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https://www.readbyqxmd.com/read/27911048/fluorescent-oligonucleotide-probes-for-screening-high-affinity-nucleobase-surrogates
#1
Asmo Aro-Heinilä, Tuomas Lönnberg
Double-helical oligonucleotide probes featuring a single-nucleotide gap opposed by one of the canonical nucleobases and flanked by the fluorescent nucleobase analogue pyrrolocytosine have been synthesized and titrated with PdII chelates of dipicolinamide and its N2,N6-dialkylated derivatives. The fluorometric titrations revealed greatly increased affinity of the PdII chelates for the nucleobases opposing the gap compared to the respective free nucleotides in solution. Owing to the constrained environment of the single-nucleotide gap, the relative stabilities of the various PdII mediated base pairs were also significantly different from those previously reported at monomer level...
December 2, 2016: Chemistry: a European Journal
https://www.readbyqxmd.com/read/27905903/immediate-effect-of-cpap-titration-on-perceived-health-related-quality-of-life-a-prospective-observational-study
#2
Serena Iacono Isidoro, Adriana Salvaggio, Anna Lo Bue, Salvatore Romano, Oreste Marrone, Giuseppe Insalaco
BACKGROUND: Perceived Health Related Quality of Life (HRQoL) is impaired in obstructive sleep apnea (OSA). This study examines changes in HRQoL aspects occurring immediately after CPAP titration. Furthermore, we analyzed variations in each gender and in patients undergoing home or laboratory-based CPAP titration pathways. METHODS: Twohundredfive outpatients (151 M) (56.7 ± 10.3 years) were evaluated, before first visit and nocturnal diagnostic examination (T0), and the morning after CPAP titration (T1)...
December 1, 2016: BMC Pulmonary Medicine
https://www.readbyqxmd.com/read/27904731/clinical-usefulness-of-long-term-application-of-fentanyl-matrix-in-chronic-non-cancer-pain-improvement-of-pain-and-physical-and-emotional-functions
#3
Jaewon Lee, Joon Shik Yoon, Jae Hyup Lee, So-Hak Chung, Kyu-Yeol Lee, Young Yul Kim, Jong Moon Kim, Min Ho Kong, Ung Gu Kang, Ye-Soo Park
BACKGROUND: Opioids are recently recommended for those who do not gain adequate pain relief from the use of acetaminophen or nonsteroidal anti-inflammatory drugs. Medical opioids are administered in various routes, and transdermal opioid products that can make up for the weaknesses of the oral or intravenous products have been developed. This study is to evaluate the clinical usefulness of fentanyl matrix in terms of the long-term improvement in pain and physical and mental functions...
December 2016: Clinics in Orthopedic Surgery
https://www.readbyqxmd.com/read/27903799/cxcr6-mediated-sivagmsab-entry-into-sabaeus-african-green-monkey-lymphocytes-implicates-widespread-use-of-non-ccr5-pathways-in-natural-host-infections
#4
Katherine S Wetzel, Yanjie Yi, Sarah T C Elliott, Dino Romero, Beatrice Jacquelin, Beatrice H Hahn, Michaela Muller-Trutwin, Cristian Apetrei, Ivona Pandrea, Ronald G Collman
: African green monkeys (AGM) and sooty mangabeys (SM) are well-studied natural hosts of SIV, which do not progress to AIDS when infected with their species-specific viruses. SIV natural hosts express very low levels of the canonical entry coreceptor CCR5, and recent studies have shown that CCR5 is dispensable for SIV infection of SM in vivo, and blocking CCR5 does not prevent ex vivo infection of PBMC from SM or vervet AGM. In both hosts, CXCR6 is an efficient entry pathway in vitro...
November 30, 2016: Journal of Virology
https://www.readbyqxmd.com/read/27903664/practical-considerations-for-therapies-targeting-the-prostacyclin-pathway
#5
REVIEW
Harrison W Farber, Wendy Gin-Sing
Therapies that target the prostacyclin pathway play a key role in the treatment of both early- and late-stage pulmonary arterial hypertension, and provide significant clinical benefits for patients. A number of agents have been approved, which are administered via intravenous, subcutaneous, inhaled or oral routes. The use of these therapies is associated with practical challenges, relating to the need for up-titration and their routes of administration. We discuss here a number of measures that can be taken to support patients and healthcare professionals in order to address the complexities of using these therapies and to encourage compliance...
December 2016: European Respiratory Review: An Official Journal of the European Respiratory Society
https://www.readbyqxmd.com/read/27902935/g-quadruplex-fluorescence-sensing-by-core-extended-naphthalene-diimides
#6
Michela Zuffo, Filippo Doria, Silvia Botti, Greta Bergamaschi, Mauro Freccero
BACKGROUND: Fluorescent sensing of G-quadruplex nucleic acids (G4s) is an effective strategy to elucidate their role in vitro and in vivo. Small molecule ligands have often been exploited, producing an emission light up upon binding. Naphthalene diimides (NDIs), although potent G4 binders exhibiting red-NIR fluorophores, have only been marginally exploited, as they are usually quenched upon binding. Contrary, aggregating core-extended naphthalene diimides (cex-NDIs) proved to be effective probes...
November 27, 2016: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/27901586/long-single-molecule-reads-can-resolve-the-complexity-of-the-influenza-virus-composed-of-rare-closely-related-mutant-variants
#7
Alexander Artyomenko, Nicholas C Wu, Serghei Mangul, Eleazar Eskin, Ren Sun, Alex Zelikovsky
As a result of a high rate of mutations and recombination events, an RNA-virus exists as a heterogeneous "swarm" of mutant variants. The long read length offered by single-molecule sequencing technologies allows each mutant variant to be sequenced in a single pass. However, high error rate limits the ability to reconstruct heterogeneous viral population composed of rare, related mutant variants. In this article, we present two single-nucleotide variants (2SNV), a method able to tolerate the high error rate of the single-molecule protocol and reconstruct mutant variants...
November 30, 2016: Journal of Computational Biology: a Journal of Computational Molecular Cell Biology
https://www.readbyqxmd.com/read/27901516/psychotropic-drug-changes-contributing-to-readmissions-in-medically-hospitalized-psychiatric-patients-a-retrospective-study
#8
Subramoniam Madhusoodanan, Biling Xu, Srikanth Prayaga, Piotr Slowik, Ronald Brenner, Wallace Thomas, Natalie Schwartz
BACKGROUND: Psychotropic drug changes during medical hospitalizations may lead to psychiatric and medical readmissions. METHODS: One-year hospitalization records of nursing home patients with chronic mental illness and a psychotropic drug change during medical admission were reviewed. We calculated the readmission rates for 30, 60, and 90 days; the classes of the psychotropic drugs changed; the reason for change; and the specialties of the responsible physicians...
November 2016: Annals of Clinical Psychiatry: Official Journal of the American Academy of Clinical Psychiatrists
https://www.readbyqxmd.com/read/27901465/livestock-susceptibility-to-infection-with-middle-east-respiratory-syndrome-coronavirus
#9
Júlia Vergara-Alert, Judith M A van den Brand, W Widagdo, Marta Muñoz, Stalin Raj, Debby Schipper, David Solanes, Ivan Cordón, Albert Bensaid, Bart L Haagmans, Joaquim Segalés
Middle East respiratory syndrome (MERS) cases continue to be reported, predominantly in Saudi Arabia and occasionally other countries. Although dromedaries are the main reservoir, other animal species might be susceptible to MERS coronavirus (MERS-CoV) infection and potentially serve as reservoirs. To determine whether other animals are potential reservoirs, we inoculated MERS-CoV into llamas, pigs, sheep, and horses and collected nasal and rectal swab samples at various times. The presence of MERS-CoV in the nose of pigs and llamas was confirmed by PCR, titration of infectious virus, immunohistochemistry, and in situ hybridization; seroconversion was detected in animals of both species...
February 15, 2017: Emerging Infectious Diseases
https://www.readbyqxmd.com/read/27900961/efficacy-and-safety-of-calcium-acetate-magnesium-carbonate-in-the-treatment-of-hyperphosphatemia-in-dialysis-patients
#10
Imed Helal, Hanene Elkateb, Hafedh Hedri, Malika Hajri, Fethi Ben Hamida
A phosphate binder combining calcium and magnesium offers an interesting therapeutic option to control hyperphosphatemia in dialysis patients. We investigated the effectiveness and tolerance of calcium acetate-magnesium carbonate (Ca-Mg). This is a 16-week prospective study including 16 dialysis patients. After an initial two-week washout period, serum phosphorus (sPho) ≥1.8 mmol/L, serum calcium (sCa) ≤2.6 mmol/L, and serum magnesium ≤1.5 mmol/L were the main inclusion criteria. The initial dose of Ca-Mg depended on sPho level and was titrated for every two weeks to have a sPho ≤ 1...
November 2016: Saudi Journal of Kidney Diseases and Transplantation
https://www.readbyqxmd.com/read/27900561/mineralocorticoid-antagonists-as-adjuncts-in-neovascular-age-related-macular-degeneration
#11
Kapil G Kapoor, Niket Todi, Alan L Wagner
INTRODUCTION: The purpose of this project was to evaluate the role of MR antagonists as an adjunct in patients with neovascular age-related macular degeneration (AMD) who have chronic subretinal fluid. METHODS: Inclusion criteria were patients with a diagnosis of neovascular AMD, who had completed at least six anti-VEGF injections, and had persistent subretinal fluid (SRF) on optical coherence tomography (OCT). Treatment with oral eplerenone was initiated and dose titrated according to protocol...
November 29, 2016: Ophthalmology and Therapy
https://www.readbyqxmd.com/read/27899400/study-protocol-a-phase-iii-randomised-double-blind-parallel-arm-stratified-block-randomised-placebo-controlled-trial-investigating-the-clinical-effect-and-cost-effectiveness-of-sertraline-for-the-palliative-relief-of-breathlessness-in-people-with-chronic-breathlessness
#12
Gareth J Watts, Katherine Clark, Meera Agar, Patricia M Davidson, Christine McDonald, Lawrence T Lam, Dimitar Sajkov, Nicola McCaffrey, Matthew Doogue, Amy P Abernethy, David C Currow
INTRODUCTION: Breathlessness remains a highly prevalent and distressing symptom for many patients with progressive life-limiting illnesses. Evidence-based interventions for chronic breathlessness are limited, and there is an ongoing need for high-quality research into developing management strategies for optimal palliation of this complex symptom. Previous studies have suggested that selective serotonin reuptake inhibitors such as sertraline may have a role in reducing breathlessness...
November 29, 2016: BMJ Open
https://www.readbyqxmd.com/read/27897343/optimization-of-the-alkyl-linker-of-to-base-surrogate-in-triplex-forming-pna-for-enhanced-binding-to-double-stranded-rna
#13
Takaya Sato, Yusuke Sato, Seiichi Nishizawa
A series of triplex-forming PNA probes carrying a thiazole orange (TO) base surrogate through an alkyl linker was synthesized, and the interactions between these so-called tFIT probes and purine-rich sequences within double-stranded RNA (dsRNA) were examined. We found the TO base surrogate linker significantly affected both the binding affinity and the fluorescence response upon triplex formation with the target dsRNA. Among the probes examined, the TO base surrogate connected through the propyl linker in the tFIT probes increased the binding affinity by a factor of ten while maintaining its function as the fluorescent universal base...
November 29, 2016: Chemistry: a European Journal
https://www.readbyqxmd.com/read/27895178/conserved-region-c-functions-to-regulate-pd-1-expression-and-subsequent-cd8-t-cell-memory
#14
Alexander P R Bally, Yan Tang, Joshua T Lee, Benjamin G Barwick, Ryan Martinez, Brian D Evavold, Jeremy M Boss
Expression of programmed death 1 (PD-1) on CD8 T cells promotes T cell exhaustion during chronic Ag exposure. During acute infections, PD-1 is transiently expressed and has the potential to modulate CD8 T cell memory formation. Conserved region C (CR-C), a promoter proximal cis-regulatory element that is critical to PD-1 expression in vitro, responds to NFATc1, FoxO1, and/or NF-κB signaling pathways. Here, a CR-C knockout mouse was established to determine its role on PD-1 expression and the corresponding effects on T cell function in vivo...
November 28, 2016: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/27894861/development-of-a-competitive-double-antibody-lateral-flow-assay-for-the-detection-of-antibodies-specific-to-glycoprotein-b-of-aujeszky-s-disease-virus-in-swine-sera
#15
V V Vrublevskaya, V N Afanasyev, A A Grinevich, Yu Y Skarga, P P Gladyshev, S A Ibragimova, D V Krylsky, O S Morenkov
Three lateral flow assays (LFAs) for the detection of antibodies against glycoprotein B (gB) of Aujeszky's disease virus (ADV) in swine sera: a competitive double antibody sandwich LFA without a preincubation step (CDAS-gB-LFA), a CDAS-gB-LFA with a preincubation step (pCDAS-gB-LFA), and a competitive direct gB-LFA have been developed and were compared with each other and with a gB-ELISA. The assays are based on monoclonal antibodies to immunodominant epitopes of ADV gB. The pCDAS-gB-LFA proved to be the most specific and sensitive assay to detect antibodies directed to ADV gB...
November 25, 2016: Journal of Virological Methods
https://www.readbyqxmd.com/read/27894842/energetic-basis-on-interactions-between-ferredoxin-and-ferredoxin-nadp-reductase-at-varying-physiological-conditions
#16
Misaki Kinoshita, Ju Yaen Kim, Satoshi Kume, Yuxi Lin, K Hun Mok, Yosky Kataoka, Koichiro Ishimori, Natalia Markova, Genji Kurisu, Toshiharu Hase, Young-Ho Lee
In spite of a number of studies to characterize ferredoxin (Fd):ferredoxin NADP(+) reductase (FNR) interactions at limited conditions, detailed energetic investigation on how these proteins interact under near physiological conditions and its linkage to FNR activity are still lacking. We herein performed systematic Fd:FNR binding thermodynamics using isothermal titration calorimetry (ITC) at distinct pH (6.0 and 8.0), NaCl concentrations (0-200 mM), and temperatures (19-28 °C) for mimicking physiological conditions in chloroplasts...
November 25, 2016: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/27893511/continuous-infusion-antiepileptic-medications-for-refractory-status-epilepticus-a-review-for-nurses
#17
Adam L Wiss, Michael Samarin, Jacob Marler, G Morgan Jones
Status epilepticus requires treatment with emergent initial therapy with a benzodiazepine and urgent control therapy with an additional antiepileptic drug (AED) to terminate clinical and/or electrographic seizure activity. However, nearly one-third of patients will prove refractory to the aforementioned therapies and are prone to a higher degree of neuronal injury, resistance to pharmacotherapy, and death. Current guidelines for refractory status epilepticus (RSE) recommend initiating a continuous intravenous (CIV) anesthetic over bolus dosing with a different AED...
January 2017: Critical Care Nursing Quarterly
https://www.readbyqxmd.com/read/27892585/elemental-steps-of-the-thermodynamics-of-dihydropyrimidine-a-new-class-of-organic-hydride-donors
#18
Fan-Kun Meng, Xiao-Qing Zhu
25 Dihydropyrimidine derivatives, a new class of organo-hydrides, were designed and synthesized by the Biginelli reaction. For the first time, the thermodynamic driving forces of the six elemental steps to obtain a hydride in acetonitrile were determined by isothermal titration and electrochemical methods, respectively. The effects of molecular structures and substituents on these thermodynamic parameters were examined, uncovering some interesting structure-reactivity relationships. Both the thermodynamic and kinetic studies show that the hydride transfer from dihydropyrimidines to 9-phenylxanthylium (PhXn(+)ClO4(-)) prefers a concerted mechanism...
November 28, 2016: Organic & Biomolecular Chemistry
https://www.readbyqxmd.com/read/27890528/pathological-concentration-of-zinc-dramatically-accelerates-abnormal-aggregation-of-full-length-human-tau-and-thereby-significantly-increases-tau-toxicity-in-neuronal-cells
#19
Ji-Ying Hu, De-Lin Zhang, Xiao-Ling Liu, Xue-Shou Li, Xiao-Qing Cheng, Jie Chen, Hai-Ning Du, Yi Liang
A pathological hallmark of Alzheimer disease and other tauopathies is the formation of neurofibrillary tangles mainly composed of bundles of fibrils formed by microtubule-associated protein Tau. Here we study the effects of Zn(2+) on abnormal aggregation and cytotoxicity of a pathological mutant ΔK280 of full-length human Tau. As revealed by Congo red binding assays, transmission electron microscopy, immunofluorescence, Western blot, and immunogold electron microscopy, pathological concentration of Zn(2+) dramatically accelerates the fibrillization of ΔK280 both in vitro and in SH-SY5Y neuroblastoma cells...
November 23, 2016: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/27890471/rationale-and-study-design-of-motion-a-phase-4-prospective-single-arm-open-label-study-to-measure-outcomes-in-patients-with-pulmonary-arterial-hypertension-not-on-active-treatment
#20
Stephen C Mathai, Omar Minai, Sean D Sullivan, Debra Lerner, Deborah Levine
In clinical trials of treatments for pulmonary arterial hypertension (PAH), objective measures, such as 6-min walking distance (6MWD) are limited in their ability to characterize the impact of PAH therapy from a patient's perspective. Few clinical studies have evaluated the primary effects of pharmacologic treatment on patient-reported outcomes, such as symptoms, health-related quality of life (HRQoL), and productivity. MOTION (NCT02191137) is a prospective, multicenter, single-arm, open-label, phase 4 trial designed to assess whether riociguat monotherapy will improve patient-reported outcomes in patients with PAH in the United States who are not currently on treatment...
November 2, 2016: Respiratory Medicine
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