE-induced cell proliferation, migration, and vascular inflammation. Thus, in the present study, the authors investigated the molecular mechanism by which statins decrease AGE-induced cell proliferation and VSMC migration...
2017: PloS One
https://www.readbyqxmd.com/read/28542523/impact-of-maintenance-immunosuppressive-therapy-on-the-fecal-microbiome-of-renal-transplant-recipients-comparison-between-an-everolimus-and-a-standard-tacrolimus-based-regimen
#19
Gianluigi Zaza, Alessandra Dalla Gassa, Giovanna Felis, Simona Granata, Sandra Torriani, Antonio Lupo
BACKGROUND: The gut microbiome is the full set of microbes living in the gastrointestinal tract and is emerging as an important dynamic/fluid system that, if altered by environmental, dietetic or pharmacological factors, could considerably influence drug response. However, the immunosuppressive drug-induced modifications of this system are still poorly defined. METHODS: We employed an innovative bioinformatics approach to assess differences in the whole-gut microbial metagenomic profile of 20 renal transplant recipients undergoing maintenance treatment with two different immunosuppressive protocols...
2017: PloS One
https://www.readbyqxmd.com/read/28542029/the-impact-of-the-sepsis-3-septic-shock-definition-on-previously-defined-septic-shock-patients
#20
Sarah A Sterling, Michael A Puskarich, Andrew F Glass, Faheem Guirgis, Alan E Jones
OBJECTIVE: The Third International Consensus Definitions Task Force (Sepsis-3) recently recommended changes to the definitions of sepsis. The impact of these changes remains unclear. Our objective was to determine the outcomes of patients meeting Sepsis-3 septic shock criteria versus patients meeting the "old" (1991) criteria of septic shock only. DESIGN: Secondary analysis of two clinical trials of early septic shock resuscitation. SETTING: Large academic emergency departments in the United States...
May 24, 2017: Critical Care Medicine
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