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https://www.readbyqxmd.com/read/29665687/identification-of-fast-acting-2-6-disubstituted-imidazopyridines-that-are-efficacious-in-the-in-vivo-humanized-plasmodium-falciparum-nodscidil2r%C3%AE-null-mouse-model-of-malaria
#1
Aloysius T Nchinda, Claire Le Manach, Tanya Paquet, Diego Gonzalez Cabrera, Kathryn J Wicht, Christel Brunschwig, Mathew Njoroge, Efrem Abay, Dale Taylor, Nina Lawrence, Sergio Wittlin, Maria-Belen Jimenez-Diaz, Maria Santos Martínez-Martínez, Santiago Ferrer, Iñigo Angulo-Barturen, Maria Jose Lafuente-Monasterio, James Duffy, Jeremy N Burrows, Leslie J Street, Kelly Chibale
Optimization of a chemical series originating from whole-cell phenotypic screening against the human malaria parasite, Plasmodium falciparum, led to the identification of two promising 2,6-disubstituted imidazopyridine compounds, 43 and 74. These compounds exhibited potent activity against asexual blood stage parasites that, together with their in vitro Absorption, Distribution, Metabolism, and Excretion (ADME) properties, translated to in vivo efficacy with clearance of parasites in the PfSCID mouse model for malaria within 48 h of treatment...
April 17, 2018: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/29662168/genome-wide-association-meta-analysis-of-individuals-of-european-ancestry-identifies-new-loci-explaining-a-substantial-fraction-of-hair-color-variation-and-heritability
#2
Pirro G Hysi, Ana M Valdes, Fan Liu, Nicholas A Furlotte, David M Evans, Veronique Bataille, Alessia Visconti, Gibran Hemani, George McMahon, Susan M Ring, George Davey Smith, David L Duffy, Gu Zhu, Scott D Gordon, Sarah E Medland, Bochao D Lin, Gonneke Willemsen, Jouke Jan Hottenga, Dragana Vuckovic, Giorgia Girotto, Ilaria Gandin, Cinzia Sala, Maria Pina Concas, Marco Brumat, Paolo Gasparini, Daniela Toniolo, Massimiliano Cocca, Antonietta Robino, Seyhan Yazar, Alex W Hewitt, Yan Chen, Changqing Zeng, Andre G Uitterlinden, M Arfan Ikram, Merel A Hamer, Cornelia M van Duijn, Tamar Nijsten, David A Mackey, Mario Falchi, Dorret I Boomsma, Nicholas G Martin, David A Hinds, Manfred Kayser, Timothy D Spector
Hair color is one of the most recognizable visual traits in European populations and is under strong genetic control. Here we report the results of a genome-wide association study meta-analysis of almost 300,000 participants of European descent. We identified 123 autosomal and one X-chromosome loci significantly associated with hair color; all but 13 are novel. Collectively, single-nucleotide polymorphisms associated with hair color within these loci explain 34.6% of red hair, 24.8% of blond hair, and 26.1% of black hair heritability in the study populations...
April 16, 2018: Nature Genetics
https://www.readbyqxmd.com/read/29660440/the-long-term-effect-of-maternal-dietary-protein-restriction-on-5-ht-1a-receptor-function-and-behavioral-responses-to-stress-in-adulthood
#3
Wenrui Ye, Michael Duffy Pitlock, Martin A Javors, Brent Thompson, James D Lechleiter, Julie G Hensler
Maternal nutrition impacts fetal development, and may play a role in determining resilience to stress and vulnerability to stress-precipitated psychiatric disorders, such as anxiety and depression. In this study, we examined the effect of a reduction in maternal dietary protein during pregnancy on the brain neurochemistry and behavior of offspring. We focused specifically on the serotonin system, the 5-HT1A receptor and the responsivity of offspring as adults to stress. Dams were fed either a low protein diet (10% protein by weight) or isocaloric control diet (20% protein by weight)...
April 13, 2018: Behavioural Brain Research
https://www.readbyqxmd.com/read/29659910/household-transmission-of-ebola-virus-risks-and-preventive-factors-freetown-sierra-leone-2015
#4
Mary R Reichler, James Bangura, Dana Bruden, Charles Keimbe, Nadia Duffy, Harold Thomas, Barbara Knust, Ishmail Farmar, Erin Nichols, Amara Jambai, Oliver Morgan, Thomas Hennessy
BACKGROUND: Knowing risk factors for household transmission of Ebola virus is important to guide preventive measures during Ebola outbreaks. METHODS: We enrolled all confirmed persons with Ebola who were the first case in a household from December 2014-April 2015 in Freetown, Sierra Leone, and their household contacts. Cases and contacts were interviewed, contacts followed prospectively through the 21-day incubation period, and secondary cases confirmed by laboratory testing...
April 6, 2018: Journal of Infectious Diseases
https://www.readbyqxmd.com/read/29653033/organometallic-conjugates-of-the-drug-sulfadoxine-for-combatting-antimicrobial-resistance
#5
Peter J Sadler, Prinessa Chellan, Vicky Avery, Sandra Duffy, James Triccas, Gayathri Nagalingam, Christina Tam, Luisa Cheng, Jenny Liu, Kirkwood Land, Guy Clarkson, Isolda Romero
Fourteen novel arene RuII, and cyclopentadienyl (Cpx) RhIII and IrIII complexes containing an N,N'-chelated pyridylimino- or quinolylimino ligand functionalized with the antimalarial drug sulfadoxine have been synthesized and characterized, including three by x-ray crystallography. Rhodium and iridium complexes exhibited potent antiplasmodial activity with IC50 values of 0.10 - 2.0 µM in either all, or one of the three Plasmodium falciparum assays (3D7 chloroquine sensitive, Dd2 chloroquine resistant and NF54 sexual late stage gametocytes), but were only moderately active towards Trichomonas vaginalis...
April 13, 2018: Chemistry: a European Journal
https://www.readbyqxmd.com/read/29648638/ovulatory-induction-of-scg2-in-human-non-human-primate-and-rodent-granulosa-cells-stimulates-ovarian-angiogenesis
#6
Patrick R Hannon, Diane M Duffy, Katherine L Rosewell, Mats Brännström, James W Akin, Thomas E Curry
The luteinizing hormone (LH) surge is essential for ovulation, but the intrafollicular factors induced by LH that mediate ovulatory processes (e.g. angiogenesis) are poorly understood, especially in women. The role of secretogranin II (SCG2) and its cleaved bioactive peptide, secretoneurin (SN), were investigated as potential novel mediators of ovulation by testing the hypothesis that SCG2/SN is induced in granulosa cells by human chorionic gonadotropin (hCG), via a downstream LH receptor signaling mechanism, and stimulates ovarian angiogenesis...
April 10, 2018: Endocrinology
https://www.readbyqxmd.com/read/29627798/health-status-variation-across-practices-in-outpatients-with-heart-failure-insights-from-the-champ-hf-change-the-management-of-patients-with-heart-failure-registry
#7
Yevgeniy Khariton, Adrian F Hernandez, Gregg C Fonarow, Puza P Sharma, Carol I Duffy, Laine Thomas, Xiaojuan Mi, Nancy M Albert, Javed Butler, Kevin McCague, Michael E Nassif, Fredonia B Williams, Adam DeVore, J Herbert Patterson, John A Spertus
BACKGROUND: Although a key treatment goal for patients with heart failure with reduced ejection fraction is to optimize their health status (their symptoms, function, and quality of life), the variability across outpatient practices in achieving this goal is unknown. METHODS AND RESULTS: In the CHAMP-HF (Change the Management of Patients With Heart Failure) registry, associations between baseline practice characteristics and Kansas City Cardiomyopathy Questionnaire (KCCQ) Overall Summary (OS) and Symptom Frequency (SF) scores were assessed in 3494 patients across 140 US practices using hierarchical regression after accounting for 23 patient and 11 treatment characteristics...
April 2018: Circulation. Cardiovascular Quality and Outcomes
https://www.readbyqxmd.com/read/29626579/naturally-complex-perspectives-and-challenges-associated-with-botanical-dietary-supplement-safety-assessment
#8
REVIEW
Kelly A Shipkowski, Joseph M Betz, Linda S Birnbaum, John R Bucher, Paul M Coates, D Craig Hopp, Duffy MacKay, Hellen Oketch-Rabah, Nigel J Walker, Cara Welch, Cynthia V Rider
No abstract text is available yet for this article.
April 4, 2018: Food and Chemical Toxicology
https://www.readbyqxmd.com/read/29625249/accurate-typing-of-human-leukocyte-antigen-class-i-genes-by-oxford-nanopore-sequencing
#9
Chang Liu, Fangzhou Xiao, Jessica Hoisington-Lopez, Kathrin Lang, Philipp Quenzel, Brian Duffy, Robi David Mitra
Oxford Nanopore Technologies' MinION has expanded the current DNA sequencing toolkit by delivering long read lengths and extreme portability. The MinION has the potential to enable expedited point-of-care human leukocyte antigen (HLA) typing, an assay routinely used to assess the immunological compatibility between organ donors and recipients, but the platform's high error rate makes it challenging to type alleles with accuracy. Here, we developed and validated accurate typing of HLA by Oxford nanopore (Athlon), a bioinformatic pipeline that i) maps nanopore reads to a database of known HLA alleles, ii) identifies candidate alleles with the highest read coverage at different resolution levels that are represented as branching nodes and leaves of a tree structure, iii) generates consensus sequences by remapping the reads to the candidate alleles, and iv) calls the final diploid genotype by blasting consensus sequences against the reference database...
April 3, 2018: Journal of Molecular Diagnostics: JMD
https://www.readbyqxmd.com/read/29625089/a-possible-molecular-basis-for-photoprotection-in-the-minor-antenna-proteins-of-plants
#10
Kieran F Fox, Caner Ünlü, Vytautas Balevičius, Baboo Narottamsing Ramdour, Carina Kern, Xiaowei Pan, Mei Li, Herbert van Amerongen, Christopher D P Duffy
The bioenergetics of light-harvesting by photosynthetic antenna proteins in higher plants is well understood. However, investigation into the regulatory non-photochemical quenching (NPQ) mechanism, which dissipates excess energy in high light, has led to several conflicting models. It is generally accepted that the major photosystem II antenna protein, LHCII, is the site of NPQ, although the minor antenna complexes (CP24/26/29) are also proposed as alternative/additional NPQ sites. LHCII crystals were shown to exhibit the short excitation lifetime and several spectral signatures of the quenched state...
April 3, 2018: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/29624071/four-gene-pan-african-blood-signature-predicts-progression-to-tuberculosis
#11
Sara Suliman, Ethan Thompson, Jayne Sutherland, January Weiner Rd, Martin O C Ota, Smitha Shankar, Adam Penn-Nicholson, Bonnie Thiel, Mzwandile Erasmus, Jeroen Maertzdorf, Fergal J Duffy, Philip C Hill, E Jane Hughes, Kim Stanley, Katrina Downing, Michelle L Fisher, Joe Valvo, Shreemanta K Parida, Gian van der Spuy, Gerard Tromp, Ifedayo M O Adetifa, Simon Donkor, Rawleigh Howe, Harriet Mayanja-Kizza, W Henry Boom, Hazel Dockrell, Tom H M Ottenhoff, Mark Hatherill, Alan Aderem, Willem A Hanekom, Thomas J Scriba, Stefan He Kaufmann, Daniel E Zak, Gerhard Walzl
RATIONALE: Contacts of tuberculosis (TB) patients constitute an important target population for preventative measures as they are at high risk of infection with Mycobacterium tuberculosis and progression to disease. OBJECTIVES: We investigated biosignatures with predictive ability for incident tuberculosis. METHODS: In a case-control study nested within the Grand Challenges 6-74 longitudinal HIV-negative African cohort of exposed household contacts, we employed RNA sequencing, polymerase chain reaction (PCR) and the Pair Ratio algorithm in a training/test set approach...
April 6, 2018: American Journal of Respiratory and Critical Care Medicine
https://www.readbyqxmd.com/read/29623683/essential-ocean-variables-for-global-sustained-observations-of-biodiversity-and-ecosystem-changes
#12
Patricia Miloslavich, Nicholas J Bax, Samantha E Simmons, Eduardo Klein, Ward Appeltans, Octavio Aburto-Oropeza, Melissa Andersen Garcia, Sonia D Batten, Lisandro Benedetti-Cecchi, David M Checkley, Sanae Chiba, J Emmett Duffy, Daniel C Dunn, Albert Fischer, John Gunn, Raphael Kudela, Francis Marsac, Frank E Muller-Karger, David Obura, Yunne-Jai Shin
Sustained observations of marine biodiversity and ecosystems focused on specific conservation and management problems are needed around the world to effectively mitigate or manage changes resulting from anthropogenic pressures. These observations, while complex and expensive, are required by the international scientific, governance and policy communities to provide baselines against which the effects of human pressures and climate change may be measured and reported, and resources allocated to implement solutions...
April 5, 2018: Global Change Biology
https://www.readbyqxmd.com/read/29621893/facilitating-home-hospice-transitions-of-care-in-oncology-evaluation-of-clinical-pharmacists-interventions-hospice-program-satisfaction-and-patient-representation-rates
#13
Alison P Duffy, Nina M Bemben, Jueli Li, James Trovato
BACKGROUND: The importance of medication reconciliation and the pharmacist's role within the interdisciplinary team at the point of transition to home hospice is understudied. A transitions of care pilot initiative was developed to streamline the transition for patients at end of life from inpatient cancer center care to home hospice. The initiative consisted of using a hospice discharge checklist, pharmacist-led discharge medication reconciliation in consultation with the primary team responsible for inpatient care, review of discharge prescriptions, and facilitation of bedside delivery of discharge medications...
January 1, 2018: American Journal of Hospice & Palliative Care
https://www.readbyqxmd.com/read/29615488/development-and-clinical-validation-of-the-genedrive-point-of-care-test-for-qualitative-detection-of-hepatitis-c-virus
#14
Alba Llibre, Yusuke Shimakawa, Estelle Mottez, Shaun Ainsworth, Tan-Phuc Buivan, Rick Firth, Elliott Harrison, Arielle R Rosenberg, Jean-François Meritet, Arnaud Fontanet, Pablo Castan, Antonio Madejón, Mark Laverick, Allison Glass, Raquel Viana, Stanislas Pol, C Patrick McClure, William Lucien Irving, Gino Miele, Matthew L Albert, Darragh Duffy
OBJECTIVE: Recently approved direct acting antivirals provide transformative therapies for chronic hepatitis C virus (HCV) infection. The major clinical challenge remains to identify the undiagnosed patients worldwide, many of whom live in low-income and middle-income countries, where access to nucleic acid testing remains limited. The aim of this study was to develop and validate a point-of-care (PoC) assay for the qualitative detection of HCV RNA. DESIGN: We developed a PoC assay for the qualitative detection of HCV RNA on the PCR Genedrive instrument...
April 3, 2018: Gut
https://www.readbyqxmd.com/read/29614676/regional-distribution-asymmetry-and-clinical-correlates-of-tau-uptake-on-18f-av-1451-pet-in-atypical-alzheimer-s-disease
#15
Katerina A Tetzloff, Jonathan Graff-Radford, Peter R Martin, Nirubol Tosakulwong, Mary M Machulda, Joseph R Duffy, Heather M Clark, Matthew L Senjem, Christopher G Schwarz, Anthony J Spychalla, Daniel A Drubach, Clifford R Jack, Val J Lowe, Keith A Josephs, Jennifer L Whitwell
BACKGROUND: Despite common pathology, Alzheimer's disease (AD) can have multiple clinical presentations which pathological studies suggest result from differences in the regional distribution of tau pathology. Positron emission tomography (PET) ligands are now available that can detect tau proteins in vivo and hence can be used to investigate the biological mechanisms underlying atypical AD. OBJECTIVE: To assess regional patterns of tau uptake on PET imaging in two atypical AD variants, posterior cortical atrophy (PCA) and logopenic progressive aphasia (lvPPA)...
2018: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/29613846/association-between-screening-mammography-recall-rate-and-interval-cancers-in-the-uk-breast-cancer-service-screening-program-a-cohort-study
#16
Elizabeth S Burnside, Daniel Vulkan, Roger G Blanks, Stephen W Duffy
Purpose To determine whether low levels of recall lead to increased interval cancers and the magnitude of this effect. Materials and Methods The authors retrospectively analyzed prospectively collected data from the UK National Health Service Breast Screening Programme during a 36-month period (April 1, 2005 to March 31, 2008), with 3-year follow-up in women aged 50-70 years. Data on recall, cancers detected at screening, and interval cancers were available for each of the 84 breast screening units and for each year (n = 252)...
April 3, 2018: Radiology
https://www.readbyqxmd.com/read/29608365/primary-care-practices-abilities-and-challenges-in-using-electronic-health-record-data-for-quality-improvement
#17
Deborah J Cohen, David A Dorr, Kyle Knierim, C Annette DuBard, Jennifer R Hemler, Jennifer D Hall, Miguel Marino, Leif I Solberg, K John McConnell, Len M Nichols, Donald E Nease, Samuel T Edwards, Winfred Y Wu, Hang Pham-Singer, Abel N Kho, Robert L Phillips, Luke V Rasmussen, F Daniel Duffy, Bijal A Balasubramanian
Federal value-based payment programs require primary care practices to conduct quality improvement activities, informed by the electronic reports on clinical quality measures that their electronic health records (EHRs) generate. To determine whether EHRs produce reports adequate to the task, we examined survey responses from 1,492 practices across twelve states, supplemented with qualitative data. Meaningful-use participation, which requires the use of a federally certified EHR, was associated with the ability to generate reports-but the reports did not necessarily support quality improvement initiatives...
April 2018: Health Affairs
https://www.readbyqxmd.com/read/29607558/outcome-reporting-across-randomised-trials-and-observational-studies-evaluating-treatments-for-twin-twin-transfusion-syndrome-a-systematic-review
#18
REVIEW
Helen Perry, James M N Duffy, Ogochukwu Umadia, Asma Khalil
BACKGROUND: Twin-Twin Transfusion syndrome is associated with significant mortality and morbidity. Potential treatments require robust evaluation. The aim of this study was to evaluate outcome reporting across observational studies and randomised controlled trials assessing treatments for twin-twin transfusion syndrome (TTTS). METHODS: Cochrane Central Register of Controlled Trials, EMBASE and Medline were searched from inception to August 2016. Observational studies and randomised controlled trials reporting outcomes following a treatment for TTTS in monochorionic-diamniotic twin pregnancies and monochorionic-triamniotic or dichorionic-triamniotic triplet pregnancies were included...
April 1, 2018: Ultrasound in Obstetrics & Gynecology
https://www.readbyqxmd.com/read/29606435/vitamin-d-biofortified-beef-a-comparison-of-cholecalciferol-with-synthetic-versus-uvb-mushroom-derived-ergosterol-as-feed-source
#19
Sarah K Duffy, John V O'Doherty, Gaurav Rajauria, Louise C Clarke, Aoife Hayes, Kirsten G Dowling, Michael N O'Grady, Joseph P Kerry, Jette Jakobsen, Kevin D Cashman, Alan K Kelly
This study investigates dietary fortification of heifer feeds with cholecalciferol and ergocalciferol sources and effects on beef total vitamin D activity, vitamer, respective 25-hydroxymetabolite contents, and meat quality. Thirty heifers were allocated to one of three dietary treatments [(1) basal diet + 4000 IU of vitamin D3 (Vit D3 ); (2) basal diet + 4000 IU of vitamin D2 (Vit D2 ); and (3) basal diet + 4000 IU of vitamin D2 -enriched mushrooms (Mushroom D2 )] for a 30 day pre-slaughter period...
August 1, 2018: Food Chemistry
https://www.readbyqxmd.com/read/29602204/high-levels-of-fecundity-in-small-and-isolated-populations-of-a-self-compatible-aloe-pollinated-by-opportunistic-birds-and-bees
#20
Kirsten L Patrick, Steven D Johnson, Karl J Duffy
Plant species that are effective colonizers of transient habitats are expected to have a capacity for uniparental reproduction and show flexibility in pollination systems. Such traits may enable populations to be established from a small number of founding individuals without these populations succumbing to reductions in fecundity arising from pollinator limitation. We tested these predictions for Aloe thraskii (Xanthorrhoeaceae), a succulent treelet that colonizes shifting coastal dunes and has both bird and bee pollinators...
March 30, 2018: Plant Biology
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