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https://www.readbyqxmd.com/read/29661873/characterising-blood-stage-antimalarial-drug-minimum-inhibitory-concentrations-in-vivo-using-reinfection-patterns
#1
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
https://www.readbyqxmd.com/read/29643348/publisher-correction-new-noninvasive-index-for-predicting-liver-fibrosis-in-asian-patients-with-chronic-viral-hepatitis
#2
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
https://www.readbyqxmd.com/read/29629128/direct-sulfonylation-of-anilines-mediated-by-visible-light
#3
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
https://www.readbyqxmd.com/read/29590311/primaquine-pharmacokinetics-in-lactating-women-and-breastfed-infant-exposures
#4
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
https://www.readbyqxmd.com/read/29581187/rbm4-modulates-radial-migration-via-alternative-splicing-of-dab1-during-cortex-development
#5
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
https://www.readbyqxmd.com/read/29566683/population-pharmacokinetic-and-pharmacodynamic-properties-of-artesunate-in-patients-with-artemisinin-sensitive-and-resistant-infections-in-southern-myanmar
#6
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
https://www.readbyqxmd.com/read/29566677/acidosis-and-acute-kidney-injury-in-severe-malaria
#7
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
https://www.readbyqxmd.com/read/29555901/in-vivo-optical-imaging-in-head-and-neck-oncology-basic-principles-clinical-applications-and-future-directions
#8
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
https://www.readbyqxmd.com/read/29538635/acetaminophen-as-a-renoprotective-adjunctive-treatment-in-patients-with-severe-and-moderately-severe-falciparum-malaria-a-randomized-controlled-open-label-trial
#9
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
https://www.readbyqxmd.com/read/29484299/alternative-splicing-in-neurogenesis-and-brain-development
#10
REVIEW
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
https://www.readbyqxmd.com/read/29480830/a-novel-approach-for-medical-research-on-lymphomas-a-study-validation-of-claims-based-algorithms-to-identify-incident-cases
#11
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)
https://www.readbyqxmd.com/read/29474655/systemic-interferon-type-i-and-type-ii-signatures-in-primary-sj%C3%A3-gren-s-syndrome-reveal-differences-in-biological-disease-activity
#12
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...
February 20, 2018: Rheumatology
https://www.readbyqxmd.com/read/29465764/comparison-of-two-prognostic-models-in-trauma-outcome
#13
A Cook, T Osler, L Glance, F Lecky, O Bouamra, J Weddle, B Gross, J Ward, F O Moore, F Rogers, D Hosmer
BACKGROUND: The Trauma Audit and Research Network (TARN) in the UK publicly reports hospital performance in the management of trauma. The TARN risk adjustment model uses a fractional polynomial transformation of the Injury Severity Score (ISS) as the measure of anatomical injury severity. The Trauma Mortality Prediction Model (TMPM) is an alternative to ISS; this study compared the anatomical injury components of the TARN model with the TMPM. METHODS: Data from the National Trauma Data Bank for 2011-2015 were analysed...
February 21, 2018: British Journal of Surgery
https://www.readbyqxmd.com/read/29463542/population-pharmacokinetic-properties-of-sulfadoxine-and-pyrimethamine-a-pooled-analysis-to-inform-optimal-dosing-in-african-children-with-uncomplicated-malaria
#14
Miné de Kock, Joel Tarning, Lesley Workman, Elizabeth N Allen, Mamadou M Tekete, Abdoulaye A Djimde, David J Bell, Steve A Ward, Karen I Barnes, Paolo Denti
Sulfadoxine/pyrimethamine with amodiaquine is recommended by the World Health Organization as seasonal malaria chemoprevention for children between 3 to 59 months in the sub-Sahel regions of Africa. Sub-optimal dosing in children may lead to treatment failure and increased resistance. Pooled individual patient data from four previously published trials on the pharmacokinetics of sulfadoxine and pyrimethamine in 415 paediatric and 386 adult patients were analysed using nonlinear mixed effects modelling to evaluate the current dosing regimen and, if needed, propose an optimised dosing regimen in children under five years old...
February 20, 2018: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/29444080/promising-approach-to-reducing-malaria-transmission-by-ivermectin-sporontocidal-effect-against-plasmodium-vivax-in-the-south-american-vectors-anopheles-aquasalis-and-anopheles-darlingi
#15
Yudi T Pinilla, Stefanie C P Lopes, Vanderson S Sampaio, Francys S Andrade, Gisely C Melo, Alessandra S Orfanó, Nágila F C Secundino, Maria G V B Guerra, Marcus V G Lacerda, Kevin C Kobylinski, Karin S Escobedo-Vargas, Victor M López-Sifuentes, Craig A Stoops, G Christian Baldeviano, Joel Tarning, Gissella M Vasquez, Paulo F P Pimenta, Wuelton M Monteiro
BACKGROUND: The mosquito resistance to the insecticides threatens malaria control efforts, potentially becoming a major public health issue. Alternative methods like ivermectin (IVM) administration to humans has been suggested as a possible vector control to reduce Plasmodium transmission. Anopheles aquasalis and Anopheles darlingi are competent vectors for Plasmodium vivax, and they have been responsible for various malaria outbreaks in the coast of Brazil and the Amazon Region of South America...
February 14, 2018: PLoS Neglected Tropical Diseases
https://www.readbyqxmd.com/read/29395998/treatment-of-uncomplicated-and-severe-malaria-during-pregnancy
#16
REVIEW
Umberto D'Alessandro, Jenny Hill, Joel Tarning, Christopher Pell, Jayne Webster, Julie Gutman, Esperanca Sevene
Over the past 10 years, the available evidence on the treatment of malaria during pregnancy has increased substantially. Owing to their relative ease of use, good sensitivity and specificity, histidine rich protein 2 based rapid diagnostic tests are appropriate for symptomatic pregnant women; however, such tests are less appropriate for systematic screening because they will not detect an important proportion of infections among asymptomatic women. The effect of pregnancy on the pharmacokinetics of antimalarial drugs varies greatly between studies and class of antimalarial drugs, emphasising the need for prospective studies in pregnant and non-pregnant women...
April 2018: Lancet Infectious Diseases
https://www.readbyqxmd.com/read/29364004/motorcyclists-and-pillion-passengers-with-open-lower-limb-fractures-a-study-using-tarn-data-2007-2014
#17
Agc Hay-David, T Stacey, I Pallister
Introduction We aimed to identify population demographics of motorcyclists and pillion passengers with isolated open lower-limb fractures, to ascertain the impact of the revised 2009 British Orthopaedic Association/British Association of Plastic Reconstructive and Aesthetic Surgeons joint standards for the management of open fractures of the lower limb (BOAST 4), in terms of time to skeletal stabilisation and soft-tissue coverage, and to observe any impact on patient movement. Methods Retrospective cohort data was collected by the Trauma Audit and Research Network (TARN)...
January 24, 2018: Annals of the Royal College of Surgeons of England
https://www.readbyqxmd.com/read/29316466/metal-complexation-capacity-of-antarctic-lacustrine-sediments
#18
Giancarla Alberti, Matteo Mussi, Federico Quattrini, Maria Pesavento, Raffaela Biesuz
The purpose of this study is to implement a work that is a part of a project funded by the Italian National Antarctic Research Program (PNRA, Piano Nazionale di Ricerche in Antartide) within the main thematic focus "Chemical Contamination-Global Change". This research was devoted to detect and characterize micro and nano components with strong complexing capability towards metal ions at trace level in sea water, lakes and lacustrine sediments, sampled during the XXII expedition of PNRA. In particular, in the present work, the sorption complexation capacity of an Antarctic lacustrine sediments toward Cu(II) and Pb(II) is described...
April 2018: Chemosphere
https://www.readbyqxmd.com/read/29306138/spatial-and-length-dependent-variation-of-the-risks-and-benefits-of-consuming-walleye-sander-vitreus
#19
Ursula Strandberg, Satyendra P Bhavsar, Tarn Preet Parmar, Michael T Arts
Restricted fish consumption due to elevated contaminant levels may limit the intake of essential omega-3 fatty acids, such as eicosapentaenoic (EPA; 20:5n-3) and docosahexaenoic (DHA; 22:6n-3) acids. We analyzed lake- and length-specific mercury and EPA+DHA contents in Walleye (Sander vitreus; Mitchell 1818) from 20 waterbodies in Ontario, Canada, and used this information to calculate the theoretical intake of EPA+DHA when the consumption advisories are followed. The stringent consumption advisory resulted in decreased EPA+DHA intake regardless of the EPA+DHA content in Walleye...
January 2, 2018: Environment International
https://www.readbyqxmd.com/read/29244851/inhibition-of-merozoite-invasion-and-transient-de-sequestration-by-sevuparin-in-humans-with-plasmodium-falciparum-malaria
#20
RANDOMIZED CONTROLLED TRIAL
Anna M Leitgeb, Prakaykaew Charunwatthana, Ronnatrai Rueangveerayut, Chirapong Uthaisin, Kamolrat Silamut, Kesinee Chotivanich, Patima Sila, Kirsten Moll, Sue J Lee, Maria Lindgren, Erik Holmer, Anna Färnert, Mpungu S Kiwuwa, Jens Kristensen, Christina Herder, Joel Tarning, Mats Wahlgren, Arjen M Dondorp
SEVERE MALARIA: Even with the best available treatment, the mortality from severe Plasmodium falciparum malaria remains high. Typical features at death are high parasite loads and obstructed micro- vasculature. Infected erythrocytes (IE) containing mature parasites bind to the host receptor heparan sulfate, which is also an important receptor for merozoite invasion. To block merozoite invasion has not previously been proposed as an adjunctive therapeutic approach but it may preclude the early expansion of an infection that else leads to exacerbated sequestration and death...
2017: PloS One
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