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Fabrizio Buffolo, Silvia Monticone, Jacopo Burrello, Martina Tetti, Franco Veglio, Tracy Ann Williams, Paolo Mulatero
Primary aldosteronism (PA) was first reported by Jerome W. Conn in 1954 when it was considered a rare disorder, only suspected in cases of hypertension and spontaneous hypokalemia. Over the last 30 years, with the wide application of the plasma aldosterone to plasma renin activity ratio as screening test, the clinical spectrum of PA has dramatically changed. Different studies displayed significant differences in term of patients investigated, diagnostic criteria and hormonal assays; however, large prospective studies with robust diagnostic criteria indicated that the prevalence of PA is around 6% of the general hypertensive population and 11% of the patients referred to hypertension centers...
November 16, 2017: Hormone and Metabolic Research, Hormon- und Stoffwechselforschung, Hormones et Métabolisme
Giulia Furlanis, Stella Bernardi, Monica Cavressi, Lorenzo Zandonà, Renzo Carretta, Bruno Fabris, Moreno Bardelli
Primary aldosteronism (PA), also known as Conn's syndrome, is a frequent cause of secondary hypertension. If PA is due to a documented unilateral adrenal adenoma, adrenalectomy is the treatment of choice. Endocrine Society guidelines suggest monitoring potassium after adrenalectomy, while there is no mention of sodium disorders after surgery. Here we report the case of a patient with Conn's syndrome who developed hyponatremia after surgery. This was an unexpected event in the course of the treatment, which sheds light on the fact that low levels of aldosterone strongly influence sodium concentration, and advises clinicians to monitor sodium after adrenalectomy...
October 2017: Journal of the Renin-angiotensin-aldosterone System: JRAAS
Mariano Altamiranda-Saavedra, Jan E Conn, Margarita M Correa
This study evaluated the influence of environmental heterogeneity on Anopheles darlingi genetic and morphometric traits at a microgeographic level. Specimens of An. darlingi collected from multiple municipalities in the Colombian malaria endemic region Urabá-Bajo Cauca and Alto Sinú (UCS) were analyzed using 13 microsatellite loci. Spatial genetic structure, population variation and wing geometric morphometric analyses were performed. Microsatellite results showed low genetic differentiation and high gene flow among populations; four highly admixed subpopulations were detected with no particular association to the municipalities...
November 11, 2017: Infection, Genetics and Evolution
Branden J Stansley, Nicole M Fisher, Rocco G Gogliotti, Craig W Lindsley, P Jeffrey Conn, Colleen M Niswender
Dysregulated fear memory can lead to a broad spectrum of anxiety disorders. The brain systems underlying fear memory are manifold, with the hippocampus being prominently involved by housing fear-related spatial memories as engrams, which are created and stored through neural changes such as synaptic plasticity. Although metabotropic glutamate (mGlu) receptors contribute significantly to both fear behavior and hippocampal synaptic plasticity, the relationship between these two phenomena has not been fully elucidated...
November 9, 2017: Cerebral Cortex
Mayank Gupta, Dinesh De, Kapil Tomar, Parimal K Bharadwaj
The ligand H2L has been built by linking an imidazole moiety to the 5-position of isophthalic acid. It forms two types of porous frameworks, {[Zn(L)]·2DMF·2H2O}n (1) and {[(CH3)2NH2][Zn2(L)(H2O)PO4]·2DMF}n (2). 1 is a porous neutral framework and has rtl rutile 3,6-conn topology, while 2 is an organo-metallophosphate anionic porous framework with double-walled hexagonal channels. Framework 1' (desolvated) exhibits moderate CO2 adsorption (58 cc g(-1) at 273 K, 1 bar), whereas 2' (desolvated) shows a microporous nature with a high adsorption of CO2 (111...
November 13, 2017: Inorganic Chemistry
Ruth E Conn, Donna Warren-Morris, Thomas J Prihoda, Beatriz M Hicks, Emelda E Hernandez
Purpose: This pilot study compared the effectiveness of plaque removal of two manual toothbrushes; a novel toothbrush design and a control reference toothbrush.Methods: Thirty-eight individuals meeting specific criteria consented to participate and were randomly assigned to one of two groups. Subjects were given both study toothbrushes eight days prior to data collection to use on alternate days for two minutes twice daily for familiarization. Subjects refrained from any oral hygiene procedures for twenty-four hours prior to data collection at which time a baseline plaque score was recorded using the O'Leary Plaque Control Record...
April 2017: Journal of Dental Hygiene: JDH
Ashish Verma, Kapil Tomar, Parimal K Bharadwaj
A thermally stable cadmium-based chiral metal-organic framework (MOF), {[Cd2(L)(H2O)(DMF)]·3DMF·2H2O}n (1; DMF = N,N-dimethylformamide), has been synthesized from an achiral ligand by spontaneous resolution. The MOF features 1D open channels with a large density of active metal sites and has a 3,6-c binodal net with a rare sit 3,6-conn topology. The metal-bound water and DMF solvents could be easily removed along with the guest molecules in the lattice upon activation to afford the desolvated framework 1'...
November 3, 2017: Inorganic Chemistry
Conn Sugihara, Steve Furniss, Jonathan Hyde, Michael Lewis, Neil Sulke
Aims: To investigate the effect of minimally invasive thoracoscopic surgical ablation and nMARQ irrigated multi-electrode phased radiofrequency (RF) ablation to treat paroxysmal atrial fibrillation (AF) compared with PVAC multi-electrode phased RF ablation, with beat-to-beat device-derived Holter monitoring throughout the study duration. Methods and results: An investigator-initiated prospective trial of patients with paroxysmal AF randomized (1:1:1) to initial surgical, nMARQ or PVAC ablation...
October 30, 2017: Europace: European Pacing, Arrhythmias, and Cardiac Electrophysiology
Rafael Barreto, Yukiko Kitase, Tsutomu Matsumoto, Fabrizio Pin, Kyra C Colston, Katherine E Couch, Thomas M O'Connell, Marion E Couch, Lynda F Bonewald, Andrea Bonetto
Chemotherapy promotes the development of cachexia, a debilitating condition characterized by muscle and fat loss. ACVR2B/Fc, an inhibitor of the Activin Receptor 2B signaling, has been shown to preserve muscle mass and prolong survival in tumor hosts, and to increase bone mass in models of osteogenesis imperfecta and muscular dystrophy. We compared the effects of ACVR2B/Fc on muscle and bone mass in mice exposed to Folfiri. In addition to impairing muscle mass and function, Folfiri had severe negative effects on bone, as shown by reduced trabecular bone volume fraction (BV/TV), thickness (Tb...
October 31, 2017: Scientific Reports
James C Tarr, Michael R Wood, Meredith J Noetzel, Bruce J Melancon, Atin Lamsal, Vincent B Luscombe, Alice L Rodriguez, Frank W Byers, Sichen Chang, Hyekyung P Cho, Darren W Engers, Carrie K Jones, Colleen M Niswender, Michael W Wood, Nicholas J Brandon, Mark E Duggan, P Jeffrey Conn, Thomas M Bridges, Craig W Lindsley
Herein we describe the continued optimization of M4 positive allosteric modulators (PAMs) within the 5-amino-thieno[2,3-c]pyridazine series of compounds. In this letter, we disclose our studies on tertiary amides derived from substituted azetidines. This series provided excellent CNS penetration, which had been challenging to consistently achieve in other amide series. Efforts to mitigate high clearance, aided by metabolic softspot analysis, were unsuccessful and precluded this series from further consideration as a preclinical candidate...
October 24, 2017: Bioorganic & Medicinal Chemistry Letters
Kin-Hing William Lau, Virginia M Stiffel, Charles H Rundle, Mehran Amoui, Jordan Tapia, Tyler D White, Matilda H-C Sheng
This study sought to understand the regulation of an osteoclastic protein-tyrosine phosphatase (PTP-oc), a positive regulator of osteoclast activaty. Our past studies suggested that PTP-oc is regulated post-transcriptionally. The 3'-UTR of PTP-oc mRNA contains a target site for miR17. During osteoclastic differentiation, there was an inverse relationship between the cellular levels of miR17 (expressed as one of the six cluster genes of miR17~92) and PTP-oc mRNA. Overexpression of pre-miR17~92 in mouse osteoclast precursors reduced PTP-oc mRNA level and the size of the derived osteoclasts; whereas deletion of miR17~92 or inhibition of miR17 resulted in the formation of larger osteoclasts containing more nuclei that expressed higher PTP-oc mRNA levels and created larger resorption pits...
October 5, 2017: JBMR Plus
Paweł J Zawadzki, Konrad Perkowski, Marcin Padzik, Elżbieta Mierzwińska-Nastalska, Jacek P Szaflik, David Bruce Conn, Lidia Chomicz
The oral cavity environment may be colonized by polymicrobial communities with complex, poorly known interrelations. The aim of this study was to determine oral microbiota diversity in order to prevent the spread of infectious microorganisms that are risk factors for human health complications in patients requiring treatment due to various disabilities. The study examined Polish adults aged between 40 and 70 years; parasitological, microbiological, and mycological data collected before treatment were analyzed...
2017: BioMed Research International
Luisa Di Menna, Max E Joffe, Luisa Iacovelli, Rosamaria Orlando, Craig W Lindsley, Jèrome Mairesse, Pierre Gressèns, Milena Cannella, Filippo Caraci, Agata Copani, Valeria Bruno, Giuseppe Battaglia, P Jeffrey Conn, Ferdinando Nicoletti
mGlu5 receptors are involved in mechanisms of activity-dependent synaptic plasticity, and are targeted by drugs developed for the treatment of CNS disorders. We report that mGlu3 receptors, which are traditionally linked to the control of neurotransmitter release, support mGlu5 receptor signaling in neurons and largely contribute to the robust mGlu5 receptor-mediated polyphosphoinositide hydrolysis in the early postnatal life. In cortical pyramidal neurons, mGlu3 receptor activation potentiated mGlu5 receptor-mediated somatic Ca(2+) mobilization, and mGlu3 receptor-mediated long-term depression in the prefrontal cortex required the endogenous activation of mGlu5 receptors...
October 25, 2017: Neuropharmacology
Masahito Abe, Mabel Seto, Rocco G Gogliotti, Matthew T Loch, Katrina A Bollinger, Sichen Chang, Eileen M Engelberg, Vincent B Luscombe, Joel M Harp, Michael Bubser, Darren W Engers, Carrie K Jones, Alice L Rodriguez, Anna L Blobaum, P Jeffrey Conn, Colleen M Niswender, Craig W Lindsley
Herein, we report the structure-activity relationships within a series of mGlu7 PAMs based on a pyrazolo[1,5-a]pyrimidine core with excellent CNS penetration (Kps > 1 and Kp,uus > 1). Analogues in this series proved to display a range of Group III mGlu receptor selectivity, but VU6005649 emerged as the first dual mGlu7/8 PAM, filling a void in the Group III mGlu receptor PAM toolbox and demonstrating in vivo efficacy in a mouse contextual fear conditioning model.
October 12, 2017: ACS Medicinal Chemistry Letters
Madeline F Long, Julie L Engers, Sichen Chang, Xiaoyan Zhan, Rebecca L Weiner, Vincent B Luscombe, Alice L Rodriguez, Hyekyung P Cho, Colleen M Niswender, Thomas M Bridges, P Jeffrey Conn, Darren W Engers, Craig W Lindsley
This Letter details our efforts to replace the 3-amino moiety, an essential pharmacophore for M4 PAM activity in most M4 PAMs to date, within the thieno[2,3-b]pyridine core, as the β-amino carboxamide motif has been shown to engender poor solubility, varying degrees of P-gp efflux and represents a structural alert. A scaffold hopping exercise identified a novel 2,4-dimethylquinoline carboxamide core that provided M4 PAM activity and good CNS penetration without an amino moiety. In addition, MacMillan photoredox catalysis chemistry was essential for construction of the 2,4-dimethylquinoline core...
November 15, 2017: Bioorganic & Medicinal Chemistry Letters
David K Conn
No abstract text is available yet for this article.
September 20, 2017: American Journal of Geriatric Psychiatry
Richard L Conn, Steven McVea, Angela Carrington, Tim Dornan
INTRODUCTION: Recent National Institute for Health and Care Excellence (NICE) guidelines aim to improve intravenous (IV) fluid prescribing for children, but existing evidence about how and why fluid prescribing errors occur is limited. Studying this can lead to more effective implementation, through education and systems design. AIMS: Identify types of IV fluid prescribing errors reported in practiceAnalyse factors that contribute to errorsProvide guidance to educators and those responsible for designing systems...
2017: PloS One
Ezinne I Ogbureke, Ruth E Conn, Dennis E Garcia, Cleverick D Johnson
A 56-year-old white man presented at our dental clinic for routine care. The intraoral examination revealed an asymptomatic red lesion with white vesicle-like areas on the right side of the soft palate. The extraoral examination was normal, and regional lymph nodes were nonpalpable. The patient's medical history included liver cirrhosis and pancreatitis. He also had a 30-year history of alcohol misuse (1-5 drinks per day) and a 30-pack-year smoking history. (The patient had stopped drinking at the time of presentation, and had quit smoking 2 years earlier...
October 2017: Journal of Family Practice
Lesley Gotlib Conn, Ashley Zwaiman, Tracey DasGupta, Brigette Hales, Aaron Watamaniuk, Avery B Nathens
BACKGROUND: Challenges delivering quality care are especially salient during hospital discharge and care transitions. Severely injured patients discharged from a trauma centre will go either home, to rehabilitation or another acute care hospital with complex management needs. This purpose of this study was to explore the experiences of trauma patients and families treated in a regional academic trauma centre to better understand and improve their discharge and care transition experiences...
September 28, 2017: Injury
Haitian Fan, Adam B Conn, Preston B Williams, Stephen Diggs, Joseph Hahm, Howard B Gamper, Ya-Ming Hou, Seán E O'Leary, Yinsheng Wang, Gregor M Blaha
In prokaryotes, RNA polymerase and ribosomes can bind concurrently to the same RNA transcript, leading to the functional coupling of transcription and translation. The interactions between RNA polymerase and ribosomes are crucial for the coordination of transcription with translation. Here, we report that RNA polymerase directly binds ribosomes and isolated large and small ribosomal subunits. RNA polymerase and ribosomes form a one-to-one complex with a micromolar dissociation constant. The formation of the complex is modulated by the conformational and functional states of RNA polymerase and the ribosome...
August 16, 2017: Nucleic Acids Research
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