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https://www.readbyqxmd.com/read/28315760/medication-adherence-outcomes-of-771-intervention-trials-systematic-review-and-meta-analysis
#1
REVIEW
Vicki S Conn, Todd M Ruppar
Excellent medication adherence contributes to decreases in morbidity, mortality, and health care costs. Although researchers have tested many interventions to increase adherence, results are sometimes conflicting and often unclear. This systematic review applied meta-analytic procedures to integrate primary research that tested medication adherence interventions. Comprehensive searching completed in 2015 located 771 published and unpublished intervention studies with adherence behavior outcomes. Random-effects model analysis calculated standardized mean difference effect sizes...
March 15, 2017: Preventive Medicine
https://www.readbyqxmd.com/read/28289026/substrate-recognition-and-modification-by-a-pathogen-associated-aminoglycoside-resistance-16s-rrna-methyltransferase
#2
Kellie Vinal, Graeme L Conn
The pathogen-associated 16S rRNA methyltransferase NpmA catalyzes m(1)A1408 modification to block the action of structurally diverse aminoglycoside antibiotics. Here we describe the development of a fluorescence polarization binding assay and its use, together with complementary functional assays, to dissect the mechanism of NpmA substrate recognition. These studies reveal that electrostatic interactions made by the NpmA β2/3 linker are collectively critical for docking of NpmA on a conserved 16S rRNA tertiary surface...
March 13, 2017: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/28280815/lyotropic-liquid-crystal-engineering-moving-beyond-binary-compositional-space-ordered-nanostructured-amphiphile-self-assembly-materials-by-design
#3
REVIEW
Leonie van 't Hag, Sally L Gras, Charlotte E Conn, Calum J Drummond
Ordered amphiphile self-assembly materials with a tunable three-dimensional (3D) nanostructure are of fundamental interest, and crucial for progressing several biological and biomedical applications, including in meso membrane protein crystallization, as drug and medical contrast agent delivery vehicles, and as biosensors and biofuel cells. In binary systems consisting of an amphiphile and a solvent, the ability to tune the 3D cubic phase nanostructure, lipid bilayer properties and the lipid mesophase is limited...
March 10, 2017: Chemical Society Reviews
https://www.readbyqxmd.com/read/28276092/bone-microarchitecture-assessed-by-hr-pqct-as-predictor-of-fracture-risk-in-postmenopausal-women-the-ofely-study
#4
Elisabeth Sornay-Rendu, Stephanie Boutroy, François Duboeuf, Roland D Chapurlat
Several cross-sectional studies have shown that impairment of bone microarchitecture (MA) contributes to skeletal fragility. The aim of this study was to prospectively investigate the prediction of fracture (Fx) by bone MA assessed by HR-pQCT in postmenopausal women. We measured MA at the distal radius and tibia with HR-pQCT in the OFELY study, in addition to areal BMD with DXA in 589 women, mean(SD) age 68(9) yr. During a median [IQ] 9.4[1.0] yr of follow-up, 135 women sustained an incident fragility Fx, including 81 women with a major osteoporotic Fx (MOP Fx)...
March 9, 2017: Journal of Bone and Mineral Research: the Official Journal of the American Society for Bone and Mineral Research
https://www.readbyqxmd.com/read/28237763/continued-optimization-of-the-m5-nam-ml375-discovery-of-vu6008667-an-m5-nam-with-high-cns-penetration-and-a-desired-short-half-life-in-rat-for-addiction-studies
#5
Kevin M McGowan, Kellie D Nance, Hykeyung P Cho, Thomas M Bridges, P Jeffrey Conn, Carrie K Jones, Craig W Lindsley
This letter describes the continued optimization of M5 NAM ML375 (VU0483253). While a valuable in vivo tool compound, ML375has an excessively long elimination half-life in rat (t1/2=80h), which can be problematic in certain rodent addiction paradigms (e.g., reinstatement). Thus, we required an M5 NAM of comparable potency to ML375, but with a rat t1/2 of less than 4h. Steep SAR plagued this chemotype, and here we detail aniline replacements that offered some improvements over ML375, but failed to advance. Ultimately, incorporation of a single methyl group to the 9b-phenyl ring acted as a metabolic shunt, providing (S)-11 (VU6008667), an equipotent M5 NAM, with high CNS penetration, excellent selectivity versus M1-4 and the desired short half-life (t1/2=2...
February 13, 2017: Bioorganic & Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/28231248/intensive-trapping-of-blood-fed-anopheles-darlingi-in-amazonian-peru-reveals-unexpectedly-high-proportions-of-avian-blood-meals
#6
Marta Moreno, Marlon P Saavedra, Sara A Bickersmith, Catharine Prussing, Adrian Michalski, Carlos Tong Rios, Joseph M Vinetz, Jan E Conn
Anopheles darlingi, the main malaria vector in the Neotropics, has been considered to be highly anthropophilic. However, many behavioral aspects of this species remain unknown, such as the range of blood-meal sources. Barrier screens were used to collect resting Anopheles darlingi mosquitoes from 2013 to 2015 in three riverine localities (Lupuna, Cahuide and Santa Emilia) in Amazonian Peru. Overall, the Human Blood Index (HBI) ranged from 0.58-0.87, with no significant variation among years or sites. Blood-meal analysis revealed that humans are the most common blood source, followed by avian hosts (Galliformes-chickens and turkeys), and human/Galliforme mixed-meals...
February 2017: PLoS Neglected Tropical Diseases
https://www.readbyqxmd.com/read/28230352/disease-modifying-effects-of-m1-muscarinic-acetylcholine-receptor-activation-in-an-alzheimer-s-disease-mouse-model
#7
Evan P Lebois, Jason P Schroeder, Thomas J Esparza, Thomas M Bridges, Craig W Lindsley, P Jeffrey Conn, David L Brody, John Scott Daniels, Allan I Levey
Alzheimer's Disease (AD) is the leading cause of dementia worldwide and currently no disease-modifying therapy is available to slow or prevent AD, underscoring the urgent need for neuroprotective therapies. Selective M1 muscarinic acetylcholine receptor (mAChR) activation is an attractive mechanism for AD therapy since M1 mediates key effects on memory, cognition, and behavior and has potential for disease-modifying effects on Aβ formation and tau phosphorylation. To validate M1 as a neuroprotective treatment target for AD, the M1-selective agonist, VU0364572, was chronically dosed to 5XFAD mice from a young age preceding Aβ pathology (2 months) to an age where these mice are known to display memory impairments (6 months)...
February 23, 2017: ACS Chemical Neuroscience
https://www.readbyqxmd.com/read/28229354/genetic-differentiation-of-colombian-populations-of-anopheles-darlingi-root-diptera-culicidae
#8
C Y Rosero, G I Jaramillo, R Gonzalez, H Cardenas
Anopheles darlingi Root is a primary vector of malaria in the neotropic region, a species not just highly anthropophilic but very efficient in transmitting Plasmodium species and considered the most important vector in the Amazon region. The main goal of this study was to determine the genetic structure of the A. darlingi populations using microsatellites (STR) in western and eastern regions of Colombia. DNA extraction was done with the cited protocol of band using the Genomic Prep™ cell and tissue isolation commercial kits...
February 23, 2017: Neotropical Entomology
https://www.readbyqxmd.com/read/28222463/changes-in-body-mass-index-in-pheochromocytoma-patients-following-adrenalectomy
#9
Ariadni Spyroglou, Christian Adolf, Stefanie Hahner, Marcus Quinkler, Roland Ladurner, Martin Reincke, Felix Beuschlein
Catecholamine excess from pheochromocytoma results in cardiovascular symptoms such as arterial hypertension and tachycardia and induces metabolic alterations including glucose intolerance and increase in resting metabolic rate. The objective of our study was to investigate the effect of surgical cure of pheochromocytoma on body-mass-index and the correlation of body-mass-index changes to preoperative endocrine parameters. Pheochromocytoma patients from the Munich ENSAT Registry were matched (1:2) for age and gender to patients from the German Conn's Registry, who had undergone surgery for aldosterone-producing-adenomas...
February 21, 2017: Hormone and Metabolic Research, Hormon- und Stoffwechselforschung, Hormones et Métabolisme
https://www.readbyqxmd.com/read/28220062/anatomical-and-molecular-properties-of-long-descending-propriospinal-neurons-in-mice
#10
Jamie R Flynn, Victoria L Conn, Kieran A Boyle, David I Hughes, Masahiko Watanabe, Tomoko Velasquez, Martyn D Goulding, Robert J Callister, Brett A Graham
Long descending propriospinal neurons (LDPNs) are interneurons that form direct connections between cervical and lumbar spinal circuits. LDPNs are involved in interlimb coordination and are important mediators of functional recovery after spinal cord injury (SCI). Much of what we know about LDPNs comes from a range of species, however, the increased use of transgenic mouse lines to better define neuronal populations calls for a more complete characterisation of LDPNs in mice. In this study, we examined the cell body location, inhibitory neurotransmitter phenotype, developmental provenance, morphology and synaptic inputs of mouse LDPNs throughout the cervical and upper thoracic spinal cord...
2017: Frontiers in Neuroanatomy
https://www.readbyqxmd.com/read/28217529/study-of-awareness-of-adrenal-disorders-among-interns-and-postgraduate-students-of-hamidia-hospital-bhopal
#11
Sachin Chittawar, T N Dubey, Jitendra Sharma, Sagar Khandare
INTRODUCTION: Adrenal disorders could be a life-threatening emergency, hence requires immediate therapeutic management. For this awareness regarding its diagnosis, management, and treatment is prime important. AIMS AND OBJECTIVE: To study the awareness of adrenal disorders among interns and postgraduates students of Hamidia Hospital, Bhopal. MATERIALS AND METHODS: A cross-sectional questionnaire-based study was performed. Fifty-six participants, i...
January 2017: Indian Journal of Endocrinology and Metabolism
https://www.readbyqxmd.com/read/28197318/discovery-of-vu0467485-az13713945-an-m4-pam-evaluated-as-a-preclinical-candidate-for-the-treatment-of-schizophrenia
#12
Michael R Wood, Meredith J Noetzel, Bruce J Melancon, Michael S Poslusney, Kellie D Nance, Miguel A Hurtado, Vincent B Luscombe, Rebecca L Weiner, Alice L Rodriguez, Atin Lamsal, Sichen Chang, Michael Bubser, Anna L Blobaum, Darren W Engers, Colleen M Niswender, Carrie K Jones, Nicholas J Brandon, Michael W Wood, Mark E Duggan, P Jeffrey Conn, Thomas M Bridges, Craig W Lindsley
Herein, we report the structure-activity relationships within a series of potent, selective, and orally bioavailable muscarinic acetylcholine receptor 4 (M4) positive allosteric modulators (PAMs). Compound 6c (VU0467485) possesses robust in vitro M4 PAM potency across species and in vivo efficacy in preclinical models of schizophrenia. Coupled with an attractive DMPK profile and suitable predicted human PK, 6c (VU0467485) was evaluated as a preclinical development candidate.
February 9, 2017: ACS Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/28196708/design-synthesis-and-biological-evaluation-of-2-4-disubstituted-oxazole-derivatives-as-potential-pde4-inhibitors
#13
Ya-Sheng Li, De-Kun Hu, Dong-Sheng Zhao, Xing-Yu Liu, Hong-Wei Jin, Gao-Peng Song, Zi-Ning Cui, Lian-Hui Zhang
In this study, a series of pyrazole derivatives containing 4-phenyl-2-oxazole moiety were designed and synthesized in a concise way, some of which exhibited considerable inhibitory activity against PDE4B and blockade of LPS-induced TNF-α release. Compound 4c displayed the strongest inhibition activity (IC50=1.6±0.4μM) and good selectivity against PDE4B. Meanwhile, compound 4c showed good in vivo activity in animal models of asthma/COPD and sepsis induced by LPS. The primary structure-activity relationship study showed the 3,5-dimethylpyrazole residue was essential for the bioactivity, and the substituted group R1 at the benzene ring also affected the activity...
February 3, 2017: Bioorganic & Medicinal Chemistry
https://www.readbyqxmd.com/read/28193289/microgeographical-structure-in-the-major-neotropical-malaria-vector-anopheles-darlingi-using-microsatellites-and-snp-markers
#14
Melina Campos, Jan E Conn, Diego Peres Alonso, Joseph M Vinetz, Kevin J Emerson, Paulo Eduardo Martins Ribolla
BACKGROUND: In recent decades, throughout the Amazon Basin, landscape modification contributing to profound ecological change has proceeded at an unprecedented rate. Deforestation that accompanies human activities can significantly change aspects of anopheline biology, though this may be site-specific. Such local changes in anopheline biology could have a great impact on malaria transmission. The aim of this study was to investigate population genetics of the main malaria vector in Brazil, Anopheles darlingi, from a microgeographical perspective...
February 13, 2017: Parasites & Vectors
https://www.readbyqxmd.com/read/28170340/adrenocortical-neoplasms-in-adulthood-and-childhood-distinct-presentation-review-of-the-clinical-pathological-and-imaging-characteristics
#15
Andréa Farias de Melo-Leite, Paula Condé Lamparelli Elias, Sara Reis Teixeira, Silvio Tucci, Gyl Eanes Barros, Sonir R Antonini, Valdair Francisco Muglia, Jorge Elias
Adrenocortical tumors (ACT) in adulthood and childhood vary in clinical, histopathological, molecular, prognostic, and imaging aspects. ACT are relatively common in adults, as adenomas are often found incidentally on imaging. ACT are rare in children, though they have a significantly higher prevalence in the south and southeast regions of Brazil. In clinical manifestation, adults with ACT present more frequently with glucocorticoid overproduction (Cushing syndrome), mineralocorticoid syndromes (Conn syndrome), or the excess of androgens in women...
March 1, 2017: Journal of Pediatric Endocrinology & Metabolism: JPEM
https://www.readbyqxmd.com/read/28168828/relative-bioavailability-of-a-dolutegravir-dispersible-tablet-and-the-effects-of-low-and-high-mineral-content-water-on-the-tablet-in-healthy-adults
#16
Ann M Buchanan, Michael Holton, Ian Conn, Mark Davies, Mike Choukour, Brian R Wynne
Dolutegravir (DTG) is approved in the United States to treat HIV-1-infected patients weighing ≥30 kg. A dispersible DTG tablet formulation was recently developed for pediatric patients. This study compares the pharmacokinetics (PK) of the dispersible tablet with that of a previously evaluated granule formulation. In this randomized, open-label, crossover study, 15 healthy adults received single oral doses of DTG 20 mg every 7 days across 5 treatment arms: granules consumed immediately after mixture with purified water, dispersible DTG consumed immediately after reconstitution in low-mineral-content (LMC) or high-mineral-content (HMC) water, and dispersible DTG consumed 30 minutes after dispersal in LMC or HMC water...
February 7, 2017: Clinical Pharmacology in Drug Development
https://www.readbyqxmd.com/read/28138537/confirmation-of-a-de-novo-structure-prediction-for-an-atomically-precise-monolayer-coated-silver-nanoparticle
#17
Brian E Conn, Aydar Atnagulov, Bokwon Yoon, Robert N Barnett, Uzi Landman, Terry P Bigioni
Fathoming the principles underpinning the structures of monolayer-coated molecular metal nanoparticles remains an enduring challenge. Notwithstanding recent x-ray determinations, coveted veritable de novo structural predictions are scarce. Building on recent syntheses and de novo structure predictions of M3Au x Ag17-x (TBBT)12, where M is a countercation, x = 0 or 1, and TBBT is 4-tert-butylbenzenethiol, we report an x-ray-determined structure that authenticates an a priori prediction and, in conjunction with first-principles theoretical analysis, lends force to the underlying forecasting methodology...
November 2016: Science Advances
https://www.readbyqxmd.com/read/28125111/direct-demonstration-of-lipid-phosphorylation-in-the-lipid-bilayer-of-the-biomimetic-bicontinuous-cubic-phase-using-the-confined-enzyme-lipid-a-phosphoethanolamine-transferase
#18
Leonie van 't Hag, Anandhi Anandan, Shane A Seabrook, Sally L Gras, Calum J Drummond, Alice Vrielink, Charlotte E Conn
Retention of amphiphilic protein activity within the lipid bilayer membrane of the nanostructured biomimetic bicontinuous cubic phase is crucial for applications utilizing these hybrid protein-lipid self-assembly materials, such as in meso membrane protein crystallization and drug delivery. Previous work, mainly on soluble and membrane-associated enzymes, has shown that enzyme activity may be modified when immobilized, including membrane bound enzymes. The effect on activity may be even greater for amphiphilic enzymes with a large hydrophilic domain, such as the Neisserial enzyme lipid A phosphoethanolamine transferase (EptA)...
January 26, 2017: Soft Matter
https://www.readbyqxmd.com/read/28123218/the-promise-of-electronic-case-reporting
#19
REVIEW
William R Mac Kenzie, Arthur J Davidson, Andrew Wiesenthal, Jeffrey P Engel, Kathryn Turner, Laura Conn, Scott J Becker, Sharon Moffatt, Samuel L Groseclose, Jim Jellison, John Stinn, Nedra Y Garrett, Lesliann Helmus, Bob Harmon, Chesley L Richards, John R Lumpkin, Michael F Iademarco
No abstract text is available yet for this article.
November 2016: Public Health Reports
https://www.readbyqxmd.com/read/28108498/mglur2-versus-mglur3-metabotropic-glutamate-receptors-in-primate-dorsolateral-prefrontal-cortex-postsynaptic-mglur3-strengthen-working-memory-networks
#20
Lu E Jin, Min Wang, Veronica C Galvin, Taber C Lightbourne, Peter Jeffrey Conn, Amy F T Arnsten, Constantinos D Paspalas
The newly evolved circuits in layer III of primate dorsolateral prefrontal cortex (dlPFC) generate the neural representations that subserve working memory. These circuits are weakened by increased cAMP-K(+) channel signaling, and are a focus of pathology in schizophrenia, aging, and Alzheimer's disease. Cognitive deficits in these disorders are increasingly associated with insults to mGluR3 metabotropic glutamate receptors, while reductions in mGluR2 appear protective. This has been perplexing, as mGluR3 has been considered glial receptors, and mGluR2 and mGluR3 have been thought to have similar functions, reducing glutamate transmission...
January 19, 2017: Cerebral Cortex
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