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Paul W Denny
The rise of antimicrobial resistance, coupled with a lack of industrial focus on antimicrobial discovery over preceding decades, has brought the world to a crisis point. With both human and animal health set to decline due to increased disease burdens caused by near untreatable microbial pathogens, there is an urgent need to identify new antimicrobials. Central to this is the elucidation of new, robustly validated, drug targets. Informed by industrial practice and concerns, the use of both biological and chemical tools in validation is key...
November 16, 2017: Parasitology
Amedee Renand, Mohamed H Shamji, Kristina M Harris, Tielin Qin, Erik Wambre, Guy W Scadding, Peter A Wurtzen, Stephen J Till, Alkis Togias, Gerald T Nepom, William W Kwok, Stephen R Durham
BACKGROUND: Three years treatment with either sublingual or subcutaneous allergen immunotherapy has been shown to be effective and to induce long-term tolerance. The GRASS(∗) trial demonstrated that two years treatment via either route was effective in suppressing the response to nasal allergen challenge, although was insufficient for inhibition one year after discontinuation. OBJECTIVE: To examine in the GRASS trial the time-course of immunologic changes during two years sublingual and subcutaneous immunotherapy and for one year after treatment discontinuation...
November 8, 2017: Journal of Allergy and Clinical Immunology
Lauren M Abbate, Amy S Jeffreys, Cynthia J Coffman, Todd A Schwartz, Liubov Arbeeva, Leigh F Callahan, Nicole A Negbenebor, Wendy M Kohrt, Robert S Schwartz, Ernest Vina, Kelli D Allen
OBJECTIVE: To identify patient demographic and clinical characteristics associated with osteoarthritis (OA) treatment use. METHODS: This was a secondary data analysis of three clinical trials among patients with hip or knee OA conducted in 1) Duke Primary Care practices, 2) the Durham Veterans Affairs Health Care System (DVAHCS), and 3) the University of North Carolina-Chapel Hill (UNC). At baseline, participants reported socio-demographic characteristics, OA-related pain and function, and OA treatment use including oral analgesia, topical creams, joint injections and physical therapy...
November 10, 2017: Arthritis Care & Research
Christy Hanson, Mike Osberg, Jessie Brown, George Durham, Daniel P Chin
Background: Despite significant progress in diagnosis and treatment of tuberculosis over the past 2 decades, millions of patients with tuberculosis go unreported every year. The patient-pathway analysis (PPA) is designed to assess the alignment between tuberculosis care-seeking patterns and the availability of tuberculosis services. The PPA can help programs understand where they might find the missing patients with tuberculosis. Methods: This analysis aggregates and compares the PPAs from case studies in Kenya, Ethiopia, Indonesia, the Philippines, and Pakistan...
November 6, 2017: Journal of Infectious Diseases
Christy L Hanson, Mike Osberg, Jessie Brown, George Durham, Daniel P Chin
Patient-centered care is a central pillar of the World Health Organization's End TB Strategy. Understanding where patients access health services is a first step to planning for the placement of services to meet patient needs and preferences. The patient-pathway analysis (PPA) methodology detailed in this article was developed to better understand the alignment between patient care seeking and tuberculosis service availability. A PPA describes the steps that people with tuberculosis take from the initial care visit to cure...
November 6, 2017: Journal of Infectious Diseases
Mohamed H Shamji, Jeff N Temblay, Wei Cheng, Susan M Byrne, Ellen Macfarlane, Amy R Switzer, Natalia D C Francisco, Fedina Olexandra, Fabian Jacubczik, Stephen R Durham, Philip G Ashton-Rickardt
BACKGROUND: The mechanisms regulating the maintenance of persistent Th2 cells that potentiate allergic inflammation are not well understood. OBJECTIVE: The function of Serine Protease Inhibitor 2A (Spi2A) was studied in mouse Th2 cells and Serine Protease Inhibitor (SERPIN) B3 and B4 genes were studied in Th2 cells from grass pollen allergic individuals. METHODS: Spi2A deficient Th2 cells were studied in vitro culture or in vivo after challenge of Spi2A Knock-Out (KO) mice with ovalbumin in alum...
October 26, 2017: Journal of Allergy and Clinical Immunology
Kevin R Fales, F George Njoroge, Harold B Brooks, Stefan Thibodeaux, Alicia Torrado, Chong Si, James L Toth, Jefferson R Mc Cowan, Kenneth D Roth, Kenneth Jeff Thrasher, Kwame Frimpong, Matthew R Lee, Robert D Dally, Timothy A Shepherd, Timothy Barrett Durham, Brandon J Margolis, Zhipei Wu, Yong Wang, Shane Atwell, Jing Wang, Yu-Hua Hui, Timothy I Meier, Susan A Konicek, Sandaruwan Geeganage
A hallmark of cancer is unbridled proliferation that can result in increased demand for de novo synthesis of purine and pyrimidine bases required for DNA and RNA biosynthesis. These synthetic pathways are frequently upregulated in cancer and involve various folate-dependent enzymes. Anti-folates have a proven record as clinically used oncolytic agents. Our recent research efforts have produced LSN 3213128 (compound 28a), a novel, selective, non-classical, orally-bioavailable anti-folate with potent and specific inhibitory activity for aminoimidazole-4-carboxamide ribonucleotide formyltransferase (AICARFT), an enzyme in the purine biosynthetic pathway...
October 26, 2017: Journal of Medicinal Chemistry
Sara Koo, Bidour Awadelkarim, Anjan Dhar
INTRODUCTION: Oesophageal and gastric cancer is common. Despite advances in investigation and treatment, the outcomes from these cancers remain poor. As part of the Be Clear On Cancer Campaign, the Department of Health runs the National Oesophagogastric Cancer Campaign each year, with key messages of (1) 'Having heartburn most days, for 3 weeks or more could be a sign of cancer' and (2) 'if food is sticking when you swallow, tell your doctor'. METHODS: We evaluated the effect of the National Oesophagogastric Cancer Campaign in our locality...
October 2017: Frontline Gastroenterology
Ann M Carracher, Payal H Marathe, Kelly L Close
More than 15,000 attendees from more than130 countries gathered in Lisbon, Portugal for the 2017 European Association for the Study of Diabetes annual meeting. Dr Adrian Hernandez (Duke University, Durham, NC, USA) presented outcomes data from AstraZeneca's (Cambridge, UK) cardiovascular outcomes trial of GLP-1 agonist Bydureon (exenatide once weekly), Exenatide Study of Cardiovascular Event Lowering Trial (EXSCEL).(1).
October 20, 2017: Journal of Diabetes
Anne Z Steiner, David Pritchard, Frank Z Stanczyk, James S Kesner, Juliana W Meadows, Amy H Herring, Donna D Baird
Importance: Despite lack of evidence of their utility, biomarkers of ovarian reserve are being promoted as potential markers of reproductive potential. Objective: To determine the associations between biomarkers of ovarian reserve and reproductive potential among women of late reproductive age. Design, Setting, and Participants: Prospective time-to-pregnancy cohort study (2008 to date of last follow-up in March 2016) of women (N = 981) aged 30 to 44 years without a history of infertility who had been trying to conceive for 3 months or less, recruited from the community in the Raleigh-Durham, North Carolina, area...
October 10, 2017: JAMA: the Journal of the American Medical Association
Marianne L Durham, AnnMarie Egan, Ann Jankiewicz, Marcia P Murphy, Patricia Nedved, Renee Luvich, Ann Goh, Louis Fogg
OBJECTIVE: The aims of the project are to increase knowledge related to opioids and improve adherence to evidence-based interventions for sedation monitoring and assessment in adult inpatients receiving opioids for pain through delivery of an interprofessional online program. BACKGROUND: Preventable opioid-induced respiratory depression is a patient safety risk in hospitals. Sedation and respiratory assessment and monitoring guidelines and tools are available to improve practice...
November 2017: Journal of Nursing Administration
Mohamed H Shamji, Jan Ceuppens, Claus Bachert, Peter Hellings, Gaël Placier, Gaëtan Thirion, Nicolas Bovy, Stephen R Durham, Jean Duchateau, Thierry Legon, Sabine Pirotton
No abstract text is available yet for this article.
October 10, 2017: Journal of Allergy and Clinical Immunology
T Renton, J Durham, C M Hill
The maxillary sinus is the largest of the four paranasal sinuses and, being anatomically adjacent to the dentate region of the maxilla, is commonly a source of problems - not simply in terms of conditions affecting the sinus but also in establishing an accurate diagnosis. As anyone who has suffered both sinusitis and a dental abscess in the posterior maxilla will tell you, the symptoms are almost indistinguishable. For this reason, a sound understanding of the maxillary sinus is an essential requisite for all dentists...
October 13, 2017: British Dental Journal
Edmond J Walsh, Alexander Feuerborn, James H R Wheeler, Ann Na Tan, William M Durham, Kevin R Foster, Peter R Cook
Microfluidics has great potential, but the complexity of fabricating and operating devices has limited its use. Here we describe a method - Freestyle Fluidics - that overcomes many key limitations. In this method, liquids are confined by fluid (not solid) walls. Aqueous circuits with any 2D shape are printed in seconds on plastic or glass Petri dishes; then, interfacial forces pin liquids to substrates, and overlaying an immiscible liquid prevents evaporation. Confining fluid walls are pliant and resilient; they self-heal when liquids are pipetted through them...
October 10, 2017: Nature Communications
John D DeLamater, Kevin P Weinfurt, Kathryn E Flynn
BACKGROUND: Measurement of sexual function typically uses self-report, which, to work as intended, must use language that is understood consistently by diverse respondents. Commonly used measures employ multiple terms, primarily (sexual) interest, desire, and arousal, that might not be understood in the same way by laypeople and professionals. AIM: To inform self-reported measurement efforts for research and clinical settings by examining how US men and women recruited from a health care setting understand and interpret different terms...
November 2017: Journal of Sexual Medicine
Ty B Palmer, Jose G Pineda, Rachel M Durham
This study aimed to examine the effects of knee position on the reliability and production of peak force (PF) and rate of force (RFD) development characteristics during an isometric squat. Fourteen resistance-trained females performed isometric squats at 90, 120, and 150° knee angles (corresponding to parallel, half, and quarter squat positions, respectively) on two different occasions, from which PF, peak RFD, and early (RFD30,RFD50,RFD100) and late (RFD200) phase RFD variables were extracted. PF and RFD200 were highly consistent across trials for all three squat positions, with intraclass correlation coefficients (ICCs) ranging between 0...
October 10, 2017: Journal of Applied Biomechanics
Adam Powell
Durham University's 'Hearing the Voice' project involves a multi-disciplinary exploration of hallucinatory-type phenomena in an attempt to revaluate and reframe discussions of these experiences. As part of this project, contemporaneous religious experiences (supernatural voices and visions) in the United States from the first half of the nineteenth century have been analysed, shedding light on the value and applicability of contemporary bio-cultural models of religious experience for such historical cases. In particular, this essay outlines four historical cases, seeking to utilise and to refine four theoretical models, including anthropologist Tanya Luhrmann's 'absorption hypothesis', by returning to something like William James' concern with 'discordant personalities'...
2017: J Study Relig Exp
Kristina Durham, Kevin Chathely, Kei Cheng Mak, Abdul Momen, Cyrus T Thomas, Yuan-Yuan Zhao, Melissa E MacDonald, Jonathan M Curtis, Mansoor Husain, Bernardo L Trigatti
Doxorubicin is a widely used chemotherapeutic with deleterious cardiotoxic side effects. HDL has been shown to protect cardiomyocytes in vitro against doxorubicin-induced apoptosis. The scavenger receptor class B type I (SR-B1), a high affinity HDL receptor, mediates cytoprotective signaling by HDL through AKT. Here we assess whether increased HDL levels protects against doxorubicin-induced cardiotoxicity in vivo, and in cardiomyocytes in culture, and explore the intracellular signaling mechanisms involved, in particular the role of SR-B1...
October 6, 2017: American Journal of Physiology. Heart and Circulatory Physiology
Michael Tibshirani, Beibei Zhao, Benoit J Gentil, Sandra Minotti, Christine Marques, Julia Keith, Ekaterina Rogaeva, Lorne Zinman, Caroline Rouaux, Janice Robertson, Heather D Durham
Amyotrophic lateral sclerosis is a fatal neurodegenerative disease with paralysis resulting from dysfunction and loss of motor neurons. A common neuropathological finding is attrition of motor neuron dendrites, which make central connections vital to motor control. The chromatin remodelling complex, neuronal Brahma-related gene 1 (Brg1)-associated factor complex (nBAF), is critical for neuronal differentiation, dendritic extension and synaptic function. We have identified loss of the crucial nBAF subunits Brg1, Brg1-associated factor 53b and calcium responsive transactivator in cultured motor neurons expressing FUS or TAR-DNA Binding Protein 43 (TDP-43) mutants linked to familial ALS...
November 1, 2017: Human Molecular Genetics
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