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https://www.readbyqxmd.com/read/29150838/gi-530159-a-novel-selective-mechano-sensitive-k2p-channel-opener-reduces-rat-dorsal-root-ganglion-drg-neuron-excitability
#1
Alexandre J C Loucif, Pierre-Philippe Saintot, Jia Liu, Brett M Antonio, Shannon G Zellmer, Katrina Yoger, Emma L Veale, Anna Wilbrey, Kiyoyuki Omoto, Lishuang Cao, Alex Gutteridge, Neil A Castle, Edward B Stevens, Alistair Mathie
BACKGROUND AND PURPOSE: TREK two pore domain potassium channels play a critical role in regulating the excitability of somatosensory nociceptive neurons and are important mediators of pain perception. An understanding of the roles of TREK channels in pain perception and, indeed, in other pathophysiological conditions, has been severely hampered by the lack of potent and/or selective activators and inhibitors. In this study we describe a new, selective opener of TREK channels, GI-530159 (4,4'-(Hexafluoroisopropylidene)bis(p-phenyleneoxy)dianiline)...
November 18, 2017: British Journal of Pharmacology
https://www.readbyqxmd.com/read/29150766/spinobot-an-mri-guided-needle-positioning-system-for-spinal-cellular-therapeutics
#2
Alexander Squires, John N Oshinski, Nicholas M Boulis, Zion Tsz Ho Tse
The neurodegenerative disease amyotrophic lateral sclerosis (ALS) results in the death of motor neurons in voluntary muscles. There are no cures for ALS and few available treatments. In studies with small animal models, injection of cellular therapeutics into the anterior horn of the spinal cord has been shown to inhibit the progression of ALS. It was hypothesized that spinal injection could be made faster and less invasive with the aid of a robot. The robotic system presented-SpinoBot-uses MRI guidance to position a needle for percutaneous injection into the spinal cord...
November 17, 2017: Annals of Biomedical Engineering
https://www.readbyqxmd.com/read/29150506/the-swinholide-biosynthetic-gene-cluster-from-a-terrestrial-cyanobacterium-nostoc-sp-uhcc-0450
#3
Anu Humisto, Jouni Jokela, Liwei Liu, Matti Wahlsten, Hao Wang, Perttu Permi, João Paulo Machado, Agostinho Antunes, David P Fewer, Kaarina Sivonen
Swinholides are 42-carbon ring polyketides with a twofold axis of symmetry. They are potent cytotoxins that disrupt the actin cytoskeleton. Swinholides were discovered from the marine sponge Theonella sp. and were long-suspected to be produced by symbiotic bacteria. Misakinolide, a structural variant of swinholide, was recently demonstrated to be the product of the symbiotic heterotrophic proteobacterium. Here we report the production of swinholide A by an axenic strain of the terrestrial cyanobacterium Nostoc sp...
November 17, 2017: Applied and Environmental Microbiology
https://www.readbyqxmd.com/read/29150474/core-outcome-sets-in-miscarriage-trials-cosmist-study-a-study-protocol
#4
Paul Smith, Natalie Cooper, Rima Dhillon-Smith, Emily O'Toole, T Justin Clark, Arri Coomarasamy
INTRODUCTION: 'Core outcome sets' are an agreed, standardised set of outcomes based on what key stakeholders (clinicians, patients, their partners, researchers, service developers, funding organisations and so on) consider the important outcomes in the management or prevention of a condition. This paper describes the rationale and design for the development of Core Outcome Sets for Miscarriage Trials. METHODS AND ANALYSIS: Systematic reviews, interviews and focus groups with patients and their partners will be conducted to identify potential core outcomes that will be introduced into a modified Delphi survey...
November 16, 2017: BMJ Open
https://www.readbyqxmd.com/read/29150306/a-proposal-for-a-noninvasive-monitoring-of-sympathetic-nerve-activity-in-patients-with-takotsubo-syndrome
#5
John E Madias
The pathophysiology of takotsubo syndrome (TTS) is still elusive; many hypotheses of its cause have been proposed with a heightened activity of the peripheral autonomic sympathetic nervous system (PASNS) via local norepinephrine release, and direct cardiomyocyte toxicity mediated by blood-borne catecholamines, being among the most currently entertained. Monitoring of PASNS during hospitalization will provide a metric which could be of immense value in unraveling of the pathophysiology and aiding in the management of the patients with TTS by predicting in-hospital complications, long-term outcome, and its recurrence...
November 2017: Medical Hypotheses
https://www.readbyqxmd.com/read/29150280/nk-cell-recruitment-and-exercise-potential-immunotherapeutic-role-of-shear-stress-and-endothelial-health
#6
William Evans
Positive cancer patient outcomes, including increased time to recurrent events, have been associated with increased counts and function of natural killer (NK) cells. NK cell counts and function are elevated following acute exercise, and the generally accepted mechanism of increased recruitment suggests that binding of epinephrine releases NK cells from endothelial tissue via decreases in adhesion molecules following. I propose that blood flow-induced shear stress may also play a role in NK cell recruitment from the endothelium...
November 2017: Medical Hypotheses
https://www.readbyqxmd.com/read/29150170/evaluating-the-content-and-development-of-decision-aid-tools-for-the-management-of-menopause-a-scoping-review
#7
REVIEW
Tasneem Siyam, Humirah Sultani, Sue Ross, Trish Chatterley, Nese Yuksel
OBJECTIVE: Decision-making during menopause (especially surgical menopause) can be complex given the variability in risk-benefit perceptions of menopausal treatments. Decision aid tools (DATs) help women participate in decision-making about options. Our objective is to identify and evaluate the content and development of DATs for managing menopause, with a special focus on surgical menopause. METHODS: We systematically searched electronic databases, including MEDLINE and EMBASE, from inception to March 2017 for relevant records...
December 2017: Maturitas
https://www.readbyqxmd.com/read/29150132/prosthodontic-rehabilitation-with-monolithic-multichromatic-cad-cam-complete-overdentures-in-an-adolescent-patient-with-ectodermal-dysplasia-a-clinical-report
#8
Hussain D Alsayed, Nasser M Alqahtani, Yasmin M Alzayer, Dean Morton, John A Levon, Nadim Z Baba
Ectodermal dysplasia is a rare, hereditary, congenital disease that affects the normal development of certain tissues and structures of ectodermal origin. The disease is manifested to different degrees of severity and may involve the nose, eyes, hair, nails, sweat glands, and enamel. This report describes a 14-year-old boy with ectodermal dysplasia, rehabilitated with monolithic, multichromatic maxillary and mandibular computer-aided design and computer-aided manufacturing (CAD-CAM) acrylic resin complete overdentures...
November 15, 2017: Journal of Prosthetic Dentistry
https://www.readbyqxmd.com/read/29150032/thoracic-surgery-in-patients-with-aids
#9
REVIEW
Doraid Jarrar, Grace Y Song
The picture of human immunodeficiency virus (HIV)-infected patients has changed dramatically since the original description in 1981. The introduction of antiretroviral drugs in 1987 and combination antiretroviral therapy has decreased mortality by as much as 80%. We now see patients in their 60s and 70s, having lived decades with HIV and living a normal live. As outlined in the article, despite good viral control, patients with HIV may present with solid organ cancers earlier than noninfected patients and are also prone to other complications of their disease that may require the attention of a thoracic surgeon...
February 2018: Thoracic Surgery Clinics
https://www.readbyqxmd.com/read/29150026/regulatory-t-cells-friends-or-foe-in-human-mycobacterium-leprae-infection
#10
Ana T Chaves, Atvaldo F Ribeiro-Junior, Sandra Lyon, Nayara I Medeiros, Fábio Cassirer-Costa, Karina S Paula, Edilamar S Alecrim, Cristiane A S Menezes, Rodrigo Correa-Oliveira, Manoel O C Rocha, Juliana A S Gomes
Regulatory T cells (Tregs) are known to control immune responses by suppressing the antigen-presenting and effector T cells. Some mechanisms adopted by Tregs in combating Mycobacterium infections have been proposed. Nevertheless, in M. leprae infection, also known as leprosy or Hansen's disease, the role of Tregs has not been completely elucidated. Using multicolor flow cytometry, we evaluated the expression of different cell surface and intracellular molecules present in Tregs from peripheral blood samples of leprosy patients...
November 13, 2017: Immunobiology
https://www.readbyqxmd.com/read/29149935/biomarkers-in-sepsis
#11
REVIEW
Tjitske S R van Engelen, Willem Joost Wiersinga, Brendon P Scicluna, Tom van der Poll
A biomarker is a characteristic by which a (patho)physiologic process can be identified. Biomarkers can be of diagnostic value (to discriminate infection from noninfectious conditions or to determine the causative pathogen), of prognostic value (assigning risk profiles and predict outcome), and in the future may be of theranostic value (aid in selection and monitoring of therapy). Systems biology provides a promising tool for the discovery of novel biomarkers. Biomarkers can be the key to personalized targeted treatment in the future clinical management of sepsis...
January 2018: Critical Care Clinics
https://www.readbyqxmd.com/read/29149934/common-sense-approach-to-managing-sepsis
#12
REVIEW
Anders Perner, Lars B Holst, Nicolai Haase, Peter B Hjortrup, Morten H Møller
Sepsis results in many deaths, prolonged suffering among survivors and relatives, and high use of resources both in developed and developing countries. The updated Surviving Sepsis Campaign guidelines should aid clinicians in improving the identification and management of these patients, but many uncertainties remain because most of the guidance is based on low-quality evidence. This article discusses how to use some of the specific items of the guidelines together with a common-sense approach to aid clinical management of patients with sepsis while trying to balance the potential benefit and harm of the items...
January 2018: Critical Care Clinics
https://www.readbyqxmd.com/read/29149914/testing-the-effectiveness-of-a-motivational-interviewing-based-brief-intervention-for-substance-use-as-an-adjunct-to-usual-care-in-community-based-aids-service-organizations-study-protocol-for-a-multisite-randomized-controlled-trial
#13
Bryan R Garner, Heather J Gotham, Stephen J Tueller, Elizabeth L Ball, David Kaiser, Patricia Stilen, Kathryn Speck, Denna Vandersloot, Traci R Rieckmann, Michael Chaple, Erika G Martin, Steve Martino
BACKGROUND: In 2010, the first comprehensive National HIV/AIDS Strategy for the United States was released and included three goals: (1) reducing the number of people who become infected with HIV, (2) increasing access to care and improving health outcomes for people living with HIV, and (3) reducing HIV-related health disparities and health inequities. In 2013, as part of its effort to help address the National HIV/AIDS Strategy, the National Institute on Drug Abuse (NIDA) funded a type 2 effectiveness-implementation hybrid trial titled the Substance Abuse Treatment to HIV Care (SAT2HIV) Project...
November 17, 2017: Addiction Science & Clinical Practice
https://www.readbyqxmd.com/read/29149909/testing-the-implementation-and-sustainment-facilitation-isf-strategy-as-an-effective-adjunct-to-the-addiction-technology-transfer-center-attc-strategy-study-protocol-for-a-cluster-randomized-trial
#14
Bryan R Garner, Mark Zehner, Mathew R Roosa, Steve Martino, Heather J Gotham, Elizabeth L Ball, Patricia Stilen, Kathryn Speck, Denna Vandersloot, Traci R Rieckmann, Michael Chaple, Erika G Martin, David Kaiser, James H Ford
BACKGROUND: Improving the extent to which evidence-based practices (EBPs)-treatments that have been empirically shown to be efficacious or effective-are integrated within routine practice is a well-documented challenge across numerous areas of health. In 2014, the National Institute on Drug Abuse funded a type 2 effectiveness-implementation hybrid trial titled the substance abuse treatment to HIV Care (SAT2HIV) Project. Aim 1 of the SAT2HIV Project tests the effectiveness of a motivational interviewing-based brief intervention (MIBI) for substance use as an adjunct to usual care within AIDS service organizations (ASOs) as part of its MIBI Experiment...
November 17, 2017: Addiction Science & Clinical Practice
https://www.readbyqxmd.com/read/29149746/habitat-mosaics-and-path-analysis-can-improve-biological-conservation-of-aquatic-biodiversity-in-ecosystems-with-low-head-dams
#15
Sean M Hitchman, Martha E Mather, Joseph M Smith, Jane S Fencl
Conserving native biodiversity depends on restoring functional habitats in the face of human-induced disturbances. Low-head dams are a ubiquitous human impact that degrades aquatic ecosystems worldwide. To improve our understanding of how low-head dams impact habitat and associated biodiversity, our research examined complex interactions among three spheres of the total environment. i.e., how low-head dams (anthroposphere) affect aquatic habitat (hydrosphere), and native biodiversity (biosphere) in streams and rivers...
November 14, 2017: Science of the Total Environment
https://www.readbyqxmd.com/read/29149726/protein-structure-based-drug-design-from-docking-to-molecular-dynamics
#16
REVIEW
Paweł Śledź, Amedeo Caflisch
Recent years have witnessed rapid developments of computer-aided drug design methods, which have reached accuracy that allows their routine practical applications in drug discovery campaigns. Protein structure-based methods are useful for the prediction of binding modes of small molecules and their relative affinity. The high-throughput docking of up to 10(6) small molecules followed by scoring based on implicit-solvent force field can robustly identify micromolar binders using a rigid protein target. Molecular dynamics with explicit solvent is a low-throughput technique for the characterization of flexible binding sites and accurate evaluation of binding pathways, kinetics, and thermodynamics...
November 14, 2017: Current Opinion in Structural Biology
https://www.readbyqxmd.com/read/29149505/an-international-continence-society-ics-report-on-the-terminology-for-adult-neurogenic-lower-urinary-tract-dysfunction-anlutd
#17
Jerzy B Gajewski, Brigitte Schurch, Rizwan Hamid, Márcio Averbeck, Ryuji Sakakibara, Enrico F Agrò, Tamara Dickinson, Christopher K Payne, Marcus J Drake, Bernie T Haylen
INTRODUCTION: The terminology for adult neurogenic lower urinary tract dysfunction (ANLUTD) should be defined and organized in a clinically based consensus Report. METHODS: This Report has been created by a Working Group under the auspices and guidelines of the International Continence Society (ICS) Standardization Steering Committee (SSC) assisted at intervals by external referees. All relevant definitions for ANLUTD were updated on the basis of research over the last 14 years...
November 17, 2017: Neurourology and Urodynamics
https://www.readbyqxmd.com/read/29149393/challenges-in-minor-tbi-and-indications-for-head-ct-in-pediatric-tbi-an-update
#18
Navneet Singh, Ash Singhal
INTRODUCTION: Pediatric head trauma is one of the commonest presentations to emergency departments. Over 90% of such head injuries are considered mild, but still present risk acute clinical deterioration and longer term morbidity. Identifying which children are at risk of clinically important brain injuries remains challenging and much of the data on minor head injuries is based on the adult population. CHALLENGES IN PEDIATRICS: Children, however, are different, both anatomically and in terms of mechanism of injury, to adults and, even within the pediatric group, there are differences with age and stage of development...
October 2017: Child's Nervous System: ChNS: Official Journal of the International Society for Pediatric Neurosurgery
https://www.readbyqxmd.com/read/29149383/diffusion-mri-in-pediatric-brain-injury
#19
Emily L Dennis, Talin Babikian, Christopher C Giza, Paul M Thompson, Robert F Asarnow
Traumatic brain injury (TBI) is a major public health issue around the world and can be especially devastating in children as TBI can derail cognitive and social development. White matter (WM) is particularly vulnerable to disruption post-TBI, as myelination is ongoing during this period. Diffusion magnetic resonance imaging (dMRI) is a versatile modality for identifying and quantifying WM disruption and can detect diffuse axonal injury (DAI or TAI (traumatic axonal injury)). This review covers dMRI studies of pediatric TBI, including mild to severe injuries, and covering all periods post-injury...
October 2017: Child's Nervous System: ChNS: Official Journal of the International Society for Pediatric Neurosurgery
https://www.readbyqxmd.com/read/29149350/a-data-fusion-pipeline-for-generating-and-enriching-adverse-outcome-pathway-descriptions
#20
Penny Nymark, Linda Rieswijk, Friederike Ehrhart, Nina Jeliazkova, Georgia Tsiliki, Haralambos Sarimveis, Chris T Evelo, Vesa Hongisto, Pekka Kohonen, Egon Willighagen, Roland C Grafström
Increasing amounts of systems toxicology data, including omics results, are becoming publically available and accessible in databases. Data-driven and informatics-tool supported pipeline schemas for fitting such data into Adverse Outcome Pathway (AOP) descriptions could potentially aid the development of non-animal based hazard and risk assessment methods. We devised a six-step workflow that integrated diverse types of toxicology data into a novel AOP scheme for pulmonary fibrosis. Mining of literature references and diverse data sources covering previous pathway descriptions and molecular results were coupled in a stepwise manner with informatics tools applications that enabled gene linkage and pathway identification in molecular interaction maps...
November 15, 2017: Toxicological Sciences: An Official Journal of the Society of Toxicology
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