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Frank Kloprogge, Lesley Workman, Steffen Borrmann, Mamadou Tékété, Gilbert Lefèvre, Kamal Hamed, Patrice Piola, Johan Ursing, Poul Erik Kofoed, Andreas Mårtensson, Billy Ngasala, Anders Björkman, Michael Ashton, Sofia Friberg Hietala, Francesca Aweeka, Sunil Parikh, Leah Mwai, Timothy M E Davis, Harin Karunajeewa, Sam Salman, Francesco Checchi, Carole Fogg, Paul N Newton, Mayfong Mayxay, Philippe Deloron, Jean François Faucher, François Nosten, Elizabeth A Ashley, Rose McGready, Michele van Vugt, Stephane Proux, Ric N Price, Juntra Karbwang, Farkad Ezzet, Rajesh Bakshi, Kasia Stepniewska, Nicholas J White, Philippe J Guerin, Karen I Barnes, Joel Tarning
BACKGROUND: The fixed dose combination of artemether-lumefantrine (AL) is the most widely used treatment for uncomplicated Plasmodium falciparum malaria. Relatively lower cure rates and lumefantrine levels have been reported in young children and in pregnant women during their second and third trimester. The aim of this study was to investigate the pharmacokinetic and pharmacodynamic properties of lumefantrine and the pharmacokinetic properties of its metabolite, desbutyl-lumefantrine, in order to inform optimal dosing regimens in all patient populations...
June 2018: PLoS Medicine
Cindy S Chu, Aung Pyae Phyo, Khin Maung Lwin, Htun Htun Win, Thida San, Aye Aye Aung, Rattanaporn Raksapraidee, Verena I Carrara, Germana Bancone, James Watson, Kerryn A Moore, Jacher Wiladphaingern, Stéphane Proux, Kanlaya Sriprawat, Markus Winterberg, Phaik Yeong Cheah, Amy L Chue, Joel Tarning, Mallika Imwong, François Nosten, Nicholas J White
Background: Chloroquine has been recommended for Plasmodium vivax infections for >60 years, but resistance is increasing. To guide future therapies, the cumulative benefits of using slowly eliminated (chloroquine) vs rapidly eliminated (artesunate) antimalarials, and the risks and benefits of adding radical cure (primaquine) were assessed in a 3-way randomized comparison conducted on the Thailand-Myanmar border. Methods: Patients with uncomplicated P. vivax malaria were given artesunate (2 mg/kg/day for 5 days), chloroquine (25 mg base/kg over 3 days), or chloroquine-primaquine (0...
June 8, 2018: Clinical Infectious Diseases: An Official Publication of the Infectious Diseases Society of America
Rohan Ameratunga, Yeri Ahn, Anthony Jordan, Klaus Lehnert, Shannon Brothers, See-Tarn Woon
Common Variable Immunodeficiency Disorders (CVID) are the most frequent symptomatic primary immune defect in adults. Within the broad spectrum of CVID, a proportion of patients present with a predominant T cell phenotype associated with increased mortality. These patients are termed late onset combined immunodeficiency (LOCID) and are currently separated from patients suffering from CVID. Areas covered: We have recently co-discovered a new CVID-like disorder caused by mutations of the NFKB1 gene. Members of this non-consanguineous NZ kindred have a very diverse spectrum of phenotypes in spite of carrying the identical mutation...
May 28, 2018: Expert Review of Clinical Immunology
Matthew M Ippolito, Jeffrey M Jacobson, Michael M Lederman, Markus Winterberg, Joel Tarning, Theresa A Shapiro, Charles Flexner
The effect of antiretroviral therapy (ART) on chloroquine and desethyl-chloroquine plasma concentrations was evaluated in clinical trial participants. Concentrations did not differ among participants on protease inhibitor-based ART (n=9), efavirenz-based ART (n=15), other ART (n=8), and those not on ART (n=31). Efavirenz appeared to inhibit chloroquine desethylation.
May 16, 2018: Clinical Infectious Diseases: An Official Publication of the Infectious Diseases Society of America
Tarn Stroud, N M Bagnall, Philip H Pucher
BACKGROUND: Trauma is one of the major causes of morbidity and mortality globally, especially in younger populations. With an increase in obesity globally, it is important to assess the potential differences in injury pattern and management of obese patients presenting with trauma compared to lean patients to try and improve patient care. This study aims to review the available literature comparing injury patterns between obese and non-obese patients. METHODS: A systematic review of articles which assessed the association between obesity and different patterns of trauma and injury were assessed...
May 8, 2018: International Journal of Surgery
Alexandra C Battersby, Alexander J Martin, Jessica Tarn, W F Ng, Catherine M Cale, David Goldblatt, Andrew R Gennery
The original version of the article, "Raised Serum IL-8 Levels Are Associated with Excessive Fatigue in Female Carriers of X-Linked Chronic Granulomatous Disease in the UK" incorrectly listed the name of the fourth author as Fai W. Ng. The correct spelling of the author's name is WF Ng.
April 23, 2018: Journal of Clinical Immunology
Mark D Tarn, Sebastien N F Sikora, Grace C E Porter, Daniel O'Sullivan, Mike Adams, Thomas F Whale, Alexander D Harrison, Jesús Vergara-Temprado, Theodore W Wilson, Jung-Uk Shim, Benjamin J Murray
Ice-nucleating particles (INPs) play a significant role in the climate and hydrological cycle by triggering ice formation in supercooled clouds, thereby causing precipitation and affecting cloud lifetimes and their radiative properties. However, despite their importance, INP often comprise only 1 in 103 -106 ambient particles, making it difficult to ascertain and predict their type, source, and concentration. The typical techniques for quantifying INP concentrations tend to be highly labour-intensive, suffer from poor time resolution, or are limited in sensitivity to low concentrations...
2018: Microfluidics and Nanofluidics
Luigimaria Borruso, Ciro Sannino, Laura Selbmann, Dario Battistel, Laura Zucconi, Maurizio Azzaro, Benedetta Turchetti, Pietro Buzzini, Mauro Guglielmin
Brines are hypersaline solutions which have been found within the Antarctic permafrost from the Tarn Flat area (Northern Victoria Land). Here, an investigation on the possible presence and diversity of fungal life within those peculiar ecosystems has been carried out for the first time. Brines samples were collected at 4- and 5-meter depths (TF1 and TF2, respectively), from two brines separated by a thin ice layer. The samples were analyzed via Illumina MiSeq targeting the ITS region specific for both yeasts and filamentous fungi...
April 26, 2018: Scientific Reports
James Watson, Cindy S Chu, Joel Tarning, Nicholas J White
The minimum inhibitory concentration (MIC) is an essential quantitative measure of the asexual blood stage effect of an antimalarial drug. In areas of high malaria transmission, and thus frequent individual infection, patients who are treated with slowly eliminated antimalarials become reinfected as drug concentrations decline. In the frequent relapse forms of P. vivax and in P. ovale malaria, recurrent infection occurs from relapses which begin to emerge from the liver approximately two weeks after the primary illness...
April 16, 2018: Antimicrobial Agents and Chemotherapy
Hung-Wei Wang, Cheng-Yuan Peng, Hsueh-Chou Lai, Wen-Pang Su, Chia-Hsin Lin, Po-Heng Chuang, Sheng-Hung Chen, Ching-Hsiang Chen, Wei-Fan Hsu, Guan-Tarn Huang
A correction to this article has been published and is linked from the HTML and PDF versions of this paper. The error has been fixed in the paper.
April 11, 2018: Scientific Reports
Tarn C Johnson, Bryony L Elbert, Alistair J M Farley, Timothy W Gorman, Christophe Genicot, Bénédicte Lallemand, Patrick Pasau, Jakub Flasz, José L Castro, Malcolm MacCoss, Darren J Dixon, Robert S Paton, Christopher J Schofield, Martin D Smith, Michael C Willis
Sulfones feature prominently in biologically active molecules and are key functional groups for organic synthesis. We report a mild, photoredox-catalyzed reaction for sulfonylation of aniline derivatives with sulfinate salts, and demonstrate the utility of the method by the late-stage functionalization of drugs. Key features of the method are the straightforward generation of sulfonyl radicals from bench-stable sulfinate salts and the use of simple aniline derivatives as convenient readily available coupling partners...
January 21, 2018: Chemical Science
Mary Ellen Gilder, Warunee Hanpithakphong, Richard M Hoglund, Joel Tarning, Htun Htun Win, Naw Hilda, Cindy S Chu, Germana Bancone, Verena I Carrara, Pratap Singhasivanon, Nicholas J White, François Nosten, Rose McGready
Background: Primaquine is the only drug providing radical cure of Plasmodium vivax malaria. It is not recommended for breastfeeding women as it causes hemolysis in glucose-6-phosphate dehydrogenase (G6PD) deficient individuals, and breast milk excretion and thus infant exposure are not known. Methods: Healthy G6PD normal breastfeeding women with previous P.vivax infection and their healthy G6PD normal infants between 28 days and 2 years old were enrolled. Mothers took primaquine 0...
March 24, 2018: Clinical Infectious Diseases: An Official Publication of the Infectious Diseases Society of America
Dhananjaya D, Kuan-Yang Hung, Woan-Yuh Tarn
The RNA-binding motif 4 (RBM4) protein participates in cell differentiation via its role in regulating the expression of or tissue-specific or developmentally regulated mRNA splice isoforms. RBM4 is expressed in embryonic brain during development; it is initially enriched in the ventricular zone/subventricular zone and subsequently distributed throughout the cortical cortex. Rbm4a knockout brain exhibited delayed migration of late-born neurons. Using in utero electroporation, we confirmed that knockdown of RBM4 impaired cortical neuronal migration...
March 26, 2018: Molecular and Cellular Biology
Jesmin Permala Lohy Das, Myat P Kyaw, Myat H Nyunt, Khin Chit, Kyin H Aye, Moe M Aye, Mats O Karlsson, Martin Bergstrand, Joel Tarning
BACKGROUND: Artemisinins are the most effective anti-malarial drugs for uncomplicated and severe Plasmodium falciparum malaria. However, widespread artemisinin resistance in the Greater Mekong Region of Southeast Asia is threatening the possibility to control and eliminate malaria. This work aimed to evaluate the pharmacokinetic and pharmacodynamic properties of artesunate and its active metabolite, dihydroartemisinin, in patients with sensitive and resistant falciparum infections in Southern Myanmar...
March 23, 2018: Malaria Journal
Natthida Sriboonvorakul, Aniruddha Ghose, M Mahtab Uddin Hassan, Md Amir Hossain, M Abul Faiz, Sasithon Pukrittayakamee, Kesinee Chotivanich, Yaowalark Sukthana, Stije J Leopold, Katherine Plewes, Nicholas P J Day, Nicholas J White, Joel Tarning, Arjen M Dondorp
BACKGROUND: In severe falciparum malaria metabolic acidosis and acute kidney injury (AKI) are independent predictors of a fatal outcome in all age groups. The relationship between plasma acids, urine acids and renal function was investigated in adult patients with acute falciparum malaria. METHODS: Plasma and urinary acids which previously showed increased concentrations in proportion to disease severity in patients with severe falciparum malaria were quantified...
March 23, 2018: Malaria Journal
Chenzhou Wu, John Gleysteen, Nutte Tarn Teraphongphom, Yi Li, Eben Rosenthal
Head and neck cancers become a severe threat to human's health nowadays and represent the sixth most common cancer worldwide. Surgery remains the first-line choice for head and neck cancer patients. Limited resectable tissue mass and complicated anatomy structures in the head and neck region put the surgeons in a dilemma between the extensive resection and a better quality of life for the patients. Early diagnosis and treatment of the pre-malignancies, as well as real-time in vivo detection of surgical margins during en bloc resection, could be leveraged to minimize the resection of normal tissues...
March 18, 2018: International Journal of Oral Science
Katherine Plewes, Hugh W F Kingston, Aniruddha Ghose, Thanaporn Wattanakul, Md Mahtab Uddin Hassan, Md Shafiul Haider, Prodip K Dutta, Md Akhterul Islam, Shamsul Alam, Selim Md Jahangir, A S M Zahed, Md Abdus Sattar, M A Hassan Chowdhury, M Trent Herdman, Stije J Leopold, Haruhiko Ishioka, Kim A Piera, Prakaykaew Charunwatthana, Kamolrat Silamut, Tsin W Yeo, Sue J Lee, Mavuto Mukaka, Richard J Maude, Gareth D H Turner, Md Abul Faiz, Joel Tarning, John A Oates, Nicholas M Anstey, Nicholas J White, Nicholas P J Day, Md Amir Hossain, L Jackson Roberts, Arjen M Dondorp
Background: Acute kidney injury independently predicts mortality in falciparum malaria. It is not known whether acetaminophen's capacity to inhibit plasma hemoglobin-mediated oxidation is renoprotective in severe malaria. Methods: A phase 2, open-label, randomized controlled trial at two hospitals in Bangladesh was conducted to assess effects on renal function, safety, pharmacokinetic properties and pharmacodynamic effects of acetaminophen. Febrile patients ( >12 years) with severe and moderately severe falciparum malaria were randomly assigned to receive acetaminophen (1g 6-hourly for 72 hours) or no acetaminophen, as an adjunct to intravenous artesunate...
March 12, 2018: Clinical Infectious Diseases: An Official Publication of the Infectious Diseases Society of America
Chun-Hao Su, Dhananjaya D, Woan-Yuh Tarn
Alternative splicing of precursor mRNA is an important mechanism that increases transcriptomic and proteomic diversity and also post-transcriptionally regulates mRNA levels. Alternative splicing occurs at high frequency in brain tissues and contributes to every step of nervous system development, including cell-fate decisions, neuronal migration, axon guidance, and synaptogenesis. Genetic manipulation and RNA sequencing have provided insights into the molecular mechanisms underlying the effects of alternative splicing in stem cell self-renewal and neuronal fate specification...
2018: Frontiers in Molecular Biosciences
Cécile Conte, Aurore Palmaro, Pascale Grosclaude, Laetitia Daubisse-Marliac, Fabien Despas, Maryse Lapeyre-Mestre
The use of claims database to study lymphomas in real-life conditions is a crucial issue in the future. In this way, it is essential to develop validated algorithms for the identification of lymphomas in these databases. The aim of this study was to assess the validity of diagnosis codes in the French health insurance database to identify incident cases of lymphomas according to results of a regional cancer registry, as the gold standard.Between 2010 and 2013, incident lymphomas were identified in hospital data through 2 algorithms of selection...
January 2018: Medicine (Baltimore)
Iris L A Bodewes, Shereen Al-Ali, Cornelia G van Helden-Meeuwsen, Naomi I Maria, Jessica Tarn, Dennis W Lendrem, Marco W J Schreurs, Eline C Steenwijk, Paul L A van Daele, Tim Both, Simon J Bowman, Bridget Griffiths, Wan-Fai Ng, Marjan A Versnel
Objective: To assess the relationships between systemic IFN type I (IFN-I) and II (IFN-II) activity and disease manifestations in primary SS (pSS). Methods: RT-PCR of multiple IFN-induced genes followed by principal component analysis of whole blood RNA of 50 pSS patients was used to identify indicator genes of systemic IFN-I and IFN-II activities. Systemic IFN activation levels were analysed in two independent European cohorts (n = 86 and 55, respectively) and their relationships with clinical features were analysed...
May 1, 2018: Rheumatology
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