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https://www.readbyqxmd.com/read/29352704/treatment-of-adult-chronic-indeterminate-chagas-disease-with-benznidazole-and-three-e1224-dosing-regimens-a-proof-of-concept-randomised-placebo-controlled-trial
#1
Faustino Torrico, Joaquim Gascon, Lourdes Ortiz, Cristina Alonso-Vega, María-Jesús Pinazo, Alejandro Schijman, Igor C Almeida, Fabiana Alves, Nathalie Strub-Wourgaft, Isabela Ribeiro
BACKGROUND: Chagas disease is a major neglected vector-borne disease. In this study, we investigated the safety and efficacy of three oral E1224 (a water-soluble ravuconazole prodrug) regimens and benznidazole versus placebo in adult chronic indeterminate Chagas disease. METHOD: In this proof-of-concept, double-blind, randomised phase 2 clinical trial, we recruited adults (18-50 years) with confirmed diagnosis of Trypanosoma cruzi infection from two outpatient units in Bolivia...
January 15, 2018: Lancet Infectious Diseases
https://www.readbyqxmd.com/read/29352631/we-could-learn-much-more-from-1918-pandemic-the-mis-fortune-of-research-relying-on-original-death-certificates
#2
Wladimir J Alonso, Francielle C Nascimento, Gerardo Chowell, Cynthia Schuck-Paim
PURPOSE: The analysis of historical death certificates has enormous potential for understanding how the health of populations was shaped by diseases and epidemics and by the implementation of specific interventions. In Brazil, the systematic archiving of mortality records was initiated only in 1944-hence the analysis of death registers before this time requires searching for these documents in public archives, notaries, parishes, and especially ancient cemeteries, which are often the only remaining source of information about these deaths...
January 9, 2018: Annals of Epidemiology
https://www.readbyqxmd.com/read/29352575/double-plication-for-spring-mediated-intestinal-lengthening-of-a-defunctionalized-roux-limb
#3
Genia Dubrovsky, Nhan Huynh, Anne-Laure Thomas, Shant Shekherdimian, James C Y Dunn
BACKGROUND: Spring-mediated distraction enterogenesis has been shown to increase the length of an intestinal segment. The goal of this study is to use suture plication to confine a spring within an intestinal segment while maintaining luminal patency to the rest of the intestine. METHODS: Juvenile mini-Yucatan pigs underwent placement of nitinol springs within a defunctionalized Roux limb of jejunum. A 20 French catheter was passed temporarily, and sutures were used to plicate the intestinal wall around the catheter at both ends of the encapsulated spring...
December 26, 2017: Journal of Pediatric Surgery
https://www.readbyqxmd.com/read/29352564/optical-metabolic-imaging-of-irradiated-rat-heart-exposed-to-ischemia-reperfusion-injury
#4
Mette Funding la Cour, Shima Mehrvar, James S Heisner, Mohammad Masoudi Motlagh, Meetha Medhora, Mahsa Ranji, Amadou K S Camara
Whole thoracic irradiation (WTI) is known to cause deterioration in cardiac function. Whether irradiation predisposes the heart to further ischemia and reperfusion (IR) injury is not well known. The aim of this study is to examine the susceptibility of rat hearts to IR injury following a single fraction of 15 Gy WTI and to investigate the role of mitochondrial metabolism in the differential susceptibility to IR injury. After day 35 of irradiation, ex vivo hearts from irradiated and nonirradiated rats (controls) were exposed to 25-min global ischemia followed by 60-min IR, or hearts were perfused without IR for the same protocol duration [time controls (TC)]...
January 2018: Journal of Biomedical Optics
https://www.readbyqxmd.com/read/29352482/influence-of-pharmacogenetic-polymorphisms-and-demographic-variables-on-metformin-pharmacokinetics-in-an-admixed-brazilian-cohort
#5
Ana Beatriz Santoro, Mariana Rodrigues Botton, Claudio José Struchiner, Guilherme Suarez-Kurtz
AIM: To identify pharmacogenetic and demographic variables that influence the systemic exposure to metformin in an admixed Brazilian cohort. METHODS: The extreme discordant phenotype was used to select 106 data sets from nine metformin bioequivalence trials, comprising 256 healthy adults. Eleven single-nucleotide polymorphisms in SLC22A1, SLC22A2, SLC47A1 SLC47A2 and in transcription factor SP1 were genotyped and a validated panel of ancestry informative markers was used to estimate the individual proportions of biogeographical ancestry...
January 20, 2018: British Journal of Clinical Pharmacology
https://www.readbyqxmd.com/read/29352455/clinical-features-in-a-series-of-258-japanese-pediatric-patients-with-thrombotic-microangiopathy
#6
Akira Ashida, Hideki Matsumura, Toshihiro Sawai, Rika Fujimaru, Yuko Fujii, Akihiko Shirasu, Hyogo Nakakura, Kazumoto Iijima
BACKGROUND: Thrombotic microangiopathy (TMA) includes hemolytic uremic syndrome (HUS) and thrombotic thrombocytopenic purpura (TTP). This study examined the epidemiological characteristics of pediatric patients with TMA classified according to etiology. METHODS: The survey evaluated 258 Japanese pediatric patients diagnosed with TMA between 2012 and 2015. RESULTS: The primary diseases responsible for TMA were categorized as TTP (15 cases), Shiga toxin-producing Escherichia coli-associated HUS (STEC-HUS) (166 cases), atypical HUS (aHUS) (40 cases), and secondary TMA (27 cases)...
January 19, 2018: Clinical and Experimental Nephrology
https://www.readbyqxmd.com/read/29352448/mesenchymal-stem-cell-deformability-and-implications-for-microvascular-sequestration
#7
Herbert H Lipowsky, Daniel T Bowers, Britany L Banik, Justin L Brown
Mesenchymal stem cells (MSCs) have received considerable attention in regenerative medicine, particularly in light of prospects for targeted delivery by intra-arterial injection. However, little is known about the mechanics of MSC sequestration in the microvasculature and the yield pressure (PY), above which MSCs will pass through microvessels of a given diameter. The objectives of the current study were to delineate the dependency of PY on cell size and the heterogeneity of cell mechanical properties and diameters (DCELL) of cultured MSCs...
January 19, 2018: Annals of Biomedical Engineering
https://www.readbyqxmd.com/read/29352436/posterolateral-tibial-plateau-fractures-how-to-buttress-reversed-l-posteromedial-or-the-posterolateral-approach-a-comparative-cadaveric-study
#8
Wich Orapiriyakul, Theerachai Apivatthakakul, Chanakarn Phornphutkul
INTRODUCTION: The selection of a surgical approach for buttressing posterolateral tibial plateau fractures is controversial. OBJECTIVE: This study compared the surgical exposure area between the reversed L posteromedial approach (R-PM) and the posterolateral (PL) approach using the lateral plateau width as a metric. MATERIALS AND METHODS: Twenty lower extremities from fresh frozen cadavers were included. The R-PM approach was used first and the boundary of the posterior tibial cortex exposure was marked with metal pins...
January 19, 2018: Archives of Orthopaedic and Trauma Surgery
https://www.readbyqxmd.com/read/29352366/a-new-class-of-cest-experiment-based-on-selecting-different-magnetization-components-at-the-start-and-end-of-the-cest-relaxation-element-an-application-to-1h-cest
#9
Tairan Yuwen, Lewis E Kay
Chemical exchange saturation transfer (CEST) experiments are becoming increasingly popular for investigating biomolecular exchange dynamics with rates on the order of approximately 50-500 s-1 and a rich toolkit of different methods has emerged over the past few years. Typically, experiments are based on the evolution of longitudinal magnetization, or in some cases two-spin order, during a fixed CEST relaxation delay, with the same class of magnetization prepared at the start and selected at end of the CEST period...
January 19, 2018: Journal of Biomolecular NMR
https://www.readbyqxmd.com/read/29352333/long-term-results-of-custom-cementless-stem-total-hip-arthroplasty-performed-in-hip-fusion
#10
Xavier Flecher, Matthieu Ollivier, Pascal Maman, Sébastien Pesenti, Sébastien Parratte, Jean-Noël Argenson
INTRODUCTION: Due to complex anatomical considerations, results of cementless-stem total hip arthroplasty (THA) in hip fusion remain controversial compared with conventional THA. We therefore aimed to analyse 3D anatomy of the fused hip based on pre-operative computed tomography (CT) scans, functional outcomes based on the Harris Hip Score (HHS) and the Hip Disability and Osteoarthritis Outcome Score (HOOS), modifications of hip anatomy based on post-operative standardised radiography, and determine complication rate and long-term survival based on Kaplan-Meier analysis...
January 19, 2018: International Orthopaedics
https://www.readbyqxmd.com/read/29352322/qportal-a-platform-for-data-driven-biomedical-research
#11
Christopher Mohr, Andreas Friedrich, David Wojnar, Erhan Kenar, Aydin Can Polatkan, Marius Cosmin Codrea, Stefan Czemmel, Oliver Kohlbacher, Sven Nahnsen
Modern biomedical research aims at drawing biological conclusions from large, highly complex biological datasets. It has become common practice to make extensive use of high-throughput technologies that produce big amounts of heterogeneous data. In addition to the ever-improving accuracy, methods are getting faster and cheaper, resulting in a steadily increasing need for scalable data management and easily accessible means of analysis. We present qPortal, a platform providing users with an intuitive way to manage and analyze quantitative biological data...
2018: PloS One
https://www.readbyqxmd.com/read/29352227/ly2087101-and-dfbr-share-transmembrane-binding-sites-in-the-%C3%AE-4-3-%C3%AE-2-2-nicotinic-acetylcholine-receptor
#12
Farah Deba, Hamed I Ali, Abisola Tairu, Kara Ramos, Jihad Ali, Ayman K Hamouda
Positive allosteric modulators (PAMs) of nicotinic acetylcholine receptors (nAChRs) have potential therapeutic application in neuropathologies associated with decrease in function or loss of nAChRs. In this study, we characterize the pharmacological interactions of the nAChRs PAM, LY2087101, with the α4β2 nAChR using mutational and computational analyses. LY2087101 potentiated ACh-induced currents of low-sensitivity (α4)3(β2)2 and high-sensitivity (α4)2(β2)3 nAChRs with similar potencies albeit to a different maximum potentiation (potentiation I max  = ~840 and 450%, respectively)...
January 19, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29352178/compositional-bias-in-na%C3%A3-ve-and-chemically-modified-phage-displayed-libraries-uncovered-by-paired-end-deep-sequencing
#13
Bifang He, Katrina F Tjhung, Nicholas J Bennett, Ying Chou, Andrea Rau, Jian Huang, Ratmir Derda
Understanding the composition of a genetically-encoded (GE) library is instrumental to the success of ligand discovery. In this manuscript, we investigate the bias in GE-libraries of linear, macrocyclic and chemically post-translationally modified (cPTM) tetrapeptides displayed on the M13KE platform, which are produced via trinucleotide cassette synthesis (19 codons) and NNK-randomized codon. Differential enrichment of synthetic DNA {S}, ligated vector {L} (extension and ligation of synthetic DNA into the vector), naïve libraries {N} (transformation of the ligated vector into the bacteria followed by expression of the library for 4...
January 19, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29352093/excessive-daytime-sleepiness-independently-predicts-increased-cardiovascular-risk-after-myocardial-infarction
#14
Jiang Xie, Fatima H Sert Kuniyoshi, Naima Covassin, Prachi Singh, Apoor S Gami, C Anwar A Chahal, Virend K Somers
BACKGROUND: Excessive daytime sleepiness (EDS), a common symptom among patients with sleep-disordered breathing, is closely associated with the development of cardiovascular diseases, but its long-term prognostic value is not completely understood. The aim of this study was to investigate whether EDS would be an independent prognostic factor after myocardial infarction. METHODS AND RESULTS: We prospectively recruited 112 post-myocardial infarction patients. The Epworth Sleepiness Scale was completed before polysomnography, and EDS was defined as a score ≥11...
January 19, 2018: Journal of the American Heart Association
https://www.readbyqxmd.com/read/29352073/right-ventricular-myofilament-functional-differences-in-humans-with-systemic-sclerosis-associated-versus-idiopathic-pulmonary-arterial-hypertension
#15
Steven Hsu, Kristen M Kokkonen-Simon, Jonathan A Kirk, Todd M Kolb, Rachel L Damico, Stephen C Mathai, Monica Mukherjee, Ami A Shah, Fredrick M Wigley, Kenneth B Margulies, Paul M Hassoun, Marc K Halushka, Ryan J Tedford, David A Kass
Background -Patients with systemic sclerosis-associated pulmonary arterial hypertension (SSc-PAH) have a far worse prognosis than those with idiopathic PAH (IPAH). In the intact heart, SSc-PAH exhibits depressed rest and reserve right ventricular (RV) contractility as compared to IPAH. We tested whether this disparity involves underlying differences in myofilament function. Methods -Cardiac myocytes were isolated from RV septal endomyocardial biopsies from patients with SSc-PAH, IPAH, or SSc with exertional dyspnea but no resting PAH (SSc-d); control RV septal tissue was obtained from non-diseased donor hearts (6-7/group)...
January 19, 2018: Circulation
https://www.readbyqxmd.com/read/29352030/the-daunting-polygenicity-of-mental-illness-making-a-new-map
#16
REVIEW
Steven E Hyman
An epochal opportunity to elucidate the pathogenic mechanisms of psychiatric disorders has emerged from advances in genomic technology, new computational tools and the growth of international consortia committed to data sharing. The resulting large-scale, unbiased genetic studies have begun to yield new biological insights and with them the hope that a half century of stasis in psychiatric therapeutics will come to an end. Yet a sobering picture is coming into view; it reveals daunting genetic and phenotypic complexity portending enormous challenges for neurobiology...
March 19, 2018: Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences
https://www.readbyqxmd.com/read/29352017/keeping-it-real-mrx-sae2-clipping-of-natural-substrates
#17
REVIEW
Robert Gnügge, Lorraine S Symington
The yeast Mre11-Rad50-Xrs2 (MRX) complex and Sae2 function together to initiate DNA end resection, an essential early step in homology-dependent repair of DNA double-strand breaks (DSBs). In this issue of Genes & Development, Wang and colleagues (pp. 2331-2336) and Reginato and colleagues (pp. 2325-2330) report that a variety of physiological protein blocks, including Ku, RPA, and nucleosomes, stimulate MRX-Sae2 endonuclease cleavage in vitro. These studies have important implications for how cells deal with a range of barriers to end resection and highlight the crucial role of Sae2 in activating MRX cleavage at the correct cell cycle stage...
December 1, 2017: Genes & Development
https://www.readbyqxmd.com/read/29351965/cost-effectiveness-of-cognitive-behavioral-therapy-for-depressed-youth-declining-antidepressants
#18
John F Dickerson, Frances L Lynch, Michael C Leo, Lynn L DeBar, John Pearson, Gregory N Clarke
BACKGROUND AND OBJECTIVES: Adolescents with depression identified in primary care settings often have limited treatment options beyond antidepressant (AD) therapy. We assessed the cost-effectiveness of a brief cognitive behavioral therapy (CBT) program among depressed adolescents who declined or quickly stopped using ADs. METHODS: A total of 212 youth with depression were randomly assigned to treatment as usual (TAU) or TAU plus brief individual CBT. Clinical outcomes included depression-free days (DFDs) and estimated quality-adjusted life-years (QALYs)...
January 19, 2018: Pediatrics
https://www.readbyqxmd.com/read/29351934/continuous-subcutaneous-levetiracetam-in-end-of-life-care
#19
Inês Furtado, Fernando Gonçalves, João Gonçalves, João Neves
Seizures constitute a determining aspect in quality of life and are frequently challenging in palliative care-a field where treatment has yet to be standardised. Levetiracetam-a new generation anticonvulsant-has proved efficacy both through oral, as well as intravenous administration in the general population. This case reports on the use of continuous subcutaneous levetiracetam to effectively control seizures in a terminally ill patient without patent oral route.
January 18, 2018: BMJ Case Reports
https://www.readbyqxmd.com/read/29351882/surface-characterization-of-arsenopyrite-during-chemical-and-biological-oxidation
#20
Sha Deng, Guohua Gu, Baoke Xu, Lijuan Li, Bichao Wu
The surface properties of arsenopyrite during chemical and biological oxidation were investigated by synchrotron X-ray diffraction (S-XRD), X-ray absorption near-edge structure (XANES) and scanning electron microscope (SEM), accompanying with leaching behaviors elucidation. The moderate thermophile S. thermosulfidooxdians was used as the bioleaching microorganism. Leaching experiments showed that only 16.26% and 44.37% of total arsenic extractions were obtained for sterile acid and culture medium controls, whereas 79...
January 16, 2018: Science of the Total Environment
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