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https://www.readbyqxmd.com/read/29342416/identification-of-novel-quinazolinedione-derivatives-as-ror%C3%AE-t-inverse-agonist
#1
Yoshiyuki Fukase, Ayumu Sato, Yoshihide Tomata, Atsuko Ochida, Mitsunori Kono, Kazuko Yonemori, Keiko Koga, Toshitake Okui, Masashi Yamasaki, Yasushi Fujitani, Hideyuki Nakagawa, Ryoukichi Koyama, Masaharu Nakayama, Robert Skene, Bi-Ching Sang, Isaac Hoffman, Junya Shirai, Satoshi Yamamoto
Novel small molecules were synthesized and evaluated as retinoic acid receptor-related orphan receptor-gamma t (RORγt) inverse agonists for the treatment of inflammatory and autoimmune diseases. A hit compound, 1, was discovered by high-throughput screening of our compound library. The structure-activity relationship (SAR) study of compound 1 showed that the introduction of a chlorine group at the 3-position of 4-cyanophenyl moiety increased the potency and a 3-methylpentane-1,5-diamide linker is favorable for the activity...
December 28, 2017: Bioorganic & Medicinal Chemistry
https://www.readbyqxmd.com/read/29342381/long-term-follow-up-of-monoclonal-gammopathy-of-undetermined-significance
#2
Robert A Kyle, Dirk R Larson, Terry M Therneau, Angela Dispenzieri, Shaji Kumar, James R Cerhan, S Vincent Rajkumar
Background Monoclonal gammopathy of undetermined significance (MGUS) occurs in approximately 3% of persons 50 years of age or older. Methods We studied 1384 patients who were residing in southeastern Minnesota and in whom MGUS was diagnosed at the Mayo Clinic in the period from 1960 through 1994; the median follow-up was 34.1 years (range, 0.0 to 43.6). The primary end point was progression to multiple myeloma or another plasma-cell or lymphoid disorder. Results During 14,130 person-years of follow-up, MGUS progressed in 147 patients (11%), a rate that was 6...
January 18, 2018: New England Journal of Medicine
https://www.readbyqxmd.com/read/29342366/evaluation-of-the-get-active-questionnaire-in-community-dwelling-older-adults
#3
Andrea F M Petrella, Dawn P Gill, Robert J Petrella
BACKGROUND: Physical activity screening prior to starting a physical activity program is important to identify if there are any underlying health conditions. However, many older adults do not complete such assessments prior to beginning their physical activity program. This project compared the Canadian Society for Exercise Physiology's newly developed Get Active Questionnaire (GAQ) to a standardized exercise stress test in terms of screening out versus screening in false positive GAQ tests...
January 17, 2018: Applied Physiology, Nutrition, and Metabolism, Physiologie Appliquée, Nutrition et Métabolisme
https://www.readbyqxmd.com/read/29342322/an-ethenoadenine-fad-analog-accelerates-uv-dimer-repair-by-dna-photolyase
#4
Madhavan Narayanan, Vijay R Singh, Goutham Kodali, Katarina Moravcevic, Robert J Stanley
No abstract text is available yet for this article.
January 2018: Photochemistry and Photobiology
https://www.readbyqxmd.com/read/29342321/contributions-of-material-properties-and-structure-to-increased-bone-fragility-for-a-given-bone-mass-in-the-ucd-t2dm-rat-model-of-type-2-diabetes
#5
Claire Acevedo, Meghan Sylvia, Eric Schaible, James L Graham, Kimber L Stanhope, Lionel N Metz, Bernd Gludovatz, Ann V Schwartz, Robert O Ritchie, Tamara N Alliston, Peter J Havel, Aaron J Fields
Adults with type 2 diabetes (T2D) have a higher fracture risk for a given bone quantity, but the mechanisms remain unclear. Using a rat model of polygenic obese T2D, we demonstrate that diabetes significantly reduces whole-bone strength for a given bone mass (micro-CT-derived BMC), and we quantify the roles of T2D-induced deficits in material properties versus bone structure, i.e., geometry and microarchitecture. Lumbar vertebrae and ulnae were harvested from 6-month-old lean Sprague-Dawley rats, obese Sprague-Dawley rats, and diabetic obese UCD-T2DM rats (diabetic for 69 ± 7 days; blood glucose >200 mg/dl)...
January 17, 2018: Journal of Bone and Mineral Research: the Official Journal of the American Society for Bone and Mineral Research
https://www.readbyqxmd.com/read/29342288/association-between-abcg2-rs2231142-and-poor-response-to-allopurinol-replication-and-meta-analysis
#6
Mary C Wallace, Rebecca L Roberts, Payal Nanavati, Jeffrey N Miner, Nicola Dalbeth, Ruth Topless, Tony R Merriman, Lisa K Stamp
Objective: ABCG2 rs2231142 (Q141K) has been reported to be associated with poor response to allopurinol, while there are conflicting data on the association between the genetically independent ABCG2 rs10011796 variant and allopurinol response. The aim of this study was to replicate the association of ABCG2 rs2231142 and rs10011796 with allopurinol response and perform a meta-analysis. Methods: Participants in the Long-term Allopurinol Safety Study Evaluating Outcomes in Gout Patients (LASSO) (n = 299) were studied...
January 12, 2018: Rheumatology
https://www.readbyqxmd.com/read/29342269/a-silent-epidemic-the-prevalence-incidence-and-persistence-of-mycoplasma-genitalium-among-young-asymptomatic-high-risk-women-in-the-united-states
#7
Arlene C Seña, Jeannette Y Lee, Jane Schwebke, Susan S Philip, Harold C Wiesenfeld, Anne M Rompalo, Robert L Cook, Marcia M Hobbs
Background: Mycoplasma genitalium (MG) is a sexually transmitted infection (STI) that can result in pelvic inflammatory disease and adverse pregnancy outcomes. We analyzed data collected from a prospective study of asymptomatic bacterial vaginosis (BV) to determine the natural history of MG. Methods: Women aged 15-25 years, with ≥2 STI risk factors and asymptomatic BV were recruited from 10 sites throughout the United States. Vaginal swabs were collected at enrollment, and by home-based testing every 2 months over 12 months...
January 12, 2018: Clinical Infectious Diseases: An Official Publication of the Infectious Diseases Society of America
https://www.readbyqxmd.com/read/29342251/kinetics-of-serological-responses-in-critically-ill-patients-hospitalized-with-influenza-a-h1n1-pdm09-virus-infection-in-canada-2009-2011
#8
Melissa A Rolfes, F Liaini Gross, Brendan Flannery, Adrienne F A Meyers, Ma Luo, Nathalie Bastien, Robert A Fowler, Jacqueline M Katz, Min Z Levine, Anand Kumar, Timothy M Uyeki
Background: The kinetics of the antibody response during severe influenza are not well documented. Methods: Critically ill patients with influenza A(H1N1)pdm09 virus infection, confirmed by RT-PCR or seroconversion (≥4-fold rise in titers), during 2009-2011 in Canada were prospectively studied. Antibody titers in serially collected sera were determined using hemagglutinin inhibition (HAI) and microneutralization assays. Average antibody curves were estimated using linear mixed effects models and compared by patient outcome, age, and corticosteroid treatment...
January 12, 2018: Journal of Infectious Diseases
https://www.readbyqxmd.com/read/29342250/pneumococcal-community-acquired-pneumonia-detected-by-serotype-specific-urinary-antigen-detection-assays
#9
Richard G Wunderink, Wesley H Self, Evan J Anderson, Robert Balk, Sherene Fakhran, Daniel Mark Courtney, Chao Qi, Derek J Williams, Yuwei Zhu, Cynthia G Whitney, Matthew R Moore, Anna Bramley, Seema Jain, Kathryn M Edwards, Carlos G Grijalva
Background: Streptococcus pneumoniae is considered the leading bacterial cause of pneumonia in adults. Yet, it was not commonly detected by traditional culture-based and conventional urinary testing in a recent multicenter etiology study of adults hospitalized with community-acquired pneumonia (CAP). We used novel serotype-specific urinary antigen detection (SSUAD) assays to determine whether pneumococcal cases were missed by traditional testing. Methods: We studied adult patients hospitalized with CAP at 5 hospitals in Chicago and Nashville (2010-2012) and enrolled in the Etiology of Pneumonia in the Community (EPIC) study...
January 12, 2018: Clinical Infectious Diseases: An Official Publication of the Infectious Diseases Society of America
https://www.readbyqxmd.com/read/29342189/the-microbiota-metabolite-indole-inhibits-salmonella-virulence-involvement-of-the-phopq-two-component-system
#10
Nandita Kohli, Zeni Crisp, Rebekah Riordan, Michael Li, Robert C Alaniz, Arul Jayaraman
The microbial community present in the gastrointestinal tract is an important component of the host defense against pathogen infections. We previously demonstrated that indole, a microbial metabolite of tryptophan, reduces enterohemorrhagic Escherichia coli O157:H7 attachment to intestinal epithelial cells and biofilm formation, suggesting that indole may be an effector/attenuator of colonization for a number of enteric pathogens. Here, we report that indole attenuates Salmonella Typhimurium (Salmonella) virulence and invasion as well as increases resistance to colonization in host cells...
2018: PloS One
https://www.readbyqxmd.com/read/29342172/driving-factors-of-retention-in-care-among-hiv-positive-msm-and-transwomen-in-indonesia-a-cross-sectional-study
#11
Adi Nugroho, Vicki Erasmus, Robert W S Coulter, Sushil Koirala, Oranuch Nampaisan, Wirastra Pamungkas, Jan Hendrik Richardus
Little is known about the prevalence of and factors that influence retention in HIV-related care among Indonesian men who have sex with men (MSM) and transgender women (transwomen, or waria in Indonesian term). Therefore, we explored the driving factors of retention in care among HIV-positive MSM and waria in Indonesia. This cross-sectional study involved 298 self-reported HIV-positive MSM (n = 165) and waria (n = 133). Participants were recruited using targeted sampling and interviewed using a structured questionnaire...
2018: PloS One
https://www.readbyqxmd.com/read/29342106/adrenergic-agonists-bind-to-adrenergic-receptor-like-regions-of-the-mu-opioid-receptor-enhancing-morphine-and-methionine-enkephalin-binding-a-new-approach-to-biased-opioids
#12
Robert Root-Bernstein, Miah Turke, Udaya K Tiruttani Subhramanyam, Beth Churchill, Joerg Labahn
Extensive evidence demonstrates functional interactions between the adrenergic and opioid systems in a diversity of tissues and organs. While some effects are due to receptor and second messenger cross-talk, recent research has revealed an extracellular, allosteric opioid binding site on adrenergic receptors that enhances adrenergic activity and its duration. The present research addresses whether opioid receptors may have an equivalent extracellular, allosteric adrenergic binding site that has similar enhancing effects on opioid binding...
January 17, 2018: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29342057/audiologic-natural-history-of-small-volume-cochleovestibular-schwannomas-in-neurofibromatosis-type-2
#13
Alvin T deTorres, Carmen C Brewer, Chris K Zalewski, Kelly A King, Robert Walker, Gretchen C Scott, Ashok R Asthagiri, Prashant Chittiboina, Hung Jeffrey Kim
OBJECTIVE: To characterize the audiometric natural progression in patient-ears with small volume (<1,000 mm), treatment-naïve cochleovestibular schwannomas (CVSs) in Neurofibromatosis Type 2 (NF2). STUDY DESIGN: Prospective, longitudinal cohort study. SETTING: Quaternary medical research institute. PATIENTS: One hundred eleven ears in 71 NF2 patients with small, treatment-naïve CVSs observed from July 2006 to July 2016...
January 16, 2018: Otology & Neurotology
https://www.readbyqxmd.com/read/29342043/the-american-otological-society-at-its-sesquicentennial-insights-into-the-society-s-formative-years
#14
Robert K Jackler, Jennifer C Alyono, Albert C Mudry
OBJECTIVE: To elucidate the sequence of events which led to the formation of the American Otological Society (AOS) in 1868 and to examine the lives and contributions of the nine founding members of the Society. METHODS: Study of primary historical documents, biographical material, and previous histories of the AOS. RESULTS: Earlier treatments of the history of the AOS minimally covered the events and personalities from the Society's formative period...
January 16, 2018: Otology & Neurotology
https://www.readbyqxmd.com/read/29341996/retinal-arterio-arterial-collaterals-in-susac-syndrome
#15
Robert A Egan, Guy Jirawuthiworavong, Norah S Lincoff, John J Chen, Courtney E Francis, Jacqueline A Leavitt
BACKGROUND: The ophthalmic findings of Susac syndrome (SS) consist of visual field defects related to branch retinal artery occlusion (BRAO), and fluorescein angiography (FA) reveals a unique staining pattern. To date, retinal arterial collateral development has been described only in a single patient. Given that the immunopathological process in SS induces retinal ischemia, it is conceivable that abnormal blood vessel development may occur in affected individuals. METHODS: This is a retrospective observational study...
January 16, 2018: Journal of Neuro-ophthalmology: the Official Journal of the North American Neuro-Ophthalmology Society
https://www.readbyqxmd.com/read/29341982/extensive-necrotic-skin-lesions-due-to-post-varicella-protein-s-deficiency
#16
Aymeric De Geyer, Guillaume Robert, Sylvette Marleix, Bernard Fraisse, Grégory Lucas, Pierre Tattevin, Philippe Violas
Post-varicella protein S deficiency is a rare and severe disease. We report a case of extensive necrotic skin lesions of acute onset 7 days after varicella in a 4-year old girl. Protein S antigen and activity were <10%, anti-protein S antibodies were detected. She was treated with anticoagulation, plasmapheresis, and fresh frozen plasma. She survived, but required leg amputation.
January 16, 2018: Pediatric Infectious Disease Journal
https://www.readbyqxmd.com/read/29341875/beyond-jaad-april-2018
#17
REVIEW
Andrew Bronin, Robert Phelps, Robert Sidbury
No abstract text is available yet for this article.
January 13, 2018: Journal of the American Academy of Dermatology
https://www.readbyqxmd.com/read/29341869/a-report-of-the-24th-annual-congress-on-women-s-health-workshop-on-transforming-women-s-health-from-research-to-practice
#18
Jennifer L Plank-Bazinet, Annie Sampson, Susan G Kornstein, Gregory G Germino, Marjorie Robert-Guroff, Stephen E Gilman, Cora Lee Wetherington, Nakela Cook, Terri L Cornelison, Lisa Begg, Janine Austin Clayton
Sex and gender are critical contributors to overall health and disease, and considering both in research informs the development of prevention strategies and treatment interventions for both men and women. The National Institutes of Health (NIH) Office of Research on Women's Health sponsored a preconference workshop on this topic at the 24th Annual Women's Health Congress, which was held in Crystal City, VA, in April 2016. The workshop featured presentations by NIH intramural and extramural scientists who presented data on a variety of topics including polycystic kidney disease, vaccine protection, depression, drug addiction, and cardiovascular disease...
January 2018: Journal of Women's Health
https://www.readbyqxmd.com/read/29341866/identifying-low-grade-cellular-rejection-after-heart-transplantation-in-children-using-gene-expression-profiling
#19
Annie Xin, Melissa G Y Lee, Yifang Hu, Vera Ignjatovic, William Y Shi, Anne Shipp, Slavica Praporski, Axel Kallies, Robert G Weintraub, Paul T Monagle, Gordon K Smyth, Igor Konstantinov
BACKGROUND: Endomyocardial biopsy (EMB) remains the gold standard for detecting rejection after heart transplantation but is costly and invasive. This study aims to distinguish no rejection (0R) from low-grade rejection (1R/2R) after heart transplantation in children by global gene expression profiling in blood. METHODS: A total of 106 blood samples with corresponding EMB from 18 children who underwent heart transplantation from 2011-2014 were analyzed (18 baseline/pre-transplantation samples, 88 EMB samples)...
December 20, 2017: Physiological Genomics
https://www.readbyqxmd.com/read/29341848/protection-of-root-apex-meristem-during-stress-responses
#20
Mohamed M Mira, Shuanglong Huang, Robert D Hill, Claudio Stasollaa
By regulating the levels of nitric oxide (NO) in a cell and tissue specific fashion, Phytoglobins (Pgbs), plant hemoglobin-like proteins, interfere with many NO-mediated pathways participating in developmental and stress-related responses. Recent evidence reveals that one of the functions of Pgbs is to protect the root apical meristem (RAM) from stress conditions by retaining the viability and function of the quiescent center (QC), required to maintain the stem cells in an undifferentiated state and ensure proper tissue patterning and root viability...
January 17, 2018: Plant Signaling & Behavior
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