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https://read.qxmd.com/read/30776227/discovery-of-the-second-generation-ror%C3%AE-inhibitors-composed-of-an-azole-scaffold
#1
Masayuki Kotoku, Takaki Maeba, Shingo Fujioka, Masahiro Yokota, Noriyoshi Seki, Keisuke Ito, Yoshihiro Suwa, Taku Ikenogami, Kazuyuki Hirata, Yasunori Hase, Yoshiaki Katsuda, Naoki Miyagawa, Kojo Arita, Kota Asahina, Masato Noguchi, Akihiro Nomura, Satoki Doi, Tsuyoshi Adachi, Paul Crowe, Haiyan Tao, Scott Thacher, Hiromasa Hashimoto, Takayoshi Suzuki, Makoto Shiozaki
Starting from a previously reported RORγ inhibitor (1), successive efforts to improve in vivo potency were continued. Introduction of metabolically beneficial motifs in conjunction with scaffold hopping was examined, resulting in discovery of the second generation RORγ inhibitor composed of a 4-(isoxazol-3-yl)butanoic acid scaffold (24). Compound 24 achieved a 10-fold improvement in in vivo potency in a mouse CD3 challenge model along with significant anti-inflammatory effects in a mouse dermatitis model.
February 18, 2019: Journal of Medicinal Chemistry
https://read.qxmd.com/read/30768501/confirming-the-clinical-safety-and-feasibility-of-a-bundled-methodology-to-improve-cardiopulmonary-resuscitation-involving-a-head-up-torso-up-chest-compression-technique
#2
Paul E Pepe, Kenneth A Scheppke, Peter M Antevy, Remle P Crowe, Daniel Millstone, Charles Coyle, Craig Prusansky, Sebastian Garay, Richard Ellis, Raymond L Fowler, Johanna C Moore
OBJECTIVES: Combined with devices that enhance venous return out of the brain and into the thorax, preclinical outcomes are improved significantly using a synergistic bundled approach involving mild elevation of the head and chest during cardiopulmonary resuscitation. The objective here was to confirm clinical safety/feasibility of this bundled approach including use of mechanical cardiopulmonary resuscitation provided at a head-up angle. DESIGN: Quarterly tracking of the frequency of successful resuscitation before, during, and after the clinical introduction of a bundled head-up/torso-up cardiopulmonary resuscitation strategy...
March 2019: Critical Care Medicine
https://read.qxmd.com/read/30767303/phototactic-tails-evolution-and-molecular-basis-of-a-novel-sensory-trait-in-sea-snakes
#3
Jenna M Crowe-Riddell, Bruno F Simões, Julian C Partridge, David M Hunt, Steven Delean, Julian G Schwerdt, James Breen, Alastair Ludington, David J Gower, Kate L Sanders
Dermal phototaxis has been reported in a few aquatic vertebrate lineages spanning fish, amphibians and reptiles. These taxa respond to light on the skin of their elongate hind-bodies and tails by withdrawing under cover to avoid detection by predators. Here, we investigated tail phototaxis in sea snakes (Hydrophiinae), the only reptiles reported to exhibit this sensory behaviour. We conducted behavioural tests in 17 wild-caught sea snakes of eight species by illuminating the dorsal surface of the tail and midbody skin using cold white, violet, blue, green and red light...
February 15, 2019: Molecular Ecology
https://read.qxmd.com/read/30766687/associations-between-medical-students-beliefs-about-obesity-and-clinical-counseling-proficiency
#4
Victoria Fang, Colleen Gillespie, Ruth Crowe, Dennis Popeo, Melanie Jay
Background: Despite evidence that biological and genetic factors contribute strongly to obesity, many healthcare providers still attribute obesity more to controllable behavioral issues rather than factors outside a person's control. We evaluated whether medical school students' beliefs about obesity correlate with ability to effectively counsel patients with obesity. Methods: Clerkship-year medical students at NYU School of Medicine completed an Objective Structured Clinical Experience (OSCE) that tests ability to effectively counsel standardized actor-patients with obesity...
2019: BMC Obesity
https://read.qxmd.com/read/30764808/qualitative-assessment-of-south-african-healthcare-worker-perspectives-on-an-instrument-free-rapid-cd4-test
#5
Fiona Scorgie, Yasmin Mohamed, David Anderson, Suzanne M Crowe, Stanley Luchters, Matthew F Chersich
BACKGROUND: Accurate measurement of CD4 cell counts remains an important tenet of clinical care for people living with HIV. We assessed an instrument-free point-of-care CD4 test (VISITECT® CD4) based on a lateral flow principle, which gives visual results after 40 min. The test involves five steps and categorises CD4 counts as above or below 350 cells/μL. As one component of a performance evaluation of the test, this qualitative study explored the views of healthcare workers in a large women and children's hospital on the acceptability and feasibility of the test...
February 14, 2019: BMC Health Services Research
https://read.qxmd.com/read/30764648/benefits-of-sequentially-adding-cognitive-behavioral-therapy-or-antidepressant-medication-for-adults-with-nonremitting-depression
#6
Boadie W Dunlop, Devon LoParo, Becky Kinkead, Tanja Mletzko-Crowe, Steven P Cole, Charles B Nemeroff, Helen S Mayberg, W Edward Craighead
OBJECTIVE: Adults with major depressive disorder frequently do not achieve remission with an initial treatment. Addition of psychotherapy for patients who do not achieve remission with antidepressant medication alone can target residual symptoms and protect against recurrence, but the utility of adding antidepressant medication after nonremission with cognitive-behavioral therapy (CBT) has received little study. The authors aimed to evaluate the acute and long-term outcomes resulting from both sequences of combination treatments...
February 15, 2019: American Journal of Psychiatry
https://read.qxmd.com/read/30761503/goal-directed-unequal-attention-allocation-during-multiple-object-tracking
#7
Emily M Crowe, Christina J Howard, Angela S Attwood, Christopher Kent
In standard multiple object tracking (MOT) tasks the relative importance of the targets being tracked is equal. This is atypical of everyday situations in which an individual may need to prioritize one target relative to another and so allocate attention unequally. We report three experiments that examined whether participants could unequally split attention using a modified MOT task in which target priority was manipulated. Specifically, we examined the effect of priority on participants' magnitude of error and used a distribution mixture analysis to investigate how priority affected both participants' probability of losing an item and tracking precision...
February 13, 2019: Attention, Perception & Psychophysics
https://read.qxmd.com/read/30761426/cementless-hip-arthroplasty-and-transverse-shortening-femoral-osteotomy-with-the-s-rom-stem-for-crowe-type-iv-developmental-dysplasia
#8
Libor Necas, Maros Hrubina, Marian Melisik, Zoltan Cibula, Michal Chmurny, Matej Daniel, Boris Steno
INTRODUCTION: The aim of this study has been to present outcomes after cementless arthroplasty for developmental dysplasia Crowe type IV of the hip, with transverse subtrochanteric shortening osteotomy and using the S-ROM stem. METHODS: We evaluated radiographs, functional scores and complications in a consecutive series of 23 patients (28 hips) with high dislocation of the hip. The average age of patients at surgery was 49.9 (range 22-68) years. The operations were performed between 2007 and 2013...
February 13, 2019: European Journal of Orthopaedic Surgery & Traumatology: Orthopédie Traumatologie
https://read.qxmd.com/read/30760926/high-frequency-of-shared-clonotypes-in-human-b-cell-receptor-repertoires
#9
Cinque Soto, Robin G Bombardi, Andre Branchizio, Nurgun Kose, Pranathi Matta, Alexander M Sevy, Robert S Sinkovits, Pavlo Gilchuk, Jessica A Finn, James E Crowe
The human genome contains approximately 20 thousand protein-coding genes1 , but the size of the collection of antigen receptors of the adaptive immune system that is generated by the recombination of gene segments with non-templated junctional additions (on B cells) is unknown-although it is certainly orders of magnitude larger. It has not been established whether individuals possess unique (or private) repertoires or substantial components of shared (or public) repertoires. Here we sequence recombined and expressed B cell receptor genes in several individuals to determine the size of their B cell receptor repertoires, and the extent to which these are shared between individuals...
February 13, 2019: Nature
https://read.qxmd.com/read/30758867/age-related-biophysical-changes-of-the-epidermal-and-dermal-skin-in-korean-women
#10
Changhui Cho, Eunbyul Cho, Nahee Kim, Juhee Shin, Sanga Woo, Eunyoung Lee, Jaesung Hwang, Jaehyoun Ha
INTRODUCTION: The clinical characteristics of skin were investigated to study the inter-relationship and changes in the biophysical properties of the epidermal and dermal layers associated with aging using noninvasive methods. METHODS: Our study included 100 healthy women aged between the early 20s and late 60s. Biophysical characteristics of skin such as color (brightness and spots), transparency, wrinkle on crow's feet, elasticity, hydration, sebum content, glossiness, and transepidermal water loss measured under controlled conditions...
February 13, 2019: Skin Research and Technology
https://read.qxmd.com/read/30757951/adaptation-of-the-robust-method-to-large-distributions-of-reference-values-program-modifications-and-comparison-of-alternative-computational-methods
#11
Charles M Beasley, Brenda Crowe, Mary Nilsson, Lieling Wu, Rebeka Tabbey, Ryan T Hietpas, Robert A Dean, Paul S Horn
The objective of this research was to compute reference limits using reference values from patients entering pharmaceutical development clinical trials by the nonparametric method and the robust method of Horn and Pesce, with and without outlier exclusion, and compare the methods with respect to influence on the limits. Reference limits were computed for 38 analytes with over 130,000 subjects contributing reference values. Subjects were partitioned into 10 demographic strata for limit computation. Limits were computed for both 95- and 98-percentile reference intervals by both methods...
February 13, 2019: Journal of Biopharmaceutical Statistics
https://read.qxmd.com/read/30756500/new-age-surgical-oncology
#12
EDITORIAL
Philip Crowe
No abstract text is available yet for this article.
January 2019: ANZ Journal of Surgery
https://read.qxmd.com/read/30756297/watermelon-juice-a-novel-functional-food-to-increase-circulating-lycopene-in-older-adult-women
#13
Amy C Ellis, Tanja Dudenbostel, Kristi Crowe-White
Because of accruing oxidative stress with advancing age, older adults may benefit from increased dietary intake of lycopene, a lipophilic carotenoid with potent antioxidant properties. Yet, intake of dietary lycopene as well as circulating lycopene levels are known to decrease with aging. Watermelon is one of the few food sources of dietary lycopene. Because heat treatment increases lycopene bioavailability, ingestion of watermelon in pasteurized juice form may be an optimal delivery vehicle to increase lycopene levels in older adults...
February 12, 2019: Plant Foods for Human Nutrition
https://read.qxmd.com/read/30755631/exposure-to-nanoscale-particulate-matter-from-gestation-to-adulthood-impairs-metabolic-homeostasis-in-mice
#14
Nicholas C Woodward, Amanda L Crow, Yang Zhang, Sam Epstein, Jaana Hartiala, Richard Johnson, Heidi Kocalis, Arian Saffari, Ishwarya Sankaranarayanan, Omid Akbari, Gajalakshmi Ramanathan, Jesus A Araujo, Caleb E Finch, Sebastien G Bouret, Constantinos Sioutas, Todd E Morgan, Hooman Allayee
Emerging evidence from epidemiological and animal studies suggests that exposure to traffic-related air pollutants and particulate matter less than 2.5 µm in diameter (PM2.5 ) contributes to development of obesity and related metabolic abnormalities. However, it is not known whether nanoscale particulate matter (nPM) with aerodynamic diameter ≤200 nm have similar adverse metabolic effects. The goal of the present study was to determine the effects of prenatal and early life exposure to nPM on metabolic homeostasis in mice...
February 12, 2019: Scientific Reports
https://read.qxmd.com/read/30744978/new-caledonian-crows-use-mental-representations-to-solve-metatool-problems
#15
Romana Gruber, Martina Schiestl, Markus Boeckle, Anna Frohnwieser, Rachael Miller, Russell D Gray, Nicola S Clayton, Alex H Taylor
One of the mysteries of animal problem-solving is the extent to which animals mentally represent problems in their minds. Humans can imagine both the solution to a problem and the stages along the way [1-3], such as when we plan one or two moves ahead in chess. The extent to which other animals can do the same is far less clear [4-25]. Here, we presented New Caledonian crows with a series of metatool problems where each stage was out of sight of the others and the crows had to avoid either a distractor apparatus containing a non-functional tool or a non-functional apparatus containing a functional tool...
January 30, 2019: Current Biology: CB
https://read.qxmd.com/read/30742713/exploring-the-structure-of-narcissism-towards-an-integrated-solution
#16
Michael L Crowe, Donald R Lynam, W Keith Campbell, Joshua D Miller
OBJECTIVE: Despite decades of work on narcissism there remain many active areas of exploration and debate including a clear and consensual description of its underlying components. Understanding narcissism's factor structure is necessary for precise measurement and investigation of specific psychological and behavioral processes. The aim of the current study was to explore the structure of narcissism by examining it at varying hierarchical levels. METHOD: Participants recruited from Amazon's Mechanical Turk (N = 591) completed 303 narcissism items encompassing 46 narcissism scales and subscales...
February 11, 2019: Journal of Personality
https://read.qxmd.com/read/30741010/effect-of-dislocation-timing-following-primary-total-hip-arthroplasty-on-the-risk-of-redislocation-and-revision
#17
German A Norambuena, Cody C Wyles, Robert E Van Demark, Robert T Trousdale
INTRODUCTION: There is little data regarding timing of index dislocation in patients who undergo primary total hip arthroplasty (THA) and subsequent risk of redislocation and revision. METHODS: Between 1992 and 2013, 21,490 primary THAs were performed at a single institution. 189 patients (190 hips) had a first episode of dislocation within one year of index surgery (0.9 %). 32 patients (32 hips) were excluded for the following reasons: complex THA secondary to fracture malunion, Crowe III/IV developmental hip dysplasia, periprosthetic fracture, prior hip surgery, incomplete information, and hip abductor avulsion...
February 11, 2019: Hip International: the Journal of Clinical and Experimental Research on Hip Pathology and Therapy
https://read.qxmd.com/read/30740294/immunosuppression-for-lung-transplantation-current-and-future
#18
Satish Chandrashekaran, Stacy A Crow Pharm, Sadia Z Shah, Chris J Arendt Pharm, Cassie C Kennedy
Purpose of the review: The number of lung transplantations performed worldwide continues to increase. There is a growing need in these patients for more effective immunosuppressive medications with less toxicity. Recent findings: This review article summarizes the recent studies and developments in lung transplant immunosuppression. Novel immunosuppressive medications and strategies used in other solid organ transplantations are being trialed in lung transplantation...
September 2018: Current Transplantation Reports
https://read.qxmd.com/read/30738170/new-onset-post-transplant-diabetes-mellitus-after-allogeneic-hematopoietic-cell-transplant-is-initiated-by-insulin-resistance-not-immunosuppressive-medications
#19
Brian G Engelhardt, Ujjawal Savani, Dae Kwang Jung, Alvin C Powers, Madan Jagasia, Heidi Chen, Jason J Winnick, Robyn A Tamboli, James E Crowe, Naji N Abumrad
New-onset post-transplant diabetes mellitus (PTDM) occurs frequently following allogeneic hematopoietic cell transplant (HCT). Although calcineurin inhibitors and corticosteroids are assumed the cause for hyperglycemia, patients developing PTDM have elevated fasting C-peptide levels before HCT and prior to immunosuppressive medications. To determine if PTDM results from established insulin resistance present before transplant, we performed oral glucose tolerance tests (OGTT) and measured whole-body, peripheral, and hepatic insulin sensitivity with euglycemic hyperinsulinemic clamps before and 90 days after HLA-identical sibling donor HCT in 20 patients without pre-transplant diabetes...
February 6, 2019: Biology of Blood and Marrow Transplantation
https://read.qxmd.com/read/30733521/satellite-based-soil-moisture-provides-missing-link-between-summertime-precipitation-and-surface-temperature-biases-in-cmip5-simulations-over-conterminous-united-states
#20
A Al-Yaari, A Ducharne, F Cheruy, W T Crow, J-P Wigneron
Past studies have shown that climate simulations have substantial warm and dry biases during the summer in the conterminous United States (CONUS), particularly in the central Great Plains (CGP). These biases have critical implications for the interpretation of climate change projections, but the complex overlap of multiple land-atmosphere feedback processes make them difficult to explain (and therefore correct). Even though surface soil moisture (SM) is often cited as a key control variable in these processes, there are still knowledge gaps about its specific role...
February 7, 2019: Scientific Reports
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