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https://www.readbyqxmd.com/read/29030829/review-diagnosing-common-variable-immunodeficiency-disorder-in-the-era-of-genome-sequencing
#1
REVIEW
Rohan Ameratunga, Klaus Lehnert, See-Tarn Woon, David Gillis, Vanessa L Bryant, Charlotte A Slade, Richard Steele
Common variable immunodeficiency disorders (CVID) are an enigmatic group of often heritable conditions, which may manifest for the first time in early childhood or as late as the eighth decade of life. In the last 5 years, next generation sequencing (NGS) has revolutionised identification of genetic disorders. However, despite the best efforts of researchers around the globe, CVID conditions have been slow to yield their molecular secrets. We have previously described the many clinical advantages of identifying the genetic basis of primary immunodeficiency disorders (PIDs)...
October 14, 2017: Clinical Reviews in Allergy & Immunology
https://www.readbyqxmd.com/read/29018051/phase-iii-heat-study-adding-lyso-thermosensitive-liposomal-doxorubicin-to-radiofrequency-ablation-in-patients-with-unresectable-hepatocellular-carcinoma-lesions
#2
Won Young Tak, Shi-Ming Lin, Yijun Wang, Jiasheng Zheng, Aldo Vecchione, Soo Young Park, Min Hua Chen, Stephen Wong, Ruocai Xu, Cheng-Yuan Peng, Yi-You Chiou, Guan-Tarn Huang, Jianqiang Cai, Basri Johan Abdullah, June Sung Lee, Jae Young Lee, Jong Young Choi, Julieta Gopez-Cervantes, Morris Sherman, Richard S Finn, Masao Omata, Michael O'Neal, Lukas Makris, Nicholas Borys, Ronnie Poon, Riccardo Lencioni
PURPOSE: Lyso-thermosensitive liposomal doxorubicin (LTLD) consists of doxorubicin contained within a heat-sensitive liposome. When heated to >=40ºC, LTLD locally releases a high concentration of doxorubicin. We aimed to determine whether adding LTLD improves the efficacy of radiofrequency ablation (RFA) for hepatocellular carcinoma (HCC) lesions with a maximum diameter (dmax) of 3 to 7 cm. PATIENTS AND METHODS: The HEAT Study was a randomized, double-blind, dummy-controlled trial of RFA +/- LTLD...
October 10, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28992431/model-informed-drug-development-for-malaria-therapeutics
#3
Kayla Ann Andrews, David Wesche, James McCarthy, Jörg J Möhrle, Joel Tarning, Luann Phillips, Steven Kern, Thaddeus Grasela
Malaria is a critical public health problem resulting in substantial morbidity and mortality, particularly in developing countries. Owing to the development of resistance toward current therapies, novel approaches to accelerate the development efforts of new malaria therapeutics are urgently needed. There have been significant advancements in the development of in vitro and in vivo experiments that generate data used to inform decisions about the potential merit of new compounds. A comprehensive disease-drug model capable of integrating discrete data from different preclinical and clinical components would be a valuable tool across all stages of drug development...
October 6, 2017: Annual Review of Pharmacology and Toxicology
https://www.readbyqxmd.com/read/28991297/on-chip-polyelectrolyte-coating-onto-magnetic-droplets-towards-continuous-flow-assembly-of-drug-delivery-capsules
#4
Ali Q Alorabi, Mark D Tarn, Jenifer Gómez-Pastora, Eugenio Bringas, Inmaculada Ortiz, Vesselin N Paunov, Nicole Pamme
Polyelectrolyte (PE) microcapsules for drug delivery are typically fabricated via layer-by-layer (LbL) deposition of PE layers of alternating charge on sacrificial template microparticles, which usually requires multiple incubation and washing steps that render the process repetitive and time-consuming. Here, ferrofluid droplets were explored for this purpose as an elegant alternative of templates that can be easily manipulated via an external magnetic field, and require only a simple microfluidic chip design and setup...
October 9, 2017: Lab on a Chip
https://www.readbyqxmd.com/read/28971847/the-civilian-validation-of-the-modified-physiological-triage-tool-mptt-an-evidence-based-approach-to-primary-major-incident-triage
#5
James Vassallo, Jason Smith, Omar Bouamra, Fiona Lecky, Lee A Wallis
INTRODUCTION: Triage is a key principle in the effective management of a major incident. Existing triage tools have demonstrated limited performance at predicting need for life-saving intervention (LSI). Derived on a military cohort, the Modified Physiological Triage Tool (MPTT) has demonstrated improved performance. Using a civilian trauma registry, this study aimed to validate the MPTT in a civilian environment. METHODS: Retrospective database review of the Trauma Audit and Research Network (TARN) database for all adult patients (>18 years) between 2006 and 2014...
September 29, 2017: Emergency Medicine Journal: EMJ
https://www.readbyqxmd.com/read/28967808/understanding-factors-contributing-to-inappropriate-critical-care-a-mixed-methods-analysis-of-medical-record-documentation
#6
Thanh H Neville, Derjung M Tarn, Myrtle Yamamoto, Bryan J Garber, Neil S Wenger
BACKGROUND: Factors leading to inappropriate critical care, that is treatment that should not be provided because it does not offer the patient meaningful benefit, have not been rigorously characterized. OBJECTIVE: We explored medical record documentation about patients who received inappropriate critical care and those who received appropriate critical care to examine factors associated with the provision of inappropriate treatment. DESIGN: Medical records were abstracted from 123 patients who were assessed as receiving inappropriate treatment and 66 patients who were assessed as receiving appropriate treatment but died within six months of intensive care unit (ICU) admission...
June 22, 2017: Journal of Palliative Medicine
https://www.readbyqxmd.com/read/28926642/a-late-holocene-pollen-record-from-proglacial-oblong-tarn-mount-kenya
#7
Colin J Courtney Mustaphi, Konrad Gajewski, Rob Marchant, Gunhild Rosqvist
High-elevation ecosystems, such as those on Mount Kenya are undergoing significant changes, with accelerated glacial ice losses over the twentieth century creating new space for alpine plants to establish. These ecosystems respond rapidly to climatic variability and within decades of glacial retreat, Afroalpine pioneering taxa stabilize barren land and facilitate soil development, promoting complex patches of alpine vegetation. Periglacial lake sediment records can be used to examine centennial and millennial scale variations in alpine and montane vegetation compositions...
2017: PloS One
https://www.readbyqxmd.com/read/28895080/population-pharmacokinetic-and-pharmacodynamic-modeling-of-artemisinin-resistance-in-southeast-asia
#8
Jesmin Lohy Das, Arjen M Dondorp, Francois Nosten, Aung Pyae Phyo, Warunee Hanpithakpong, Pascal Ringwald, Pharath Lim, Nicholas J White, Mats O Karlsson, Martin Bergstrand, Joel Tarning
Orally administered artemisinin-based combination therapy is the first-line treatment against uncomplicated P. falciparum malaria worldwide. However, the increasing prevalence of artemisinin resistance is threatening efforts to treat and eliminate malaria in Southeast Asia. This study aimed to characterize the exposure-response relationship of artesunate in patients with artemisinin sensitive and resistant malaria infections. Patients were recruited in Pailin, Cambodia (n = 39), and Wang Pha, Thailand (n = 40), and received either 2 mg/kg/day of artesunate mono-therapy for 7 consecutive days or 4 mg/kg/day of artesunate monotherapy for 3 consecutive days followed by mefloquine 15 and 10 mg/kg for 2 consecutive days...
September 11, 2017: AAPS Journal
https://www.readbyqxmd.com/read/28886522/quantification-of-the-antimalarial-drug-pyronaridine-in-whole-blood-using-lc-ms-ms-increased-sensitivity-resulting-from-reduced-non-specific-binding
#9
Daniel Blessborn, Karnrawee Kaewkhao, Lijiang Song, Nicholas J White, Nicholas P J Day, Joel Tarning
Malaria is one of the most important parasitic diseases of man. The development of drug resistance in malaria parasites is an inevitable consequence of their widespread and often unregulated use. There is an urgent need for new and effective drugs. Pyronaridine is a known antimalarial drug that has received renewed interest as a partner drug in artemisinin-based combination therapy. To study its pharmacokinetic properties, particularly in field settings, it is necessary to develop and validate a robust, highly sensitive and accurate bioanalytical method for drug measurements in biological samples...
August 26, 2017: Journal of Pharmaceutical and Biomedical Analysis
https://www.readbyqxmd.com/read/28857411/trajectories-of-serum-hepatitis-b-surface-antigen-kinetics-in-patients-with-chronic-hepatitis-b-receiving-long-term-nucleos-t-ide-analogue-therapy
#10
Wei-Fan Hsu, Chuen-Fei Chen, Hsueh-Chou Lai, Wen-Pang Su, Chia-Hsin Lin, Po-Heng Chuang, Sheng-Hung Chen, Ching-Hsiang Chen, Hung-Wei Wang, Guan-Tarn Huang, Cheng-Yuan Peng
BACKGROUND & AIMS: The kinetics of serum hepatitis B surface antigen (HBsAg) levels during long-term nucleos(t)ide analogue (NA) therapy in chronic hepatitis B (CHB) patients remains unclear. We investigated the patterns of serum HBsAg kinetics and their association with therapeutic outcomes in genotype B- or C-infected CHB patients receiving long-term NA therapy. METHODS: We enrolled 329 treatment-naive CHB patients receiving NA therapy for >5 years to analyse the kinetic patterns by using group-based trajectory models (GBTMs)...
August 31, 2017: Liver International: Official Journal of the International Association for the Study of the Liver
https://www.readbyqxmd.com/read/28851530/van-de-graaff-generator-for-capillary-electrophoresis
#11
Seung Jae Lee, Eric R Castro, Rosanne M Guijt, Mark D Tarn, Andreas Manz
A new approach for high voltage capillary electrophoresis (CE) is proposed, which replaces the standard high voltage power supply with a Van de Graaff generator, a low current power source. Because the Van de Graaff generator is a current-limited source (10μA), potentials exceeding 100kV can be generated for CE when the electrical resistance of the capillary is maximized. This was achieved by decreasing the capillary diameter and reducing the buffer ionic strength. Using 2mM borate buffer and a 5μm i.d. capillary, fluorescently labeled amino acids were separated with efficiencies up to 3...
August 12, 2017: Journal of Chromatography. A
https://www.readbyqxmd.com/read/28835283/identifying-pre-hospital-factors-associated-with-outcome-for-major-trauma-patients-in-a-regional-trauma-network-an-exploratory-study
#12
Lee Thompson, Michael Hill, Caroline Davies, Gary Shaw, Matthew D Kiernan
BACKGROUND: Major trauma is often life threatening and the leading cause of death in the United Kingdom (UK) for adults aged less than 45 years old. This study aimed to identify pre-hospital factors associated with patient outcomes for major trauma within one Regional Trauma Network. METHOD: Secondary analysis of pre-hospital audit data and patient outcome data from the Trauma Audit Research Network (TARN) was undertaken. The primary outcome used in analysis was 'Status at Discharge' (alive/deceased)...
August 23, 2017: Scandinavian Journal of Trauma, Resuscitation and Emergency Medicine
https://www.readbyqxmd.com/read/28833674/a-c-h-cyanation-of-6-ring-n-containing-heteroaromatics
#13
Bryony Elbert, Alistair Farley, Timothy Gorman, Tarn Johnson, Christophe Genicot, Benedicte Lallemand, Patrick Pasau, Jakub Flasz, Jose Castro, Malcolm Maccoss, Robert Paton, Christopher Schofield, Martin Smith, Michael Willis, Darren James Dixon
Heteroaromatic nitriles are important compounds in drug discovery, both for their prevalence in the clinic and due to the diverse range of transformations they can undergo. As such, efficient and reliable methods to access them have the potential for far-reaching impact across synthetic chemistry and the biomedical sciences. Here we report an approach to heteroaromatic C-H cyanation through triflic anhydride activation, nucleophilic addition of cyanide, and concomitant elimination of trifluoromethanesulfinate to regenerate the cyanated heteroaromatic ring...
August 23, 2017: Chemistry: a European Journal
https://www.readbyqxmd.com/read/28753730/a-microfluidic-device-for-rapid-screening-of-e-%C3%A2-coli-o157-h7-based-on-ifast-and-atp-bioluminescence-assay-for-water-analysis
#14
Bongkot Ngamsom, Alma Truyts, Louis Fourie, Shavon Kumar, Mark D Tarn, Alexander Iles, Klariska Moodley, Kevin J Land, Nicole Pamme
We present a simple microfluidic system for rapid screening of Escherichia coli (E. coli) O157:H7 employing the specificity of immunomagnetic separation (IMS) via immiscible filtration assisted by surface tension (IFAST), and the sensitivity of the subsequent adenosine triphosphate (ATP) assay by the bioluminescence luciferin/luciferase reaction. The developed device was capable of detecting E. coli O157:H7 from just 6 colony forming units (CFU) in 1 mL spiked buffer within 20 min. When tested with wastewater discharged effluent samples, without pre-concentration, the device demonstrated the ability to detect 10(4)  CFU per mL seeded; suggesting great potential for point-of-need microbiological water quality monitoring...
July 28, 2017: Chemistry: a European Journal
https://www.readbyqxmd.com/read/28720134/in-vitro-antioxidant-and-antimalarial-activities-of-leaves-pods-and-bark-extracts-of-acacia-nilotica-l-del
#15
Muhammad Bilal Sadiq, Pattamon Tharaphan, Kesinee Chotivanich, Joel Tarning, Anil Kumar Anal
BACKGROUND: The emergence of drug resistant malaria is threatening our ability to treat and control malaria in the Southeast Asian region. There is an urgent need to develop novel and chemically diverse antimalarial drugs. This study aimed at evaluating the antimalarial and antioxidant potentials of Acacia nilotica plant extracts. METHODS: The antioxidant activities of leaves, pods and bark extracts were determined by standard antioxidant assays; reducing power capacity, % lipid peroxidation inhibition and ferric reducing antioxidant power assay...
July 18, 2017: BMC Complementary and Alternative Medicine
https://www.readbyqxmd.com/read/28695570/population-pharmacokinetics-and-electrocardiographic-effects-of-dihydroartemisinin-piperaquine-in-healthy-volunteers
#16
Palang Chotsiri, Thanaporn Wattanakul, Richard Hoglund, Borimas Hanboonkunupakarn, Sasithon Pukrittayakamee, Daniel Blessborn, Podjanee Jittamala, Nicholas J White, Nicholas P J Day, Joel Tarning
AIMS: The aims of the presented study were to evaluate the pharmacokinetic properties of dihydroartemisinin and piperaquine, potential drug-drug interactions with concomitant primaquine treatment, and piperaquine effects on the electrocardiogram in healthy volunteers. METHODS: Population pharmacokinetic properties of dihydroartemisinin and piperaquine were assessed in 16 in healthy Thai adults using an open-label randomized crossover study. Drug concentration-time data and electrocardiographic measurements were evaluated with nonlinear mixed-effects modelling...
July 11, 2017: British Journal of Clinical Pharmacology
https://www.readbyqxmd.com/read/28687086/ivermectin-susceptibility-and-sporontocidal-effect-in-greater-mekong-subregion-anopheles
#17
Kevin C Kobylinski, Ratawan Ubalee, Alongkot Ponlawat, Chanyapat Nitatsukprasert, Siriporn Phasomkulsolsil, Thanaporn Wattanakul, Joel Tarning, Kesara Na-Bangchang, Patrick W McCardle, Silas A Davidson, Jason H Richardson
BACKGROUND: Novel vector control methods that can directly target outdoor malaria transmission are urgently needed in the Greater Mekong Subregion (GMS) to accelerate malaria elimination and artemisinin resistance containment efforts. Ivermectin mass drug administration (MDA) to humans has been shown to effectively kill wild Anopheles and suppress malaria transmission in West Africa. Preliminary laboratory investigations were performed to determine ivermectin susceptibility and sporontocidal effect in GMS Anopheles malaria vectors coupled with pharmacokinetic models of ivermectin at escalating doses...
July 7, 2017: Malaria Journal
https://www.readbyqxmd.com/read/28607450/new-noninvasive-index-for-predicting-liver-fibrosis-in-asian-patients-with-chronic-viral-hepatitis
#18
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
We developed an optimal noninvasive index comprising routine laboratory parameters for predicting cirrhosis in chronic hepatitis B (CHB) and chronic hepatitis C (CHC) patients. This study included 992 CHB patients and 1,284 CHC patients who received liver biopsy. We developed the new index, named modified Fibrosis-4 (mFIB-4) according to four independent variables of the model: age, aspartate aminotransferase (AST), alanine aminotransferase (ALT), and platelet count. The formula of the mFIB-4 index is 10 × Age(years) × AST(U/L)/Platelet count(10(9)/L) × AST(U/L)...
June 12, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28602178/differential-effects-of-the-glasgow-coma-scale-score-and-its-components-an-analysis-of-54-069-patients-with-traumatic-brain-injury
#19
Florence C M Reith, Hester F Lingsma, Belinda J Gabbe, Fiona E Lecky, Ian Roberts, Andrew I R Maas
INTRODUCTION: The Glasgow Coma Scale (GCS) is widely used in the assessment of clinical severity and prediction of outcome after traumatic brain injury (TBI). The sum score is frequently applied, but the differential influence of the components infrequently addressed. We aimed to investigate the contribution of the GCS components to the sum score, floor and ceiling effects of the components, and their prognostic effects. METHODS: Data on adult TBI patients were gathered from three data repositories: TARN (n=50,064), VSTR (n=14,062), and CRASH (n=9,941)...
September 2017: Injury
https://www.readbyqxmd.com/read/28597978/pharmacokinetics-of-sulfadoxine-and-pyrimethamine-for-intermittent-preventive-treatment-of-malaria-during-pregnancy-and-after-delivery
#20
M de Kock, J Tarning, L Workman, M M Nyunt, I Adam, K I Barnes, P Denti
Sulfadoxine/pyrimethamine is recommended for intermittent preventative treatment of malaria during pregnancy. Data from 98 women during pregnancy and 77 after delivery in four African countries were analyzed using nonlinear mixed-effects modeling to characterize the effects of pregnancy, postpartum duration, and other covariates such as body weight and hematocrit on sulfadoxine/pyrimethamine pharmacokinetic properties. During pregnancy, clearance increased 3-fold for sulfadoxine but decreased by 18% for pyrimethamine...
July 2017: CPT: Pharmacometrics & Systems Pharmacology
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