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https://www.readbyqxmd.com/read/28430437/discovery-of-an-hcv-ns5b-replicase-palm-site-allosteric-inhibitor-bms-929075-advanced-to-phase-1-clinical-studies
#1
Kap-Sun Yeung, Brett R Beno, Kyle Parcella, John A Bender, Katherine A Grant-Young, Andrew Nickel, Prashantha Gunaga, Prakash Anjanappa, Rajesh Onkardas Bora, Kumaravel Selvakumar, Karen Rigat, Ying-Kai Wang, Mengping Liu, Julie A Lemm, Kathy Mosure, Steven Sheriff, Changhong Wan, Mark Witmer, Kevin Kish, Umesh M Hanumegowda, Xiaoliang Zhuo, Yue-Zhong Shu, Dawn Parker, Roy Haskell, Alicia Ng, Qi Gao, Elizabeth Colston, Joseph Raybon, Dennis M Grasela, Kenneth S Santone, Min Gao, Nicholas A Meanwell, Michael W Sinz, Matthew G Soars, Jay O Knipe, Susan B Roberts, John F Kadow
The hepatitis C virus NS5B replicase is a prime target for the development of direct-acting antiviral drugs for the treatment of chronic HCV infection. Inspired by the overlay of bound structures of three structurally distinct NS5B palm site allosteric inhibitors, the high throughput screening hit anthranilic acid 4, the known benzofuran analog 5 and the benzothiadiazine derivative 6, an optimization process utilizing the simple benzofuran template 7 as a starting point for a fragment growing approach was pursued...
April 21, 2017: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28430419/prediction-of-hydrolysis-products-of-organic-chemicals-under-environmental-ph-conditions
#2
Caroline Tebes-Stevens, Jay M Patel, W Jack Jones, Eric J Weber
Cheminformatics-based software tools can predict the molecular structure of transformation products using a library of transformation reaction schemes. This paper presents the development of such a library for abiotic hydrolysis of organic chemicals under environmentally relevant conditions. The hydrolysis reaction schemes in the library encode the process science gathered from peer-reviewed literature and regulatory reports. Each scheme has been ranked on a scale of one to six based on the median half-life in a data set compiled from literature-reported hydrolysis rates...
April 21, 2017: Environmental Science & Technology
https://www.readbyqxmd.com/read/28429798/sensory-system-plasticity-in-a-visually-specialized-nocturnal-spider
#3
Jay A Stafstrom, Peter Michalik, Eileen A Hebets
The interplay between an animal's environmental niche and its behavior can influence the evolutionary form and function of its sensory systems. While intraspecific variation in sensory systems has been documented across distant taxa, fewer studies have investigated how changes in behavior might relate to plasticity in sensory systems across developmental time. To investigate the relationships among behavior, peripheral sensory structures, and central processing regions in the brain, we take advantage of a dramatic within-species shift of behavior in a nocturnal, net-casting spider (Deinopis spinosa), where males cease visually-mediated foraging upon maturation...
April 21, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28428893/characteristics-and-racial-variations-of-polypoidal-choroidal-vasculopathy-in-tertiary-centers-in-the-united-states-and-united-kingdom
#4
Tarek Alasil, Nelida Munoz, Pearse A Keane, Adnan Tufail, Patrick A Coady, Eduardo Novais, Talisa E de Carlo, Caroline R Baumal, Nadia K Waheed, Jay S Duker, Ron A Adelman
PURPOSE: To evaluate the characteristics and racial variations amongst patients with polypoidal choroidal vasculopathy (PCV) in the United States and the United Kingdom. METHODS: Fundus photos and indocyanine green angiography images were evaluated in a multicenter retrospective study to establish the diagnosis of PCV. Visual acuity (VA) was recorded in ETDRS letter count. RESULTS: Eighty eyes of 71 PCV patients (average age of 69.4 ± 10...
2017: International Journal of Retina and Vitreous
https://www.readbyqxmd.com/read/28428537/human-cytomegalovirus-induces-cellular-and-humoral-virus-specific-immune-responses-in-humanized-blt-mice
#5
Lindsey B Crawford, Rebecca Tempel, Daniel N Streblow, Craig Kreklywich, Patricia Smith, Louis J Picker, Jay A Nelson, Patrizia Caposio
The strict species specificity of Human Cytomegalovirus (HCMV) has impeded our understanding of antiviral adaptive immune responses in the context of a human immune system. We have previously shown that HCMV infection of human hematopoietic progenitor cells engrafted in immune deficient mice (huNSG) results in viral latency that can be reactivated following G-CSF treatment. In this study, we characterized the functional human adaptive immune responses in HCMV latently-infected huBLT (humanized Bone marrow-Liver-Thymus) mice...
April 20, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28428384/rewiring-metabolism-under-oxygen-deprivation
#6
Jay F Storz, Grant B McClelland
No abstract text is available yet for this article.
April 21, 2017: Science
https://www.readbyqxmd.com/read/28427054/preceding-intravenous-thrombolysis-in-patients-receiving-endovascular-therapy
#7
Hong-Kyun Park, Jong-Won Chung, Jeong-Ho Hong, Min Uk Jang, Hyun-Du Noh, Jong-Moo Park, Kyusik Kang, Soo Joo Lee, Youngchai Ko, Jae Guk Kim, Jae-Kwan Cha, Dae-Hyun Kim, Hyun-Wook Nah, Moon-Ku Han, Beom Joon Kim, Tai Hwan Park, Sang-Soon Park, Kyung Bok Lee, Jun Lee, Keun-Sik Hong, Yong-Jin Cho, Byung-Chul Lee, Kyung-Ho Yu, Mi-Sun Oh, Ki-Hyun Cho, Joon-Tae Kim, Dong-Eog Kim, Wi-Sun Ryu, Jay Chol Choi, Wook-Joo Kim, Dong-Ick Shin, Min-Ju Yeo, Sung Il Sohn, Ji Sung Lee, Juneyoung Lee, Byung-Woo Yoon, Hee-Joon Bae
BACKGROUND: The beneficial effects of endovascular therapy (EVT) in acute ischemic stroke have been demonstrated in recent clinical trials using new-generation thrombectomy devices. However, the comparative effectiveness and safety of preceding intravenous thrombolysis (IVT) in this population has rarely been evaluated. METHODS: From a prospective multicenter stroke registry database in Korea, we identified patients with acute ischemic stroke who were treated with EVT within 8 h of onset and admitted to 14 participating centers during 2008-2013...
April 21, 2017: Cerebrovascular Diseases
https://www.readbyqxmd.com/read/28427020/experiences-with-premorbid-sudep-discussion-among-participants-in-the-north-american-sudep-registry-nasr
#8
Jay Louik, Kyra Doumlele, Fizza Hussain, Laura Crandall, Jeffrey Buchhalter, Dale Hesdorffer, Elizabeth Donner, Orrin Devinsky, Daniel Friedman
The North American SUDEP Registry (NASR) is a repository of clinical data and biospecimens in cases of sudden unexpected death in epilepsy (SUDEP), a leading cause of epilepsy-related deaths. We assessed whether bereaved families were aware of SUDEP before their family member's death and their preferences for SUDEP disclosure. At enrollment, next-of-kin of SUDEP cases completed an intake interview, including questions assessing premorbid SUDEP discussions. Only 18.1% of the 138 next-of-kin recalled a previous discussion of SUDEP with a healthcare provider or support resource...
April 17, 2017: Epilepsy & Behavior: E&B
https://www.readbyqxmd.com/read/28427010/leveraging-microbial-biosynthetic-pathways-for-the-generation-of-drop-in-biofuels
#9
REVIEW
Amin Zargar, Constance B Bailey, Robert W Haushalter, Christopher B Eiben, Leonard Katz, Jay D Keasling
Advances in retooling microorganisms have enabled bioproduction of 'drop-in' biofuels, fuels that are compatible with existing spark-ignition, compression-ignition, and gas-turbine engines. As the majority of petroleum consumption in the United States consists of gasoline (47%), diesel fuel and heating oil (21%), and jet fuel (8%), 'drop-in' biofuels that replace these petrochemical sources are particularly attractive. In this review, we discuss the application of aldehyde decarbonylases to produce gasoline substitutes from fatty acid products, a recently crystallized reductase that could hydrogenate jet fuel precursors from terpene synthases, and the exquisite control of polyketide synthases to produce biofuels with desired physical properties (e...
April 17, 2017: Current Opinion in Biotechnology
https://www.readbyqxmd.com/read/28426852/an-outbreak-of-endogenous-fungal-endophthalmitis-among-intravenous-drug-abusers-in-new-england
#10
Aubrey R Tirpack, Jay S Duker, Caroline R Baumal
Importance: Intravenous drug abuse (IVDA) is a known risk factor for endogenous fungal endophthalmitis (EFE), a severe intraocular infection caused by hematogenous seeding of mycotic organisms to the eye. Reporting significant increases in heroin-related deaths since 2014, the New England region is in the midst of an opioid crisis that has led to a substantial increase in patients at risk for this vision-threatening disease. Objective: To present an update on characteristics, management, and visual outcomes in patients with EFE...
April 20, 2017: JAMA Ophthalmology
https://www.readbyqxmd.com/read/28426386/new-zealanders-working-non-standard-hours-also-have-greater-exposure-to-other-workplace-hazards
#11
Sarah M Jay, Philippa H Gander, Amanda Eng, Soo Cheng, Jeroen Douwes, Lis Ellison-Loschmann, Dave McLean, Neil Pearce, Andrea 'tMannetje
Exposure to workplace hazards, such as dust, solvents, and fumes, has the potential to adversely affect the health of people. However, the effects of workplace hazards on health may differ when exposure occurs at different times in the circadian cycle, and among people who work longer hours or who do not obtain adequate sleep. The aim of the present study was to document exposures to workplace hazards across a national sample of New Zealanders, comparing people who work a standard 08:00 -17:00 h Monday-to-Friday working week (Std hours) and those who do not (N-Std hours)...
2017: Chronobiology International
https://www.readbyqxmd.com/read/28426346/correlates-of-current-smoking-among-adults-served-by-the-public-mental-health-system
#12
Margaret A Swarbrick, Judith A Cook, Lisa A Razzano, Jessica A Jonikas, Ni Gao, Jill Williams, Jay Yudof
OBJECTIVE: As part of a study of health status among 457 adults with diagnostically heterogeneous serious mental illnesses served by the public mental health system in four U.S. states, we assessed predictors of current cigarette smoking. METHODS: We examined bivariate relationships between smoking status and risks for drug and alcohol use disorders, residential setting, parental status, and employment. Finally, we used multivariable logistic regression to predict current smoking, controlling for significant confounds...
April 20, 2017: Journal of Dual Diagnosis
https://www.readbyqxmd.com/read/28426310/a-public-health-approach-to-hepatitis-c-in-an-urban-setting
#13
Fabienne Laraque, Jay K Varma
The clinical consequences of HCV infection are increasing because the population with the highest prevalence of the infection, persons born between 1945 and 1965, is aging. As a result, health care expenditures are expected to increase. Now that a cure for HCV infection is the norm, a public health approach is necessary to identify, link to care, and treat infected persons and prevent new infections. We believe that the success of public health interventions, such as those for tuberculosis, can be translated to HCV infection...
April 20, 2017: American Journal of Public Health
https://www.readbyqxmd.com/read/28424239/aim2-inflammasome-is-critical-for-influenza-induced-lung-injury-and-mortality
#14
Hongbo Zhang, Jiadi Luo, John F Alcorn, Kong Chen, Songqing Fan, Joseph Pilewski, Aizhong Liu, Wei Chen, Jay K Kolls, Jieru Wang
The absent in melanoma 2 (AIM2) inflammasome plays an important role in many viral and bacterial infections, but very little is known about its role in RNA virus infection, including influenza A virus (IAV). In this study, we have designed in vivo and in vitro studies to determine the role of AIM2 in infections with lethal doses of IAVs A/PR8/34 and A/California/07/09. In wild-type mice, IAV infection enhanced AIM2 expression, induced dsDNA release, and stimulated caspase-1 activation and release of cleaved IL-1β in the lung, which was significantly reduced in AIM2-deficient mice...
April 19, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28423205/the-impact-of-biogas-and-fuelwood-use-on-institutional-kitchen-air-quality-in-kampala-uganda
#15
Aleia Ingulli McCord, Sarah Adel Stefanos, Vianney Tumwesige, Dorothy Lsoto, Anna Hillstrom Meding, Angela Adong, James Jay Schauer, Rebecca Anne Larson
Experts have suggested that microscale biogas systems offer a source of renewable energy that improves indoor air quality, but such impacts have not been directly measured. This study documented cooking behaviors and measured 2.5 μm particulate matter (PM2.5 ), carbon monoxide (CO), and sulfur dioxide (SO2 ) concentrations within 14 institutional kitchens in Kampala, Uganda that prepare meals using biogas (n=5), a mixture of biogas and fuelwood (n=3), and fuelwood (n=6). Small institutions (10-30 people) with biogas kitchens had 99% lower concentrations of PM2...
April 19, 2017: Indoor Air
https://www.readbyqxmd.com/read/28422919/the-lung-rescue-unit-lru-does-a-dedicated-intensive-care-unit-for-veno-venous-extra-corporeal-membrane-oxygenation-vv-ecmo-improve-survival-to-discharge
#16
Jay Menaker, Katelyn Dolly, Raymond Rector, Joseph Kufera, Eugenia E Lee, Ali Tabatabai, Ronald P Rabinowitz, Zachary Kon, Pablo Sanchez, Si Pham, Daniel L Herr, James V O'Connor, Deborah M Stein, Thomas M Scalea
BACKGROUND: The use of veno-venous extra corporeal membrane oxygenation (VV ECMO) for acute respiratory failure/distress syndrome (ARF/ARDS) has increased since 2009. Specialized units for patients requiring VV ECMO are not standard and patients are often cohorted with other critically ill patients. The purpose of this study was to report the outcome of adult patients admitted in 2015 to the LRU, which, to our knowledge, is the first intensive care unit in the United States that has been specifically created to provide care for patients requiring VV ECMO...
April 18, 2017: Journal of Trauma and Acute Care Surgery
https://www.readbyqxmd.com/read/28422310/adult-onset-cystic-fibrosis-liver-disease-diagnosis-and-characterization-of-an-underappreciated-entity
#17
Christopher Koh, Sasan Sakiani, Pallavi Surana, Xiongce Zhao, Jason Eccleston, David E Kleiner, David Herion, T Jake Liang, Jay H Hoofnagle, Milica Chernick, Theo Heller
BACKGROUND & AIMS: Cystic fibrosis liver disease (CFLD), a leading cause of death in cystic fibrosis (CF), is mostly described in pediatric populations. Adult-onset CFLD lacks sufficient characterization and diagnostic tools. METHODS: A cohort of CF patients without CFLD during childhood were followed for up to 38 years with serologic testing, imaging, and noninvasive fibrosis markers. Historical CFLD diagnostic criteria were compared with a newly proposed CFLD criteria...
April 19, 2017: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
https://www.readbyqxmd.com/read/28421890/inmate-health-care-provided-in-an-emergency-department
#18
Lindsey Koester, Jay M Brenner, Aimee Goulette, Susan M Wojcik, William Grant
The United States has the highest rate of incarceration in the world. Many correctional facilities have outsourced the medical care for this population that often presents with complex health issues. This study evaluates the reasons that inmates present to an emergency department (ED) and compares them to the general population ED visits. The most common presenting complaints were trauma (16.8%), abdominal pain (13.5%), chest pain (9.0%), and self-injury (8.7%). These presenting complaints differed significantly from those of the general population (abdominal pain [8...
April 2017: Journal of Correctional Health Care
https://www.readbyqxmd.com/read/28420874/therapeutic-targeting-using-tumor-specific-peptides-inhibits-long-non-coding-rna-hotair-activity-in-ovarian-and-breast-cancer
#19
Ali R Özeş, Yinu Wang, Xingyue Zong, Fang Fang, Jay Pilrose, Kenneth P Nephew
Long non-coding RNAs (lncRNAs) play key roles in human diseases, including cancer. Functional studies of the lncRNA HOTAIR (HOX transcript antisense RNA) provide compelling evidence for therapeutic targeting of HOTAIR in cancer, but targeting lncRNAs in vivo has proven to be difficult. In the current study, we describe a peptide nucleic acids (PNA)-based approach to block the ability of HOTAIR to interact with EZH2 and subsequently inhibit HOTAIR-EZH2 activity and resensitize resistant ovarian tumors to platinum...
April 18, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28420344/erratum-to-the-jbei-quantitative-metabolic-modeling-library-jqmm-a-python-library-for-modeling-microbial-metabolism
#20
Garrett W Birkel, Amit Ghosh, Vinay S Kumar, Daniel Weaver, David Ando, Tyler W H Backman, Adam P Arkin, Jay D Keasling, Héctor García Martín
No abstract text is available yet for this article.
April 18, 2017: BMC Bioinformatics
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