keyword
MENU ▼
Read by QxMD icon Read
search

conn

keyword
https://www.readbyqxmd.com/read/28633897/discovery-and-optimization-of-3-4-aryl-heteroarylsulfonyl-piperazin-1-yl-6-piperidin-1-yl-pyridazines-as-novel-cns-penetrant-pan-muscarinic-antagonists
#1
Aaron M Bender, Rebecca L Weiner, Vincent B Luscombe, Sonia Ajmera, Hyekyung P Cho, Sichen Chang, Xiaoyan Zhan, Alice L Rodriguez, Colleen M Niswender, Darren W Engers, Thomas M Bridges, P Jeffrey Conn, Craig W Lindsley
This letter describes the synthesis and structure activity relationship (SAR) studies of structurally novel M4 antagonists, based on a 3-(4-aryl/heteroarylsulfonyl)piperazin-1-yl)-6-(piperidin-1-yl)pyridazine core, identified from a high-throughput screening campaign. A multi-dimensional optimization effort enhanced potency at human M4 (hM4 IC50s<200nM), with only moderate species differences noted, and with enantioselective inhibition. Moreover, CNS penetration proved attractive for this series (rat brain:plasma Kp=2...
May 15, 2017: Bioorganic & Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/28630679/molecular-interactions-of-amyloid-nanofibrils-with-biological-aggregation-modifiers-implications-for-cytotoxicity-mechanisms-and-biomaterial-design
#2
REVIEW
Durga Dharmadana, Nicholas P Reynolds, Charlotte E Conn, Céline Valéry
Amyloid nanofibrils are ubiquitous biological protein fibrous aggregates, with a wide range of either toxic or beneficial activities that are relevant to human disease and normal biology. Protein amyloid fibrillization occurs via nucleated polymerization, through non-covalent interactions. As such, protein nanofibril formation is based on a complex interplay between kinetic and thermodynamic factors. The process entails metastable oligomeric species and a highly thermodynamically favoured end state. The kinetics, and the reaction pathway itself, can be influenced by third party moieties, either molecules or surfaces...
August 6, 2017: Interface Focus
https://www.readbyqxmd.com/read/28624257/moderate-exercise-training-decreases-inflammation-in-transgenic-sickle-cell-mice
#3
Emmanuelle Charrin, John J Dubé, Philippe Connes, Vincent Pialoux, Samit Ghosh, Camille Faes, Solomon F Ofori-Acquah, Cyril Martin
Chronic systemic inflammation is a pathophysiological feature of sickle cell disease (SCD). Considering that regular exercise exerts multiple beneficial health effects including anti-inflammatory actions, we investigated whether a treadmill training program could minimize the inflammatory state in transgenic sickle cell (SS) mice. To test this hypothesis, SS mice were subjected to a treadmill training protocol of 1h/day, 5days a week for 8weeks. Exercise training increased the percent of venous oxyhemoglobin and sharply decreased the percent of carboxyhemoglobin suggesting that exercise training may limit the proportion of erythrocytes that were deoxygenated in the venous circulation...
June 13, 2017: Blood Cells, Molecules & Diseases
https://www.readbyqxmd.com/read/28588171/clinical-and-laboratory-predictors-of-esophageal-varices-in-children-with-chronic-liver-disease
#4
M I Hasan, M Rukunuzzaman, M Nurullah, F Sultana
Esophageal varices are a serious consequence of portal hypertension in patients with chronic liver diseases. Several studies have evaluated possible noninvasive markers of esophageal varices to reduce the number of unnecessary endoscopies in patients with chronic liver disease. Aim of this study was to identify clinical and laboratory predictors of esophageal varices in children with chronic liver disease. This cross sectional observational study was done at Pediatric Gastroenterology and Nutrition Department of Bangabandhu Sheikh Mujib Medical University, Dhaka, over a period of 6 months...
April 2017: Mymensingh Medical Journal: MMJ
https://www.readbyqxmd.com/read/28561262/quantification-of-regional-variations-in-glenoid-trabecular-bone-architecture-and-mineralization-using-clinical-computed-tomography-images
#5
Bong-Jae Jun, Amit Vasanji, Eric T Ricchetti, Eric Rodriguez, Naveen Subhas, Zong-Ming Li, Joseph P Iannotti
The purpose of this study was to demonstrate feasibility of a clinical CT imaging and analysis technique to quantify regional variations in trabecular bone architecture and mineralization of glenoid bones. Specifically, our objective was to determine to what extent clinical CT imaging of intact upper extremities can describe variations of trabecular bone architectures at anatomic and peri-implant regions by comparing trabecular bone architectures as measured by high-resolution, micro CT imaging of same excised glenoid bones...
May 31, 2017: Journal of Orthopaedic Research: Official Publication of the Orthopaedic Research Society
https://www.readbyqxmd.com/read/28554971/the-67p-churyumov-gerasimenko-observation-campaign-in-support-of-the-rosetta-mission
#6
C Snodgrass, M F A'Hearn, F Aceituno, V Afanasiev, S Bagnulo, J Bauer, G Bergond, S Besse, N Biver, D Bodewits, H Boehnhardt, B P Bonev, G Borisov, B Carry, V Casanova, A Cochran, B C Conn, B Davidsson, J K Davies, J de León, E de Mooij, M de Val-Borro, M Delacruz, M A DiSanti, J E Drew, R Duffard, N J T Edberg, S Faggi, L Feaga, A Fitzsimmons, H Fujiwara, E L Gibb, M Gillon, S F Green, A Guijarro, A Guilbert-Lepoutre, P J Gutiérrez, E Hadamcik, O Hainaut, S Haque, R Hedrosa, D Hines, U Hopp, F Hoyo, D Hutsemékers, M Hyland, O Ivanova, E Jehin, G H Jones, J V Keane, M S P Kelley, N Kiselev, J Kleyna, M Kluge, M M Knight, R Kokotanekova, D Koschny, E A Kramer, J J López-Moreno, P Lacerda, L M Lara, J Lasue, H J Lehto, A C Levasseur-Regourd, J Licandro, Z Y Lin, T Lister, S C Lowry, A Mainzer, J Manfroid, J Marchant, A J McKay, A McNeill, K J Meech, M Micheli, I Mohammed, M Monguió, F Moreno, O Muñoz, M J Mumma, P Nikolov, C Opitom, J L Ortiz, L Paganini, M Pajuelo, F J Pozuelos, S Protopapa, T Pursimo, B Rajkumar, Y Ramanjooloo, E Ramos, C Ries, A Riffeser, V Rosenbush, P Rousselot, E L Ryan, P Santos-Sanz, D G Schleicher, M Schmidt, R Schulz, A K Sen, A Somero, A Sota, A Stinson, J M Sunshine, A Thompson, G P Tozzi, C Tubiana, G L Villanueva, X Wang, D H Wooden, M Yagi, B Yang, B Zaprudin, T J Zegmott
We present a summary of the campaign of remote observations that supported the European Space Agency's Rosetta mission. Telescopes across the globe (and in space) followed comet 67P/Churyumov-Gerasimenko from before Rosetta's arrival until nearly the end of the mission in September 2016. These provided essential data for mission planning, large-scale context information for the coma and tails beyond the spacecraft and a way to directly compare 67P with other comets. The observations revealed 67P to be a relatively 'well-behaved' comet, typical of Jupiter family comets and with activity patterns that repeat from orbit to orbit...
July 13, 2017: Philosophical Transactions. Series A, Mathematical, Physical, and Engineering Sciences
https://www.readbyqxmd.com/read/28553882/functional-brain-connectivity-of-remembered-fatigue-or-happiness-in-healthy-adults-use-of-arterial-spin-labeling
#7
Jeff Boissoneault, Landrew Sevel, Michael E Robinson, Roland Staud
INTRODUCTION: Chronic fatiguing illnesses like cancer, multiple sclerosis, chronic fatigue syndrome, or depression are frequently associated with comorbidities including depression, pain, and insomnia, making the study of their neural correlates challenging. To study fatigue without such comorbidities, functional connectivity (FC) analyses were used in healthy individuals to study brain activity during recall of a fatiguing event inside the MRI scanner. A positive mood induction served as control condition...
May 29, 2017: Journal of Clinical and Experimental Neuropsychology
https://www.readbyqxmd.com/read/28547632/compliance-with-urinary-catheter-removal-guidelines-leads-to-improved-outcome-in-enhanced-recovery-after-surgery-patients
#8
Allan Okrainec, Mary-Anne Aarts, Lesley Gotlib Conn, Stuart McCluskey, Marg McKenzie, Emily A Pearsall, Ori Rotstein, J Charles Victor, Robin S McLeod
OBJECTIVE: The objective of the study was to determine whether compliance with Enhanced Recovery after Surgery (ERAS) urinary catheter recommendations is associated with decreased urinary tract infections (UTI) and length of stay (LOS). METHODS: Patients having colorectal surgery at 15 academic hospitals were included. Patient and outcome data were collected prospectively. The guideline recommends that urinary catheters following colonic and rectal procedures should be removed at or before 24 and 72 h, respectively...
May 25, 2017: Journal of Gastrointestinal Surgery: Official Journal of the Society for Surgery of the Alimentary Tract
https://www.readbyqxmd.com/read/28544993/muscarinic-receptor-m4-positive-allosteric-modulators-attenuate-central-effects-of-cocaine
#9
Camilla Dall, Pia Weikop, Ditte Dencker, Anna C Molander, Gitta Wörtwein, P Jeffrey Conn, Anders Fink-Jensen, Morgane Thomsen
BACKGROUND: Cocaine addiction is a chronic brain disease affecting neurotransmission. Muscarinic cholinergic receptors modulate dopaminergic signaling in the reward system, and muscarinic receptor stimulation can block direct reinforcing effects of cocaine. Here, we tested the hypothesis that specific muscarinic M4 receptor stimulation can attenuate the discriminative stimulus effects and conditioned rewarding effects of cocaine, measures believed to predict the ability of cocaine and cocaine-associated cues to elicit relapse to drug taking...
July 1, 2017: Drug and Alcohol Dependence
https://www.readbyqxmd.com/read/28542412/low-rates-of-antibiotic-resistance-and-infectious-mortality-in-a-cohort-of-high-risk-hematology-patients-a-single-center-retrospective-analysis-of-blood-stream-infection
#10
Jason R Conn, Elizabeth M Catchpoole, Naomi Runnegar, Sally J Mapp, Kate A Markey
Febrile neutropenia (FN) is a medical emergency and can represent a life-threatening complication for hematology patients treated with intensive chemotherapy regimens. In clinical practice, the diagnostic yield of blood cultures and other investigations which aim to identify a causative organism or site of infection is low. We have retrospectively examined all blood cultures collected in a "real world" cohort of patients receiving chemotherapy for acute leukemia and patients with aggressive lymphoma treated with Hyper-CVAD/MTX-cytarabine, at a single tertiary center over a five-year period...
2017: PloS One
https://www.readbyqxmd.com/read/28539186/temporary-removal-a-survey-of-inpatient-practitioner-knowledge-of-penicillin-allergy-at-2-community-teaching-hospitals
#11
Mary L Staicu, Dipekka Soni, Kelly M Conn, Allison Ramsey
No abstract text is available yet for this article.
May 20, 2017: Annals of Allergy, Asthma & Immunology
https://www.readbyqxmd.com/read/28530802/discovery-of-n-5-fluoropyridin-2-yl-6-methyl-4-pyrimidin-5-yloxy-picolinamide-vu0424238-a-novel-negative-allosteric-modulator-of-metabotropic-glutamate-receptor-subtype-5-selected-for-clinical-evaluation
#12
Andrew S Felts, Alice L Rodriguez, Anna L Blobaum, Ryan D Morrison, Brittney S Bates, Analisa Thompson Gray, Jerri M Rook, Mohammed N Tantawy, Frank W Byers, Sichen Chang, Daryl F Venable, Vincent B Luscombe, Gilles D Tamagnan, Colleen M Niswender, J Scott Daniels, Carrie K Jones, P Jeffrey Conn, Craig W Lindsley, Kyle A Emmitte
Preclinical evidence in support of the potential utility of mGlu5 NAMs for the treatment of a variety of psychiatric and neurodegenerative disorders is extensive, and multiple such molecules have entered clinical trials. Despite some promising results from clinical studies, no small molecule mGlu5 NAM has yet to reach market. Here we present the discovery and evaluation of N-(5-fluoropyridin-2-yl)-6-methyl-4-(pyrimidin-5-yloxy)picolinamide (27, VU0424238), a compound selected for clinical evaluation. Compound 27 is more than 900-fold selective for mGlu5 versus the other mGlu receptors, and binding studies established a Ki value of 4...
May 31, 2017: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28528268/optimistic-honesty-understanding-surgeon-and-patient-perspectives-on-hopeful-communication-in-pancreatic-cancer-care
#13
Kim Blakely, Paul J Karanicolas, Frances C Wright, Lesley Gotlib Conn
BACKGROUND: Prognosis conversations between surgical oncologists and patients with pancreatic cancer are critically important and challenging. Surgeons and their patients often have discrepant understandings of prognosis despite extensive conversations. Little is known about how surgeons approach prognosis conversations with these patients; patients' experiences with these conversations are also not well understood. This qualitative study sought to better understand surgeon and patient perspectives on communication in pancreatic cancer care with a view toward improvement...
May 17, 2017: HPB: the Official Journal of the International Hepato Pancreato Biliary Association
https://www.readbyqxmd.com/read/28525727/some-of-the-canmat-recommendations-for-the-pharmacological-treatment-of-late-life-depression-are-not-congruent-with-available-evidence-or-expert-opinion
#14
Daniel Blumberger, David Conn, John S Kennedy, Benoit H Mulsant, Bruce G Pollock, Kiran Rabheru, Mark J Rapoport, Dallas Seitz
No abstract text is available yet for this article.
May 2017: Canadian Journal of Psychiatry. Revue Canadienne de Psychiatrie
https://www.readbyqxmd.com/read/28522971/altered-functional-connectivity-of-the-basal-nucleus-of-meynert-in-mild-cognitive-impairment-a-resting-state-fmri-study
#15
Hui Li, Xiuqin Jia, Zhigang Qi, Xiang Fan, Tian Ma, Hong Ni, Chiang-Shan R Li, Kuncheng Li
Background: Cholinergic dysfunction plays an important role in mild cognitive impairment (MCI). The basal nucleus of Meynert (BNM) provides the main source of cortical cholinergic innervation. Previous studies have characterized structural changes of the cholinergic basal forebrain in individuals at risk of developing Alzheimer's disease (AD). However, whether and how functional connectivity of the BNM (BNM-FC) is altered in MCI remains unknown. Objective: The aim of this study was to identify alterations in BNM-FC in individuals with MCI as compared to healthy controls (HCs), and to examine the relationship between these alterations with neuropsychological measures in individuals with MCI...
2017: Frontiers in Aging Neuroscience
https://www.readbyqxmd.com/read/28522253/challenges-in-the-development-of-an-m4-pam-preclinical-candidate-the-discovery-sar-and-in-vivo-characterization-of-a-series-of-3-aminoazetidine-derived-amides
#16
James C Tarr, Michael R Wood, Meredith J Noetzel, Jeanette L Bertron, Rebecca L Weiner, Alice L Rodriguez, Atin Lamsal, Frank W Byers, Sichen Chang, Hyekyung P Cho, Carrie K Jones, Colleen M Niswender, Michael W Wood, Nicholas J Brandon, Mark E Duggan, P Jeffrey Conn, Thomas M Bridges, Craig W Lindsley
This letter details the continued chemical optimization of a novel series of M4 positive allosteric modulators (PAMs) based on a 5-amino-thieno[2,3-c]pyridazine core by incorporating a 3-amino azetidine amide moiety. The analogs described within this work represent the most potent M4 PAMs reported for this series to date. The SAR to address potency, clearance, subtype selectivity, CNS exposure, and P-gp efflux are described. This work culminated in the discovery of VU6000918, which demonstrated robust efficacy in a rat amphetamine-induced hyperlocomotion reversal model at a minimum efficacious dose of 0...
July 1, 2017: Bioorganic & Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/28498785/laparoscopic-adrenalectomy-for-conn-s-syndrome-is-beneficial-to-patients-and-is-cost-effective-in-england
#17
Ioannis Christakis, John A Livesey, Gregory P Sadler, Radu Mihai
PURPOSE: Adrenalectomy has the potential to cure or improve the control of hypertension in patients with primary hyperaldosteronism due to unilateral adrenal adenoma (Conn's syndrome). This study assesses the patients' perception of, and costs associated with, laparoscopic adrenalectomy for Conn's syndrome. MATERIALS AND METHODS: Clinical, radiological, operative, and pathological data were collected on patients undergoing adrenalectomy for Conn's syndrome over 8-years period in a UK tertiary referral center...
May 12, 2017: Journal of Investigative Surgery: the Official Journal of the Academy of Surgical Research
https://www.readbyqxmd.com/read/28489923/differences-of-microparticle-patterns-between-sickle-cell-anemia-and-hemoglobin-sc-patients
#18
Yohann Garnier, Séverine Ferdinand, Maryse Etienne-Julan, Gisèle Elana, Marie Petras, Lydia Doumdo, Benoit Tressières, Marie-Laure Lalanne-Mistrih, Marie-Dominique Hardy-Dessources, Philippe Connes, Marc Romana
Sickle cell anemia (SCA) and hemoglobin SC (HbSC) disease are the two most common forms of sickle cell disease (SCD), a frequent hemoglobinopathy which exhibits a highly variable clinical course. Although high levels of microparticles (MPs) have been consistently reported in SCA and evidence of their harmful impact on the SCA complication occurrences have been provided, no data on MP pattern in HbSC patients has been reported so far. In this study, we determined and compared the MP patterns of 84 HbSC and 96 SCA children, all at steady-state, using flow cytometry...
2017: PloS One
https://www.readbyqxmd.com/read/28472649/allosteric-modulation-of-gpcrs-new-insights-and-potential-utility-for-treatment-of-schizophrenia-and-other-cns-disorders
#19
REVIEW
Daniel J Foster, P Jeffrey Conn
G-protein-coupled receptors (GPCRs) play critical roles in regulating brain function. Recent advances have greatly expanded our understanding of these receptors as complex signaling machines that can adopt numerous conformations and modulate multiple downstream signaling pathways. While agonists and antagonists have traditionally been pursued to target GPCRs, allosteric modulators provide several mechanistic advantages, including the ability to distinguish between closely related receptor subtypes. Recently, the discovery of allosteric ligands that confer bias and modulate some, but not all, of a given receptor's downstream signaling pathways can provide pharmacological modulation of brain circuitry with remarkable precision...
May 3, 2017: Neuron
https://www.readbyqxmd.com/read/28466542/association-between-oxidative-stress-and-vascular-reactivity-in-children-with-sickle-cell-anaemia-and-sickle-haemoglobin-c-disease
#20
Berenike Möckesch, Philippe Connes, Keyne Charlot, Sarah Skinner, Marie-Dominique Hardy-Dessources, Marc Romana, Stéphane Jumet, Marie Petras, Lydia Divialle-Doumdo, Cyril Martin, Benoît Tressières, Vanessa Tarer, Olivier Hue, Maryse Etienne-Julan, Sophie Antoine, Vincent Pialoux
Oxidative stress and haemolysis-associated nitric oxide (NO) depletion plays a crucial role in the development of vasculopathy in sickle cell anaemia (SS). However it remains unknown whether oxidative stress and haemolysis levels influence vascular function in patients with sickle haemoglobin C disease (SC). Microvascular response to heat (using Laser Doppler flowmetry on finger), oxidative stress biomarkers, NO metabolites, endothelin-1 and haematological parameters were compared between patients with SS and SC...
May 3, 2017: British Journal of Haematology
keyword
keyword
82192
1
2
Fetch more papers »
Fetching more papers... Fetching...
Read by QxMD. Sign in or create an account to discover new knowledge that matter to you.
Remove bar
Read by QxMD icon Read
×

Search Tips

Use Boolean operators: AND/OR

diabetic AND foot
diabetes OR diabetic

Exclude a word using the 'minus' sign

Virchow -triad

Use Parentheses

water AND (cup OR glass)

Add an asterisk (*) at end of a word to include word stems

Neuro* will search for Neurology, Neuroscientist, Neurological, and so on

Use quotes to search for an exact phrase

"primary prevention of cancer"
(heart or cardiac or cardio*) AND arrest -"American Heart Association"