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https://www.readbyqxmd.com/read/27914364/structure-based-exploration-and-exploitation-of-the-s4-subsite-of-norovirus-3cl-protease-in-the-design-of-potent-and-permeable-inhibitors
#1
Anushka C Galasiti Kankanamalage, Yunjeong Kim, Athri D Rathnayake, Vishnu C Damalanka, Pathum M Weerawarna, Sean T Doyle, Amer F Alsoudi, D M Padmasankha Dissanayake, Gerald H Lushington, Nurjahan Mehzabeen, Kevin P Battaile, Scott Lovell, Kyeong-Ok Chang, William C Groutas
Human noroviruses are the primary cause of epidemic and sporadic acute gastroenteritis. The worldwide high morbidity and mortality associated with norovirus infections, particularly among the elderly, immunocompromised patients and children, constitute a serious public health concern. There are currently no approved human vaccines or norovirus-specific small-molecule therapeutics or prophylactics. Norovirus 3CL protease has recently emerged as a potential therapeutic target for the development of anti-norovirus agents...
November 14, 2016: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/27914316/does-the-proportion-of-pay-linked-to-performance-affect-the-job-satisfaction-of-general-practitioners
#2
Thomas Allen, William Whittaker, Matt Sutton
There is concern that pay-for-performance (P4P) can negatively affect general practitioners (GPs) by reducing their autonomy, increasing their wage dispersion or eroding their intrinsic motivation. This is especially a concern for the Quality and Outcomes Framework (QOF), a highly powered P4P scheme for UK GPs. The QOF affected all GPs but the exposure of their income to P4P varied. GPs did not know their level of exposure before the QOF was introduced and could not choose or manage it. We examine whether changes in GPs' job satisfaction before and after the introduction of the QOF in 2004 were correlated with the proportion of their income that became exposed to P4P...
November 24, 2016: Social Science & Medicine
https://www.readbyqxmd.com/read/27914234/food-gastrointestinal-ph-and-models-of-oral-drug-absorption
#3
REVIEW
Ahmad Y Abuhelwa, Desmond B Williams, Richard N Upton, David J R Foster
This article reviews the major physiological and physicochemical principles of the effect of food and gastrointestinal (GI) pH on the absorption and bioavailability of oral drugs, and the various absorption models that are used to describe/predict oral drug absorption. The rate and extent of oral drug absorption is determined by a complex interaction between a drug's physicochemical properties, GI physiologic factors, and the nature of the formulation administered. GI pH is an important factor that can markedly affect oral drug absorption and bioavailability as it may have significant influence on drug dissolution & solubility, drug release, drug stability, and intestinal permeability...
November 30, 2016: European Journal of Pharmaceutics and Biopharmaceutics
https://www.readbyqxmd.com/read/27914115/molecular-phylogeny-and-taxonomy-of-a-new-freshwater-hymenostomatid-from-northeastern-china-with-the-establishment-of-a-new-genus-anteglaucoma-gen-n-protista-ciliophora-oligohymenophorea
#4
Xuming Pan, Zihan Shi, Chundi Wang, William A Bourland, Ying Chen, Weibo Song
The morphology, infraciliature and SSU rDNA sequence of a new freshwater hymenostomatid ciliate, Anteglaucoma harbinensis gen. nov., spec. nov., collected from a farmland pond in Harbin, China, were investigated. The new genus Anteglaucoma is characterized as follows: small to medium-sized Glaucomidae with oral apparatus in anterior one-third of cell; paroral membrane composed of almost longitudinally arranged dikinetids; three adoral membranelles nearly equal in length and arranged almost longitudinally in parallel; silverline pattern tetrahymenid...
November 7, 2016: Journal of Eukaryotic Microbiology
https://www.readbyqxmd.com/read/27914109/bcor-upregulation-in-a-poorly-differentiated-synovial-sarcoma-with-ss18l1-ssx1-fusion-a-pathologic-and-molecular-pitfall
#5
Yu-Chien Kao, Yun-Shao Sung, Lei Zhang, Samuel Kenan, Samuel Singer, William D Tap, David Swanson, Brendan C Dickson, Cristina R Antonescu
The diagnosis of poorly differentiated synovial sarcoma (PD-SS) may be challenging due to overlapping morphologic features with other undifferentiated round cell sarcomas (URCS). Particularly relevant is the histologic overlap and shared BCOR overexpression between a subset of SS and URCS with various BCOR genetic abnormalities. Here we report a case of PD-SS lacking the canonical SS18-SSX gene fusion, but showing strong BCOR immunoreactivity and BCOR gene abnormalities by FISH which were misinterpreted as a URCS with BCOR gene rearrangements...
December 3, 2016: Genes, Chromosomes & Cancer
https://www.readbyqxmd.com/read/27914106/effect-of-cranberry-extract-on-the-frequency-of-bacteriuria-in-dogs-with-acute-thoracolumbar-disk-herniation-a-randomized-controlled-clinical-trial
#6
N J Olby, S L Vaden, K Williams, E H Griffith, T Harris, C L Mariani, K R Muñana, P J Early, S R Platt, L Boozer, C Giovanella, R Longshore
BACKGROUND: Dogs with spinal cord injury are at increased risk of developing bacteriuria due to increased residual urine volume. Cranberry extract inhibits binding of E. coli to uroepithelial cells, potentially reducing risk of bacteriuria. HYPOTHESIS: Cranberry extract reduces risk of bacteriuria in dogs after acute TL-IVDH. ANIMALS: Client-owned dogs with acute onset TL-IVDH causing nonambulatory status. METHODS: Randomized, placebo-controlled, blinded, prospective clinical trial...
December 3, 2016: Journal of Veterinary Internal Medicine
https://www.readbyqxmd.com/read/27913997/mega-cecum-an-unrecognized-cause-of-symptoms-in-some-female-patients-with-uro-gynecological-symptoms-and-severe-slow-transit-constipation
#7
William Y Chey, Vincent Chang, Cameron M Hoellrich, Kae Yol Lee, Maxine Lubkin, Deborah Corcoran, Ta-Min Chang, William D Chey
BACKGROUND: A subset of female patients with severe constipation report overlapping uro-gynecological symptoms which have been attributed to visceral hypersensitivity. AIMS: To study colon morphology and motor function in female patients with medically refractory chronic constipation with or without uro-gynecological symptoms and to assess clinical outcomes following laparoscopic ileo-proctostomy. METHODS: Colon anatomy and cecal emptying time were assessed with plain films and fluoroscopy following a standardized test meal mixed with barium...
December 2, 2016: Digestive Diseases and Sciences
https://www.readbyqxmd.com/read/27913855/what-can-the-microstructure-of-stones-tell-us
#8
REVIEW
James C Williams, Elaine Worcester, James E Lingeman
How stones are retained within the kidney while small in size is still not fully understood. In this paper, we show two examples of how stones are retained during early growth: one is growth on Randall's (interstitial) plaque, and the other is growth on mineral that has formed as a luminal plug in a terminal collecting duct. These two mechanisms of stone retention during early growth have distinctive morphologic features that can be seen by methods that show the microscopic structure of the stones. Stones growing on Randall's plaque display an apatite region that is typically not large in size (<0...
December 2, 2016: Urolithiasis
https://www.readbyqxmd.com/read/27913833/tight-repulsion-linkage-between-sr36-and-sr39-was-revealed-by-genetic-cytogenetic-and-molecular-analyses
#9
Bosco Chemayek, Urmil K Bansal, Naeela Qureshi, Peng Zhang, William W Wagoire, Harbans S Bariana
The shortening of Aegilops speltoides segment did not facilitate recombination between stem rust resistance genes Sr36 and Sr39 . Robustness of marker rwgs28 for marker-assisted selection of Sr39 was demonstrated. Stem rust resistance genes Sr39 and Sr36 were transferred from Aegilops speltoides and Triticum timopheevii, respectively, to chromosome 2B of wheat. Genetic stocks RL6082 and RWG1 carrying Sr39 on a large and a shortened Ae. speltoides segments, respectively, and the Sr36-carrying Australian wheat cultivar Cook were used in this study...
December 2, 2016: TAG. Theoretical and Applied Genetics. Theoretische und Angewandte Genetik
https://www.readbyqxmd.com/read/27913714/measuring-offenders-belief-in-the-possibility-of-desistance
#10
Kevin O'Sullivan, Rochelle Williams, Xiang Yan Hong, David Bright, Richard Kemp
This article describes the use of a questionnaire to measure offenders' belief in the likelihood of their making a successful re-entry into society after having committed crime, a "belief in redeemability" (BIR) as described by Maruna and King. The 37 items for the scale were taken from statements by offenders about their prospects of making good. This set of items was tested with a pilot group of offenders recruited from clients on parole or on supervised bonds at community corrections offices in metropolitan Sydney, Australia, and their responses were coded to yield a score we called the "BIR" score...
December 1, 2016: International Journal of Offender Therapy and Comparative Criminology
https://www.readbyqxmd.com/read/27913695/a-randomized-double-blind-placebo-controlled-trial-of-coenzyme-q10-in-huntington-disease
#11
Andrew McGarry, Michael McDermott, Karl Kieburtz, Elisabeth A de Blieck, Flint Beal, Karen Marder, Christopher Ross, Ira Shoulson, Peter Gilbert, William M Mallonee, Mark Guttman, Joanne Wojcieszek, Rajeev Kumar, Mark S LeDoux, Mary Jenkins, H Diana Rosas, Martha Nance, Kevin Biglan, Peter Como, Richard M Dubinsky, Kathleen M Shannon, Padraig O'Suilleabhain, Kelvin Chou, Francis Walker, Wayne Martin, Vicki L Wheelock, Elizabeth McCusker, Joseph Jankovic, Carlos Singer, Juan Sanchez-Ramos, Burton Scott, Oksana Suchowersky, Stewart A Factor, Donald S Higgins, Eric Molho, Fredy Revilla, John N Caviness, Joseph H Friedman, Joel S Perlmutter, Andrew Feigin, Karen Anderson, Ramon Rodriguez, Nikolaus R McFarland, Russell L Margolis, Eric S Farbman, Lynn A Raymond, Valerie Suski, Sandra Kostyk, Amy Colcher, Lauren Seeberger, Eric Epping, Sherali Esmail, Nancy Diaz, Wai Lun Alan Fung, Alan Diamond, Samuel Frank, Philip Hanna, Neal Hermanowicz, Leon S Dure, Merit Cudkowicz
OBJECTIVE: To test the hypothesis that chronic treatment of early-stage Huntington disease (HD) with high-dose coenzyme Q10 (CoQ) will slow the progressive functional decline of HD. METHODS: We performed a multicenter randomized, double-blind, placebo-controlled trial. Patients with early-stage HD (n = 609) were enrolled at 48 sites in the United States, Canada, and Australia from 2008 to 2012. Patients were randomized to receive either CoQ 2,400 mg/d or matching placebo, then followed for 60 months...
December 2, 2016: Neurology
https://www.readbyqxmd.com/read/27913686/micrognathia-in-mouse-models-of-ciliopathies
#12
REVIEW
Hadeel Adel Al-Lami, William B Barrell, Karen J Liu
Defects in the development of the mandible can lead to micrognathia, or small jaw, which manifests in ciliopathic conditions, such as orofaciodigital syndrome, Meckel-Gruber syndrome, and Bardet-Biedl syndrome. Although micrognathia occurs frequently in human and mouse ciliopathies, it has been difficult to pinpoint the underlying cellular causes. In this mini-review, we shed light on the tissue-specific contributions to ciliary dysfunction in the development of the mandible. First, we outline the steps involved in setting up the jaw primordium and subsequent steps in the outgrowth of the mandibular skeleton...
December 15, 2016: Biochemical Society Transactions
https://www.readbyqxmd.com/read/27913673/structural-insights-into-functional-amyloid-inhibition-in-gram-ve-bacteria
#13
REVIEW
William Hawthorne, Sarah Rouse, Lee Sewell, Stephen J Matthews
Amyloids are proteinaceous aggregates known for their role in debilitating degenerative diseases involving protein dysfunction. Many forms of functional amyloid are also produced in nature and often these systems require careful control of their assembly to avoid the potentially toxic effects. The best-characterised functional amyloid system is the bacterial curli system. Three natural inhibitors of bacterial curli amyloid have been identified and recently characterised structurally. Here, we compare common structural features of CsgC, CsgE and CsgH and discuss the potential implications for general inhibition of amyloid...
December 15, 2016: Biochemical Society Transactions
https://www.readbyqxmd.com/read/27913637/mural-endothelial-cell-cell-interactions-stabilize-the-developing-zebrafish-dorsal-aorta
#14
Amber N Stratman, Sofia A Pezoa, Olivia M Farrelly, Daniel Castranova, Louis E Dye, Matthew G Butler, Harwin Sidik, William S Talbot, Brant M Weinstein
Mural cells (vascular smooth muscle cells and pericytes) play a critical role in the development of the vasculature, promoting vascular quiescence and long-term vessel stabilization through their interactions with endothelial cells. However, the mechanistic details of how mural cells stabilize vessels are not fully understood. We have examined the emergence and functional role of mural cells investing the dorsal aorta during early development using the zebrafish. Consistent with previous literature, our data suggest that cells ensheathing the dorsal aorta emerge from a sub-population of cells in the adjacent sclerotome...
December 2, 2016: Development
https://www.readbyqxmd.com/read/27913579/risk-factors-for-leptospirosis-seropositivity-in-slaughterhouse-workers-in-western-kenya
#15
Elizabeth Anne Jessie Cook, William Anson de Glanville, Lian Francesca Thomas, Samuel Kariuki, Barend Mark de Clare Bronsvoort, Eric Maurice Fèvre
OBJECTIVES: Leptospirosis has been documented in slaughterhouse workers around the world. Risk factors include smoking and drinking at work, and performing tasks such as cleaning offal. This paper examined risk factors for leptospirosis seropositivity in slaughterhouse workers in western Kenya. METHODS: The study was conducted between May 2011 and October 2012. Questionnaires were used to collect information from workers on demographic data, health and hygiene practices in the slaughterhouse...
December 2, 2016: Occupational and Environmental Medicine
https://www.readbyqxmd.com/read/27913572/very-low-density-lipoprotein-vldl-induced-signals-mediating-aldosterone-production
#16
Ying-Ying Tsai, William E Rainey, Wendy B Bollag
Aldosterone, secreted by the adrenal zona glomerulosa, enhances sodium retention, thus increasing blood volume and pressure. Excessive production of aldosterone results in high blood pressure, and contributes to cardiovascular and renal disease, stroke, and visual loss. Hypertension is also associated with obesity, which s correlated with other serious health risks as well. Although weight gain is associated with increased blood pressure, the mechanism by which excess fat deposits increase blood pressure remains unclear...
December 2, 2016: Journal of Endocrinology
https://www.readbyqxmd.com/read/27913432/von-economo-neurons-and-fork-cells-a-neurochemical-signature-linked-to-monoaminergic-function
#17
Anke A Dijkstra, Li-Chun Lin, Alissa L Nana, Stephanie E Gaus, William W Seeley
The human anterior cingulate and frontoinsular cortices are distinguished by 2 unique Layer 5 neuronal morphotypes, the von Economo neurons (VENs) and fork cells, whose biological identity remains mysterious. Insights could impact research on diverse neuropsychiatric diseases to which these cells have been linked. Here, we leveraged the Allen Brain Atlas to evaluate mRNA expression of 176 neurotransmitter-related genes and identified vesicular monoamine transporter 2 (VMAT2), gamma-aminobutyric acid (GABA) receptor subunit θ (GABRQ), and adrenoreceptor α-1A (ADRA1A) expression in human VENs, fork cells, and a minority of neighboring Layer 5 neurons...
December 1, 2016: Cerebral Cortex
https://www.readbyqxmd.com/read/27913423/bronchodilatory-effect-of-deep-inspiration-in-freshly-isolated-sheep-lungs
#18
William D Wong, Lu Wang, Peter D Paré, Chun Y Seow
Taking a big breath is known to reverse bronchoconstriction induced by bronchochallenge in healthy subjects; this bronchodilatory effect of deep inspiration (DI) is diminished in asthmatics. The mechanism underlying the DI effect is not clear. Observations from experiments using isolated airway smooth muscle (ASM) preparations and airway segments suggest that straining of ASM due to DI could lead to bronchodilation, possibly due to strain-induced reduction in ASM contractility. However, factors external to the lung cannot be excluded as potential causes for the DI effect...
December 2, 2016: American Journal of Physiology. Lung Cellular and Molecular Physiology
https://www.readbyqxmd.com/read/27913340/efficient-3d-reconstruction-in-ultrasound-elastography-via-a-sparse-iteration-based-on-markov-random-fields
#19
Atul Ingle, Tomy Varghese, William Sethares
Percutaneous needle-based liver ablation procedures are becoming increasingly common for treatment of small isolated tumors in hepatocellular carcinoma patients who are not candidates for surgery. Rapid three dimensional visualization of liver ablations has potential clinical value because it can enable interventional radiologists to plan and execute needle-based ablation procedures with real time feedback. Ensuring the right volume of tissue is ablated is desirable to avoid recurrence of tumors from residual untreated cancerous cells...
November 29, 2016: IEEE Transactions on Ultrasonics, Ferroelectrics, and Frequency Control
https://www.readbyqxmd.com/read/27913303/an-mtorc1-akt1-cathepsin-h-axis-controls-filaggrin-expression-and-processing-in-skin-a-novel-mechanism-for-skin-barrier-disruption-in-atopic-dermatitis
#20
Aishath S Naeem, Cristina Tommasi, Christian Cole, Stuart J Brown, Yanan Zhu, Benjamin Way, Saffron Ag Willis Owen, Miriam Moffatt, William O Cookson, John I Harper, Di Wl, Sara J Brown, Thomas Reinheckel, Ryan F L O'Shaughnessy
BACKGROUND: Filaggrin, encoded by the FLG gene, is an important component of the skin's barrier to the external environment and genetic defects in FLG strongly associate with Atopic Dermatitis (AD). However, not all AD patients have FLG mutations. OBJECTIVE: We hypothesised that these patients may possess other defects in filaggrin expression and processing, contributing to barrier disruption and AD, and therefore present novel therapeutic targets for this disease...
November 29, 2016: Journal of Allergy and Clinical Immunology
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